Thursday, June 17, 2021

Connective Tissue Disease and its Evolution on Chest CT - Juniper Publishers

 Current Trends in Clinical & Medical Imaging - Juniper Publishers

Abstract

Background/Objective: Evaluate the radiographic appearances most commonly associated with Connective Tissue Diseases (CTD) and their evolution over time.

Methods: This systematic review draws data from the IRB approved Mount Sinai Interstitial Lung Disease Registry with 381 enrolled patients at the time of this review. CT scans of 108 patients with a working diagnosis of connective tissue disease (CTD) were evaluated by a Radiologist (MS with 20 years of experience) a Pulmonologist (AM with 5 years of experience). The patient’s first CT scan demonstrating fibrosis and every CT scan at least one year later were reviewed, and the pattern of fibrosis and extent of disease were recorded by consensus agreement.

Results: 108 patients out of 381(28%) had a working diagnosis of CTD based on clinical presentation, serologic markers and chest CT. 80 had multiple CT scans allowing follow-up over time. 35% of the patients had myositis. 24% of patients had a diagnosis of scleroderma (SC). The remaining had organizing pneumonia (OP) (11%), rheumatoid arthritis (RA) (8%), interstitial pneumonia with autoimmune features (IPAF) (6%), mixed connective tissue disease (MCTD) (5%), sjogren’s (Sj) (5%), undifferentiated (UN) (4%) and vasculitis (V) (2%). The radiographic pattern of disease changed over time in 35%. 44% of patients with OP diagnosis returned to normal on follow-up. 50 (63%) of patients had worsening disease on CT over time. 12 (15%) decreased extent of disease or resolved. 18 (23%) remained stable.

Cоnclusiоn: There are many types of CTD with variable radiographic presentations, which can change over time. The diseases are frequently progressive with few returning to normal.

Keywords: Connective tissue disease, Pulmonary fibrosis, Organizing pneumonia, Nonspecific Interstitial pneumonitis, Usual interstitial pneumonitis

Intrоductiоn

There are many types of pulmonary fibrosis which are differentiated by their clinical presentation, radiology and pathology. The most common type of pulmonary fibrosis and the one with the highest morbidity and mortality is idiopathic pulmonary fibrosis (IPF). The pattern on CT scan is a usual interstitial pneumonitis (UIP) pattern which has been defined by the American Thoracic Society, the European Respiratory Society, the Japanese Respiratory Society, and the Latin American Thoracic Association (ATS/ERS/JRS/ALAT) as sub- pleural basilar predominant fibrosis with honeycombing [1]. New anti-fibrotic treatments slow the progression of the disease but do not reverse the disease so fibrosis on CT scans remains stable or progresses [2]. The CTDs affect younger individuals with a female predominance. The CTDs are subdivided based on clinical, radiology and serologic features. The findings on chest CT are more variable than with IPF. They can include nonspecific interstitial pneumonitis (NSIP), organizing pneumonia (OP), UIP, and even chronic hypersensitivity pneumonitis (CHP) patterns [3,4]. The pattern can change over time and even resolve with treatment, making radiology diagnosis challenging. Understanding the most common patterns associated with each type of CTD and the evolution can help with diagnosis and treatment recommendations. The purpose of this paper is to evaluate the radiographic appearances most commonly associated with each CTD and their evolution over time.

Methods

Internal Review Board approval was obtained. Our paper draws patients from the Mount Sinai ILD Registry, which at the time of the study contained 381 patients with pulmonary fibrosis among whom 108 had a CTD Working Diagnosis based on a multidisciplinary approach. Patients signed an informed consent to participate in the registry. The age and gender of each patient was recorded as well as the specific CTD diagnosis. The first CT scan with evidence of interstitial lung disease and all follow up CT scans that were at least 1 year apart were reviewed by a thoracic radiologist and pulmonologist and their consensus opinion was recorded. The date of the CT scan, the pattern of disease and the extent of disease were recorded. The grading of extent of disease was based on a previously reported grading system for lung fibrosis [5] (Table 1). The right upper lobe and right middle lobe are considered as one lobe in this grading system. The maximum score is 16. The pattern of disease is described in (Table2) (Figure 1).

Results

108 patients out of 381(28%) had a working diagnosis of CTD. Of those 108 patients, 80 had multiple CT scans allowing assessment of CT pattern and extent of disease over time. 28 (35%) of the patients had myositis which included dermatomyositis, polymyositis and antisynthetase diagnoses. 19 (24%) of patients with CTD had a diagnosis of scleroderma. The remaining patients had OP 9 (11%), RA 6 (8%), IPAF 5 (6%), MCTD 4 (5%), sjogren’s 4 (5%), undifferentiated 3 (4%) and vasculitis 2 (2%). The oldest patients were in the idiopathic group and the youngest patients had a working diagnosis of MCTD. All patients with MCTD and sjogren’s were females. Overall, 6 patients returned to normal on CT over the course of their disease, 4 of these patients had a diagnosis of organizing pneumonia. 50 (63%) of patients had worsening disease on CT over time. 12 (15%) decreased extent of disease or resolved. 18 (23%) remained stable. 36 patients had an NSIP pattern on first CT. 18 had OP, 14 had NSOP, 9 had UIP and 3 had CHP pattern (Figure 2 & 3).

Myositis-35% of the patients with CTD had myositis which included dermatomyositis, polymyositis and anti-synthetase diagnoses. The average age was 57 years old. The percentage of female patients was 46 %. NSIP and NSOP patterns were most common as seen with other researchers including Debray who found 45% had an NSIP pattern [6]. Half of the patient’s extent of fibrosis progressed over the study interval however the pattern of disease remained relatively stable. 1/28 patients CT returned to normal (Table 3). Scleroderma-24% of patients with CTD had a diagnosis of scleroderma. The average age was 63 and 78% were women. The NSIP pattern was most common but a few people had a UIP pattern which is similar to other authors [7]. Many patients (74%) progressed and none returned to normal suggesting overall, that this is a CTD with a worse prognosis (Table 4). Organizing Pneumonia-11% of patients with CTD had OP. The average age in our study was 57 which was relatively young. Only 11% were female. As would be expected nearly all the patients had an OP pattern on CT as has been described in the literature. Nearly half improved over the course of follow-up but some had a waxing and waning course as is typical of the disease.

Most continued to have the same pattern of disease over time. 4 CTs returned to normal supporting the idea that OP has a good prognosis (Table 5). Rheumatoid Arthritis- 9% of patients with CTD had RA. The average age in our study was 66 and 83% were female. 3/6 had a UIP pattern similar to that which has been described in the literature [8]. None improved over the course of follow-up. Most continued to have the same pattern of disease over time. No patient with RA returned to normal on CT (Table 6). Idiopathic Pulmonary Fibrosis with Autoimmune Features: 6% of patients with CTD had IPAF, defined as a combination of findings of at least 2 of the following; clinical manifestations of CTD, positive serologies or specific chest CT pattern or pathology [9]. The average age in our study was 66, which was relatively old. 80% were female. Most patients had an NSIP pattern (60%). Chung found that UIP pattern was more common in the patients he studied [10] (Table 7). Mixed Connective Tissue Disease-5% of patients with CTD had MCTD. The average age in our study was 58, which was relatively young. 100% were female. There was a variable appearance on CT with no predilection for a specific pattern [11]. Most continued to have the same pattern of disease over time. One person’s CT returned to normal (Table 8).

Discussion

Ultimately, there are many types of CTD and they have variable radiographic presentations, which can evolve differently over time. The variability of the radiographic appearance within a specific type of CTD is interesting as is the overlap in appearance between different diseases. The OP pattern which is seen in many of the CTD is typically early and often resolves. In contrast the NSIP pattern is more likely to be persistent. Lung manifestations may be present prior to joint manifestations so it is important for rheumatologists to consider the lung in evaluation of patients with suspected connective tissue diseases. Further research is needed to determine the effect of immunosuppressant drugs on the evolution of findings on chest CT and determine if clinical parameters parallel radiographic appearance [13].  

