Ectotherms in cold environments often spend long winters underground. In 1941 Raymond Cowles proposed a novel ecological trade-off involving depth at which ectotherms overwintered. On warm days, only shallow reptiles could detect warming soils and become active; but on cold days, they risked freezing. Cowles discovered that most reptiles at a desert site overwintered at shallow depths. To extend his study we compiled hourly soil temperatures (5 depths, 90 sites, continental USA) and physiological data, and then simulated consequences of overwintering at fixed depths. In warm localities shallow ectotherms have low energy costs and largest reserves in spring; but in cold localities, shallow ectotherms risk freezing. Ectotherms shifting to the coldest depth potentially reduce energy expenses, but paradoxically sometimes have higher expenses than those at fixed depths. Biophysical simulations for one desert site predict that shallow ectotherms should have elevated opportunities for mid-winter activity but may need to move deep to digest captured food. Our simulations generate testable eco-physiological predictions but rely on physiological responses to acute cold rather to natural cooling profiles. Furthermore, testing ecological predictions requires natural-history data that do not exist. Thus, our simulation approach uncovers “unknown unknowns” and suggests research agendas for studying ectotherms overwintering underground.

Under the unprecedented pressures of the global coronavirus disease 2019 (COVID-19) pandemic, there is an urgent requisite for successful strategies to safely deliver cardiac surgery. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first described in early December 2019, and the rapid spread and emergence of this virus has caused significant disruptions in the delivery of healthcare services worldwide.1,2 In particular, provision of cardiac surgery has been disproportionally affected due to reallocation of intensive care resources, such as ventilators.2Additionally, patients with pre-existing cardiovascular disease are likely to have comorbidities which are associated with poorer clinical outcomes in confirmed SARS-CoV-2 cases.3,4 Despite this, Yandrapalli and colleagues have reported the first case of a successful coronary artery bypass graft (CABG) operation in a patient with asymptomatic SARS-CoV-2 infection, which offers insights into how cardiac surgery could be adapted to solve the challenges of this pandemic.5In response to the burden of COVID-19 on healthcare systems in the United Kingdom (UK), elective cardiac surgeries have been delayed owing to the redistribution of intensive care resources and the unquantifiable risk of acquiring COVID-19.2 Likewise, cardiac surgery services have undergone structural remodelling into a centralised system in an attempt to continue provisions of emergency surgery alongside hospital management of COVID-19 patients.2Unsurprisingly, most cardiac surgery units across the globe have seen a sharp decline in surgeries as a result, and one unit reported an 83% reduction in cardiac index cases between 23rd March to 4th May 2020.2 Similar models have been used in Europe to manage healthcare services and increase intensive care capacity. For example in the Lombardy region of Italy, 16 out of 20 cardiac surgical units discontinued services and all urgent cases have been consequently diverted to the remaining four units for centralised services.6 Whilst these measures have been beneficial for supporting the focused management of COVID-19 patients, it is important to reflect upon the future consequences of delayed elective cardiac surgery. Indeed, such patients are likely to have progressive conditions and further work is needed to investigate the long-term impact of COVID-19 on mortality and morbidity in this cohort.The case report by Yandrapalli and colleagues highlight the importance of routine SARS-CoV-2 testing for all patients requiring cardiac surgery, especially for detecting asymptomatic or subclinical infections.5 Active SARS-CoV-2 infection may precipitate an overproduction of early response proinflammatory cytokines in post-operative period, leading to unfavourable surgical outcomes.7,8 Moreover, preliminary studies have shown that patients with established cardiovascular diseases may have a greater risk of increased SARS-CoV-2 infection severity and prognosis.9 Taken together, assessment for active infection is crucial for risk stratification. In addition, clinicians should consider the threshold for surgery when selecting patients for cardiac surgery. An international, multi-centre cohort study by COVIDSurg Collaborative which included 1128 confirmed SARS-CoV-2 patients undergoing a broad range of surgeries revealed that 30-day mortality risk was significantly associated with the patient demographics of male sex, an age of 70 years or older, and poor preoperative physical health status.10 Collectively, the risks and benefits of cardiac surgery should be carefully considered in such patients due to higher mortality risk.10Alternative therapeutic procedures with rapid discharge, such as percutaneous intervention or medical therapy, may be more appropriate to reduce SARS-CoV-2 related mortality and nosocomial infection risk.11Current evidence is limited for postoperative outcomes in cardiac surgery cases. In the aforementioned cohort study by COVIDSurg Collaborative, the 30-day mortality rate was 23.8%.10In addition, the study reported that 51.2% of patients had postoperative pulmonary complications, which was associated with a higher mortality rate of 38.0%.10 In another case report describing an emergency CABG operation, the asymptomatic patient succumbed to pulmonary complications arising from a SARS-CoV-2 infection confirmed postoperatively.12 The authors acknowledge that the undiagnosed infection may have triggered a refractory pathological response after cardiac surgery. Indeed, recent literature has suggested that patients with SARS-CoV-2 are at higher risk of developing thromboembolisms, possibly mediated by the interaction with angiotensin-converting enzyme 2 (ACE2) receptors.13Similarly, there is a consensus that SARS-CoV-2 has direct adverse effects on the myocardium due to high expression of ACE2.14 As such, SARS-CoV-2 can potentially trigger multisystem complications which require vigilant monitoring, especially in patients requiring cardiopulmonary bypass and at high risk of developing thromboembolisms. Cardiac surgery patients represent a vulnerable patient population, and this cohort may experience worse outcomes with SARS-CoV-2 infection based on the current available evidence. In the latest recommendation, UK currently advises all patients who are listed for elective cardiac surgery to self-isolate for 14 days prior to surgery date, in a measure to limit and contain the exposure of such cohort to the smallest possibilities of acquiring COVID-19.Currently, the future of cardiac surgery after the pandemic is unclear as the evidence is still emerging. However, the lessons learnt from these unprecedented times can be taken forward to inform future service planning. Moving forwards, routine screening of patients for SARS-CoV-2 infection will undoubtedly play a key role in identifying asymptomatic or subclinical infections. The preoperative UK National Health Service testing recommendations should be broadened so that all patients undergoing cardiac surgery are screened, given the higher risk of postoperative complications in this population. Similarly, repeat testing is important for monitoring patients for concomitant infections. Alongside changes to hospital protocol, service delivery will inevitably shift. The successful application of telemedicine during the pandemic has already been reported in the delivery of oncology services.15 Moreover, the benefits of telecardiology outside of the COVID-19 era have been previously reported, and cardiology services will likely embrace the utilisation of telemedicine for managing outpatient consultations.16 Units will also have to address the vast backlog of surgeries caused by cancellation of elective cardiac operations in a sustainable manner, with adequate hospital space and personal protective equipment availability.17 In order to resume success services, planning for this eventuality should begin now and patients at significant mortality risk due to delayed surgery need to be prioritised.Ultimately, clear guidelines should be implemented to ensure safe resumption of surgical services, whilst also reassuring patients concerned about safety.3 Whilst the future trajectory of this pandemic is uncertain, the insights from the impact of COVID-19 on cardiac surgery will undoubtedly shape the future delivery of cardiac surgery.

