Interventions to prevent pandemic-driven diversity loss

The pandemic has badly affected the most diverse career stage in UK Earth sciences: early career researchers. Disrupted careers must be rescued with contingency plans, remote networks, a focus on mental health and mentor support if we are to retain diversity and talent

Influence of wiring cost on the large-scale architecture of human cortical connectivity

In the past two decades some fundamental properties of cortical connectivity have been discovered: small-world structure, pronounced hierarchical and modular organisation, and strong core and rich-club structures. A common assumption when interpreting results of this kind is that the observed structural properties are present to enable the brain's function. However, the brain is also embedded into the limited space of the skull and its wiring has associated developmental and metabolic costs. These basic physical and economic aspects place separate, often conflicting, constraints on the brain's connectivity, which must be characterized in order to understand the true relationship between brain structure and function. To address this challenge, here we ask which, and to what extent, aspects of the structural organisation of the brain are conserved if we preserve specific spatial and topological properties of the brain but otherwise randomise its connectivity. We perform a comparative analysis of a connectivity map of the cortical connectome both on high- and low-resolutions utilising three different types of surrogate networks: spatially unconstrained (‘random’), connection length preserving (‘spatial’), and connection length optimised (‘reduced’) surrogates. We find that unconstrained randomisation markedly diminishes all investigated architectural properties of cortical connectivity. By contrast, spatial and reduced surrogates largely preserve most properties and, interestingly, often more so in the reduced surrogates. Specifically, our results suggest that the cortical network is less tightly integrated than its spatial constraints would allow, but more strongly segregated than its spatial constraints would necessitate. We additionally find that hierarchical organisation and rich-club structure of the cortical connectivity are largely preserved in spatial and reduced surrogates and hence may be partially attributable to cortical wiring constraints. In contrast, the high modularity and strong s-core of the high-resolution cortical network are significantly stronger than in the surrogates, underlining their potential functional relevance in the brain

Constraints on the Progenitor System of the Type Ia Supernova SN 2011fe/PTF11kly

Type Ia supernovae (SNe) serve as a fundamental pillar of modern cosmology, owing to their large luminosity and a well-defined relationship between light-curve shape and peak brightness. The precision distance measurements enabled by SNe Ia first revealed the accelerating expansion of the universe, now widely believed (though hardly understood) to require the presence of a mysterious "dark" energy. General consensus holds that Type Ia SNe result from thermonuclear explosions of a white dwarf (WD) in a binary system; however, little is known of the precise nature of the companion star and the physical properties of the progenitor system. Here we make use of extensive historical imaging obtained at the location of SN 2011fe/PTF11kly, the closest SN Ia discovered in the digital imaging era, to constrain the visible-light luminosity of the progenitor to be 10-100 times fainter than previous limits on other SN Ia progenitors. This directly rules out luminous red giants and the vast majority of helium stars as the mass-donating companion to the exploding white dwarf. Any evolved red companion must have been born with mass less than 3.5 times the mass of the Sun. These observations favour a scenario where the exploding WD of SN 2011fe/PTF11kly, accreted matter either from another WD, or by Roche-lobe overflow from a subgiant or main-sequence companion star.Comment: 22 pages, 6 figures, submitte

Quantifying the Link between Anatomical Connectivity, Gray Matter Volume and Regional Cerebral Blood Flow: An Integrative MRI Study

Background In the graph theoretical analysis of anatomical brain connectivity, the white matter connections between regions of the brain are identified and serve as basis for the assessment of regional connectivity profiles, for example, to locate the hubs of the brain. But regions of the brain can be characterised further with respect to their gray matter volume or resting state perfusion. Local anatomical connectivity, gray matter volume and perfusion are traits of each brain region that are likely to be interdependent, however, particular patterns of systematic covariation have not yet been identified. Methodology/Principal Findings We quantified the covariation of these traits by conducting an integrative MRI study on 23 subjects, utilising a combination of Diffusion Tensor Imaging, Arterial Spin Labeling and anatomical imaging. Based on our hypothesis that local connectivity, gray matter volume and perfusion are linked, we correlated these measures and particularly isolated the covariation of connectivity and perfusion by statistically controlling for gray matter volume. We found significant levels of covariation on the group- and regionwise level, particularly in regions of the Default Brain Mode Network. Conclusions/Significance Connectivity and perfusion are systematically linked throughout a number of brain regions, thus we discuss these results as a starting point for further research on the role of homology in the formation of functional connectivity networks and on how structure/function relationships can manifest in the form of such trait interdependency