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Wednesday, June 16, 2021

Modelling the Creep Curves of β-BOPP Film - Juniper Publishers

 Academic Journal of Polymer Science - Juniper Publishers


Abstract

The effect of annealing on the creep and recovery properties of β -BOPP film was studied. The creep resistance can be improved obviously by annealing, the modification becomes better with elongating the duration. Four-parameter Burger model and Weibull distribution function well described such cases.

Keywords: BOPP Film; Creep; Fitting; Burger Model; Weibull Distribution Function

Introduction

Biaxially oriented polypropylene (BOPP) film has become a widely used film material because of its light weight, good transparency, moisture-proof, non-toxic and simple preparation process. When the content of β crystal in BOPP is increased, the toughness and thermal deformation resistance of BOPP film is greatly improved such that its application scope is expanded. However, its internal structure will undergo such complex changes as the movement of chain segments, the unwinding of molecular chains and the change of free volume due to the long-term use [1], resulting in irrecoverable deformation causing failure. Therefore, it is of great significance to study the creep behavior of β-BOPP film for predicting its long-term reliability. As a simple and effective method to adjust polymer properties, annealing has been widely used in polymer processing. In the process, the relaxation is accelerated and the secondary crystallization may be promoted. In recent years, it is also an effective method to combine theoretical model and numerical simulation with experimental results. Drozdov [2] conducted the creep test of isotactic polypropylene under different stresses, the contributions of viscoelasticity and viscoplasticity are derived. Wang [3] found that the annealing process not only improved the crystallinity of β-PP samples, but also enhanced the mobility of amorphous segments. This paper aims to verify the validity of annealing on creep resistance of β - BOPP film.

Experimental

Materials

aPP (trade name E02ES) with a melt flow rate of 1.5 g/10 min (230 °C/2.16 kg) and a density of 0.9kg/m3 was obtained from Sinopec Zhenhai Refining and Chemical Co., Ltd. The β-nucleating agent (trade name ST-C, powder) was provided by Nanjing Chengkuan Trading Co.

Sample preparations

Firstly, PP pellets and nucleating agent were put in vacuum oven for drying at 70 °C for 60min to remove the residual moisture. After that, the nucleating agent was mixed into polypropylene in a high-speed mixer in weight percentage of 0.01% and 0.1%. The mixture was extrudated and granulated as β-PP granule in a single screw extruder, after which β-BOPP film was obtained by blow molding. They are termed as 0.01wt% β-BOPP and 0.1 wt% β-BOPP respectively. The samples of β-BOPP film were annealed at 80 °C for 5min, 15min or 30min respectively. They were then cooled to room temperature in air.

Creep test

DMA Q800 of TA company is used to test the creep properties of the film samples. The length × width of 20 mm × 8 mm of the film is clamped on the tensile fixture in spacing of 10 mm. The set invariants was the preload of 0.001 N at 80°C for the duration of 3 min. The creep and recovery curves were obtained in test under the applied stress of 3 MPa in the creep time of 15 min and the subsequent recovery time of 15 min. The un-annealed samples refers to UA, ‘80-5’ refers to being annealed at 80 °C for 5min.

Results and Discussion

Experimental Results

Figure 1 presents the creep-recovery curves of 0.01wt%β-BOPP (a) and 0.1wt% β-BOPP (b) annealed in different durations at 80°C. The first half of the curve is creep stage without creep fracture under the relatively small applied stress in short creep time. Upon unloading, the specimens can only recover to irrecoverable strain instead of zero strain irrespectively of a sudden drop in strain representing a quick part of elastic recovery followed by a gradual and slow recovery. The un-annealed 0.01wt%β-BOPP in Figure 1a creeps to a higher content than the un-annealed 0.1wt% β-BOPP in Figure 1b due to higher β- crystallinity in the latter than the former. After annealing, the maximum creep strain and the final irrecoverable strain decrease obviously. Under the same stress, the dimensional stability of the film increases and the recovery property increases, indicating that the better creep resistance due to the static viscoelasticity. The higher the content of β - crystal, the weaker the effects of annealing on creep resistance and elastic recovery. For the films with 0.01% β crystal content, the maximum strain decreases by 13.7%, 34.8% and 52.9%, and the irrecoverable strain decreases by 41.1%, 47.7% and 65.9%, respectively for annealing in durations of 5,15 and 30min. In camparison, for the films with 0.1% β crystal content, the maximum strain decreases by 9.6%, 14.5% and 23.5%, respectively, and the irrecoverable strain decreases by 12.8%, 15.6% and 34.4%, respectively.

Modelling the creep and recovery

Burger model

The Burger model, also known as four parameter model, is composed of Maxwell element and Kelvin Voigt element in series as shown in Figure 2, which is often used to analyze the creeprecovery. For linear viscoelastic solids, creep usually consists of three parts: instantaneous elastic deformation , delayed elastic deformation and flow deformation. The function of total strain with time under specific stress can be expressed by the following Eq.1.

where t is the loading time, m E is the modulus of the spring while m η is the viscosity of the adhesive pot in Maxwell model. k E is the modulus of the spring while k η is the viscosity in Kelvin model. k k τ =η / E is the delay time for deformation of 63.2%(1- e-1 ) in Kelvin model. The values of those parameters ( m E , m η , k E and k η ) are calculated by nonlinear fitting of Eq.1 using Origin software. The coefficient R2 of fitting curve from experimental data is above 0.98, which indicates that the fitting effect is acceptable. The fitting curve is shown in Figure 3. The larger the value of in Maxwell model, the stronger the elasticity of the material. Once the stress is relieved, the strain produced in this part will disappear immediately. k E is used to characterize the rigidity of molecular chain in the material, which corresponds to the elastic modulus of spring element in Kelvin Voigt model. k η corresponds to the viscosity of the viscous pot assembly on the Kelvin Voigt model. The ratio of two represents relaxation time τ. For specimens annealed in longer duration, m E , k E and k η all become larger, indicating stronger elasticity and higher viscosity. m η is related to bulk viscosity of the material, which has a much higher effect on creep than k η . The larger m η , the smaller the irreversible deformation in the deformation process while the stronger the ability to restore the original size. The increase in m η means the strengthened friction resistance between molecules, being embodied by the decreased creep rate and the larger residual strain that cannot be recovered. Fitted values of parameters are also illustrated in Figure 4.The variations are very obvious.

Weibull distribution function

Weibull distribution function is widely used to fit the strain recovery data of various polymers. When the load is removed, the elastic strain recovers instantaneously, and the subsequent strain is a time-dependent function as Eq.2.

In the formula of Eq.2, is the stress relief time. v ε represents the delayed recovery strain, which is a function of time and is determined by the shape parameter r β and the characteristic life r η . v ε is the permanent strain resulted by the viscous flow, which is the maximum permanent strain corresponding to the longest time in the creep test. The Weibull distribution function is used to fit the experimental data of recovery stage at 80 °C. The coefficient of determination R2 is above 0.99, which shows that the fitting effect is reliable. The fitting curve is shown in Figure 3. The values of the parameters such as r η , r β , v ε and p ε are shown in Figure 5. The delayed recovery strain ( v ε ) first increases and then decreases after annealing while the unrecoverable strain ( p ε ) obviously decreases after annealing. The dimensional stability of the films under external force is enhanced.

Conclusion

The creep and recovery of β - BOPP films annealed for different durations are provided to be numerically described.
i. The resistance to creep and the size stability in recovery are improved by annealing at 80 °C. More β-crystallinity is also favorable for such modification of film.
ii. The Burger model and Weibull distribution function are well used to fit the experimental results. It is found that annealing can improve the elastic modulus, the bulk viscosity and the recovery ability of the film while reducing the creep rate and the irreversible deformation.