Mirror syndrome is a rare disease associated with a high fetal mortality of up to 67.2%. It is thought to be underdiagnosed and is often mistaken for preeclampsia. Mirror syndrome is characterized by ‘triple edema’: generalized maternal, placental, and fetal edema. A comprehensive search of several databaseswas conducted. Mirror syndrome is associated with high fetal morbidity and mortality; it is an important differential diagnosis with pre-eclampsia and thought to be currently underdiagnosed. Minimal is known about its pathogenesis. Maternal symptoms usually regress with resolution of pregnancy and management is dependent on the cause of fetal hydrops.

Objective To explore the effect of different delivery modes, vaginal delivery compared to caesarean section with or without initiation of labour, on the immune system and brain of the infants. Further, we aimed to elucidate gender and gestational ages’ effect on these biomarkers. Design Retrospective case control study Setting Dried blood spots from new-born screening biobank drawn 2-4 days after birth Population or Sample Mature new-borns divided into delivery by pre-labour (n=714), in-labour caesarean section (n=655), and vaginally (n=5897). Method The samples were analysed for inflammatory markers (IL-18, MCP-1, CRP, sTNF RI), stress- (HSP-70), growth- (EGF, VEGF-A), and neurotrophic factors (BDNF, NT-3, S100B). Main Outcome Measures Delivery by caesarean section with or without initiation of labour Results The neonatal levels of inflammatory and stress-markers were significantly lower, while the levels of growth factors were higher after pre-labour caesarean section compared to vaginal delivery. The biomarker levels were similar after in-labour caesarean section and vaginal delivery. Males had generally higher levels of inflammation and lower levels of growth and neurotrophic factors. Overall, the levels of inflammatory markers increased, and the growth factors decreased with increasing gestational age. Conclusion The biomarker levels indicates that the labour process has an important effect on the foetal immune system and level of stress, regardless if the delivery ends with caesarean section or vaginal birth. Funding ”Læge Sofus Carl Emil Friis og hustru Olga Doris Friis’ legat” and ”Fonden til Lægevidenskabens Fremme”. Keywords Inflammation; brain; CODIBINE; caesarean section; dried blood spot samples

Objectives Otorhinolaryngology trainees in the United Kingdom are required to perform ten septorhinoplasty procedures as the main operating surgeon in order to achieve a certificate of completion of training (CCT). The COVID-19 pandemic has profoundly reduced operative opportunities for surgical trainees around the world. Our aim was to assess UK otorhinolaryngology trainees’ perceptions of their septorhinoplasty training in the pre-COVID-19 era and frame this within the current training environment brought about by the COVID-19 pandemic. Design Cross-sectional survey. Setting United Kingdom. Participants UK otorhinolaryngology trainees. Main outcome measures Information on trainees’ previous operative experience, courses attended, learning materials used and challenges faced gaining septorhinoplasty training was collected. Results 64 trainees responded. All Deaneries and Local Education and Training Boards were represented. 63/64 (98.4%) trainees had operative exposure septorhinoplasty. 60/64 (93.8%) trainees were currently at a trust where septorhinoplasty was performed. A variety of challenges regarding septorhinoplasty training were highlighted, the most common problem being the low number of cases being performed. Nearly one-third (8/25) of ST7-8 trainees in this sample had still not yet performed a septorhinoplasty on at least one occasion even though they were into the final third of their training. Conclusions The COVID-19 pandemic is a new and additional threat to septorhinoplasty training for otorhinolaryngology trainees, particularly those in the final third of the programme. In the short term, clarification is required on what level of operative proficiency is required for a CCT. Longer-term, threats to training can be mitigated by providing cadaveric courses, embracing simulation and considering private sector placements in areas of low NHS volume.

Rationale, aims, and objectives An inefficient health system wastes scarce resources even if it makes considerable gains in accountability and equity. Such a system is expected to perform better. Therefore, it is vital to examine the current performance of health systems and their constituents as well as assess how to reach their full potential. The aim of this study was to evaluate the technical and economic efficiency of medical diagnostic laboratories in hospitals affiliated with Urmia Medical Sciences University (UMSU) in 2016. Methods In this descriptive-analytical study, the data of all diagnostic laboratories of the hospitals of UMSU were inputted into Frontier 4.1 software after taking the logarithm. Then, the technical and economic efficiency of the laboratories were obtained by estimating the production and cost function using the stochastic frontier analysis method, assuming input minimization for 2016. Results The average technical and economic efficiency of the diagnostic laboratories was obtained as 0.931±0.34 and 0.519±0.33, respectively. These laboratories must reduce their inputs and costs to achieve full efficiency without changing the amount of their output. Conclusion Although the average economic efficiency of the diagnostic laboratories of the studied hospitals was high, there is still an increase in the efficiency of these units given the cost of inputs at the time of allocating resources. In addition, it is possible to improve the technical efficiency of the clinical laboratories of hospitals affiliated with UMSU by 48.1% by applying the same level of inputs and without increasing the costs.

Despite important implications for biological conservation and public health, the potential generality of a prophylactic effect of biodiversity on zoonotic pathogen transmission (e.g., dilution effect) remains hotly debated, potentially because existing studies focus on different kinds of analyses as well as different spatial scales. Here, we test if changing the spatial scale of analysis can affect the detection of a relationship between hantavirus infection prevalence and rodent species richness throughout the World. We found that these relationships are always negative, whatever the spatial scale. Nevertheless, the dilution effect magnitude decreases if larger spatial scales are considered. These results, which remain consistent for all regions, highlight that the dilution effect should be a general phenomenon for hantaviruses, but that its detection can be hampered by the spatial scale considered. Finally, we discuss the mechanisms that can hinder the observation of a dilution effect and the necessity to consider other host-pathogen systems.

The forest people around the world through their indigenous knowledge contribute to the sustainable management of forests. This article argues that the Sheka people in southwestern Ethiopia by their ecological knowledge, values, and spiritual use could manage the Ororo tree (Ekebergia capensis). The Ororo tree (Ekebergia capensis) is one of the most important endemic tree species in the Sheka zone southwestern Ethiopia and, at the same time, one of the most endangered species. Data collected on the indigenous ecological knowledge of the Sheka people and how the Ororo tree could be managed and conserved through the DEDO culture documented and the spiritual connection between the Ororo trees and the Sheka people traditional belief system measured. The findings revealed that through their traditional forest-related knowledge, the Sheka people conserve and manage a single larger tree called Ororo. The Ororo tree is a special type of tree that has cultural and spiritual attachments that are presently non-existent. This unique forest conservation practice has been referred to as the DEDO culture. The culture of DEDO comes up with worshiping around the Ororo tree. Thus, the culture of DEDO played an important role in maintaining the conservation of the DEDO sacred tree (Ororo) and biodiversity therein. Over time, the DEDO sacred tree (Ororo) conservation culture has been decline, and various factors have contributed to the decline of this useful ecological knowledge.

Online educational videos have the potential to enhance undergraduate biology learning, for example by showcasing contemporary scientific research and providing content coverage. Here, we describe the integration of nine videos into a large-enrollment introductory evolution and ecology course via weekly homework assignments. We predicted that videos that feature research stories from contemporary scientists could reinforce topics introduced in lecture and provide students with novel insights into the nature of scientific research. Using qualitative analysis of open-ended written feedback from the students on each video assigned throughout the term (n=133-229 responses per video), we identified ten common themes in student perspectives. On the whole, the video homework assignments received more positive than negative comments and all videos received comments suggesting that they were engaging and contributed to learning goals. We discuss opportunities and challenges for the use of online educational videos in teaching ecology and evolution, and we provide guidelines instructors can use to integrate them into their courses.

Competence based education (CBE) has become increasingly popular as of late among health professions training programs. Models of CBE have been developed and implemented by major licensing bodies and professional Colleges (and affiliated education programs), such as the Royal College of Physicians and Surgeons of Canada (RCPSC) and the Association of American Medical Colleges (AAMC). In this month’s issue of theJournal of Evaluation in Clinical Practice , several studies describe an experience with designing and implementing a CBE model [1-6]. On the surface, the desire to ensure that health professions trainees are competent is commendable – just as it is likely few would argue that the care they receive should not be evidence based, I suspect that few (if any) would be comfortable with the clinician prescribing or managing said care being less than competent. However, the notion of a need for a CBE model might suggest that there was some issue with competence in the training of past clinicians that needed remedy, i.e. there is a lack of competence among some clinicians entering their profession that is in part a product of their training.When considering public perception of clinician competence, that of physicians in particular, history is not kind. Over the past two millennia, medicine got it wrong more often than right – humoral theory, bloodletting, miasma and contagion were all highly subscribed among the healthcare community but are now relics of a bygone era. In fact, the poor track record of medicine was the basis for a need for evidence based medicine (EBM). Practitioners of healthcare were often portrayed as ineffective, as providing little more than palliative support while nature took its course for better or worse, or even crueler, as charlatans peddling nostrums [7]. Artists were no kinder to clinicians. For example, Shaw’s The Doctors Dilemma portrays a group of physicians as self-absorbed, greedy, overly confident in their unproven (and presumably, ineffective) pet “cures”, with only the poorest among them as having any sense of humility and patient centred focus in his practice [8]. It seems that only within the last century did clinicians develop a good public reputation, much of which might be more appropriately attributed to improvements in hygiene practices/standards of living at a societal level (e.g. the McKeown Thesis[9]) or likewise to medical science and the discovery of “silver bullet” cures (e.g. antibiotics, insulin, etc.) rather than to a change in how clinicians approached the learning of their craft and care of their patients. However, a historical lack of curative success and a poor reputation does not entail a lack of competence. A clinician working in Europe during the first millennium of the Common Era would have been considered competent provided he (or much rarer, she) mastered humoralism according to the teachings of Galen. Is it possible that future generations will look at the clinicians of today – even those who train under CBE – in the same light as we do clinicians of the past? Should a failure of today’s medicine in the eyes of future generations invalidate the competence of contemporary clinicians? I suppose the impact of the answer to such questions on the issue of competence hinges on how we define (and measure) competence.What then makes a clinician competent? The obvious answer is technical knowledge in the clinician’s given area. By that, I assume that for a clinician to be considered competent, she requires a minimum understanding of the content and technique of her given profession contemporaneous with the period of practice.11A minimum understanding of content and technique is required to be accepted into the profession, but it is not the desirable end. Clinicians are expected to participate in a model of lifelong learning with a goal of mastery over that content and technique. However, knowledge might be considered the minimum requirement. Several frameworks of competence outline additional requirements. For example, the “CanMEDS” framework, issued by the RCPSC, identifies “the abilities physicians require to effectively meet the health care needs of the people they serve”22http://www.royalcollege.ca/rcsite/canmeds/canmeds-framework-e, accessed on June 8, 2020., which includes the roles of the physician as medical expert, communicator, collaborator, leader, health advocate, scholar, and professional. The criteria by which these “roles” were selected (and other “roles” excluded), including the theoretical and/or empirical justification for their inclusion as part of “competence” is not clear to me, nor is it entirely clear if available metrics are sufficient in demonstrating that the roles have in fact been achieved by the trainee or how one operationalizes those roles in practice. Are clinicians who lack ability in any of these “roles” incompetent? Does meeting all of them according to some threshold ensure competence? As health professions are typically self-regulating, it is up to the governing bodies of each profession to decide, which might suggest that competence is a product of the times rather than akin to a “natural kind”33If it is the case that “competence” in medical practice, for example, is in fact a standard set by the profession (which I think most people would agree is the case), then judging the competence of past or future physicians by the current standard might be inappropriate. That raises issues about differing standards of competency for currently practicing physicians who trained at different times. In Canada, we are currently going through a transition whereby our training programs have two cohorts – one that is training under the previous “time based” model and the other under the current “competence by design” model. Is it the case that there is a relatively less (or no) guarantee that those training under the previous model are competent? The answer to that question might impact the extent to which we should have confidence in currently practicing clinicians, or at least relative to the next generation. Regardless, all practicing clinicians are accountable to a standard set by their respective professional Colleges, which likely makes the issue moot once trainees enter independent practice..It would be silly to suggest that clinicians who trained under a pre-CBE model are not competent any more than it is to suggest that clinical decisions prior to the adoption of the EBM movement were not based on evidence. Certainly, we have no shortage of competent clinicians practicing today. Those clinicians were accepted into the profession (and maintain standing) on some assessment of competence. However, institutions may have good reason for implementing CBE beyond simple competence concerns. For example, CBE programs can facilitate the development of an infrastructure of accountability that extends beyond activities of remediation or accelerating advancement to independent practice. That infrastructure can be leveraged to ensure transparency in assessment and advancement, identify individualized training needs, etc. that can be important components of ensuring and achieving equitable access to health professions, particularly for traditionally underrepresented populations.44It is important to note that while CBE might drive the development of such an infrastructure, a CBE training model is not necessary to do so. Certainly, institutions can and should be striving to improve on accountability, equitable access, etc., irrespective of a CBE model.On the other hand, we have no shortage of experience with poor decisions, suboptimal patient outcomes, iatrogenic effects, etc., that often raise concern about clinician ability (or competence). Poor outcomes, or at least those not aligned with the expectations of the public (irrespective of if those expectations are realistic) could be construed by some as a result of incompetence. Likewise, inequitable access (within or between communities) to appropriate expertise might raise concern of a lack of professional competence (i.e. the profession is not meeting the needs of the population inclusively). One way such perceptions by the public can be problematic for healthcare professions is that may erode the powerful position of institutionalized healthcare (and its providers) that exists in many societies. One could argue that EBM had a powerful effect on securing the public’s trust in healthcare by leveraging public perception of science as apolitical, objective, etc. Does CBE play a similar role by highlighting high professional standards only achievable by those “worthy” of the profession, who were rigorously assessed using quantifiable (often presented as “objective”) metrics, irrespective of whether that results in better care for patients? If so, then CBE may constitute a political move to retain or grow power rather than a remedial exercise to ensure no one joins the profession without having the skills necessary to provide appropriate care (by some defined public standard) for those seeking service. In other words, one might argue that CBE is not a response to a concern about competence – it is a response to a potential loss of standing relative to alternative modes of care or other social services. I am not suggesting that is necessarily the case, as I know several health professions educators who are honest in their pursuit to train clinicians who will excel in serving and providing care for the community. That seems to be the rule rather than the exception. However, the goals of the educators may not always tightly align with the goals of the institution, which may also be responsible for securing funding, maintaining status, public accountability, etc.Models of health professions training that focus on assessing and achieving defined competencies rather than hoping that important abilities are acquired over a defined time period (that also relies on the reliability and validity of licensing exams) are admirable. It is difficult to argue that achieving competence should not be the explicit focus of training. Perhaps one of the greatest benefits of CBE is that it puts competence to the forefront, just as EBM did for evidence. However, we must be vigilant to ensure that “competence” stays more than a buzzword or a tool of branding. Terms lacking substance can have a negative effect on patient care – too often the terms “patient centred” and “evidence based”, for example, are invoked as placeholders for quality patient care without any evidence to support that whatever intervention or program those terms are describing has any positive impact beyond rhetorical. We have not entered into an era of clinician competence simply because CBE has been implemented. Rather, what I see as the greatest benefit of CBE is the opportunity for improving and ensuring accountability.ReferencesRich J, Young SF, Donnelly C, et al. Competency-based education calls for programmatic assessment: But what does this look like in practice? Journal of Evaluation in Clinical Practice 2020;26(4):Hamza DM, Ross S, Oandasan I. Process and outcome evaluation of a CBME intervention guided by program theory. Journal of Evaluation in Clinical Practice 2020;26(4):Egan R, Chaplin T, Szulewski A, et al. A case for feedback and monitoring assessment in competency-based medical education. Journal of Evaluation in Clinical Practice 2020;26(4):Katoue MG, Schwinghammer TL. Competency-based education in pharmacy: A review of its development, applications, and challenges. Journal of Evaluation in Clinical Practice 2020;26(4):Crawford L, Cofie N, McEwen L, Dagnone D, Taylor SW. Perceptions and barriers to competency-based education in Canadian postgraduate medical education. Journal of Evaluation in Clinical Practice 2020;26(4):Railer J, Stockley D, Flynn L, Hastings-Truelove A, Hussain A. Using outcome harvesting: Assessing the efficacy of CBME Implementation. Journal of Evaluation in Clinical Practice 2020;26(4):Porter R. The Greatest Benefit to Mankind: A Medical History of Humanity. New York: W.W. Norton & Company; 1997.Shaw, B. The Doctor’s Dilemma: A Tragedy. London: Constable and Co.; 1922.McKeown T. The role of medicine: Dream, mirage or nemesis? Nuffield Trust; 1976. Available at: https://www.nuffieldtrust.org.uk/files/2017-01/1485273106_the-role-of-medicine-web-final.pdf. Accessed on June 8, 2020.

The outbreak of the Covid-19 pandemic obliged us all to handle many dilemmas, some of which we took upon ourselves as philosophers, ethicists, doctors and nurses to discuss around four key ethical notions : responsibility, dignity, fairness and honouring death. The following collection of the symposium acts held online in May 2020 with the Paris Global Center of Columbia University and Columbia Global Centers, attempts to testify to the ongoing pandemic emergency and difficult challenges while evaluating whether the ethical principles in the official recommendations were able to meet the lived reality. Looking at accountability and consistency in regard to the context of exercise, it seemed equally important to examine, through an international exchange, whether the contextuality of Coronavirus across countries and cultures affected the ethical decision making processes. We hope that our discussion can serve as a resource for advanced care planning, helping medical providers and other specialists to consider the shared important aspects of medical ethics in times of great uncertainty.

Atopic dermatitis (AD) is the chronic relapsing inflammatory skin disorder that affects both in childhood and adulthood. Mounting evidence indicates that gut dysbiosis contributes to AD via the gut-skin axis. Constipation could result in alteration of the gut microflora. The clinical impact of constipation on AD has not been researched. Therefore, we aim to assess the risk of AD in constipated patients by the longitudinal nationwide population-based cohort study. We collected 87015 people with constipation and 87015 patients without constipation between 1999 and 2013 from the Longitudinal Health Insurance Database, which is the subset of Taiwanese National Health Insurance Research Database. Propensity score analysis was administrated to match age, gender, comorbidities, and medications at a ratio of 1:1. Multiple Cox regression analysis was utilized to evaluate the adjusted hazard ratio of AD. In addition, sensitivity tests and a stratified analysis were conducted. The incidence of AD was 4.7 per 1,000 person-years in the constipation group, which was higher than the rate of 2.2 per 1,000 person-years observed in the non-constipation group. After adjustment for age, gender, comorbidities, corticosteroids, and antihistamine, people with constipation had a 2.11-fold greater risk of AD compared to those without constipation (adjusted hazard ratio [aHR]: 2.11 (95% C.I. 1.98-2.24). In subgroup analyses, people aged 12-19 years had a 2.34-fold higher risk of AD in the constipation cohort (aHR; 95% CI, 1.84-2.98). Moreover, people with constipation had a higher likelihood of AD, regardless of gender, and with or without comorbidities, as well as the usage of corticosteroids, and antihistamines. Constipation is connected with a significantly risk factor of AD. Clinicians should be careful of the possibility of AD in people with constipation. Further study is warranted to investigate the possible pathological mechanisms of underlying this relationship.

Afforestation of degraded lands using both exotic and indigenous species is used to reduce land degradation and to reforest degraded areas. Acacia saligna is one of the common exotic plantation species planted in Ethiopia. This study analyzed the existing carbon stock and some soil physico-chemical properties of A. saligna plantation at two districts in Tigray, northern Ethiopia. Soil samples were collected from 204 samples at three soil depths from plantation site and adjacent grazing lands. Paired t-test was used to analyze data. Soil organic carbon (SOC) stock was higher at lower depth (40-60cm) than middle and upper depths at plantation sites while the second depth (20-40cm) was found higher SOC at grazing lands. Furthermore, in Mai-Brazio, soil properties except Total nitrogen(TN) and Available Phosphorus (Av,P), Cation Exchange Capacity (CEC), Available Potassium (Av,K) and soil pH were significantly (P<0.05) higher than adjacent grazing lands While CEC and Av.K were non-significant in Barka-Adisbha site (p>0.05). Area converted to plantation site showed lower soil bulk density than the open grazing land. Further, CEC is negatively correlated (P < 0.001) with soil pH, this may shows that CEC is affected by the variation of soil pH.

1. Urban areas are often considered to be a hostile environment for wildlife as they are highly fragmented and frequently disturbed. However, these same habitats can contain abundant resources, while lacking many common competitors and predators. The urban environment can have a direct impact on the species living there, but can also have indirect effects on their parasites and pathogens. To date, relatively few studies have measured how fine-scale spatial heterogeneity within urban landscapes can affect parasite transmission and persistence. 2. Here we surveyed 237 greenspaces across the urban environment of Edinburgh (UK) to investigate how fine-scale variation in socio-economic and ecological variables can affect red fox (Vulpes vulpes) marking behaviour, gastrointestinal (GI) parasite prevalence and parasite community diversity, 3. We found that the presence and abundance of red fox faecal markings was non-uniformly distributed across greenspaces, and instead was dependent on the ecological characteristics of a site. Specifically, common foraging areas were left largely unmarked, which indicates that suitable resting and denning sites may be limiting factor in urban environments. In addition, the amount of greenspace around each site was positively correlated with overall GI parasite prevalence, species richness and diversity, highlighting the importance of greenspace (a commonly used measure of landscape connectivity) in determining the composition of the parasite community in urban areas. 4. Our results suggest that fine scale variation within urban environments can be important for understanding the ecology of infectious diseases in urban wildlife and could have wider implication for the management of urban carnivores.

Background and Purpose: COVID-19 patients treated with RAAS blockers are among the patients at highest risk of poor outcome. ACE2 is the functional receptor for SARS-CoV-2. Animal studies suggest that RAAS blockers might increase the expression of ACE2 and potentially increase the risk of SARS-Cov-2 infection. Experimental Approach and Key Results: The effect of ACE inhibitor treatment on the incidence of pneumonia in non-COVID-19 patients was analyzed in 25 studies (330,780 patients). ACE inhibitor use was associated with a 27% reduction of pneumonia risk (OR: 0.73, p<0.001). Pneumonia related death cases in ACE inhibitor treated non-COVID-19 patients were reduced by 27% (OR: 0.73, p=0.004). ARB treatment was analyzed in 10 studies (275,621 non-COVID-19 patients). The risk of pneumonia was not different between patients who did or did not use ARBs. Pooled results from 16 studies in 22,333 COVID-19 patients showed that COVID-19 related server adverse clinical outcomes (admission to ICU, need for assisted ventilation or death) were reduced by 26% when using RAAS blocking agents (OR=0.74, p=0.04). Pooled results from 10 studies in 11,514 COVID-19 patients showed that RAAS blockede reduces all-cause mortality by 41% (OR=0.59, p=0.01). Conclusion and Implications: Given the weak evidence coming from animal studies and the clear beneficial data of ACE inhibition in non-COVID-19 patients and the promising data in COVID-19 patients, the use of RAAS blocking agents in patients with SARS-CoV-2 infection is justified and should be maintained. Further clinical studies analysing ARBs and ACE inhibitors separately in COVID-19 patients are needed.

Abstract- The ongoing outbreak of COVID-19 that began in Wuhan, China, has constituted a Public Health Emergency of International Concern, with cases confirmed in more than 200 countries. Currently, infected individuals are the primary source of infection and multiple cases of relapse are also reported following the recovery. It is highly concerning about the nature of relapse which may be caused due to reactivation or reinfection. While the present testing scenario of using different molecular techniques has several loop holes that can report false results and hamper the process of effectively preventing the transmission of the virus. Various recommendations need modifications as to effectively stop the horizontal transmission of the virus and look deeply into the links with relapse cases to prevent a second wave during a pandemic.

A document by Rafaela Minsky, written on Authorea.

A document by Shu Zhu, written on Authorea.

This paper reviews the tools available to assess outcomes of treatment in irritable bowel syndrome, especially the effect on pain. It critically considers their development, relevance and reliability. Its conclusion is that there are few tools which meet the criteria necessary to place confidence in their validity as appropriate measures of patient outcomes.

Therapeutic monoclonal antibodies and related products have steadily grown to become the dominant product class within the biopharmaceutical market. Production of antibodies requires special precautions to ensure safety and efficacy of the product. In particular, minimizing antibody product heterogeneity is crucial as drug substance variants may impair the activity, efficacy, safety and pharmacokinetic properties of an antibody, consequently resulting in the failure of a product in pre-clinical and clinical development. This review will cover the manufacturing and formulation challenges and advances of therapeutic monoclonal antibodies, with a focus on improved processes to minimize variants and ensure batch-to-batch consistency. Processes put in place by regulatory agencies such as Quality-by-Design (QbD) and current Good Manufacturing Practices (cGMP) will be reviewed, and how their implementation has aided drug development in pharmaceutical companies. Advances in formulation and considerations on the intended use of a therapeutic antibody, including route of administration and patient compliance, will be discussed.

Biofilm streamer motion under different flow conditions is important for a wide range of industries. The existing work has largely focused on experimental characterisations of these streamers, which is often time-consuming and expensive. To better understand the physics of biofilm streamer oscillation and their interactions in fluid flow, a CFD-DEM (Computational Fluid Dynamics – Discrete Element Method) model has been developed. The model was used to study the flow-induced oscillations of single and multiple biofilm streamers. We have studied the effect of streamer length on the oscillation at varied flow rates. The predicted single biofilm streamer oscillations in various flow rates agreed well with experimental measurements. Furthermore, we have investigated the effect of the spatial arrangement of streamers on interactions between two oscillating streamers, which have not been achieved previously.

The potential use of gene- modified cell therapy in hematologic malignancies is often limited by complications related to effectively engineering and manufacturing cells with conventional delivery systems and is challenge specifically for immune cells. In fact, this life-saving therapy requires use of inefficient reagents and specialized equipment that can drive up the price of the treatment. Herein, we compared two different approaches for gene transfer into target cells: Nucleofection as a 2D gene delivery and microfluidic device as a 3D gene transfer technology. In fact, we developed and used serpentine microfluidic chip for cell membrane penetration that permits delivery of DNA into Multiple myeloma cells. We achieved high transfection efficiency (55.7% GFP) in myeloma cells with high cell viability (by PI staining) 24-48 hours after microfluidic processing compared to nucleofection that is toxic and rate of dead cells is very high. The significant differences in outcomes from the two techniques underscores the importance of understanding the impact of intracellular delivery techniques on cell function for research and clinical applications. Altogether, these results highlight the use of microfluidic device as a rapid and gentle delivery method with promising potential to engineer primary human cells for research and clinical applications.

A 47 year-old man who was successfully treated for PE . later on Discovered to have left sided venous engorgement in the abdomen and left lower limb . He was later discovered to have congenital absence of inferior vena cava and was prepared for investigations including venography and coagulation profile

Retrieval of central venous catheters fragments often puts us in front of different situations. Having more techniques available for strategic planning of the procedure is imporatnt. The authors propose the simultaneous use of two different approaches for the recovery of a CVC fragment from the pulmonary artery.