Health and health care utilisation among asylum seekers and refugees in the Netherlands: design of a study

BACKGROUND: This article discusses the design of a study on the prevalence of health problems (both physical and mental) and the utilisation of health care services among asylum seekers and refugees in the Netherlands, including factors that may be related to their health and their utilisation of these services. METHODS/DESIGN: The study will include random samples of adult asylum seekers and refugees from Afghanistan, Iran and Somali (total planned sample of 600), as these are among the largest groups within the reception centres and municipalities in the Netherlands. The questionnaire that will be used will include questions on physical health (chronic and acute diseases and somatization), mental health (Hopkins Symptoms Checklist-25 and Harvard Trauma Questionnaire), utilisation of health care services, pre- and post-migratory traumatic experiences, life-style, acculturation, social support and socio-demographic background. The questionnaire has gone through a translation process (translation and back-translation, several checks and a pilot-study) and cross-cultural adaptation. Respondents will be interviewed by bilingual and bicultural interviewers who will be specifically trained for this purpose. This article discusses the selection of the study population, the chosen outcome measures, the translation and cross-cultural adaptation of the measurement instrument, the training of the interviewers and the practical execution of the study. The information provided may be useful for other researchers in this relatively new field of epidemiological research among various groups of asylum seekers and refugees

Thermography and thermoregulation of the face

BACKGROUND: Although clinical diagnosis of thermoregulation is gaining in importance there is no consistent evidence on the value of thermography of the facial region. In particular there are no reference values established with standardised methods. METHODS: Skin temperatures were measured in the facial area at 32 fixed measuring sites in 26 health subjects (7–72 years) with the aid of a contact thermograph (Eidatherm). A total of 6 measurements were performed separately for the two sides of the face at intervals of equal lengths (4 hours) over a period of 24 hours. Thermoregulation was triggered by application of a cold stimulus in the region of the ipsilateral ear lobe. RESULTS: Comparison of the sides revealed significant asymmetry of face temperature. The left side of the face showed a temperature that was on the average 0.1°C lower than on the right. No increase in temperature was found following application of the cold stimulus. However, a significant circadian rhythm with mean temperature differences of 0.7°C was observed. CONCLUSION: The results obtained should be seen as an initial basis for compiling an exact thermoprofile of the surface temperature of the facial region that takes into account the circadian rhythm, thus closing gaps in studies on physiological changes in the temperature of the skin of the face

Functional divergence in the role of N-linked glycosylation in smoothened signaling

The G protein-coupled receptor (GPCR) Smoothened (Smo) is the requisite signal transducer of the evolutionarily conserved Hedgehog (Hh) pathway. Although aspects of Smo signaling are conserved from Drosophila to vertebrates, significant differences have evolved. These include changes in its active sub-cellular localization, and the ability of vertebrate Smo to induce distinct G protein-dependent and independent signals in response to ligand. Whereas the canonical Smo signal to Gli transcriptional effectors occurs in a G protein-independent manner, its non-canonical signal employs Gαi. Whether vertebrate Smo can selectively bias its signal between these routes is not yet known. N-linked glycosylation is a post-translational modification that can influence GPCR trafficking, ligand responsiveness and signal output. Smo proteins in Drosophila and vertebrate systems harbor N-linked glycans, but their role in Smo signaling has not been established. Herein, we present a comprehensive analysis of Drosophila and murine Smo glycosylation that supports a functional divergence in the contribution of N-linked glycans to signaling. Of the seven predicted glycan acceptor sites in Drosophila Smo, one is essential. Loss of N-glycosylation at this site disrupted Smo trafficking and attenuated its signaling capability. In stark contrast, we found that all four predicted N-glycosylation sites on murine Smo were dispensable for proper trafficking, agonist binding and canonical signal induction. However, the under-glycosylated protein was compromised in its ability to induce a non-canonical signal through Gαi, providing for the first time evidence that Smo can bias its signal and that a post-translational modification can impact this process. As such, we postulate a profound shift in N-glycan function from affecting Smo ER exit in flies to influencing its signal output in mice

