Tuesday, February 14, 2023

Lysine-Specific Demethylase 1: A Promising Target Therapy - Juniper Publishers

 Cancer Therapy & Oncology International Journal - Juniper Publishers


Histone demethylases are a new class of emerging epigenetic modulators. The first described histone demethylase enzyme in this group is lysine-specific demethylase 1A. It removes methyl groups from histones H3K4me1/2 and H3K9me1/2. LSD1 is abnormally overexpressed in various types of solid tumors and acute leukemias, where it impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, and is associated with inferior prognosis. LSD1 inhibitors significantly attenuate tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia.

Abbreviations: ESC: Embryonic Stem Cell; MAOs: Monoamine Oxidases; FAD: Flavin Adenine Dinucleotide; LSD1: Lysine-Specific Demethylase 1; TCP: Tranylcypromine; AML: Acute Myeloid Leukemia; JMJD: JUMONJI C Domain-Containing; DNMT1: DNA-Methyltransferase 1; STAT3: Signal Transducer and Activator of Transcription 3; E2F1: E2F Transcription factor 1; 2-OG: 2-Oxoglutarate; ATRA: All Trans Retinoic Acid.


Epigenetic events serve an important function in carcinogenesis. Post-translational Histone modifications are critical for control of transcription and chromatin architecture. Histone demethylases is a new class of emerging epigenetic modulators [1] that catalyze N-demethylation of histone lysine’s [2]. Demethylation differs from histone acetylation in the fact that methylation occurs on both lysine and arginine (R), and in being linked to both transcriptional activation and repression [1]. Demethylases are divided into two subgroups based on their catalytic mechanisms: the flavin adenine dinucleotide (FAD)-dependent LSD1 and LSD2 and JMJD family containing JmjC domain [2].

The flavin adenine dinucleotide (FAD)-dependent LSD1 and LSD2

Lysine-specific demethylase 1A (LSD1), is known also as KDM1A, KIAA0601, BHC110, and AOF2) [3]. It is the first described histone demethylase enzyme. LSD1 enzyme consisted of 3 major domains: an amine oxidase (AO)-like domain, which is FAD cofactor dependent, a SWIRM domain, which is unique to chromatin-associated proteins and a coiled-coil TOWER domain [4]. It is located in the cell nucleus and is a key epigenetic regulator that acts as a histone methylation eraser. It demethylates di- and mono-methyl groups from the fourth and nine positions on histone 3 protein (H3K4me2/1 and H3K9me2/1), but not H3K4me3. This results in transcriptional repression or activation, respectively [3]. LSD1 can also remove mono- and di-methylated lysine residues from few non-histone targets (such as DNMT1, p53, E2F1, HIF-1α and STAT3) which are associated with angiogenesis, cell cycle arrest, chromatin remolding and proliferation of cancer cells [3]. In addition, LSD1 functions as a H3K9 demethylase when recruited by androgen or estrogen receptor [4]. LSD2 is also important in epigenetic regulation. LSD2 is a histone H3K4me1/2 demethylase with different structural organization and functions relative to LSD1 [2].

JMJD family containing JmjC domain

The JMJD family has key roles in cell differentiation, proliferation, and stem cell self-renewal. They oxidatively remove the trimethyl group of histone lysine residues preferably in a Fe2+ and 2-oxoglutarate (2-OG) dependent manner [2].

Lysine-specific demethylase 1A (LSD1)

LSD1 and biological functions

LSD1 is highly expressed in embryonic stem cells (ESC) and is downregulated during differentiation [3]. LSD1 shows differential expression in adult tissues [5]. It regulates vital cellular processes, ranging from embryonic development to adult tissue homeostasis [3]. LSD1 maintains self-renewal potential of embryonic stem cells and adult stem cells and regulates cellular differentiation of stem cells in various tissues, including myogenic differentiation, adipogenesis, hematopoiesis and epithelial differentiation [6]. In hematopoiesis, LSD1 negatively regulates HSCs self-renewal and help terminal erythroid, granulocytic, and megakaryocytic maturation [3]. LSD1-defeciency causes severe pancytopenia and impaired HSCs differentiation [3]. LSD1 also plays a significant role in development, thermogenesis, inflammation, neuronal and cerebral physiology, and the maintenance of stemness in stem cells [6].

LSD1 and pathological conditions

In emergency hematopoiesis as in severe viral or bacterial infections, the inflammatory cytokines TNFα and IL1β suppress LSD1 activity and induce HSCs proliferation, differentiation, and immune cells production [3]. LSD1 participates in pathological conditions including cancer and viral infection. LSD1 is involved in various stages of cancer including development, progression, metastasis, and recurrence after therapy [3]. LSD1 is not a potent oncogene [3]. It promotes tumor-cell growth [6] and facilitates cancer cells survival [6] by regulating gene expression in favor of cancer cells adaptation to a pro-cancer microenvironment [6].

LSD1 inhibitors in clinical trials

LSD1 inhibition is a potential anti-cancer therapeutic strategy [5] due to its high enzymatic activity and level of expression in various types of tumors [4] as breast cancer, prostate cancer, neuroblastoma as well as in hematological malignancies [3]. LSD1 is considered a homology protein of MAO-A/B. Six MAO inhibitors were tested for their ability to inhibit LSD1 activity; three were nonselective (a) tranylcypromine/trans-2- phenyl cyclopropylamine (TCP/2-PCPA), (b) phenelzine, and (c) nialamide and three were selective for MAOA or MAOB (a) clorgiline, (b) deprenyl, and (c) pargyline [1].

LSD1 inhibitors in clinical trials in solid tumors

Several LSD1 inhibitors have been explored in the treatment of lung cancer and other solid tumors in clinical trials or even clinical use [6]. LSD1 inhibition in cancer cells enhances immunogenicity of tumor and secretion of chemokines that attract T cells, and reverse resistance to PD-(L)1 blockade. LSD1 inhibitors upregulate proinflammatory cytokines in Treg cells. It also promotes macrophages polarization to anti-tumor M1-like macrophages and enhances the infiltration of these macrophages and CD8 + T cells into the tumor. Furthermore, LSD1 inhibition activates innate immune cells, including macrophages and natural killer cells [6]. The insufficiency of LSD1 catalytic inhibition in some cancers may be explained by LSD1 demethylase-independent activity during carcinogenesis [2].

LSD1 inhibitors in clinical trials in solid tumors

LSD1 inhibitors are a promising epigenetic approach to treat AML. They alter stem cell programs, inhibit proliferation, and restore myeloid differentiation in AML cells. They have increased efficacy in leukemia subtypes carrying AML1 and MLL rearrangements, NPM1 mutations, and erythroid and megakaryoblastic differentiation block. Their effects are enhanced markedly when combined with histone deacetylase inhibitors (HDACs) or ATRA with little toxicity. Clinical trials are currently aim at treatment of refractory AML by blocking LSD1 activity [3].

The following LDS1 inhibitors are under clinical trial in AML

ORY-1001 induces cell differentiation followed by reduction of cell growth and clonogenicity particularly in M4 and M5 FAB subtypes and AML cells carrying MLL translocations [3]. INCB059872 (Incyte) is a potent selective LDS1 inhibitor that delays cellular proliferation and induces human AML cells differentiation [3]. T3775440 is a potent selective LSD1 inhibitor against erythroid and megakaryocytic leukemic cell lines [3]. SP2509 (Salarius Pharmaceuticals) is lethal against AML expressing NMP1 mutation and MLL-rearrangements [3].

Problems associated with LSD1 inhibitors

The need to use more than single screening method due to the high rate of false-positive or -negative results [5].

The difficulty to develop selective LSD1 inhibitors due to the high similarity of LSD1 with LSD2 and MAOs [5].

Low anti-cancer potency of many LSD1 inhibitors, as many tumor suppressor genes or oncogenes are often regulated by multiple enzymes [5]. Combining LSD1 inhibitors with other drugs such as HDACs, or EZH2 (enhancer of zeste homolog 2) inhibitors may be a solution. For example, combining SP2509 with Panobinostat (HDAC inhibitor) shows promising results compared to either agent alone in AML clinical trials. Combined inhibitors of LSD1 and EZH2 act synergistically by inhibiting different histone methylation-modulating proteins with apparently opposite enzyme activities [3].

Some LSD1 inhibitors are associated with acute anemia and decreased platelets’ numbers [5].

The different role played by LSD1 in different cancers [5].


LSD1 acts as a key epigenetic regulator of gene expression that controls cellular homeostasis. It can be a therapeutic target in certain diseases. Gaining an accurate understanding of the mechanism of action of LSD1 is essential for overcoming several diseases.

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The Death of Police Officers at The Scene of Incident: A New Approach within The South African Police Services Response to Crime - Juniper Publishers

 Annals of Social Sciences & Management Studies - Juniper Publishers


Policing encompasses a multitude of diverse tasks, including peacekeeping, criminal investigation, traffic control, and providing emergency medical service. Being a law enforcement officer is to engage one’s own life to save the state and its citizens, to ensure the safety and security of the people and to ensure people are respecting the rules and regulations that govern the country including its constitution and the Bill of rights. The significance of this study is to analyze the circumstances in which police officers are killed by examining their tactics used to respond to the scene of the incident and suggesting new approaches that can help in preventing the loss of manpower within the law enforcement structure. The study used a qualitative secondary data approach to generate data with a systematic method for data analysis. The findings reveal that the proliferation of firearms in South Africa, the suspect’s perseverance in violence, suspect protection, and defense are some of the causes of the killing of the police officers on duty. This study suggests that the interventions of law enforcement officers should depend on the type or nature of the crime. A violent crime that involved murder should be attended to carefully to neutralize or incapacitate the suspect by all means. Intelligence-led policing involving ununiformed members of the community, the zero tolerance and community policing approaches must be applied to curb or prevent the killing of on-duty law enforcement officers.

Keywords: Policing; Crime; The scene of the Incident; Death of police


Let us first remind the public that the South African Police Service is governed by Chapter 11 of the Constitution of the Republic of South Africa, 1996 (Act 108 of 1996) that stipulates the South African Police Service has a responsibility to:

- prevent, combat, and investigate crime.

- maintain public order.

- protect and secure the inhabitants of the Republic and their property; and

- uphold and enforce the law.

- create a safe and secure environment for all people in South Africa.

- prevent anything that may threaten the safety or security of any community.

- investigate any crimes that threaten the safety or security of any community.

- ensure criminals are brought to justice, and

- participate in efforts to address the causes of crime.

Following long and often bitter negotiations, the ANC, Inkatha and the government signed a National Peace Accord on 14 September 1991. The agreement contained ‘general provisions’ which included the following: The police shall endeavor to protect the people of South Africa from all criminal acts and shall do so in a rigorously non-partisan fashion, regardless of the political belief and affiliation, race, religion, gender or ethnic origin of the perpetrators or victims of such acts… The police shall be guided by the belief that they are accountable to society in rendering their policing services and shall therefore conduct themselves to secure and retain the respect and approval of the public. Through such accountability and friendly, effective, and prompt service, the police shall endeavor to obtain the cooperation of the public whose partnership in the task of crime control and prevention is essential…… the police must ‘preserve the fundamental and constitutional rights of each individual in South Africa, to ‘secure the favor and approval of the public’, to use the least possible degree of force, to ‘be sensitive to the ‘balance between individual freedom and collective security and to act professionally and honestly.

Concerning the above, Kreuzer [1] points out that with the state’s means of legitimate force under their control, why should regimes resort to or tolerate vigilantism, instead of employing the state security apparatus? One obvious answer is a weakness of the police and the judiciary branch that undermines their capacity to enforce the rule of law.

Research on on-duty police violence hardly encounters such problems because the police do not conceal such activities. In the case of on-duty police killings, the challenge is to distinguish between real self-defense, individual acts of excessive violence, and signs of a systemic application of such violence. In this study, the terms Police officer and law enforcement will be used interchangeably.

Police brutality, but in which circumstance do they become brutal?

One of the most important decisions the state can make is to cause the death of one of its citizens and perhaps the most difficult and controversial decision a police officer can make as an agent of the state is to take the life of a fellow citizen [2]. The authority of the police to use force represents one of the most misunderstood powers granted to representatives of the government. Police officers are authorized to use both psychological and physical force to apprehend criminals and solve crimes [3]. The use of force typically occurs when police are to make an arrest and the suspect is resisting. Research indicates that the police are most likely to use force when pursuing a suspect and attempting to exercise their arrest powers [3].

Deadly force is justified when an individual poses a serious threat to the safety of the on-scene officers or bystanders [4]. An armed individual is a prime example of such a threat. Klinger et al. [5], in an analysis of police shootings in St. Louis, MO, report that in 79 per cent of incidents in which police discharge their weapon, at least one of the suspects possessed a firearm. Zimring (2017: 56) analyzed a dataset assembled by The Guardian of fatal police shootings in the United States in 2015 and reports that in 56 per cent of those instances, the decedent possessed a firearm.

The major reason police shoot so often is that guns appear to be in the hands of civilians. Because firearms are also the cause of death in more than 90 per cent of all fatal assaults on police, the dominant role of fear of opponents with guns is easy to comprehend (Zimring, 2017: 57). It is thus a commonplace that the proliferation of concealable firearms in the civilian population is a major source of the singularly high rate of killings by the police in the United States (Zimring, 2017).

Because firearms, unlike most other weapons, provide the capacity to inflict bodily harm at a distance, suspects possessing firearms pose a particularly high risk to police officers. Zimring (2017) argues that weapon availability is the only plausible explanation for the vastly higher rates of fatal police shootings in the United States compared to European countries. Still, the linkage between firearm availability and fatal police shootings is not obvious. As described by Cook [6] presently only 31 per cent of U.S. households possess firearms. For the vast majority of those owners, there is no realistic prospect of their using the weapon for an illegal purpose. But Cook [6] goes on to observe, “in jurisdictions in which gun possession is common, offenders may find it easier to access a gun in the informal or underground market. Indeed, the stock of guns in private possession serves as a reservoir from which most problematic transactions originate.”

By this mechanism, higher overall firearm availability may translate into more frequent encounters between police and armed suspects, even though most guns are held by law-abiding individuals. The general availability of firearms may also affect the probability of fatal shootings in circumstances in which the decedent is later found to be unarmed. Police officers must make judgements about the risk of harm at the beginning of each encounter. In places where gun availability is higher, police officers may surmise that they are at greater risk of harm via what economists and statisticians call statistical prediction/ discrimination and act accordingly [7].

Nevertheless, police officers have been blamed for being brutal, but what remains to know is to find out what makes them brutal. In contemporary South Africa, people tend to forget the mission of the police and its challenges. The name “Law enforcement” itself says it all. They can only be law enforcement where there is disobedience of the law, where there is a breach of the law. In most cases, the breach of the law is done in a violent way threatening the lives of the surrounding people together with their properties. This calls for the intervention of law enforcement officers whose mission is to protect the people and their properties from danger.

However, law enforcement is an inherently hazardous profession. Officers are at risk for duty-related accidents and illness, as well as intentional assaults that result in injury or death [8]. Assaults occur spontaneously during arrests, investigations, or the pursuit of suspects. In most cases, these assaults are unplanned acts of violence that arise to resist arrest, although they may also be opportunistic expressions of hostility during an encounter between law enforcement officers and someone who rejects police authority and presence [9]. These unplanned assaults have been referred to by some scholars as spontaneous ambushes [10].

In 1 month in 1980, four New York City police officers were murdered and six more were badly wounded in gunfights. Over the past 26 months, 14 police officers have been killed, 53 were hit by gunfire, and another 150 have been shot at but not hit. Of the four men charged with killing police officers in 1980, two had backgrounds of severe mental disorders, while the remaining two carried extremely long records for assault, robbery, and drug offences but had spent little time in prison [11]. These last two offenders typify a new breed of criminal who accepts brief periods of incarceration as a way of life and learns to manipulate the criminal justice system.

Police are charged with preventing crime and apprehending perpetrators, putting them in conflict with suspected and actual perpetrators of crimes. They actively seek encounters with suspects, who may tend towards violence and lack respect for authority. In the form of performing their duty to protect the public, police officers can find themselves in the sensitive and potentially volatile position of protecting protesters who are protesting the actions of the police themselves. Police deal with a wide variety of situations in their work. They encounter minor to serious potentially dangerous deadly incidents. Hence, in some instances, they are obliged to be brutal to must the violent situation.

Targeted violence against law enforcement officers

The police are the instrument of the people to achieve and maintain order; their efforts are founded on principles of public service and ultimate responsibility to the public. The role the police officer plays in society is a difficult one; he must clearly understand complex social relationships to be effective. He is not only a part of the community he serves, and a part of the government that provides his formal base of authority, but he is also a part of the criminal justice system that determines what course society will pursue to deter lawbreakers or rehabilitate offenders in the interest of public order.

Nevertheless, as highly visible representatives and guardians of society, law enforcement officers are very public figures. Targeted assaults on police officers, referred to as ambushes in previous literature, are a particularly perplexing problem with significant implications for society at large [9].

Studies from the USA suggest that the rate with which law enforcement officers are killed can be predicted by the general homicide rate, the rate of justifiable homicide by police officers and by the degree of violence and social disintegration in a society [12]. On July 7, 2016, five police officers were killed and nine wounded in Dallas in an act of targeted violence. Three days later, in Baton Rouge, three officers were killed and three wounded in a targeted attack [9]. By 2015, the majority of the American public (58%) supported the view that there was a “war on police” in the United States [13].

The murder of police officials in South Africa

Death and injury to serving South African Police Service (SAPS) is a major concern. Recent spates of police murders in South Africa confirm that policing is a high-risk profession (Correspondent, 2018, Huffington Post, 2018/06/27; Correspondent, 2018, South African Government Agency, 2018/09/11, Hosken, 2018). South African society is characterized by high levels of violent crime and interpersonal conflict and police officials serve on the front line in this context with many deaths occurring among serving officials [14]. This means that police officials in South Africa are exposed to the darkest elements of human nature.

Kempen (2005:19) states that the high incidence of attacks and the killing of police officials is cause for concern. According to the Centre for the Study of Violence and Reconciliation [CSVR] (2009:65), the rate at which members of the police are murdered in South Africa is considered exceptionally high. During the 2016/2017 financial year, 57 police officials were killed during active duty, while 29 were killed in the line of duty during the 2017/218 financial year (Peterson, 2018, News24, 2018/09/02).

In the first six months of 2019, 26 police officials were killed while on active duty (Correspondent, 2019, South African Government Agency, 2019/06/27. Between 2014 and 2017, a total of 325 police officials died, which is an average of 81 police officials annually. What is noteworthy, is that approximately 60% of police officials are murdered while they are off duty (Correspondent, 2019, South African Government Agency, 2019/06/27). The killing of police officials was highlighted as a problem in the Quarterly Report of the SAPS before the turn of the new millennium (CIMC, 1998:42). In conjunction with this, Conradie [15] emphasized that attacks on police officials have a detrimental effect on police morale and poses a stumbling block to their effectiveness.

Geldenhuys (2007:11) echoes the same sentiments by reiterating that “there are many police heroes who have paid the highest price to protect us and our property from criminals who walk our streets”. Police officials who are killed while on duty are vulnerable when they respond to crime and enter a dangerous situation. They sometimes rush into the situation without any thought for personal safety and the seriousness of the crime situation, for example, during a crime in progress [16]. The fact that the situation develops rapidly, means those police officials arrive at active crime scenes and do not have time to take proper precautions, such as wearing bullet-proof vests, thus placing themselves at greater risk of being killed. Hence the need for new approaches to the scene of an incident by police officials when attending to a crime situation.

In South Africa, the killing of police officers by criminals has become a norm. South Africa has lost many of its SAPS at the crime scene in the past years. In 2021, more than 27 police officers have lost their lives in the line of duty with considerable consequences attached to the death of police and their families victims of the losses. This can be condoned by the current policy denying police officers the right to shoot, even in the event of self-defense.

Police and Prisons Civil Rights Union provincial secretary Nthabeleng Molefe said: “they were deeply saddened by the widespread police killings”. According to Police Minister Bheki Cele, by Friday, seven police officers had been killed in 15 days in South Africa (2021)1

The police officer’s distraught sister, Sindi Gule said the family was on their way to Cape Town from Makhanda in the Eastern Cape. She did not want to comment further. SA Policing Union (Sapu) acting deputy general secretary Peter Ntsime said the continued killing of police officers in the country, whether on or off-duty, reached an alarming rate a long time ago (2021). Ntsime said the union had consistently condemned police killings, and there had been national summits and other plans to curb the scourge, but to no avail.

The killing of police officers was “a pandemic that the whole population should be concerned about. The justice system should show no mercy to police killers,” said Ntsime (2021). There should be a unit dedicated to investigating incidents where police are killed, because if a police officer is suspected of having done something in the community, then there is the Independent Police Investigative Directorate, said Molefe. We have also asked the police to shoot and kill, and we will represent them as a union because we see that now the police attacks are on the rise as if it is a matter of leaving the community alone so that criminals are left to fend for themselves. Molefe.

Molefe urged the public to work with the police to arrest criminals.

We strongly urge that those who have been arrested be charged with treason and receive a heavier sentence than in the past so that others who wish to do the same can see the consequences. They should be made an example of, he said.

Five police officers have been killed in the province in the past three weeks which is a clear indication that criminals are on a warpath against the police. The murder of a police officer is a direct attack on the state and the rule of law, therefore the only bodies we should be counting are those of criminals and not of police officers. Police must not die with a gun in their hands, but they must defend themselves decisively, said Mshengu2.

Police officers killed in KwaZulu-Natal in 2021

March 6: Sergeant Thamsanqa Mbedu from Empangeni FCS was shot dead 27 times while performing investigation duties.

March 4: Detective-Captain Sam Nyawose, 55, of the Umkomaas SAPS Detective Service, was gunned down in an alleged hit while on his way to work.

February 20: Sergeant Makhosaze Mdlangathi, 33, and Sergeant Mfikelwa Mtolo, 36, were killed execution-style while off duty in Taylor’s Halt, near Pietermaritzburg.

February 18: Constable Mfihloyakhe Ndlovu, 45, was killed when he and his colleague responded to a domestic violence complaint in Welbedacht East, Chatsworth.

February 7: Constable Sizwe Mthethwa, stationed at Inanda police station, was stabbed, and killed while off duty.

On top of the police dearth in KwaZulu-Natal, the latest quarterly crime statistics show 32 officers were killed between April and June 2021 in the country at large of whom nine were on duty3.

Police officers are of any threat to the community, instead, they are here for our safety and security. Generally, criminals and delinquents are the ones who shout about police brutality forgetting that to some extent police officers are called to be brutal when they deal with violent situations due to the nature of the incidents they deal with on a daily basis. Any law-abiding member of the community will feel protected by the presence of the police during police patrol, but those who will see their unlawful business deterred will always cry out about policing activities in their areas. The killing of a police officer must be severely punished since such a killing is a threat to the sovereignty of the state. The purpose of this study is to seek to make a society where criminals will be afraid of law enforcement officers and not vice versa. This paper will address the following objectives: (1) to determine the causes of death of police officers at the Scene of the Incident. (2) to evaluate their strategies to respond to the Scene of the Incident. (3) to establish different approaches to respond to the scene of the incident.


Because qualitative researchers examine how people learn about and make sense of themselves and others and how they structure and give meaning to their daily lives, this research adopted a qualitative approach in a quest to respond to the objectives of the study. According to Walters [17], qualitative research involves the collection and interpretation of subjective data that often is shaped by social, cultural, and political realities that are evident at the time of data collection. However, due to the difficulty of obtaining Ethical approval and reaching the targeted population (police officers) during this period of the Covid-19 pandemic, the researchers decided to use secondary data collection following a systematic method. Secondary analysis is an empirical exercise that applies the same basic research principles as studies utilizing primary data and has steps to be followed just as any research method [18].

    1https://www.iol.co.za/dailynews/news/concerns-grow-after-five-cops-killed-in-kzn-in-three-weeks-a25a36d8-ecb3-4e42-a2f3-6a3f2695972a, Accessed 16 March 2021

    2https://www.iol.co.za/dailynews/news/concerns-grow-after-five-cops-killed-in-kzn-in-three-weeks-a25a36d8-ecb3-4e42-a2f3-6a3f2695972a. Accessed 16 March 2021

    3https://www.msn.com/en-za/news/other/off-duty-cop-shot-dead-in-eersterivier/ar AAO1IQY?ocid=msedgntp. Accessed 03 September 2021.

    Using large secondary data sets provides an alternative to the collection of primary data, often giving the researcher access to more information than would be available in primary data sets [19]. One of the advantages of secondary data is that it can include any data that are examined to answer a research question other than the question (s) for which the data were initially collected, but also it includes access to large amounts of information, coverage of a broad range of individuals or other entities (e.g., schools, hospitals), [19]. They tend to be far less costly and take far less time to organize relatively to primary data sets. This article used secondary data from accredited journals by the institution for which this research was conducted, the University of KwaZulu- Natal. These journals and books were accessed online through web-based resources leading to the institution’s online libraries, the South African government website, and online newspapers.

    Despite that secondary data presents many opportunities for researchers, there are still good reasons for using primary data. One of the problems with using secondary data is the lack of control over the framing a wording of survey items [19]. This may mean that questions important to your study are not included in the data. Trzesniewski et al. [20] point out that the primary disadvantage of secondary data is the flip side of the major advantage – the data have already been collected.

    Nevertheless, to access the data, the internet was used in a way that the researchers formulated a search strategy using appropriate keywords, through Google scholar and Jstor.org, but also some official websites were visited, which then allowed for a collection of estimated relevant articles, books and other webbases resources from which secondary data were extracted to respond to the purpose of this study. The ethical procedures were taken into consideration by describing articles that protect human subjects in their analysis. Such data were de-identified before the secondary data analysis was conducted.


    The causes of death of police officers at the Scene of the Incident

    The motives of police assailants range from spontaneous to planned, simply too convoluted, and bizarre to rational. Often the timing of police intervention plays a critical role in the offenders’ perceptions and reactions [21].

    Household firearm availability in South Africa

    Firearms or guns in the hands of civilians are one of the root causes of police death on and off duty. Police officers’ concern about encounters with armed suspects is real. Zimring (2017: 57) reports that in more than 90 per cent of killings of police officers in the line of duty, the killer inflicted fatal injury to the officer with a firearm. However, South Africa has had a long history with arms, and by its first democratic elections in April 1994, it had been identified as one of the top ten arms manufacturers in the world [22]. Robinson [23] points out that the Apartheid government developed a strong domestic arms industry in addition to building and strengthening its national defense force. In addition to its highly militarized state, Robinson [23] concedes that South Africa was able to develop a wide range of military hardware including nuclear bombs, rockets, launchers, grenades and various light and heavy machine guns including pistols and assault rifles. Robinson [23] noted that during Apartheid, the South African government participated in the illegal manufacturing sales and purchase of Small Arms and Light Weapons (SALWs) due to its isolation from the international arena.

    The Apartheid era was characterized by the accumulation of SALWs as nationalist groups armed themselves for violent clashes. The end of the Cold War –resulted in the influx of arms to the African continent, resulting in their circulation within South Africa [22]. Thus, in developing their caches, liberation armies had access to these weapons. SALWs thus gained dominance in the Apartheid era, continuing even after the Independence in 1994. The proliferation of these weapons in South Africa is also due to the remnants from the Apartheid era where weapons were accumulated and kept for private use.

    However, in South Africa’s current democratic dispensation (post-1994), the threat of SALWs continues to affect communities. These weapons have contributed to high levels of insecurity in communities. According to Ettang [24], there has been a rapid increase in the use of illegal firearms to carry out violent criminal activities throughout the country. Thus, authors like Shaw & Gastrow [25] wrote that South Africa sits as one of the most violent countries in the world when it comes to crimes, including rape and armed robbery.

    Beyond the apartheid remnants, these illegal firearms have been identified as coming from three primary sources: fraud and corruption where unfit individuals obtain firearm licenses; guns smuggled in from different countries and the loss or theft of firearms from licensed owners and the state (SAPS 2015/2016) [24]. In 2017, 33 firearms went missing from two police stations in Cape Town4. Guns have gone missing in police stations in areas plagued with gang violence like Mitchell Plains and Bellville South in Cape Town5. These lost and stolen firearms are used in gang hits, taxi violence and politically motivated attacks. For example, in KwaZulu-Natal, two police officers were arrested for selling police-issued weapons and ammunition, including bulletproof vests and pepper spray6. Thus, South Africa continues to face a significant security challenge in the proliferation and illicit trafficking of SALW [24]. The problem is highly challenging and persistent in a way that the possession of illegal weapons has a bearing on individual security. As long as these weapons are in the wrong hands (including rogue security officials), they will be easily used to perpetrate extreme levels of violence against innocent victims [22]. The existence of firearms in the hands of civilians is a serious threat to law enforcement officers when conducting their operations, mostly when they attend a crime scene where firearms were used, in most cases, they meet resistance on the part of the suspect if this last is holding a firearm.


    Perseverance is one of the causes of killing on-duty police officers. Perseverance in the transfer of or extension of violence as a motive of police assailants occurs when violence exists before the arrival of a rape, an argument, or perhaps in the less personal context of a robbery in progress [21]. The attack on the responding officer may be a reaction to the officer’s interference in or interruption of some act of violence, or it may be a reaction to the assailant’s perception of the officer as siding with the original victim – the officer serves as an additional source of frustration.

    For example, in 1917, an officer on solo foot patrol was summoned to the scene of a domestic disturbance by a widow, who told the officer she was afraid of the man in her apartment. When the officer walked into the apartment, the incensed boyfriend, a professional prizefighter, grabbed the interfering officer’s club and beat him to death. This is one of the rare cases of domestic argument leading to a police officer killing. More typically, perseverance in violence involves situations in which a person is engaged in some act of violence when the officer arrives at the scene, and the realm of violence is expanded to include the officer.


    Violence is also used to seek protection by persons who perceive the victim officer as an “instrument to impending doom” [26]. Assailants may use violence in the course of fleeing or escaping arrest; to prevent transport, for example, from the station house to the jail; to avoid the discovery of incriminating evidence; or to avoid perceived personal injury [21]. However, some police assailants use violence to avoid or escape arrest and some try to prevent the discovery of evidence, others react violently after the arrest as a manifestation of displeasure with the run of events.

    Defense of others

    The motive refers to actions taken by one offender to aid or rescue a friend, acquaintance, or fellow conspirator who is engaged in a physical struggle with the victim officer, someone who is being arrested, or someone subject to the threat of physical danger [21]. Margarita [21] reports that the most common motivating factor, present in almost two-thirds of police homicides, was the perceived need for protection against the concrete danger posed by the officer – usually during an escape attempt following the commission of a violent crime. Most victim officers responding to robberies – the largest single category of precipitant incidents – were killed by offenders who perceived the officer as presenting some imminent danger [21].

    Similarly qualified by a small number of cases, the evidence suggests that one-half of rapists and mentally deranged persons killed police to avoid or retard the imposition of fearful consequences [21]. Investigations of suspicious circumstances accounted for more attacks in defense of other activities. Offenders expressing contempt, hostility, or disapproval of specific policy actions or the police function, in general, were more likely to kill police during ambush attacks on civilians, service calls, and routine patrols than in other incidents [21].

    Strategies used by the police officers to respond to the Scene of the Incident

    Initial arrival at the scene may be chaotic, depending on the scope and nature of the crime. The presence of first responders, law enforcement, fire or rescue, emergency medical services, and multiple jurisdictions’ agencies has an impact on scene order [27]. Baxter Jr [28] concedes that the first officer to arrive at the scene often finds a very chaotic, uncontrolled situation. This includes the identification of potential victims and witnesses and identifying suspects and involved parties. Once these individuals have been identified, they should be separated from each other [28]. it should be noted that the actions the first officers take or choose not to take at the scene affect the case in many ways.

    Nevertheless, police agencies use uniformed or patrol divisions as well as detectives to process crime scenes. The patrol officer, who is usually the first police officer to respond to the crime scene, and the detective, who may arrive later, are responsible for the investigation and processing of the crime scene [29]. The first officers’ most important task at the scene is to prevent the destruction or diminished value of potential evidence that may lead to the apprehension of the criminal and the ultimate resolution of the crime [29]. The responsibility of the first uniformed officers at the scene can never be minimized. What these officers do or do not do, whether innocent or intentional, may have serious ramifications for the course of the investigation [29]. Ogle & Plotkin [3] state that the safety and physical wellbeing of officers and other individuals, in and around the crime scene, are the first responders’ priority.

      4https://www.news24.com/news24/SouthAfrica/News/hunting-rifles-drugs-and-child-suspects-what-guns-seized-in-cape-townreveals- 20171114, Accessed on 14 Sep. 21

      5https://www.news24.com/news24/SouthAfrica/News/hunting-rifles-drugs-and-child-suspects-what-guns-seized-in-cape-townreveals- 20171114, Accessed on 14 Sep. 21

      6https://www.news24.com/news24/SouthAfrica/News/kzn-cop-arrested-for-allegedly-selling-police-guns-ammo-to-criminals-20171030, Accessed on 14 Sep. 21

      The duties of the first officer to arrive at the crime scene are the same, no matter what his/her rank, and remain the same regardless of the seriousness of the crime. The first responder at the scene must assume that the criminal left clues or physical evidence behind. The first responder’s actions or inactions must not be allowed to destroy, change reconstruct the crime or prove the identity of the suspect. Furthermore, the first officer must not inadvertently add material that may mislead investigators. In certain serious crimes, it may not be possible to preserve the crime scene because of its location. A busy street or highway with heavy traffic is an example of a situation in which it may not be possible to protect a crime scene properly for a sufficient period.

      Nevertheless, first responders should not approach the scene in haste. All movements should be calm and deliberate. Officers should expect the worst and take the position that it is better to be overly cautious and remember the popular wisdom: if something can go wrong, it will! Approaching the assignment with an open mind helps an officer avoid carelessness and false moves that may prove to be disastrous [29].

      According to Fisher & Fisher [29] in today’s terrorist atmosphere, seemingly innocent items may harbor explosive devices. While officers should not become overly paranoid of such possibilities, they must keep this and other possibilities of danger in mind as they begin their investigation at a crime scene. The eventual success of the investigation may be dependent on the preventative and preliminary measures taken by the first officer to arrive at the crime scene. Because police work is so tightly connected to the community and its daily life, police work covers a wide spectrum of very different tasks. Police officers go on patrol, investigate, direct traffic, counsel and mediate, administer, warn, or threaten – but the fluidity between these tasks means they are not easily separated. Police work, in contrast to military work, is a daily task that of its nature is never finite because it is centered on the daily life of a community.

      Suggested approaches respond to the scene of the incident

      Police should change their strategies in attending to cases. Criminals know how police officers operate, hence, new approaches to police behaviors should be set, and the modus operandi of South African Police officers must change. The Federal Bureau of Investigation (FBI) has repeatedly warned law enforcement officers that “the threat is from the hardened criminal and the emotionally disturbed or insane person” [21]. This awareness should attract the attention of the police when responding to a scene of the incident. Baxter Jr [28] admits that one of the first actions officers should take after their initial arrival at the scene is to deal with the suspect, provided that they are still at the scene. According to Baxter Jr [28] “officer safety should ALWAYS be of priority”. However, when police attend to a scene of the incident, the first thing to find out before they even depart, is the nature of the crime, because if the crime involved murder, then they must get ready to incapacitate the suspect by all means. Most often when police are called for intervention, they do not ask what has happened or what is happening, they jump in the car and drive toward the scene of the incident even though they never reached the scene on time.

      First, the police should familiarize themselves with the members of the community in the area where the crime has happened. This calls us to the community policing approach. The community policing approach is the most important tool which can assist police officers in approaching the crime scene with proper guidance from community members. This allows the law enforcement officers who are called and informed by the community members mostly witnesses, to be aware of the nature of the violent incident that has happened. The community members know the whereabouts of the suspect and can cooperate with the officers to assist in the arrest or incapacitation of the suspect [29,30].

      What is needed in this case, is a proactive approach to policing within the communities. Since a reactive approach to policing is not conducive to policing in a democratic political system because it creates a particular distance between the police and the citizens and a contact and communication exchange takes place only in cases of emergency, a proactive form of policing and fundamental and trustful cooperation between the police and the population is intended to establish public security and social peace [31].

      It can be agreed upon that through active and continued communication with the residents, the police would be able to identify the most pressing problems of the respective neighborhood and try to cooperatively find workable and sustained solutions, and the same residents will be the informants of the officers about suspicious movements in the areas and if violence occurs, they will stand as witnesses and signal the whereabouts of the suspect, allowing police officers to take precautionary measures when attending the scene of incidents and trying to find the suspect.

      Integrating Intelligence into Policing Practice

      An intelligence-led approach to policing is now well established as a key element of modern accountable police work [32]. Intelligence-led policing involves a process for enhancing law enforcement effectiveness and has been defined by Ratcliffe [33] as a business model and managerial philosophy where data analysis and crime intelligence are pivotal to an objective, decisionmaking framework that facilitates crime and problem reduction, disruption and prevention through strategic management and effective enforcement strategies that target prolific and serious offenders (89). Intelligence has a central role in guiding the business of policing.

      Intelligence-led policing is a model of a police organization that invites police forces to go beyond their reactive management of events and their iterative approach to problems, and instead adopt a proactive stance focused on the early detection of crime and disorder [34]. It is characterized by the ability to look at the big picture of crime in the community and to shift from a reactive to a more proactive posture in response. The idea is to understand the crime environment and set policing priorities, then optimize police actions first better. This can only be possible if trained civilian community members are part of the deal if they are tasked to invigilate suspicious movements in the neighborhoods and if they are the eyes of the police in the community.

      Not only does intelligence-led policing intend to work in curbing the killing of police officers, but it is deemed to be an effective strategy for crime reduction if well applied by a trained detective unit. This approach assists in targeting offenders especially the targeting of active criminals through overt and covert means; the management of crime and disorder hotspots; the investigation of linked series of crimes and incidents; and the application of preventive measures, including working with local partnerships to reduce crime and disorder [35]. This intelligence approach is used to identify who is committing crimes, how they are committing them, and where they are committing such crimes. This can then be used to disrupt criminals from their activity through arrests or other methods such as making items more difficult to steal.

      The importance of intelligence-led policing is that it typically moves to police from considering the individual crime to considering the impact and threats of multiple crimes. An intelligence-led philosophy is proactive in that it seeks to predict criminal activity and pre-empt its development. It provides actionable options on which managers can base their decisions at all levels of policing. Intelligence by its nature is proactive and works towards the possibility of hypothesized future events and ways of disrupting or preventing future crimes. By putting this approach into action, police officers will reduce their tactics of approaching the crime scene because the intelligence-led policing staff will be on the ground trying to figure out who the suspects are and get the entire record of the incidents before the arrival of law enforcement. The crime scene should be approached by uniformed police officers on the call of ununiformed partners of the police who might be well-trained civilian community members.

      Zero-Tolerance Policing

      It involves frequent traffic stops, stop-and-frisk questioning of supposedly suspicious persons, and frequent arrests for disorderly conduct, vagrancy, and other minor offences. Barkan [36] is of the view that such visible, aggressive policing may reduce crime by increasing the chances that criminals get arrested and by deterring potential criminals from offending. By reducing incivilities such as disorderly youth and public drunkenness, it may also prompt potential offenders to think that residents care what happens in their neighborhoods and again deter them from offending [37].

      In a quest of eliminating the killing of the police, Ramaphosa was addressing the families of slain police officers at the police memorial site at the Union Buildings in Pretoria, where he also observed the annual SA Police Service Commemoration Day when he declared the following:

      “Let us transform the anger we feel, the frustration, into a sense of determination to jointly rid our streets of all forms of crime. To all our men and women in blue, I call on you to honor your departed colleagues by remaining vigilant at all times and ensuring no police officer dies in the hands of criminals7.”

      This statement can only work by applying the Zero-tolerance approach to criminal activities. According to Barkan [36], zerotolerance or proactive policing might also work, but the mixed results overall leave unclears the actual impact of this style of policing. Because this style may lead to abuse of police powers and worsen civilian-police relationships, cities and police forces should practice it very carefully if at all.

      Community Policing

      Community policing has been increasingly promoted, particularly in liberal democratic societies, as a suitable approach to improve police service and effectiveness along the lines of democratic governance, to reduce the fear of crime within the communities and to overcome mutual distrust between the police and the communities by enhancing police-citizen partnerships [38].

      The main idea of community policing rests on the attempt to leave behind purely reactive and traditional approaches to policing. A reactive approach to policing is according to Alderson [39] not conducive to policing in a democratic political system because it creates a particular distance between the police and the citizens since contact and communicative exchange takes place only in cases of emergency, a proactive form of policing and fundamental and trustful cooperation between the police and the population is intended to establish public security and societal peace [38]. In the situation of police murders, community policing can help decrease the killing of officers in a way that community members are very aware of the whereabouts of the criminals in their midst. Only a good relationship with police officers can push the members of the community to cooperate and develop a willing attitude to provide susceptible information that might assist in tracing the offender. This also plays the role of intelligence-led policing in a way that the intelligence policing unit involves local citizens of the community who works undercover. They mostly witness crime incidents; they know the criminals and they can provide full information about the criminals; hence they must be empowered in terms of training but also be given communicative tools and photographic devices that will assist them in information gathering in due time.

        7https://www.msn.com/en-za/news/national/stronger-ties-between-communities-and-police-will-help-tackle-criminality-says-cyril-ramaphosa/ ar-AAO96gd?ocid=msedgntp, Accessed on 06th September 2021.

        Community involvement

        Civic engagement usually extends to involving the public in some way to enhance community safety. Community policing promises to strengthen the capacity of communities to fight and prevent crime on their own. The idea that the police and the public are “co-producers” of safety, and that they cannot claim a monopoly over fighting crime, predates the community policing era. The community crime prevention movement of the 1970s was an important precursor to community policing. It promoted the idea that crime was not solely the responsibility of the police. The police were quick to endorse the claim that they could not solve crime problems without community support and assistance, for it helped share the blame for crime rates that were rising at the time [40].

        Now, police find that they are expected to lead community efforts. They are being called upon to take responsibility for mobilizing individuals and organizations around crime prevention. These efforts include neighborhood watch, citizen patrols, and education programs stressing household target-hardening and the rapid reporting of crime. Residents are asked to assist the police by reporting crimes promptly when they occur and cooperating as witnesses. Community policing often involves increases in “transparency” in how departments respond to demands for more information about what they do and how effective they are.

        To support the idea of community involvement in the war on criminals, Ramaphosa was addressing the families of slain police officers at the police memorial site at the Union Buildings in Pretoria, where he also observed the annual SA Police Service Commemoration Day when he declared the following:

        Criminals live with us in our communities. We must work together towards strengthening community-police relations and bring strategic stakeholders on board to bolster the efforts of the police to bring down the levels of serious and violent crime in our country8. Brogden & Nijhar [41]. Concede that in the community policing context, crime prevention is regarded as not just a police responsibility but also as an activity that should be conducted in liaison with other agencies and more generally with the public.


        When trying to find solutions to the killing of police officers, one should seek to understand the criminal minds which are about the worst of the worst: murderers, rapists, stalkers, kidnappers, molesters, and predators of every sort. Avid viewers know that these criminals can be categorized in several different ways. There are organized and disorganized offenders. There are serial killers, spree killers, mass murderers, and family annihilators. There are lust or thrill killers, visionary killers, mission-based killers, and power, or control killers. When looking at their crimes, it is important to consider which aspects are part of their modus operandi and which represent their signatures. In his several books devoted to his work, Douglas & Olshaker [42] point out that the better we can understand these human predators, the better we as a society can protect ourselves from them and try to prevent them from doing the things they do.

        Criminal Mind

        Criminals are uncompromising. In pursuing an objective, they are heedless as to the collateral effects of their behavior. They view other people as pawns to manipulate. Any means to achieve the desired end is acceptable. An offender commented in all seriousness to his probation officer, “This empathy thing; what is in it for me?” [43]. However, it can be argued that criminals often react to daily frustrations and disappointments in ways that differ dramatically from the reactions of ordinary people. Hence, when facing resistance from the suspect, police officers should be able to incapacitate the suspect, by all means, to prevent him/her from causing more harm than he/she has already caused.

        The continuum concept also applies to anger. Some people have a sunny disposition and seldom get angry. They maintain calmness even in the face of major challenges and disappointments. At the other extreme is the criminal who simmers with anger throughout his life. When people fail to fulfil his unrealistic expectations, he reacts as though his entire self-image is at stake. Throughout his life, he is infuriated because people do not conform to what he wants, and he is unable to control them.

        Psychology and sociology have long advanced the view that the criminal is basically like everyone else but becomes destructive because he has been traumatized or stymied in fulfilling his aspirations. A teenager “falls” in with the wrong crowd and joins a gang because he has never had a decent family life. Or a drug trafficker plies his trade because his skills qualify him only for jobs that pay minimum wage. Thus, both are perceived as people who are shaped by circumstances outside their control, ignoring the fact that most youths from dysfunctional families do not join gangs, and that the drug dealer’s lack of education and job skills is a personal failure, not a societal one. In many circles, the criminal is seen as a victim, not a victimizer. Those who hold this view go a step further, asserting that we are all, in a sense, “criminals” because we lie, lust, and yield to temptation. But it is absurd to equate the rare small lie of the responsible person with the gigantic network of lies of the criminal.

        In response to whatever transpires in our lives, we have thoughts and make critical choices about what to do with those thoughts. The person who is responsible thinks about consequences and has a conscience [44]. The problem resides in the used strategies by law enforcement when attending or approaching the scene of the incident. Where the relationship between people and police is damaged, both citizen security and police effectiveness suffer.

          8https://www.msn.com/en-za/news/national/stronger-ties-between-communities-and-police-will-help-tackle-criminality-says-cyril-ramaphosa/ ar-AAO96gd?ocid=msedgntp, Accessed on 06th September 2021.

          One is to take steps to reduce the availability of firearms to active offenders or individuals at high risk of offending. Policies that are intended to have this effect are universal background checks and barriers to straw purchases [6] (Zimring, 2017). Sherman [45], also makes numerous policy recommendations related to the governance and training of local police. Keeping weapons out of the hands of the mentally ill may also be effective.

          7 https://www.msn.com/en-za/news/national/stronger-ties-between-communities-and-police-will-help-tackle-criminality-says-cyril-ramaphosa/ ar-AAO96gd?ocid=msedgntp, Accessed on 06th September 2021.

          Mental disorder

          One of the individual risk factors for violence most commonly cited in studies is mental illness [46]. Severe mental illness alone is not predictive of violence, but there is an increased risk among those who have severe mental illness and a combination of other factors. These include a history of past violence, juvenile detention, physical abuse, or parents having been arrested; clinical features of substance abuse or perceived threats (paranoia); and dispositional factors such as age, sex, and low income [47]. Comorbid substance abuse is a consistent finding for elevated risk of violence among individuals with severe mental illness [48].

          Individuals with mental illness may engage in acts of violence that are motivated by factors other than the symptoms of their illness. In a study of inter-rater reliability of a new coding instrument for assessing the motivation for criminal acts, Penney et al. [49] examined cases of violence by people with major mental illnesses. In more than three-quarters of the cases (79.2%), the acts were judged to have been motivated by symptoms of the illness in conjunction with other motivations, such as anger, substance abuse, or other criminal goals. Such individuals will not hesitate to shoot at the police officers when they come to their arrest, again, police officers must beware of such people and act accordingly [50].


          South Africa should revise its law on firearm possession by civilians. A serious restriction should be imposed with a tough policy on who should or not be allowed to carry a gun. The availability of firearms in the hands of civilians is a serious problem that the South African government must deal with urgently. All Gun-related businesses must be closed. The government must take responsibility for gun selling with comprehensive policies with strict measures on who should carry a gun.


          Police officers are not criminals, they are peacemakers and safety keepers, hence they need people protection, they need people collaboration so that criminals can be easily identified and dealt with accordingly. To most law-abiding citizens, explanations of insanity or misdirected passion are sufficient and are accepted reassuringly as the motivating factors behind police homicides; indeed, police are supposed to protect society from lunatics and psychopathic killers. But the public may be more alarmed to know the “true” facts: most police homicides are not manifestations of mental illness, but rather indicate clear calculations made by both professional and amateur criminals who use violence against police only to avoid apprehension and to escape from the scene of some illegal activity.

          The most dangerous person for the criminal is a police officer. Criminals know that while in the operation of committing criminal activities, the only fearful people are law enforcement. Hence, criminals are ready to defend themselves during their operation and law enforcement officers are a major threat to them because they have the power to arrest them. Unfortunately, high-profile criminals know that the SAPS have no right to shoot and kill, but they can only make an arrest. They do not fear much the police, and they are ready to kill the police for their escape and the fear of being apprehended. This has made tough the work of law enforcement in the country at large.

          In contemporary South Africa, we cannot imagine a safe community without the presence of the police around. Thus, our peacekeepers (police officers) should be given more power than criminals or potential criminals, they should be allowed to exercise their power by all means to incapacitate the criminals. More training is needed in terms of tactics and intelligence strategies to combat the criminals in our midst.

          This research suggests that the police legislation should be revised, and a new policy should be crafted to give the police more power since they are employed for the general good. As it has been mentioned earlier in this paper, criminals should be afraid of a police officer and not vice-versa. This can only be effective if criminals know that the police have the right to shoot to kill in case of resistance. The police can apply shooting not to kill but to incapacitate the suspect in case of resistance. However, the police, the criminal justice per see, and the government, in general, could not control crime without the cooperation of a substantial portion of the people. In the absence of public support, there would be little that an army could not do better than the police. Hence, this study appeal to all the people of South Africa to love our law enforcement officers and to be cooperative with them by disclosing any suspicious movement within and around our communities for a safer South Africa for ALL.

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          Wednesday, January 11, 2023

          Magic Methyl Effects in Drug Design - Juniper Publishers

           Pharmacy & Pharmaceutical Sciences - Juniper Publishers


          Methyl group is one of the most commonly occurring substituents in drugs. More than 50% of drugs with high market value have methyl groups in their structures. Methyl group has a capacity to act as Electron Donating Group and modulating physicochemical and biological properties of drug molecules. These properties include effect on half-life on a drug, selectivity, potency and binding affinity. When introduction of methyl group results in profound increase biological activity of molecules, it is known as Magic Methyl Effect. These enhancements in biological activity are attributed to effect of methyl group on free energy of Desolvation. The present review explores the origin of this magic methyl effect along with some supporting case studies in drug design.

          Keywords: Drug design; Magic methyl; Methyl group; Molecules; Drug molecules; Physicochemical; Methylating; Synthetic chemistry; Side effects


          Methyl group is one of the most common substituents occurring in design of many drugs and research molecules. Methyl group has a capacity to act as electron donating group and is known to modulate physicochemical and biological properties of drug molecules. A survey of Njardarson’s Top 200 Drugs of 2011 showed that more than 67% of small-molecule drugs at that time contained at least one methyl group bound to a carbon atom [1]. Some of the drugs containing methyl group have been listed in the following figure (Figure 1).

          Importance of Methylation

          Substituting methyl group in drug design can have various benefits on pharmacokinetics and pharmacodynamics of drug molecules. Some of the effects of methylation are described below.

          Alternation in half-life of the drug

          Methylation can increase or decrease the half-life of the drug as seen from the examples of simvastatin where it is increased 2-fold while in case of Etoricoxib addition of methyl group decreases the half-life by more than 10- fold (Figure 2)

          Increase in selectivity

          Addition of methyl group may enhance the selectivity of the molecules as can be seen from the example below where selectivity of the molecule towards a particular target increased by almost (Figure 3) 87-fold.

          Increase in binding affinity and potency

          Increased methylation reduces free energy of desolvation required to remove a ligand of solvated water molecules when it transfers from an aqueous environment to the lipophilic environment (Figure 4). This results in increase binding leading to increased potency of the molecule. Jorgensen and co-workers suggested that a single methyl group might boost potency approximately 10-fold if the new methyl group sits nicely in a hydrophobic pocket of the active site. Methylation can bring in optimum lipophilicity in order to cross the phospholipid bilayer of the target organ from an aqueous environment like blood.

          This stripping into the organ requires desolvation free energy so by methylating the drug the desolvation energy expenditure is minimized to a greater extent. This process allows an optimum balance between hydrophilic and lipophilic of a drug. This is termed as ligand lipophilicity efficiency (LEE).

          Alteration of metabolism

          Similar to the interaction between a drug and its biological target, the metabolism of a drug molecule requires it to interact with the active site of the enzyme that catalyzes its metabolism. Steric hindrance is a common strategy used to block or slow a specific metabolic pathway. In this approach, additional atoms are added adjacent to the functional group undergoing metabolism in order to block the interaction of the drug molecule with the enzyme carrying out the metabolic transformation. In many cases, these additional atoms need not be very large. In acetylcholine and bethanechol (Figure 5), the additional methyl group seen on bethanechol prevents the enzyme acetyl cholinesterase from cleaving the ester bond.

          General role in drug design

          The methyl group plays an important role in the rational drug design. Introducing methyl into small molecule has become an important strategy of a lead compound optimization. Methyl can modulate the physicochemical, pharmacodynamics and pharmacokinetic properties by ortho effect, inductive effect and conformational effect. It also improves the metabolic stability as a soft metabolic point [2].

          Magic Methyl Effect

          The ‘magic methyl effect’ refers to the large and unexpected change in drug potency resulting from the addition of a single methyl group to a molecule [3]. Dramatic change in affinity that can be seen with the addition of a single methyl group in just the right place [4]. The methyl group is one of the most prevalent functionalities in biologically active molecules. A study revealed that 10-fold boost in potency with a methyl is seen in 8% of the cases, while a 100-fold difference is seen in 0.4% [3].

          Origin of magic methyl effect

          This effect was originally reported when Jorgensen and his co-workers studied set of MAP kinase inhibitors computationally in which just by adding a single methyl group the IC50 value had changed from 2500 nM to 12 nM (Figure 6). The research group observed a torsional twist induced by ortho-methyl group and concluded that this leads to a low energy conformation that closely resembles the conformer observed in X- ray crystal structure of the protein inhibitor complex. They hypothesized that an introduction of methyl group at ortho position induces aryl ring to rotate perpendicular leading to effective binding affinity with the target active site and in turn shows profound increase in potency as shown in Figure 6. It was further noticed that the dihedral angle of the biaryl bond in structure A was 50°C whereas addition of methyl at ortho twisted this angle out to 65°C making it similar to its protein bound conformer. This was hailed to be the reason behind surprisingly beneficial effect on binding affinity (Figure 7).

          Some Guidelines for The Strategic Introduction of The Methyl Group [5-14]

          After studying this effect scientists have discovered some common strategies which could be used as starting point to introduce methyl group in the design of molecules. These strategies includes:

          a) Methyl group ortho to a large rotatable substituent on an aryl ring as shown in Figure 8

          b) On substituted rings where an axial or equatorial preference of substituents can be influenced in Figure 9

          c) Between two freely rotatable bonds that are substituted with bulky groups influenced in Figure 10


          The biggest gains in the potency in drug design phase will be realized when the interplay of conformational, hydrophobic, desolvation and other effects are cooperatively aligned. The likelihood of discovering an increase in 100-fold boost in potency by installing a single methyl group is extremely low. However, with the advent of synthetic chemistry and availability of easy and simple reactions, methylated analogues of a drug lead merit such an exploration. If simple methylation could result in most effective potent drug with least side effects, then it would be indeed magical.

          Tuesday, January 10, 2023

          Empirical Examination of the Moderating influence of Dogmatism on the relationship between Adult Attention Deficit and the Operational Effectiveness of Project Managers - Juniper publishers

           Intellectual & Developmental Disabilities - Juniper Publishers

          Purpose: Empirical examination of the moderating influence of dogmatism (DG) on the relationship between adult attention deficit (AAD) and operational (traditional) project manager effectiveness (OPME).

          Design/methodology/approach: 160 actively employed business graduate students participated in a business courses where they were assigned to 4-person project teams responsible for completing a major business project. The project contained 4 sub-projects each of which was managed by a different team member. At the end of semester each team member rated the others on their project management effectiveness. Each subject completed a self-report measure of dogmatism and identified a close associate who completed an observer version of the Brown Attention Deficit Scale. Linear regression was used to test the hypothesis that DG moderates the relationship between AAD and OPME.

          Findings: DG is a statistically significant moderator of the relationship between AAD and OPME. The negative relationship between AAD and OPME significantly declines as DG increases.

          Research limitations/implications: Future research requires use of samples that are more directly associated with the workplace. Further investigation of the impact of AAD symptoms, including potentially positive manifestations like entre/intrapreneurial cognition and creativity, is needed to fully understand the impact of the disorder within the project management nomological network.

          Practical implications: Organizations need to be aware of the impact of AAD and DG on OPME. The provision of adapted project management training, productivity tools, a workspace free of unnecessary distractions and both professional and peer coaching is suggested for disordered project managers and participants. Organizations need to help disordered employees find substitutes for dogmatic thinking processes that possess similar protective and decision-making benefits but avoid the related inflexibility and social challenges. Employee assistance programs that raise awareness and provide access to assessment are an important part of multimodal management of the disorder in the workplace.

          Social implications: Employers are facing increasing social, legal and economic pressures to support and make effective use of functional but disordered employees. This research provides constructive suggestions for how to accommodate and support disordered project managers.

          Originality/value: This is the first empirical examination of the relationships between AAD, DG and OPME and is of value to researchers, organizational development specialists, human resource management specialists, managers and employees who are seeking effective multimodal management of attention related disorders in the workplace.

          Keywords: Attention deficit disorder; Adult attention deficit; Adult attention deficit disorder; Attention deficit hyperactivity-impulsivity disorder; Adult attention deficit hyperactivity-impulsivity disorder; Project management; Project manager performance; Project manager effectiveness; Dogmatism


          At least 5% of the adult global population have clinical levels of attention deficit disorders [1] costing the global economy approximately 144 million days of lost production per annum [2]. Changing role requirements for many workers is delegating and distributing increasingly complex responsibilities and associated competencies throughout organizations [3]. These new role requirements are dependent on higher order cognitive processes often disrupted by adult attention deficit disorders (AADDs) [4,5]. Managing this challenge requires research on how AADDs influence individual and team performance [6].

          Working conditions that engage more complex higher order cognitive processes intensifies the need for coping responses among disordered adults [7]. Recent research suggests that disordered adults develop rigid attachments to particular sets of beliefs in order to constrain the extent to which self-directing (higher order) cognitive processes are disrupted by external or internal stimulus [8].

          This research study examines the moderating influence of dogmatism on the relationship between adult attention deficit (AAD) and the operational effectiveness of project managers (OEPM), the component of project management most dependent on the higher order cognitive processes typically disrupted by AAD.

          The independent variable - adult attention deficit Definition

          Research conducted by Brown [9] on symptoms that commonly occur among adults with attention deficits produced the following 5 symptom clusters (factors):

          a) difficulty activating and organizing to work (difficulty getting organized and started on tasks predominantly caused by a relative higher arousal threshold and/or chronic anxiety).

          b) difficulty sustaining attention and concentration (difficulties staying focused on priority tasks that are not of high personal interest, receiving and organizing information and resisting distraction).

          c) difficulty sustaining energy and effort (insufficient and/ or inconsistent levels of general energy and difficulty sustaining effort required to complete important tasks).

          d) difficulty managing emotional interference (difficulty with intense, negative and disruptive mood states; relatively high and sustained levels of irritability and emotional reactivity; difficulty managing emotions that constrain the development of constructive relationships).

          e) difficulty utilizing working memory and accessing/ recalling learned material (episodic or consistent chronic forgetfulness, difficulty organizing, sequencing and retaining information in short term memory, and problems accessing and using learned material).

          Brown [9] uses dimensional (gradations of severity) as opposed categorical (non-disordered vs disordered) measurement of the symptom clusters to determine the overall level of AAD. This is consistent with evidence that AAD symptoms and associated impairment fall along a continuum [10,11]. AAD is defined as a persistent pattern of inattention and related cognitive, emotional and effort related symptoms that occur with varying levels of severity and creates progressively greater challenges within the personal, academic and work life of adults as severity increases [9,12]. The use of dimensional measurement and correlational analysis helps to reveal the influence of AAD within nomological networks that influence organizational behavior [12,13].

          Impact of AAD on organizational behavior and management

          Research studies using dimensional measurement of AAD has identified associations with difficulty with teamwork [14-16]; greater reliance on co-workers [17] difficulty managing conflict [16], increased stress [18], lower self-efficacy [18] and less effective task management systems [15].

          Attention related disorders are also associated with positive behaviors like the ability to work in a fast paced environment, ingenuity, innovation, creativity, determination, perseverance, risk taking and intense focus on things of interest [19,20] which may explain why entrepreneurs appear to have significantly higher prevalence rates [19]. Recent research by White & Shah [21] suggests that the disorder is associated with higher overall levels of creative achievement across a variety of occupational and task domains.

          The ability of an organization to foster employee innovativeness, creativity and an entre/intrapreneurial orientation may be one of the most significant contributors to sustained organizational success within an increasingly globalized economy [22]. Research by Zhou [23] suggests that employees with low creativity benefit from working closely with highly creative employees. Organizational innovation, creativity and success is therefore potentially influenced by the manner in which highly creative employees, many of whom may be disordered to varying degrees, are distributed and deployed throughout the organization.

          Managerial strategies that appropriately leverage the potential strengths of the disorder while removing, reducing or mitigating the deficits are needed to ensure successful deployment of disordered employees. Most researchers and practitioners agree that multimodal management of the disorder involving a combination of medicinal and non-medicinal support (counseling, coaching, training, supportive conditions and conditions aligned with strengths) has the greatest potential for success [24]. This requires a comprehensive understanding of the impact of the disorder on personal performance capacity (core workplace competencies, motivation and other performance supporting personal states); performance behavior including key mediators and moderators; and performance outcomes at the individual and team level [17].

          Dependent variable - project management

          Definition and impact

          Project management is defined as the application of knowledge, skills and techniques for executing a temporary endeavor undertaken to create a unique product, service or result [25]. The project management process (cycle) includes a variety of phases or stages that are often dependent on the type of project but typically include the stages of initiating, planning, executing, monitoring and controlling, handing off and closing the project [26].

          There are a wide variety of project types determined by the nature of the output (e.g. building a skyscraper, developing a new engine, designing and delivering a training service, producing a software update etc.), the size of the project (e.g. scope, number of stakeholders etc.), the execution culture (numerous stakeholder checks due to security issues, established and standardized processes, high level of execution autonomy etc.) and the conditions within which project execution occurs (e.g. industry, sector, organizational culture, time pressures, resource constraints etc.). Projects are also completed by either individuals or teams. In an attempt to identify the key differentiating features of projects, Shanhar & Dvir [27] and others have suggested the following general differentiating dimensions:

          a) complexity (extent of scope, number of elements that must be considered when making project decisions, project organization requirements, number and nature of constraints that must be addressed, number of participants and stakeholders, diversity of output requirements and success criteria).

          b) uncertainty (degree of clarity about project goals and execution requirements, rate and degree of change influencing project goals and execution requirements).

          c) technology (level of technology required to support the project).

          d) novelty (the level of originality in project goal, processes and/or output).

          e) pace (the criticality and rigidity of the project time frame).

          f) Obeng (1994) provided a simple classification of project types based on two dimensions - the level of clarity and detail at the outset of the project about what needs to be done and how to do it. These dimensions are used to create the following classification:

          i. closed (stakeholders know what to do and how to do it at the outset).

          i. closed (stakeholders know what to do and how to do it at the outset).

          iii. semi-closed (stakeholders are given a reasonable level of clarity about what needs to be done, although often somewhat general, but still need to figure out how to do it).

          iv. open (stakeholders are unsure of what needs to be done and unsure of how things will be done when the project is initiated and in some cases at various points along the way).

          Closed conditions are generally associated with low levels of complexity, uncertainty, technology, novelty and pace. Contemporary conditions have elevated all of the key differentiating factors resulting in a shift away from closed conditions toward more semi-closed and open conditions [28].

          Measurement of project success has traditionally focused on what is referred to as the golden triangle – meets the deadline, within budget and addresses the established scope [29]. This approach has been criticized for being too narrow [30] especially when considering the broader impact of key projects like Microsoft Windows which was considered a significant failure relative to the original deadlines, budget and scope. Criteria used to measure project performance has expanded to include the following levels [27,31]:

          a) process (optimal identification, selection, implementation and management of project processes).

          b) project management (meets time, budget, scope requirements).

          c) customer/deliverable (quality, quantity, specifications, acceptance, use, impact, satisfaction).

          d) business success (impact on business goals and performance).

          e) strategic success (impact on market, competitors, investors and other key stakeholders).

          e) strategic success (impact on market, competitors, investors and other key stakeholders).

          g) team impact (extend to which the execution of the project supports the capacity of project team members to continue working together in an efficient and effective manner).

          The clarification and expansion of performance criteria has improved the ability to identify the key determinants, mediators and moderators of project performance, including the contribution of the personality, management/leadership style and associated competencies of project managers and participants [32].

          Research on the influence of the project management competencies suggests a contingent relationship and the need for alignment with project type, conditions and stage [33,34]. In an attempt to categorize the expanding domain of project management competencies, Shenhar & Div [27] suggest that project management competencies be organized into 4 groups:

          a) traditional/operational excellence (planning and executing a sequence of project activities to ensure completion of the project scope on time and within budget).

          b) dynamic adaption (management of change within the project).

          c) strategic focus (strategic alignment of the project, creating a competitive advantage for the organization and adding value at the strategic level of the organization).

          d) inspired leadership (motivating and managing project team members and other stakeholders to evoke and maintain their support and commitment to the project, creating project spirit through supporting vision, values and artifacts) [35].

          They suggest that the profile of required project management competencies depends on the complexity, uncertainty, technology, pace and novelty of the project. Traditional (operational excellence) competencies may be both necessary and sufficient within closed project conditions that are relatively stable, simple, low tech and do require high levels of novelty. Although the traditional competencies remain necessary, they become increasingly insufficient as the complexity, uncertainty, technology, novelty and pace increase (project conditions become more open). Increasingly open project conditions requires the addition and integration of dynamic adaptation, strategic focus and inspired leadership with the traditional (operational excellence) competencies.

          Although the failure rate of projects remains a concern [32], research suggests that effective project management is a contributor to business success in a variety of industries and sectors [36,37] and that project performance is influenced by the personality, management/leadership style and competencies of the project manager [38-42].

          Many of the core project manager competencies rely on higher order cognitive processes which are typically disrupted by attention related disorders [43,44]. The significant reliance of traditional (operational excellence) competencies on higher order processes like impulse inhibition, planning, modeling, prediction, goal and priority setting, sequencing and problem solving suggests that operational effectiveness may be particularly impacted by the disorder. These are also referred to as the process competencies. The ongoing necessity and foundational nature of traditional competencies (operational excellence) in spite of growing insufficiency as project conditions become more open, suggests that AAD may have an important influence within the nomological network that determines both project manager, team member and project performance. A search of multiple databases (medline, psyc-info, academic source premier, business source premier etc.) produced no empirical studies on the relationship between attention related disorders/conditions and project management.

          Moderating variable - dogmatism

          Definition and impact

          Belief and disbelief systems satisfy the need for a cognitive framework that defines situations and provides protection from threats [45]. Dogmatism is generally defined as a closed belief system resulting from a rigid attachment to particular beliefs that are resistant to opposing beliefs. Rokeach [45] suggests that dogmatism is defensive in nature and encompasses a constellation of psychoanalytic defenses that help to shield a vulnerable mind. More recently, Altemeyer [46] defined dogmatism as “an unjustified and unchangeable certainty in one’s beliefs, reflecting conviction beyond the reach of evidence to the contrary” (p. 201). Rigid attachment to a particular set of beliefs helps to protect self-directing processes that are relatively more vulnerable to disruptive external and internal stimulus [47]. Defensive cognitive closure, rigid certainty and isolating (compartmentalizing) contradictory beliefs is a way to protect higher order cognitive processes from complex external stimulus that may create the experience of cognitive chaos, confusion, vulnerability and anxiety. Rigid cognitive structures are also a way to defend against the disruptive impact of emotions like anxiety, fear or anger that have reached a level of intensity that disrupts self-directing cognitive processes.

          Developmental psychologists have consistently identified early psychosocial conditions in the parenting process and a biological vulnerability for hyper-arousal, environmental stressors and disrupted socio-culture learning as the distal causes [47]. Anxiety that arises in childhood and persists through adolescence and into adulthood will help to rigidify the belief system as a means of personal defense. Recent research by Brown [44] identified an association between disrupted functioning of short-term memory and dogmatism suggesting a link between rigid (defensive) thinking and adult attention deficit.

          Research on the impact of dogmatism on mental health and general functioning has identified mostly detrimental but some beneficial effects [48-50]. Research on the occupational impact of dogmatism has revealed an association with both high and low performance [51,52]. Dogmatic workers are likely to struggle in situations that are dynamic, uncertain, and complex, and require high levels of reflection, flexibility and cooperation with others [7]. However, a dogmatic thinking style may be useful when performance supporting cognitive and emotional states are particularly vulnerable to external and internal stimuli that may produce disruptive cognitive dissonance [53]. The impact of dogmatism on health and performance appears to be moderated by personal vulnerability to disruptive dissonance. For workers who are prone to confusion and indecision as the complexity and intensity of external and internal stimulus increases, the benefits of a dogmatic style may outweigh the costs.

          The Relationship between AAD, dogmatism and the operational project management


          The proposition guiding this research study is that dogmatism moderates the negative relationship between AAD and the operational effectiveness of project managers (referred to as operational effectiveness). Project managers who use a more dogmatic orientation toward managing the operational aspects of a project, especially under closed or semi-closed conditions (low need for dynamic adaption), may be able to generate a higher level of cognitive protection from the disorganizing effects of the disorder.

          Employees with operational project management responsibilities who experience difficulties with getting organized and started on tasks, concentration, sustaining effort, managing emotional interference, using short term (working memory) and accessing learned material, will have greater difficulty achieving operational competence. They will be less able to activate and organize the project initiation stage, establish clear and appropriate project goals, map out and schedule the require tasks, organize and integrate the tasks into an efficient project plan, manage project participants and ensure timely completion of the project within scope and budget. Difficulties with attention and concentration will undermine the ability to consistently pay attention to the details of the project plan resulting in inefficient reexamination. Difficulties with energy and effort will constrain the consistency and duration of effort needed to ensure timely completion of critical end-to-end tasks.

          Impulsivity and emotional reactivity may be viewed by others as impatience and a lack of confidence in others which may constraint the formation of trusting, constructive and supporting relationships. Disordered adults are often indecisive [54] when facing conflicting goals and disproportionately attentive to tasks that are immediately gratifying and of relatively greater personal interest [13]. This should further constrain operational efficiency and effectiveness.

          H1: Adult attention deficit is negatively associated with the operational effectiveness of project managers

          Disordered project managers may be able to constrain the level of manifest disorganization, indecision and confusion associated with the disorder by using a more dogmatic orientation. This is more likely to be beneficial within closed/semi-closed project conditions that don’t require high levels of flexibility and dynamic adaptation. The use of a dogmatic orientation may help to shield a vulnerable mind from internal and/or external stimuli that promotes disorganization, indecision and confusion, and/ or constrain the behavioral manifestation of these symptoms resulting in levels of decisiveness expected from the operational role of a project manager.

          H2: Dogmatism moderates the relationship between adult attention deficit and the operational effectiveness of project managers


          Subjects and procedures

          The subjects were 160 actively employed business graduate students attending a university in the United States. Subjects participated in business courses that required them to work in 4 person autonomous project teams. Each team was responsible for completing a major business project which required the completion of 4 sub-projects. Each team was required to complete a strategic planning process and produce a strategic plan based on the 4 traditional elements of strategic planning - external opportunities and threats plus internal strengths and weaknesses (SWOT). Each team member was required to manage one part of the SWOT analysis and the other team members were required to work for them on that particular sub-project. Each of the 4 subproject managers (team members) were expected to integrate their sub-projects into an overall strategic plan and manage the progress of the overall project. The general operational phases of project management, related competencies and tools were briefly reviewed at the beginning of the course.

          The project conditions were semi-closed because the project outcomes (scope and timeline) were specified with a reasonable level of clarity and detail from the outset but the process of further defining the outcomes where necessary, and determining the process for achieving the outcomes, was delegated to the project managers. The project conditions represent low to medium complexity, uncertainty, technology, novelty and pace. These conditions mostly emphasize the need for operational project management competence.

          At the end of the semester each of the team members completed an assessment of the operational project management effectiveness of the other team members. Each subject was also asked to identify someone who knew them well and would be willing to complete an honest assessment of their behavior. The identified observers completed an observer version of the Brown Adult Attention Deficit Scale (BAADS) under conditions of anonymity. Each of the subjects completed a self-report measure of dogmatism.