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Tuesday, June 15, 2021

The Tall Poppy Syndrome in Medicine - Juniper Publishers

Arthritis & Bone Research - Juniper Publishers

Mini Review

An unmarked vial arrived at the White House two days into President Bill Clinton’s first term. It was alleged to be his desensitization medicine for his allergies. White House (WH) Physician Dr. Burton Lee III, President George H.W. Bush’s appointee, prolific scientific author and Presidential-Congressional influencer on HIV/AIDS legislation, refused to inject the medicine until content confirmation. Phone conversations to Clinton’s Arkansas medical doctors (on call) over the week-end were unrevealing. Dr. Lee had become conspicuous and was discharged (cut down) from duty the following Monday. President Clinton possessed the prerogative of appointing a new WH physician, but his timing reeked of payback. Lee’s crime was practicing good medicine. Was Dr. Lee tall popped; had he become a victim of the Tall Poppy Syndrome (TPS)? The Tall Poppy Syndrome is a metaphor wherein a poppy tower over the others; some want the tall poppy to cut down so that all are uniform. The Australian National Dictionary describes TPS as “a person who is conspicuously successful; freq. one whose distinction, rank, or wealth attracts notice or hostility”. The syndrome has been documented since antiquity and described in most countries.

Australia’s recognition of TPS is dominant amongst the Anglo-sphere nations while it remains relatively unknown (and undiagnosed) in the United States. High profile, conspicuous people are often victims such as athletes, people in the media/entertainment industry, business and, especially politics. The syndrome is uncommon in science, arts and medicine. Envy (on the part of the cutter) and worthiness (the tall poppy got what he/she deserved because of egregious behavior) are often causes for cutting [1]. In contradistinction to the Australian experience, I have observed TPS in medicine personally and in the world and American medical literature. American medicine is very competitive: college, medical school, internship, residency, fellowship, job seeking, practice building and “publishing or perish”. Medical and personal advancements may become contentious especially when new ideas or procedures are introduced; this leads to individual and institutional rivalries and sometimes a victor. The road to victory often entails envy as well as other emotions such as resentment, anger and even hate and includes a specific victim but may also ensnare many peoples, hospitals and even countries. One of the greatest medical rivalries existed between Robert Koch (Germany) and Louis Pasteur (France) who worked in medical microbiology and the germ theory of disease. Their rivalry was set in the backdrop of the Franco-Prussian War (1870-1871) which included Germany’s seizure of Alsace-Lorraine, where Pasteur worked, and its increasing dominance of scientific information over Europe. This compelled countrymen to defend their scientists, research and country.

Anthrax was prevalent and European farmers had a vested interest in Koch’s original anthrax work but their rivalry was exacerbated when Pasteur began anthrax research. European countries were colonizing Asia and Africa and were seeking to understand tropical diseases. Our own nascent medical leaders and schools were looking for direction in public health and infectious disease (Koch won). Their feuding reached a pinnacle after a medical meeting in London in 1881 when Koch and his students published several articles attacking Pasteur’s work. Further attacks against each other occurred at a meeting in Geneva in 1883 with their respective follow up responses. The rivalry tainted their work for years to come [2].

Our early history of anesthesia was undermined by different claimants’ invention of ether [3]. William T. G. Morton, a dentist, was given credit for ether’s discovery although Charles Jackson, a chemist, and Horace Wells, a dentist, refuted the claim for years. Sir Humphrey Davey, a Cornish chemist, previously noted nitrous oxide’s anesthetic and pain reducing effects in 1940 and Wells used it for dentistry in 1844. Dr. H. J. Bigelow, a surgeon at the Massachusetts General Hospital, published a report on the use of ether in 1847. The School of Medicine at the University of Pennsylvania was the foremost medical school and condemned its usage because of its side effects and would not use ether until 1853. Ether’s potential spread immediately to London and Paris where new rivalries erupted. Because of the confusion caused by the Boston (pro) - Philadelphia (con) rivalry, many American doctors went to Europe to learn anesthesia - ether techniques. One of America’s most famous rivalries - feuds involved heart surgeons, Doctors Michael E De Bakey and Denton Cooley [4]. Both had appointments at Baylor College of Medicine and worked at The Methodist Hospital in Houston, Texas. Less than friendly competition resulted in Dr. Cooley relocating a short distance to St. Luke’s Hospital where he founded the Texas Heart Institute.

Although Doctors De Bakey and Domingo Liotta developed an artificial heart assist, the left ventricular bypass, Doctors Cooley and Liotta redesigned it for an emergency bridge for heart transplantation. Dr. Cooley was the first to implant the artificial heart when a patient awaited a heart donor. Dr. De Bakey claimed Dr. Cooley stole his artificial heart and began a campaign to reprimand Dr. Cooley. Dr. Cooley resigned from Baylor after a dispute with its trustees and was eventually censured by the American College of Surgeons. The two protagonists never spoke to each other for forty years before finally reconciling. The preceding accounts were initially driven by envy as is the succeeding story which is the most likely TPS situation the practicing physician will encounter. The above reports may garner the most attention but the it is the close to home encounters with colleagues, close friends or other professionals that offer the opportunity for TPS occurrence. Dr. LJ entered private practice when arthroscopy and sports medicine were at their infancy. He was instrumental in a design of the motorized arthroscopic shaver as well as other arthroscopic instruments.

His surgical techniques were disparaged by his local colleagues - competitors. Memberships in state and national societies - organizations were denied or delayed many years. Original scientific papers were also opposed. Over time, Dr. L. J.’s achievements were accepted as were many” memberships and scientific papers and he eventually enjoyed a rewarding and illustrious career [5]. The risk of TPS for doctors moving from the cottage industry to the corporate world will not lessen the likelihood of TPS. They will be moving into the hierarchical world; hierarchy creates competition for advancement and envy. WH physician Navy Rear Adm. Ronny Jackson, who served as the personal physician for three presidents, was nominated for Secretary of the Department of Veteran Affairs. Adm. Jackson had a previously strained relationship with a WH Navy captain in 2013. A recent occurrence between Adm. Jackson and the doctor of Vice President Pense’s wife led to memos and accusations of drinking on the job, bullying, and improperly giving prescription medications. These allegations, not verified, were leaked to the press by Sen. Jon Tester (D. Mont.), the senior Democrat on the Senate Veterans Affairs Committee. Dr. Pense’s doctor has since resigned from the WH medical department. Adm. Jackson withdrew his name for the V.A. appointment.

Although the original cutting down began between colleagues, Senator Tester finished the task. Deservingness of the tall poppy’s status adds another dimension to TPS. In 2016, the Dean of the University of Southern California (USC) Medical School resigned his post because of drug usage and providing drugs to non-patients. He remained on the faculty treating patients while under supervision and undergoing treatment. A year later he resigned from the faculty and was stripped of his medical license in 2018. USC’s only full-time gynecologist for nearly 30 years was accused of serial misconduct. He was suspended in 2016; internal investigations were performed as well as an outside investigation which determined some of his medical behavior was outside the scope of current medical practice. He was allowed to resign quietly with severance pay in 2017. The lead physician at the student health center was fired as well as the clinical director; the physician has filed a lawsuit against the university for defamation. The female who finally initiated the investigation (cutter) resigned her post (she was cut down as well). In 2018, the USC president resigned. USC has set aside $215 million for compensation for victims.

The medical board is reviewing the gynecologist’s medical license. Our cannons for practicing medicine are constantly changing due, if for no other reason, to the complexities of our society spurred by growth and diversity. Hard work, intellectual ability and technical skills are no longer sufficient for success. Emotional intelligence, not just our time-honored empathy, is necessary to navigate the intricacies of the one on one (and group) encounter, which, by the way, no longer absolutely exists due to the iPhone and EMR. The other four elements of personal competence as described by Daniel Coleman are: self-awareness, self-regulation, motivation and social skills [6]. Practicing them will increase one’s chance of success and happiness and reduce the possibility of becoming the cutter or being cut down. Primum non nocere has guided patient care for centuries. Computers, iPhones and artificial intelligence may seem to undermine and marginalize our tasks but they,” along with movements such as #MeToo, only confirm the importance of the axiom and how far reaching a tiny task may spread [7]. The axiom should include our colleagues as well as ourselves.

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Monday, June 14, 2021

Unipotent or Multipotent Mammary Stem/Progenitor Cells in Mouse Mammary Gland Development - Juniper Publishers

 Tumor Medicine & Prevention - Juniper Publishers 


Abstract

An ongoing debate in the developmental literature is whether the mouse mammary gland arises from a unipotent or multipotent progenitor population.We believe that a review of the evidence clearly supports the argument that multipotent stem/progenitor cells exist among the epithelium of mouse mammary glands in adult animals. Here we present our published data, which does not align well with the current ideas of the mammary epithelial stem cell hierarchy. Some questions remain that must be taken into account. However it is clear from our published observations that stemmness is more properly considered as a function rather than a unique inherent property of specific cells within any given tissue.

Keywords: Mus musculus; Stem cell; Mammary; Transplantation; Reprogramming

Introduction

The purpose in this discussion is to present the argument that multipotent stem/progenitor cells exist among the epithelium of mouse mammary glands in adult animals. Mammary biologists have been informed in recent years that there is no role for multipotent mammary stem cells in mouse mammary development[1,2]. However, results in the literature argue against this interpretation. It should be noted that experiments conducted with adult allophenic mice (produced by the fusion of embryonic blastomeres of mice having distinctly different histocompatibility alleles) demonstrate that mammary glands contain cells from each donor and therefore must arise from at least two antecedent cells [3]. Thus, mammary fragments from these mice produce outgrowths in the cleared mammary fat pads in each of the donor H2 incompatible strains.

What is the Significance of the Regenerative ActivityResident in Mammary Epithelium?

Any portion of the mammary epithelium at any age or regardless of reproductive history is capable upon transplantation of regenerating an entire mammary epithelial outgrowth upon transplantation into an epithelium-divested mammary fat pad. In addition, this can be repeated serially without consideration of age or reproductive history[4,5]. Two experiments come to mind: First, if lineage-limited unipotent progenitors are paramount to mammary epithelial regeneration then transplantation of old multiparous mouse mammary gland as fragments or cells (by titration) should contain previously marked lineage-limited mammary epithelial cells. For example, ER-alpha positive and negative progenitor cells may be marked by Sox-9-CreER and Prominin-1-CreER respectively on postnatal day 28[6]. If after several pregnancies these cells give rise to ER-positive or ER-negative progeny respectively when tissue fragments or limited dilution dispersed cells then this would provide evidence that lineage-limited progenitors are responsible for the long-lived regenerative capacity of transplanted mammary tissue. However, if only unlabeled luminal cells are produced in these outgrowths then this would argue for the de-novo origination of these lineage-limited progenitors from a multipotent antecedent. A second experiment would be the separation of luminal and basal cell populations from a retrovirally-marked mammary outgrowth [7,8]and demonstration that these distinct epithelial subsets are derived from a single antecedent bythe demonstration of identical host-viral restriction fragments in each subset.

There is a striking difference in transplantation results when one compares the outgrowths produced from inoculation of dispersed cells with those obtained from implanted mammary tissue fragments containing epithelium. Barring technical difficulties, one can expect and nearly always observes a complete functional mammary epithelial outgrowth that fills the entire implanted fat pad, 10-12 weeks after transplanting mammary tissue fragments. Fragments typically contain ~7000 epithelial cells as measured by cellular dispersal of the typical implant fragments (~1.0mm3). On the other hand, to obtain similar results with freshly dispersed mammary epithelial cells, one needs to inoculate approximately 10-12 times as many cells in saline. Thus, most studies involving isolated cells at 7000 or less fail to produce full filling of the fat pad most of the time when transplanted without added stroma and growth factors. Our interpretation of this difference is that the mammary stem cell niche, an anatomically defined site where stem cells are maintained uninfluenced by signals to differentiate, is intact in the fragments throughout the lifetime of the mouse. Dispersal of the epithelial cells into single cell preparations leads to disruption of these anatomically-defined sites.Therefore, successful complete outgrowth requires the re-aggregation of the stem/progenitor with the appropriate components of its niche (including the stromal components) when dispersed epithelial cells are inoculated into the cleared mammary fat pads. This was shown dramatically by Welm et al. [9], who describe implants of lentivirus-transduced mammary cells both as tissue fragments and dispersed reporter-positive cells. A heterogeneous epithelial outgrowth comprised of both luminal and basal cells with and without hormone-receptor expression, was produced in all instances. This supports the conclusion that a multipotent epithelial mammary stem cell exists within the mammary epithelial population.In other studies[10,11]it was shown that ductal development and secretory lobular development were independent of one another[7,12]. Thus, when dispersed cells are transplanted (10-2000), one obtains outgrowths that are partial (i.e. not representative of complete mammary epithelial development following pregnancy) because independent lineagelimited progenitor cells exercised their prerogative to create an incomplete mammary epithelial outgrowth.

Can this Activity be Assigned to a Single Antecedent?

Our research [7] demonstrated by random fragment serial transplantation and retroviral tagging that an entire functional mammary epithelial outgrowth could be generated from the progeny of a single predecessor. Our conclusion, at that time, was that a single multipotent mammary epithelial stem cell was responsible for all the epithelium and was self-renewing. Recent reports [1,2] have indicated that unipotent progenitor cells can contribute extensively to mammary epithelial growth. These studies prompted us to re-examine our original conclusion and modify it to one which now recognizes that lineage-limited progenitors, present within the fragment, may contribute extensively to the epithelial progeny of clonal mammary outgrowths. The progeny of these lineage-limited cells must be the direct progeny of a single multipotent mammary epithelial stem cell because retroviral marking indicates that all outgrowths maintain the same MMTV-host DNA restriction fragments. It has been conclusively shown that a complete functional epithelial outgrowth is comprised of the offspring of a single ancestor[ 6,7-12]. This argues that, a multipotent mammary epithelial stem cell exists within the mammary gland in situ. Maintenance of the different types of luminal and basal mammary epithelium on a day to day basis may be best characterized by replacement from lineage- limited forbears. Recently the hormone-receptor-positive and hormone-receptor-negative luminal epithelium has been reported to arise from distinct lineage-limited progenitors that express distinct genetic markers [6].

Experimental Evidence that Remains Unexplained by the Current Stem/Progenitor Cell Models

In 1996, Smith [13] showed that limiting dilutions (2000) of dispersed WAP-LacZ-positive mammary epithelial cells produced lobule-limited and duct-limited outgrowths in syngeneic mammary fat pads when inoculated with 1 X 106 unmarked mammary-derived fibroblasts. Fibroblasts alone did not produce outgrowths. This was the 1st demonstration of lineage limited mammary epithelial progenitors. These structures contained both hormone-receptorpositive and negative luminal cells and myoepithelial (basal)cells [6]

Smith & Boulanger [8] demonstrated that lobular and ductal development were lost independently from one another during serial transplantation of fragments from a clonally-derived mammary outgrowth in vivo, this observation supports the presence of lineage limited epithelial progenitors in intact mammary tissue.

A series of publications [14-20] indicate that the mammary microenvironment can re-direct adult stem cells and cancer cells to mammary epithelial cell fates and that these re-directed cells contribute mammary progeny in subsequent fragment transplant outgrowths in vivo. These experiments support the notion that nonmammary cells are susceptible to the developmental signals present in the mammary microenvironment and are capable subsequently of self-renewal. In addition, cell-free preparation from adult rat or mouse mammary gland direct testicular and embryonic stem cells to form complete mammary epithelial outgrowths in vivo[20].

The immediate conclusion that is suggested by these experiments is that the microenvironment exerts a powerful influence upon cellular fate(s). This is particularly striking when one considers the effect of normal functioning cells in a normal stroma has upon cancer-forming cells. Further study of this effect and how it is manifested promises new and less debilitating treatments for cancer in situ.

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Friday, June 11, 2021

Astronomy in the Crossroads of Interdisciplinary and Multidisciplinary Sciences - Juniper Publishers

 Trends in Technical & Scientific Research - Juniper Publishers  

Abstract

Interdisciplinary and multidisciplinary sciences over the last few decades have become the major booster of science development. The most important discoveries occur just at the intersection of sciences and in collaboration of several fields. There appeared such intermediate fields as mathematical physics, physical chemistry, biophysics, biochemistry, geophysics, etc. In Astronomy, Astrophysics has long been the main field, and in present Archaeoastronomy, Astrochemistry, Astrobiology, Astroinformatics (which is tightly related to Virtual Observatories) are developing. On the other hand, in recent years many science areas surfeit of research on Earth, more and more use data coming from the Space and are being developed just due to them. It is possible that soon, various science areas create Space departments or simply develop their research in close collaboration with astronomers. Interesting discoveries have been made in studies of astronomical topics in various areas of culture; such topics are widely used in folklore, other genres of literature, painting, and architecture. Astronomy has also a leading role in Scientific Tourism, Scientific Journalism and in general, dissemination of popular science or public outreach.

Keywords: Interdisciplinary sciences; Multidisciplinary sciences; Transdisciplinary sciences, Astronomy; Astronomy in culture

Introduction: Current Trends in Astronomy Development

By studying the features of the current stage of development of astronomy, we have distinguished the current tendencies:
i. Broader usage of modern astronomical instruments and research methods (telescopes, various modes of spectroscopy (IFU, MOS, etc.), active and adaptive optics, digital receivers, software).
ii. Multiwavelength studies (γ-rays, X-rays, UV, optical, IR, sub-mm, mm, and radio; using space telescopes, etc.) and Multimessenger studies, including the development of neutrino, cosmic rays, and gravitational wave astronomy.
iii. Results based on large-scale astronomical data processing (Astrostatistics, Virtual Observatories, computer modeling, etc.).
iv. Large international astronomical projects and large collaborations (OPTICON, SDSS, ESA Gaia, PanSTARRS, SKA, ESO ELT, LSST, etc.).
v. The expansion of connection of Astronomy to other science fields (Astro Particle Physics, Astrochemistry, Astrobiology, close connection with Optics, Mechanics, Spectroscopy, Atomic and Nuclear Physics, Informatics, mathematical modeling, and with other spheres of culture).
In this article we will discuss the last point in more details. If we consider the recently revised divisions of the International Astronomical Union (IAU), we can see that only 4 out of 9 divisions are dedicated to purely astronomical fields and 4 are devoted to interdisciplinary and multidisciplinary sciences, or at least their elements are present (Figure 1): Division B - Equipment, Technology and Data Sciences (related to Optics, Modern Technologies, Astroinformatics, and Virtual Observatories); Division C - Education, Public Relations and Heritage (related to Archaeoastronomy, Astronomy in Culture, Astronomical Education and Public Outreach); Division D - High Energy and Fundamental Physics (related to Nuclear and High Energy Physics); and Division F - Planetary Systems and Biology (related to Astrobiology).

Such tendencies in astronomy are also evident by a number of interdisciplinary and multidisciplinary IAU commissions and working groups, UNESCO’s “Astronomy and World Heritage” Program, the International Virtual Observatory Alliance (IVOA), regularly held “Astronomical Data Analysis Software and Systems” (ADASS) Conferences, Committee of Space Research (COSPAR), International Council on Monuments and Sites (ICOMOS), the European Society for Astronomy in Culture (SEAC), International Science Council (ISC, formerly ICSU), World Data System (WDS), Information Theories & Applications (ITHEA) organization, the International Planetary Data Alliance (IPDA) and others. All these organizations were mainly established in the 2000

The Relation of Astronomy to other Sciences and Culture

Astronomy can really be considered as a leading link between interdisciplinary and multidisciplinary sciences. The point is that Astronomy, Astrophysics, Astrochemistry, Astrobiology, Archaeoastronomy, Theoretical Astrophysics (the use of Mathematics in Astrophysics), Astrostatistics, Astroinformatics (closely related to Virtual Observatories) have been developed for a long time. On the other hand, in the recent years, many fields of sciences being satisfied with research on the Earth, more and more use the data obtained from the Universe and are developed due to them. It is quite possible that soon different sciences will create Space divisions or simply will develop their research in close collaboration with astronomers. Interesting discoveries have been made in the study of astronomical topics in various fields of culture. Such topics have been widely used in folklore, other genres of literature, painting and architecture. Astronomy also plays a leading role in scientific tourism, scientific journalism, the dissemination of science in general, or the popularization of science (public outreach), which strengthens the connection between science and society.


At the International Year of Astronomy, declared by UNESCO (IYA-2009), the International Astronomical Union developed a ten-year strategic plan for the development of astronomy, according to which the emphasis is especially on the development of close relations between astronomy and other fields of sciences, technology and culture. The IAU has declared its Strategic Plan in 2009, according to which Astronomy will play a key role among all sciences and research, technologies and skills, and cultures and societies. Figure 2 gives the schematic picture of this plan. In frame of this, world Office of Astronomy for Development (OAD) and 11 Regional Offices of Astronomy for Development (ROADs; one in Armenia) have been founded [1]. Below we give examples of relation between astronomy and a number of other sciences, which prove the important role of astronomy in the development of interdisciplinary and multidisciplinary sciences.

Astronomy and Philosophy

Philosophical categories such as matter, space and time are directly related to the formation and development of forms of energy and matter in the Universe. By studying the origin and development of the Universe in astronomy, we significantly enrich our philosophical understanding. In Philosophy, a subject of centuries-long debates and ideological struggles has also been the discussions on Geocentrism and Heliocentrism and related to them is the religious notion of Anthropocentrism, which has been rejected by astronomical facts. However, the Problem of Extraterrestrial Civilizations (SETI/CETI) has not yet been finally resolved, although we are closer than ever to discovering other civilizations.

Astronomy and Physics

Though the modern astronomy (particularly the Byurakan Astrophysical Observatory) is mainly engaged in astrophysical research, but when we look at the sections of astronomy, we are convinced that there are many other branches: Astrometry, Chronology (Calendar and Chronology), Celestial Mechanics, Galactic Astronomy, Planetary Science, Cosmology and Cosmogony, Observational and Theoretical Astronomy, Computational Astronomy, non-optical, neutrino and gravitational wave Astronomy, etc. However, the connection between astronomy and physics plays an important role, which is expressed especially in the fields of Astrophysics, Solar Physics and Astroparticle Physics. On the other hand, almost all the branches of physics – mechanics, optics, electromagnetism, atomic and nuclear physics, the theory of relativity – are used in astronomy and are directly related to the study of the Universe. 

Moreover, at present they are mainly enriched and developed based on astronomical data, as the Universe is a huge laboratory, where there are all the conditions for Physics “experiments”. It is especially worth mentioning the development of atomic and nuclear physics due to the information received from the Space, the testing of the theory of relativity by means of cosmic phenomena. On the other hand, the development of optics is directly related to astronomy since 1609, from the first telescope made by Galileo to the largest modern optical devices, telescopes with 10m and larger in diameter mirrors. It is more interesting to consider all modern physics on a cosmological scale: quantum field theory, theories of unification of forces, formation of elementary particles, nuclear reactions and synthesis of chemical elements, black holes, etc. All these phenomena and theories can be “tested” and understood only within the framework of the “Warm Universe” theory, which is widely used in Cosmology.

Astronomy and Chemistry

Many of the chemical elements were first discovered in Space and then discovered or synthesized on Earth. The second most common element is Helium, originally in 1868, during the Solar eclipse, was discovered in the spectrum of the Sun by the French astronomer Jules Janssen and the English astronomer Norman Locker. It was named after the Sun (Greek “Helios” – Sun). It was detected only in 1882 on the Earth and obtained a final approval in 1903 at Earth conditions. Chemists and astronomers believe that other chemical elements can be found in the Universe, as well as the chemical composition of the Universe we know is still being revised, which is why Astrochemistry is currently in full swing. A comparative study of the chemical composition of the Universe and its individual systems and cosmic bodies sheds light on the chemical evolution of the Universe. In the above-mentioned “Hot Universe” cosmological theory, the problem of chemical elements, from the simplest to the most complex, the problem of synthesis and changes in their composition plays an important role. Since 1937, numerous molecules have been found in the coldest places in Space, mainly in interstellar environments, for a total of 189, including 43 two-atom ones, 41 three-atom ones, 26 four-atom ones, 19 five-atom, 15 six-atom, 9 seven-atom, 11 eight-atom, 10 nine-atom, and containing ten or more atoms – 15 types of molecules, which also enrich the modern chemistry.

Astronomy and Biology

Many organic compounds and other molecules necessary for life have been discovered in Space: water, oxygen, carbon, methane, carbon monoxide ice granules, carbon dioxide, formaldehyde, crystalline silicates, di- and tri- acetylene (C4H2 և C6H2), complex organic molecules (Polycyclic Aromatic Hydrocarbons, PAH), which are considered the “building bricks” of life, etc. The connection between Astronomy and Biology is very wide: it includes Space Biology (one of the founders of which is considered to be Norayr Sisakyan) – a science that studies unusual, unique factors in the Universe: weightlessness, Earth’s gravity, radiation, ecology of closed systems, the basics of astronauts training and selection, metabolism of organisms, and many other questions, the Problem of Extraterrestrial Civilizations (the study of the possible biological forms of aliens; SETI – Search for Extraterrestrial Intelligence and CETI – Communication with Extraterrestrial Intelligence), the Theory of Cosmic Panspermia (the theory of the possible propagation of life from one planet to another through comets), Astrobiology (which at large unifies all listed areas), Alternative Biology (consideration and study of other than Carbon-Oxygen forms of life), Astrology (in positive sense; influence of cosmic bodies on biological beings living on Earth), influence of astronomical phenomena in paleontology (destruction of dinosaurs by meteorite impact, freezing of the Earth’s surface due to disruption of Solar activity cycles, etc.). A detailed review on the Problem of Extraterrestrial Civilizations and Extrasolar Planets is given in Mickaelian [2].

Astronomy and Geology

The reason for the slow development of Geology is the limitation of the Earth, but in recent years the study of the Moon, other planets of the Solar System and their satellites has led to a significant enrichment of Geology. The fields of Lunar Science and Planetology (Planetary Science) have appeared, including individual fields of Martian Science, Venus Science and Mercury Science, which are especially developed. In contrast to the relatively flat terrain of the Earth, the mountains of Mars reach a height of 25km, active formations have been found on the planets and their satellites, in their outer layers there are many interesting “geological” formations, the study of which enriches our knowledge. The field of Comparative Planetology has been created.

Astronomy and Mathematics

Theoretical astronomy (celestial mechanics, astrodynamics) and theoretical astrophysics (the inner structure of the stars, the theory of radiative transfer, etc.) are based entirely on the study of the cosmic bodies and phenomena by mathematical methods. The most complex equations in mathematics are used in astrophysics. The study of the large-scale structure of the Universe is based on Theoretical Cosmology, which is also the mathematical apparatus of the General Theory of Relativity. Inverse Problems, Integral Equations, Mathematical Modeling, Astrostatistics the Theory of Errors are widely used and developed in astronomy. Due to the huge amount of data accumulated, the role of statistics in astronomy is so great that conferences on “Statistical Problems in Modern Astronomy” and other similar topics are regularly held.

Astronomy and Informatics

One of the most widely used applications of the Computer Science is Astronomy, which is associated with a vast amount of information in it. At present, this branch is called Astroinformatics, which includes mathematical modeling, Astrostatistics, work with large repositories and databases, Computational Astronomy, Virtual Observatories, etc. Numerous astronomical software and systems have been developed, in particular the All-Sky Virtual Observatory (ASVO). The development of astronomy is particularly facilitated using modern methods in astronomy education, including in the form of computer games, public professional astronomical programs. Regular conferences are held on “Astroinformatics”, “Big Data in Astronomy”, “Astronomical Data Analysis Software and Systems”. We give in Figure 3 a schematic view of Big Data in Astronomy. Detailed reviews on Big data in Astronomy and Computational Astrophysics are given in Mickaelian [3] and Mickaelian & Astsatryan [4].

Material Science

Astronomy and Space Flights

The role of celestial mechanics in Space flights and Astronautics is invaluable. The study of the motions of celestial bodies led first to the development of the most classical branch of physics, mechanics, and later to the possibility of controlling the motions of artificial bodies in the near Space, including the launch of many terrestrial artificial satellites, as well as the Astronautics. Moreover, the advantages of astronomy as a super-accurate science are revealed here: the movements of both celestial bodies and artificial satellites and other spacecrafts are calculated with an accuracy of seconds and centimeters. On the other hand, as in the Middle Ages, sailors, and now astronauts use the positions of the stars for navigation. This field is called Astronavigation. With the development of astronautics, reciprocally astronomy progressed rapidly, as most of the electromagnetic waves emitted by space bodies due to the influence of the atmosphere do not reach the Earth’s surface. Extra atmospheric or space observatories gave rise to IR, UV, and X-ray astronomy, which greatly expanded our understanding of the Universe. Moreover, even in the optical range, Space Astronomy made significant progress (the example of Hubble Space Telescope is the most characteristic), as both the sensitivity and spatial resolution of the observations were significantly improved.

Astronomy and Meteorology

In astronomy, the so-called Astroclimate plays an important role in choosing the location of observatories. It is the same climate that is familiar to all meteorologists, but also considering the statistical number of cloudless nights during the year, the degree of atmospheric turbulence, the quality of astronomical images, and a number of other factors that affect astronomical observations. On the other hand, the field of Space Climate is currently developing, which includes the influence of space phenomena and conditions on the Earth and its atmosphere, which is particularly due to the activity of the Sun and the Earth’s magnetosphere. Some manifestations of solar activity, such as solar flares and protuberances, dramatically alter the Earth’s magnetic field, causing geomagnetic storms that have a serious impact on power plants and all types of communications. Life-threatening ozone holes can also be caused by such influences. Cosmic particles also play an important role, including that from the point of view of the safety of spacecrafts and other space devices. Finally, global warming is also closely linked to Solar activity.

Astronomy, History and Archaeology

Ancient astronomy or archaeoastronomy (not to be confused with the history of astronomy) studies the manifestations of astronomical knowledge by ancient civilizations, the discovery of historical events through records of astronomical phenomena. These include the ancient observatories, calendars, astronomical rock art, naming of constellations, historical records of astronomical events, Medieval sky maps and astronomical instruments, other items of ancient astronomy and manifestations of the astronomical heritage. There are international organizations related to Archaeoastronomy (IAU commissions and working groups, UNESCO “Astronomy and World Heritage”, International Society for Archaeoastronomy and Astronomy in Culture (ISAAC), SEAC, etc.), international meetings are held on this subject and international journals are published also related to Archaeoastronomy (Journal for the History of Astronomy, Mediterranean Archaeology and Archaeometry, Archaeoastronomy, Culture and Cosmos, Journal of Astronomical History and Heritage).

Astronomy and Culture

Almost in all spheres of culture, such as mythology and religion, folklore, poetry, fine art, architecture, linguistics, symbolism, etc., the influence of celestial phenomena and astronomical understanding have penetrated to one degree or another. Very important is the factor of inspiration by the starry sky, which is a source of many creations, eventually leading to the many manifestations of the celestial bodies and phenomena in art and other spheres of culture. Again, calendars play a significant role in culture and all they are based on astronomical knowledge. Religions and Mythology are tightly related to astronomical knowledge as well. Other manifestations of astronomy in culture are Ethnoastronomy; astronomy in Folklore and Poetry; astronomy in Arts; astronomy in Fashion, Astrolinguistics, Astroheraldry, and Astrosymbolism; Astronomical Observatories as Astronomical Heritage; Astro Tourism and Astronomical Outreach. Figure 4 shows the logo of the meeting “Cultural Astronomy” held in 2016 in Armenia. The two last fields (Archaeostronomy and Astronomy in Culture, AAC) are very closely related and very often they collaborate having joint organizations, holding joint meetings and publishing joint journals. The IAU Working Group Archaeostronomy and Astronomy in Culture (WGAAC) unifies these disciplines as well.

Scientific Tourism, Scientific Journalism, Popular Science, Amateur Astronomy and Astronomical Education

Astronomical observatories are among the most attractive places for scientific tourism, many observatories in the world have thousands of visitors, which contributes to their recognition, scientific rating, and material benefits. Scientific tourism can be a serious addition to historical and cultural tourism, particularly in Armenia. We have developed a webpage on Astro Tourism for the South West and Central Asia region (http://astrotourism.aras. am/), which can be extended to other regions as well. In scientific journalism, according to world statistics, 50-90% of the topics in different countries are related to the Universe in one way or another: Astronomy, Space Flight, aliens, Archaeostronomy, Astrology, etc. That is why astronomy has a responsible role in the development of scientific journalism. The role of astronomy in the popularization of science is more obvious, as it is by far the most attractive science. The IAU also attaches great importance to this, having recently established the Commission #55 “Communication of Astronomy with the Public”. A journal with the same name is published. IAU runs a large-scale astronomy education program, which includes not only school and university astronomy, but also a policy of providing astronomical knowledge to the general population in all age groups.

Material Science

Relation of Astronomy to Other Sciences and Culture in Armenia

In recent years, the Byurakan Astrophysical Observatory and the Armenian Astronomical Society, has taken serious steps to strengthen the connection between astronomy and other sciences and culture. The first steps were the historicalastronomical works of Benik Tumanian, Haik Badalian, Elma Parsamian, Paris Herouni, Grigor Brutean and Karen Tokhatyan (history of Armenian astronomy, calendar, ancient observatories, rock art or petroglyphs). Grigor Gurzadian and Hrant Tovmasian made significant contribution in the field of Space Astronomy. In 2002-2007, Areg Mickaelian digitized the Markarian (the First Byurakan) Survey (FBS, digitized version: DFBS), based on which the Armenian Virtual Observatory [5] was created, the joint result by astronomers and computer specialists. Among the works of Ararat Yeghikian can be distinguished the studies related to Astrochemistry and Astrobiology.


However, a significant step forward was the International Year of Astronomy (IYA-2009) declared by UNESCO, when several international programs were launched to strengthen the cultural connection between astronomy and other sciences. IYA-2009 activities in Armenia were quite wide and multifaceted. ArAS 2009 annual conference on “Astronomy and Society” was held, where the issues of archaeoastronomy, astrobiology, astronomical education, amateur astronomy, astronomy and society were discussed. An archaeoastronomical seminar and conference were organized in 2011 և 2012. Three major events in 2014 [6], 2016 [7] and 2017 [8] were devoted to the Astronomical Heritage and related topics. A detailed review on Armenian activities on AAC is given in Mickaelian & Farmanyan [9]. In 2010, the group of scientific journalists from Armenia was established by ArAS. The issues of scientific tourism have been discussed since 2009. With such developments, astronomy can really become a leader in the connection between interdisciplinary and multidisciplinary sciences and science and culture.

The Practical Significance of Astronomy

The importance of astronomy is reinforced with its practical usage by society. First, it is significant for the formation of person’s worldview, especially for the young people. Calendars and Chronology based on astronomical knowledge or the use of astronomical information, Time service, Orientation և Location/ positioning, Earth և space navigation, optical devices, photography, Celestial Mechanics, Astronautics, further development of Physics and almost all other sciences based on information from Space have played an important role for the development of human society, development of Information Technologies (digital technology, computing methods and the Internet) and many other fields. Computed tomography (CT) and Magnetic Resonance Imaging (MRI) are the excellent examples of the astronomy achievements advancement in other areas.

A vivid example of the practical significance of astronomy is the use of nuclear energy, which became possible based on astronomical research conducted in the 1930s. In trying to explain the sources of Solar energy, trying to apply all the known forms of energy at the time, scientists were at a dead end, as thousands, millions of times more energy was required than mechanical, thermal, or chemical energy. Finally, Hans Bethe discovered nuclear reactions that release enormous amounts of energy, describing with great precision the processes going on in the Sun’s nucleus, the synthesis of 1 nucleus of helium from 4 nuclei of hydrogen. This theory was further developed by Robert Oppenheimer and others, and was later used to build atomic bombs, nuclear power plants, nuclear submarines, and other equipment. Currently, most of Armenia’s electricity comes from the Armenian Nuclear Power Plant.

The Role of Astronomy in the Development of Technology

The development of astronomy has been closely related to the development of technology. It was displayed at the measurements and calculations, angle calculating tools, optical devices, photography, photometry, spectroscopy, spectrophotometry, polarimetry, interferometry, adaptive optics, computers, IT sector, digital technology, processing systems, Internet development, e-Science and other fields. All the mentioned fields have both developed astronomy and they themselves have been developed due to the requirements set by astronomy. It is especially evident, the role of astronomy in the creation and development of optical devices, and now it is in the field of IT, because the large flow of information coming from space makes special demands and implies new approaches, in particular, computer clusters grid systems are mainly used by professionals of nuclear physics and astronomers. It can be said that astronomy has been and remains at the front of technology development and perhaps only the military industry with its demands and its role in the development of technology can be compared with astronomy.

The Role of Astronomy in Future Development of Sciences

The role of astronomy in the development of physical sciences, as well as other natural sciences is becoming more and more important due to the use of the vast amount of information coming from the Universe. We would like to mention that the Nobel Prizes are obvious indicator of the increase of the role of Astronomy during the recent years. Several the astronomers or physicists working on astronomical problems have received Nobel Prizes in Physics, which has started in 1901. During the first 100 years, only 6 such teams have been awarded Nobel Prizes. And during 2001- 2020, only 20 years, 6 more “astronomical” teams have also been awarded Nobel Prizes in Physics, including the last two, in 2019 and 2020. We give in Figure 5 the list of “astronomical” Nobel Prizes in Physics.

Material Science

We have described and analyzed the relation of Astronomy to other (mainly natural) sciences, and we have shown the leading role of Astronomy in the creation of many new inter- and multidisciplinary areas. One can regard several developments of both individual fields of natural sciences, which is already gradually happening and the development of science in general:
a) Establishment and further development of interdisciplinary sciences between individual science disciplines and Astronomy (like Astrophysics, Astrochemistry, Astrobiology, Planetology, etc.)
b) The development of multidisciplinary and transdisciplinary sciences based on involvement of many science disciplines, including Space-based knowledge.
c) Development of Space sciences related to individual science disciplines, such as Communications, Mapping, Meteorology, Remote Sensing, Space Astronomy, Space Biology and Medicine, etc. At present, in fact all explorations, when possible, move to Space and benefit from its possibilities.
d) Further development of Big Data science and computer technologies based on new data coming from the Space and being used for various science fields. Development of e-Science like the creation of Virtual Observatories (VOs) in Astronomy
e) Integration of the scientific data and all information to combined and homogeneous databases, like CODATA and WDS (World Data System) created by the International Science Council (ISC).

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Thursday, June 10, 2021

Occupational Exposure Limits for Enzymes: Practical Considerations - Juniper Publishers

 Pulmonary & Respiratory Sciences - Juniper Publishers

Commentary

A commentary article in this journal encouraged us all to work towards evidence-informed occupational airborne exposure limits for enzymes [1]. This prompted a response and a subsequent reply which explored a little more of the challenges faced [2,3]. Where there was debate, it might be best characterised as differences in the emphasis placed on the extent to which pragmatism should dominate decision-making, coupled with the ongoing need to ensure that complacency does not appear in industries that regard themselves as under control. It is a key principle that worker protection is an essential activity which should be based on the best evidence available and can be demonstrated to be successful, as in the report on 5 years of occupational health and air monitoring from a number of enzyme using detergent factories [4].

As enzymes are well known respiratory allergens, responsible users in the detergent industry have worked for half a century to an accepted and internationally recognised standard to protect worker health [5-7,4].

An important aspect here is that industry groups have taken the lead in the dissemination of best practice and have updated published industry guidance on multiple occasions, the latest version of which can be accessed here [8,9]. In addition, the knowledge originating from the enzyme manufacturing industry has been regularly published [10-12]. This has provided the basis on which best practice has been extended to other/downstream industries.

In principle, the matter of establishing an occupational exposure limit for a respiratory allergen is no different to other toxicology endpoints: identify the hazard, characterise the dose-response (potency assessment), understand the nature and extent of human exposure and use the combined information to set a safe level. For protein respiratory allergens, the challenges associated with this include the limited understanding of the dose response metrics [13-15]. This has led to a practical working solution, setting a derived minimal effect level (DMEL), which has already been published [16]. It has been argued that strict adherence to this approach involving use of the 60ng/m3 as a starting point benchmark has delivered a high level of occupational safety [7,4]. Central to this is rigorous application of occupational hygiene, with constant air monitoring and regular occupational health surveillance. Significantly, failure to adhere to the guidance leads to occupational health problems [17].

It has to be admitted that imperfections remain in the epidemiological metrics, the risk calculations and missing exposure information. Undoubtedly better epidemiological information would be a real asset. Similarly, it would be easy to assert that fuller exposure information must be helpful. These should then permit better risk calculations of course. However, there remains a genuine practical problem-that of matching exposure data, even from personal exposure monitoring to the acquisition of IgE mediated allergy. There is little evidence to indicate whether short term peak exposures are more, or less, important than repeated or constant lower level exposure and although the respiratory tract is the primary candidate, there is limited formal evidence for which route of exposure is actually critical to the induction of sensitisation. Finally, as far as we are aware, there have been no clinical experimental studies in which naïve volunteers have been subjected to defined inhalation exposures in order to characterise the parameters of exposure and dose which lead to the acquisition of IgE mediated allergy

All of these considerations and uncertainties lead inexorably to the pragmatic approach in which general airborne exposure levels are linked to the presence/absence of IgE allergies. Such an approach has the benefit that it avoids the potential inertia that can be associated with situations where there is not sufficient hard data to derive a fully evidence-based OEL. Perhaps such a problem occurred with the important efforts to establish an OEL for α-amylase, where it appeared that gaining substantial exposure data from all users sectors tended to stall the establishment of a suitable and broadly agreed value [18,19]. Of particular note was the concern from the UK perspective that the exposure-response relationships leading to the proposal for an airborne limit of <1ng/m3 was not well founded. On a more positive note, it was encouraging that the induction of antigen specific IgE was seen as the most appropriate measure on which to focus, in accord with the principle followed by the enzyme industry for several decades.

What are the essentials for a more pragmatic approach? There are three elements, each considered in a brief detail below:

The first essential has been the recognition of problematic exposure levels, and from that knowledge has evolved a definition of an exposure benchmark (usually designated as the DMEL), from which are determined exposure limits that can be achieved and accurately monitored [7,10-12,4,16]. It is not necessary here to review the history of occupational asthma problems that challenged the detergent industry in the mid-20th century [20-22]. What was gleaned from this unfortunate experience was an understanding of airborne exposure levels which delivered worker safety [5].

The second essential is that once there is general acceptance of what constitutes a suitable occupational exposure limit (OEL), the focus then must be directed towards compliance and monitoring. Any OEL is only of value where there is proper adherence thereto. Although perfection in this respect may be difficult, the data from approximately 100 industrial sites across 5 continents over a period of 5 years demonstrated a very high level of compliance (>99%) [4]. This suggests what can be achieved in the real world. Furthermore, health monitoring on the associated workforce (with almost 96% uptake) demonstrated an absence of any symptoms in 99.9%. It is worth diverting to remark that the occupational health default is to assume that symptoms (any one of rhinitis, conjunctivitis, impaired lung function and asthma) are assumed to be work-related unless they can be clearly linked to a non-occupational cause.

In other words, once proper control is achieved, the prevalence of workers with symptomatic occupational IgE allergy to enzymes in these industries is likely to be distinctly lower than 1 in a 1000. In support of this, the experience of almost 50 years of dealing with occupational allergy to enzymes in one company has been reported [12]. These authors demonstrated how with increasing experience the risk of allergy was reduced each decade, despite being paralleled in reverse by increasing production volumes, concluding “For primary prevention of enzyme allergy, exposure control is mandatory and achievable…”. These conclusions were reached via a retrospective evaluation of >5000 employees, sorted into 5 exposure group level and subject to regular health monitoring. The induction of IgE was related to exposure level and smoking; a high level of IgE was the sole risk factor for the expression of symptoms.

The third and critical aspect of the pragmatic strategy is the recognition that the hazard and the risks to human health associated with that intrinsic hazard never go away, nor do they ameliorate over time. Consequently, they require sustained vigilance. Complacency in the workforce and/or the management has to be avoided. Importantly, it is also necessary for the industry involved to promulgate best practice (whilst complying with anti-trust legislation). Enzyme producers and enzyme detergent industries have a good track record in this respect, working to ensure that advice is appropriate, clear and up to date [8,23]. Where possible, to encourage the adoption of practical best practice, that advice has been extrapolated to other downstream enzyme users, such as baking [9] and the pulp and paper industry [24] as well as to consumer products [25]. These considerations have extended even to 3rd party suppliers and logistics [26].

Whilst accepting that this industry’s approach has been based on an exposure limit that had to be defined, and broadly accepted, despite a less than an ideal level of supporting evidence, industry success has been well documented [4,12]. If this degree of success could be translated to other industries with an existing enzyme occupational respiratory allergen problem, it offers the prospect of improving significantly the working environment in those industries [2]. This conclusion that was expressed only recently continues to have merit.

Declaration

DAB was funded by the Association of Manufacturers and Formulators of Enzyme Products for the preparation and submission of this letter; NM and MS are fully paid employees of their respective organisations. DAB has been funded by both the Association of Manufacturers and Formulators of Enzyme Products and by Novozymes for a range of consultancy activities regarding enzyme allergy over the last 10 years.

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Wednesday, June 9, 2021

Acquired Chiari Malformation and Cervical Syringomyelia with Posterior Fossa Mass Accidentally Discovered After Child Delivery - Juniper Publishers

Theranostics of Brain, Spine & Neural Disorders - Juniper Publishers


Abstract

23 female patients complained of severe occipital headaches and dissociative sensory loss in form of lost hot sensation in left hand after giving birth to her child. MRI showed post fossa mass, tonsillar herniation and cervical syringomyelia. Patient underwent suboccipital decompression and mass excision. Histopathology indicated the mass is pilocytic astrocytoma. Later patient symptoms improved dramatically, and MRI showed resolution of syringomyleia 6 months after surgery.

Keywords: Acquired chiari malformation; Syringomyelia; Neck pain; Lumbar puncture

Introduction

Acquired Chiari malformation with secondary syringomyelia is a rare occurring condition due to posterior fossa space occupying lesions that causes tonsillar herniation and subsequent syrinx formation [1]. Synringomyleia occurrence is still unclear till now starting from Dr. James Gardner theory of water hammer effect [2]. Till the Oldfield theory of piston effect [3].

Case Report

Female patient aged 23 years was doing well until she had given birth to her child, she underwent spinal anesthesia delivery was cesarean section. After delivery, she started to feel annoyed by occipital pain that increased in intensity and aggravated by straining and coughing (Figures 1-5). She then started to have dissociative sensory loss manifested mainly by lost hot sensation in her right hand. Symptoms progressed dramatically in period of 4 months. She had Cranio-cervical MRI showed Posterior fossa space occupying lesion associated with tonsillar herniation and cervical syringomyelia that mostly aggravated by lumbar puncture during spinal anesthesia. Patient underwent mass excision and suboccipital craniectomy and the space occupying lesion was Pilocytic astrocytoma. With post-operative improvement in her symptoms with remarkable recovery at 6 months follow up. MRI at 6 months’ follow-up showed complete resolution of the syringomyelia.

Conclusion

Acquired Chairi malformation requires surgical management of the pathology causing the condition along with suboccipital craniectomy to relieve pressure and recovery of the syringomyleia.

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Artificial Intelligence System for Value Added Tax Collection via Self Organizing Map (SOM)- Juniper Publishers

  Forensic Sciences & Criminal Investigation - Juniper Publishers Abstract Findings:  Based on our experiments, our approach is an effec...