International guidelines for groin hernia management

Worldwide, more than 20 million patients undergo groin hernia repair annually. The many different approaches, treatment indications and a significant array of techniques for groin hernia repair warrant guidelines to standardize care, minimize complications, and improve results. The main goal of these guidelines is to improve patient outcomes, specifically to decrease recurrence rates and reduce chronic pain, the most frequent problems following groin hernia repair. They have been endorsed by all five continental hernia societies, the International Endo Hernia Society and the European Association for Endoscopic Surgery. An expert group of international surgeons (the HerniaSurge Group) and one anesthesiologist pain expert was formed. The group consisted of members from all continents with specific experience in hernia-related research. Care was taken to include surgeons who perform different types of repair and had preferably performed research on groin hernia surgery. During the Group's first meeting, evidence-based medicine (EBM) training occurred and 166 key questions (KQ) were formulated. EBM rules were followed in complete literature searches (including a complete search by The Dutch Cochrane database) to January 1, 2015 and to July 1, 2015 for level 1 publications. The articles were scored by teams of two or three according to Oxford, SIGN and Grade methodologies. During five 2-day meetings, results were discussed with the working group members leading to 136 statements and 88 recommendations. Recommendations were graded as "strong" (recommendations) or "weak" (suggestions) and by consensus in some cases upgraded. In the Results and summary section below, the term "should" refers to a recommendation. The AGREE II instrument was used to validate the guidelines. An external review was performed by three international experts. They recommended the guidelines with high scores. The risk factors for inguinal hernia (IH) include: family history, previous contra-lateral hernia, male gender, age, abnormal collagen metabolism, prostatectomy, and low body mass index. Peri-operative risk factors for recurrence include poor surgical techniques, low surgical volumes, surgical inexperience and local anesthesia. These should be considered when treating IH patients. IH diagnosis can be confirmed by physical examination alone in the vast majority of patients with appropriate signs and symptoms. Rarely, ultrasound is necessary. Less commonly still, a dynamic MRI or CT scan or herniography may be needed. The EHS classification system is suggested to stratify IH patients for tailored treatment, research and audit. Symptomatic groin hernias should be treated surgically. Asymptomatic or minimally symptomatic male IH patients may be managed with "watchful waiting" since their risk of hernia-related emergencies is low. The majority of these individuals will eventually require surgery; therefore, surgical risks and the watchful waiting strategy should be discussed with patients. Surgical treatment should be tailored to the surgeon's expertise, patient- and hernia-related characteristics and local/national resources. Furthermore, patient health-related, life style and social factors should all influence the shared decision-making process leading up to hernia management. Mesh repair is recommended as first choice, either by an open procedure or a laparo-endoscopic repair technique. One standard repair technique for all groin hernias does not exist. It is recommended that surgeons/surgical services provide both anterior and posterior approach options. Lichtenstein and laparo-endoscopic repair are best evaluated. Many other techniques need further evaluation. Provided that resources and expertise are available, laparo-endoscopic techniques have faster recovery times, lower chronic pain risk and are cost effective. There is discussion concerning laparo-endoscopic management of potential bilateral hernias (occult hernia issue). After patient consent, during TAPP, the contra-lateral side should be inspected. This is not suggested during unilateral TEP repair. After appropriate discussions with patients concerning results tissue repair (first choice is the Shouldice technique) can be offered. Day surgery is recommended for the majority of groin hernia repair provided aftercare is organized. Surgeons should be aware of the intrinsic characteristics of the meshes they use. Use of so-called low-weight mesh may have slight short-term benefits like reduced postoperative pain and shorter convalescence, but are not associated with better longer-term outcomes like recurrence and chronic pain. Mesh selection on weight alone is not recommended. The incidence of erosion seems higher with plug versus flat mesh. It is suggested not to use plug repair techniques. The use of other implants to replace the standard flat mesh in the Lichtenstein technique is currently