          Principle components factor analysis with a varimax rotation was used to confirm the dimensionality of the project manager effectiveness measure, and examine the contribution of the individual items to the factors. Product moment correlations were used to test all the hypotheses regarding associations between the measures. Linear regression that included the multiplication of standardized independent and moderator variables (moderator variable) was used to test for a significant moderating effect.


          Adult attention deficit (ADD)

          The Brown (1996) Adult Attention Deficit Scale (BAADS) contains forty self-report items that measure the five symptom clusters. Organizing and activating to work (cluster 1) measures difficulty in getting organized and started on tasks (e.g., “experiences excessive difficulty getting started on tasks”). Sustaining attention and concentration (cluster 2) measures problems in paying attention and concentrating while performing tasks (e.g., “listens and tries to pay attention but soon becomes distracted”). Sustaining Energy and effort (cluster 3) measures problems in maintaining the required energy and effort while performing tasks (e.g., “runs out of steam and doesn’t follow through”). Managing affective interference (cluster 4) measures difficulty with moods, emotional reactivity and sensitivity to criticism (e.g., “is easily irritated” and “has a short fuse with sudden outbursts of anger”). Utilizing working memory and accessing recall (cluster 5) measures forgetfulness in daily routines and problems with recall of learned material (e.g., “intends to do things but forgets”). The questions are phrased in third person singular to support observer ratings (e.g., “” the person being described is disorganized”). The instrument uses a four-point behavioral frequency scale (0=never, 1=once a week, 2=twice a week, 3=almost daily). A total score for AAD was generated by adding up the scores on all of the questions.


          The new dogmatism scale (DOG) [46,55] was used to measure dogmatism. The instrument was designed and validated for use with adults and contains 20 items that measure general dogmatism. Example items for the scale include the following: “I am absolutely certain that my ideas about the fundamental issues in life are correct”; “The things I believe in are so completely true, I could never doubt them”; and “I have never discovered a system of beliefs that explains everything to my satisfaction” (reverse coded). Subjects used a seven-point Likert scale (1=strongly disagree, 2=disagree, 3=slightly disagree, 4=neutral, 5=slightly agree, 6=agree, 7=strongly agree) to rate the extent to which they agreed with each item. Each of the subjects completed the dogmatism measure and a total score was derived by adding up the scores on the individual items (some items needed to be reversed).

          Operational project management effectiveness

          Items for measuring the operational effectiveness of project managers were developed after reviewing the core project management competencies outlined by the International Project Management Association [56], the Project Management Institute in the United States (2008) and recent research on the assessment of project managers [57-60]. There was no well-established instrument that focused exclusively on measuring the operational effectiveness of project managers as outlined by [27]. However, most existing instruments and competency profiles contained parts that referenced the operational effectiveness component of project manager performance.

          Thirteen items that represent the key operational (traditional/ process) project management responsibilities described by Shenhar and Dvir [27] were selected and worded in a general manner that encompassed most project management situations, including the situation that the subjects were embedded in (Table 1). Example items are “mapped out all the key project tasks and milestones”, “identified the critical path that determined the duration of the project” and “secured the input and support of project team members.” Observers used a seven-point Likert scale (1=strongly disagree, 2=disagree, 3=slightly disagree, 4=neutral, 5=slightly agree, 6=agree, 7=strongly agree) to rate the extent to which the project manager demonstrated each competency. Each project manager was rated by the other three members of the project team and the scores on each question were averaged and then added to get a total operational effectiveness score.


          Descriptives, factor analysis, correlations and regression

          A principle components factor analysis with an orthogonal rotation (varimax) was conducted to examine the structure of the project manager effectiveness instrument. The factor analysis for the project manager effectiveness items produced a single factor with factor loadings ranging from 0.65 to 0.82 suggesting that each item is making a meaningful contribution to the measure. The Cronbach alpha internal reliability coefficient was α = 0.89 and could not be improved by eliminating items. This suggests that the instrument has good internal reliability, and each item is making a meaningful contribution (Table 2).

          The average intra-class correlations (two-way mixed effects model with absolute type agreement) among team member ratings of project manager effectiveness ranged from 0.71 to 0.90 suggesting acceptable inter-rater reliability. Means, standard deviations and correlations among the variables appear in Table 1. All variable distributions were approximately normal and demonstrated reasonable variation across their respective scales. No univariate or bivariate outliers were considered problematic, and the product moment correlations revealed significant associations between the variables. The mean, standard deviation and maximum score for AAD (avg = 39.24, std dev = 18.34, max score = 104) are not significantly different from the instrument validation samples and previous samples of subjects taken from the same university and a similar university in western Canada.

          Cronbach alpha internal reliability coefficients ranged from (α = 0.89) to (α = 0.93) suggesting good internal reliabilities. The linear regression for testing the moderation effect produced no problematic residuals (Table 1).

          Empirical test of hypothesis

          The significance threshold for empirical tests was set at α = 0.05 (2 tailed). The correlation between AAD and project manager effectiveness (Hypothesis 1) was statistically significant (r = -0.35, p < 0.01). The linear regression of project manager effectiveness on adult attention deficit, dogmatism and the moderator (multiplication of the standardized dogmatism and adult attention deficit variables) produced a statistically significant moderator effect (β = 0.29 p = 0.000). An examination of the moderator graph (Figure 1) confirms that the negative relationship between adult attention deficit and the operational effectiveness of project managers declines as dogmatism increases (Table 3).



          The results suggest that AAD constrained the operational (traditional/process) effectiveness of project managers and that the negative relationship between AAD and operational effectiveness declines as dogmatism increases. The directionality of this relationship cannot be confirmed from this research study and both opposite and bi-directional effects are possible. The large number of studies confirming the significant contribution of genetic factors to the manifestation of the disorder [43] provides general support for the hypothesized direction in this study. Recent research suggesting that certain contextual conditions like parental conflict and inconsistent parenting may help manifest a genetic predisposition or strengthen existing symptoms [61] suggests that certain project conditions may contribute to AAD.

          Implications for organizations and education institutions

          Organizations wishing to ensure the success of key projects need to be aware of the influence of adult attention deficit and dogmatism on project manager effectiveness. The emergence of more empowered work cultures, tighter deadlines, the need for creativity/innovation and project-oriented work represents both an opportunity and challenge for disordered employees. Disordered employees without the necessary support will not be able to leverage their strengths and may constrain the performance of interdependent others.

          The protective influence of dogmatism on the execution of operational project tasks by disordered project managers suggests the need for conditions, tools and competencies that protect higher order cognitive resources from disruptive external and internal stimulus. The provision of project management training/coaching, project management tools and a workspace free of unnecessary distractions may be especially important for project teams containing disordered employees. Although a dogmatic style may be beneficial under relatively simple and stable conditions, it is unlikely that a defensive and rigid cognitive style will support project management effectiveness under increasingly dynamic and open project conditions. Organizations need to help disordered project managers and participants find substitutes for dogmatic thinking processes that possess similar protective benefits but avoid the related inflexibility and social challenges associated with being dogmatic. Helping disordered project managers to better manage anxiety, stress, emotional disruption, and find an appropriate balance between assertiveness and collaboration, is likely to play an important role in developing constructive substitutes for dogmatic thinking.

          The increasing availability of effective coaches (life, organizational, task, peer, manager as coach etc.) [62] offers a potential substitute for close supervision and a potentially more accepted and developmental resource for keeping disordered employees oriented toward successful completion of priority tasks and projects. Effective organizational coaches could address a wide range of cognitive, emotional and behavioral deficits, and protect the employee from the reinforcing cycles of failure that many disordered employees experience [63]. Establishing reciprocal peer coaching systems within project teams or the organization as a whole, that addresses challenges at the individual and relational level may add considerable mutual value, especially for disordered employees [64,65]. Coaching processes that contain the necessary structure and content for supporting disordered employees are needed.

          The effective use of project teams represents an opportunity for distributing the creative benefits associated with the disorder while managing the deficits. Team members and peer coaches can help disordered employees to activate, organize, stay on track, maintain a balance between organizational citizenship opportunities and priority work tasks, avoid experiences of failure and manage challenging emotions. They can also help disordered employees address the pitfalls of rigid thinking and behavior. In return, team members can benefit from the creativity that disordered employees may offer. This will require the careful design of teams to ensure optimal person-role fit and supportive team development interventions. Team building that educates team members about the disorder and addresses the social and task performance challenges while taking advantage of the benefits is required. Structured collaborative decision-making processes that provide team members with the opportunity to optimally locate themselves within the process should improve person-role fit, avoid the problems of excessive rigidity and ensure timely decisions. Shared management of projects that partner disordered project managers with someone who is flexible and has strong administration and social skills may support both individual and project effectiveness.

          The multi-modal approach to managing the disorder in the workplace suggests that sustained improvement will depend on other forms of support like the general education of both managers and employees, establishing supportive organizational cultures and climates, appropriate medication and coaching/training that address key underlying cognitive, emotional and behavior deficits (e.g. retention training to support effective and efficient use of short term memory). The provision of employee assistance programs that provide disordered, potentially disordered and non-disordered employees with information about the disorder and opportunities for assessment is an important part of the constructive management of employee diversity. This will help to create a more inclusive, supportive and responsive organizational culture. This will also increase the likelihood of the employee seeking out other important parts of multimodal treatment, particularly medicinal support.

          Education institutions, like management programs within universities, need to assist new project managers to recognize and respond to the symptoms of the disorder in both themselves and others. Early diagnoses and treatment may help to prevent the exacerbating cycles of failure that often accompany the condition. Educating future managers about the condition will help to ensure that they do not become a contributor to the emergence and reinforcement of such cycles through ignorance or the inability to be supportive. Project management training, peer coaching systems and student team interventions that address the disorder in a constructive manner will help prepare all future managers for the challenges of the contemporary workplace. Education and training that improves self-awareness, emotional intelligence, effective use of working memory and constructive assertiveness may help substitute for the protective use of dogmatic thinking styles.

          Increasing social, economic and legal pressures to provide reasonable accommodation for functional but disordered employees and take appropriate advantage of employee diversity underscores the general social value of this research.

          Limitations and suggestions for future research

          Future research requires use of samples that are more directly associated with the workplace. The influence of creativity within the relationship between AAD and project manager effectiveness requires further investigation and may reveal beneficial aspects of the relationship. Measures of project management effectiveness that include items related to the creative dimensions of a project, when such dimensions are required, are needed to support this research. A system for classifying the creative requirements of projects will help develop the moderating variables needed to reveal project management situations within which the disorder may be beneficial. This research supports the general proposition that the disorder has significant influence within the nomological network that determines individual, team and organizational performance.

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