not recommended. In almost all cases, mesh fixation in TEP is unnecessary. In both TEP and TAPP it is recommended to fix mesh in M3 hernias (large medial) to reduce recurrence risk. Antibiotic prophylaxis in average-risk patients in low-risk environments is not recommended in open surgery. In laparo-endoscopic repair it is never recommended. Local anesthesia in open repair has many advantages, and its use is recommended provided the surgeon is experienced in this technique. General anesthesia is suggested over regional in patients aged 65 and older as it might be associated with fewer complications like myocardial infarction, pneumonia and thromboembolism. Perioperative field blocks and/or subfascial/subcutaneous infiltrations are recommended in all cases of open repair. Patients are recommended to resume normal activities without restrictions as soon as they feel comfortable. Provided expertise is available, it is suggested that women with groin hernias undergo laparo-endoscopic repair in order to decrease the risk of chronic pain and avoid missing a femoral hernia. Watchful waiting is suggested in pregnant women as groin swelling most often consists of self-limited round ligament varicosities. Timely mesh repair by a laparo-endoscopic approach is suggested for femoral hernias provided expertise is available. All complications of groin hernia management are discussed in an extensive chapter on the topic. Overall, the incidence of clinically significant chronic pain is in the 10-12% range, decreasing over time. Debilitating chronic pain affecting normal daily activities or work ranges from 0.5 to 6%. Chronic postoperative inguinal pain (CPIP) is defined as bothersome moderate pain impacting daily activities lasting at least 3 months postoperatively and decreasing over time. CPIP risk factors include: young age, female gender, high preoperative pain, early high postoperative pain, recurrent hernia and open repair. For CPIP the focus should be on nerve recognition in open surgery and, in selected cases, prophylactic pragmatic nerve resection (planned resection is not suggested). It is suggested that CPIP management be performed by multi-disciplinary teams. It is also suggested that CPIP be managed by a combination of pharmacological and interventional measures and, if this is unsuccessful, followed by, in selected cases (triple) neurectomy and (in selected cases) mesh removal. For recurrent hernia after anterior repair, posterior repair is recommended. If recurrence occurs after a posterior repair, an anterior repair is recommended. After a failed anterior and posterior approach, management by a specialist hernia surgeon is recommended. Risk factors for hernia incarceration/strangulation include: female gender, femoral hernia and a history of hospitalization related to groin hernia. It is suggested that treatment of emergencies be tailored according to patient- and hernia-related factors, local expertise and resources. Learning curves vary between different techniques. Probably about 100 supervised laparo-endoscopic repairs are needed to achieve the same results as open mesh surgery like Lichtenstein. It is suggested that case load per surgeon is more important than center volume. It is recommended that minimum requirements be developed to certify individuals as expert hernia surgeon. The same is true for the designation "Hernia Center". From a cost-effectiveness perspective, day-case laparoscopic IH repair with minimal use of disposables is recommended. The development and implementation of national groin hernia registries in every country (or region, in the case of small country populations) is suggested. They should include patient follow-up data and account for local healthcare structures. A dissemination and implementation plan of the guidelines will be developed by global (HerniaSurge), regional (international societies) and local (national chapters) initiatives through internet websites, social media and smartphone apps. An overarching plan to improve access to safe IH surgery in low-resource settings (LRSs) is needed. It is suggested that this plan contains simple guidelines and a sustainability strategy, independent of international aid. It is suggested that in LRSs the focus be on performing high-volume Lichtenstein repair under local anesthesia using low-cost mesh. Three chapters discuss future research, guidelines for general practitioners and guidelines for patients. The HerniaSurge Group has developed these extensive and inclusive guidelines for the management of adult groin hernia patients. It is hoped that they will lead to better outcomes for groin hernia patients wherever they live. More knowledge, better training, national audit and specialization in groin hernia management will standardize care for these patients, lead to more effective and efficient healthcare and provide direction for future research

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure