Fragility of foot process morphology in kidney podocytes arises from chaotic spatial propagation of cytoskeletal instability

Kidney podocytes’ function depends on fingerlike projections (foot processes) that interdigitate with those from neighboring cells to form the glomerular filtration barrier. The integrity of the barrier depends on spatial control of dynamics of actin cytoskeleton in the foot processes. We determined how imbalances in regulation of actin cytoskeletal dynamics could result in pathological morphology. We obtained 3-D electron microscopy images of podocytes and used quantitative features to build dynamical models to investigate how regulation of actin dynamics within foot processes controls local morphology. We find that imbalances in regulation of actin bundling lead to chaotic spatial patterns that could impair the foot process morphology. Simulation results are consistent with experimental observations for cytoskeletal reconfiguration through dysregulated RhoA or Rac1, and they predict compensatory mechanisms for biochemical stability. We conclude that podocyte morphology, optimized for filtration, is intrinsically fragile, whereby local transient biochemical imbalances may lead to permanent morphological changes associated with pathophysiology

The potential impact of austerity on attainment of the Sustainable Development Goals in Brazil

In the recent decades, Brazil has outperformed comparable countries in its progress toward meeting the Millennium Development Goals. Many of these improvements have been driven by investments in health and social policies. In this article, we aim to identify potential impacts of austerity policies in Brazil on the chances of achieving the sustainable development goals (SDGs) and its consequences for population health. Austerity’s anticipated impacts are assessed by analysing the change in federal spending on different budget programmes from 2014 to 2017. We collected budget data made publicly available by the Senate. Among the selected 19 programmes, only 4 had their committed budgets increased, in real terms, between 2014 and 2017. The total amount of extra money committed to these four programmes in 2017, above that committed in 2014, was small (BR$9.7 billion). Of the 15 programmes that had budget cuts in the period from 2014 to 2017, the total decrease amounted to BR$60.2 billion (US$15.3 billion). In addition to the overall large budget reduction, it is noteworthy that the largest proportional reductions were in programmes targeted at more vulnerable populations. In conclusion, it seems clear that the current austerity policies in Brazil will probably damage the population’s health and increase inequities, and that the possibility of meeting SDG targets is lower in 2018 than it was in 2015

Development and internal validation of a diagnostic prediction model for COVID-19 at time of admission to hospital.

BACKGROUND: Early coronavirus disease 2019 (COVID-19) diagnosis prior to laboratory testing results is crucial for infection control in hospitals. Models exist predicting COVID-19 diagnosis, but significant concerns exist regarding methodology and generalizability. AIM: To generate the first COVID-19 diagnosis risk score for use at the time of hospital admission using the TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) checklist. DESIGN: A multivariable diagnostic prediction model for COVID-19 using the TRIPOD checklist applied to a large single-centre retrospective observational study of patients with suspected COVID-19. METHODS: 581 individuals were admitted with suspected COVID-19; the majority had laboratory-confirmed COVID-19 (420/581, 72.2%). Retrospective collection was performed of electronic clinical records and pathology data. RESULTS: The final multivariable model demonstrated AUC 0.8535 (95% confidence interval 0.8121-0.8950). The final model used six clinical variables that are routinely available in most low and high-resource settings. Using a cut-off of 2, the derived risk score has a sensitivity of 78.1% and specificity of 86.8%. At COVID-19 prevalence of 10% the model has a negative predictive value (NPV) of 96.5%. CONCLUSIONS: Our risk score is intended for diagnosis of COVID-19 in individuals admitted to hospital with suspected COVID-19. The score is the first developed for COVID-19 diagnosis using the TRIPOD checklist. It may be effective as a tool to rule out COVID-19 and function at different pandemic phases of variable COVID-19 prevalence. The simple score could be used by any healthcare worker to support hospital infection control prior to laboratory testing results

Inequalities in the prevalence of major depressive disorder in Brazilian slum populations : a cross-sectional analysis

The mental health of slum residents is under-researched globally, and depression is a significant source of worldwide morbidity. Brazil's large slum-dwelling population is often considered part of a general urban-poor demographic. This study aims to identify the prevalence and distribution of depression in Brazil and compare mental health inequalities between slum and non-slum populations. Data were obtained from Brazil's 2019 National Health Survey. Slum residence was defined based on the UN-Habitat definition for slums and estimated from survey responses. Doctor-diagnosed depression, Patient Health Questionnaire (PHQ-9)-screened depression and presence of undiagnosed depression (PHQ-9-screened depression in the absence of a doctor's diagnosis) were analysed as primary outcomes, alongside depressive symptom severity as a secondary outcome. Prevalence estimates for all outcomes were calculated. Multivariable logistic regression models were used to investigate the association of socioeconomic characteristics, including slum residence, with primary outcomes. Depressive symptom severity was analysed using generalised ordinal logistic regression. Nationally, the prevalence of doctor diagnosed, PHQ-9 screened and undiagnosed depression were 9.9% (95% confidence interval (CI): 9.5-10.3), 10.8% (95% CI: 10.4-11.2) and 6.9% (95% CI: 6.6-7.2), respectively. Slum residents exhibited lower levels of doctor-diagnosed depression than non-slum urban residents (8.6%; 95% CI: 7.9-9.3 v. 10.7%; 95% CI: 10.2-11.2), while reporting similar levels of PHQ-9-screened depression (11.3%; 95% CI: 10.4-12.1 v. 11.3%; 95% CI: 10.8-11.8). In adjusted regression models, slum residence was associated with a lower likelihood of doctor diagnosed (adjusted odds ratio (adjusted OR): 0.87; 95% CI: 0.77-0.97) and PHQ-9-screened depression (adjusted OR: 0.87; 95% CI: 0.78-0.97). Slum residents showed a greater likelihood of reporting less severe depressive symptoms. There were significant ethnic/racial disparities in the likelihood of reporting doctor-diagnosed depression. Black individuals were less likely to report doctor-diagnosed depression (adjusted OR: 0.66; 95% CI: 0.57-0.75) than white individuals. A similar pattern was observed in Mixed Black (adjusted OR: 0.72; 95% CI: 0.66-0.79) and other (adjusted OR: 0.63; 95% CI: 0.45-0.88) ethnic/racial groups. Slum residents self-reporting a diagnosis of one or more chronic non-communicable diseases had greater odds of exhibiting all three primary depression outcomes. Substantial inequalities characterise the distribution of depression in Brazil including in slum settings. People living in slums may have lower diagnosed rates of depression than non-slum urban residents. Understanding the mechanisms behind the discrepancy in depression diagnosis between slum and non-slum populations is important to inform health policy in Brazil, including in addressing potential gaps in access to mental healthcare

Revealing the nature of morphological changes in carbon nanotube-polymer saturable absorber under high-power laser irradiation

Composites of single-walled carbon nanotubes (SWNTs) and water-soluble polymers (WSP) are the focus of significant worldwide research due to a number of applications in biotechnology and photonics, particularly for ultrashort pulse generation. Despite the unique possibility of constructing non-linear optical SWNT-WSP composites with controlled optical properties, their thermal degradation threshold and limit of operational power remain unexplored. In this study, we discover the nature of the SWNT-polyvinyl alcohol (PVA) film thermal degradation and evaluate the modification of the composite properties under continuous high-power ultrashort pulse laser operation. Using high-precision optical microscopy and micro-Raman spectroscopy, we have examined SWNT-PVA films before and after continuous laser radiation exposure (up to 40 hours) with a maximum optical fluence of 2.3 mJ·cm−2. We demonstrate that high-intensity laser radiation results in measurable changes in the composition and morphology of the SWNT-PVA film due to efficient heat transfer from SWNTs to the polymer matrix. The saturable absorber modification does not affect the laser operational performance. We anticipate our work to be a starting point for more sophisticated research aimed at the enhancement of SWNT-PVA films fabrication for their operation as reliable saturable absorbers in high-power ultrafast lasers

Local Cattle and Badger Populations Affect the Risk of Confirmed Tuberculosis in British Cattle Herds

Background: The control of bovine tuberculosis (bTB) remains a priority on the public health agenda in Great Britain, after launching in 1998 the Randomised Badger Culling Trial (RBCT) to evaluate the effectiveness of badger (Meles meles) culling as a control strategy. Our study complements previous analyses of the RBCT data (focusing on treatment effects) by presenting analyses of herd-level risks factors associated with the probability of a confirmed bTB breakdown in herds within each treatment: repeated widespread proactive culling, localized reactive culling and no culling (survey-only). Methodology/Principal Findings: New cases of bTB breakdowns were monitored inside the RBCT areas from the end of the first proactive badger cull to one year after the last proactive cull. The risk of a herd bTB breakdown was modeled using logistic regression and proportional hazard models adjusting for local farm-level risk factors. Inside survey-only and reactive areas, increased numbers of active badger setts and cattle herds within 1500 m of a farm were associated with an increased bTB risk. Inside proactive areas, the number of M. bovis positive badgers initially culled within 1500 m of a farm was the strongest predictor of the risk of a confirmed bTB breakdown. Conclusions/Significance: The use of herd-based models provide insights into how local cattle and badger populations affect the bTB breakdown risks of individual cattle herds in the absence of and in the presence of badger culling. These measures of local bTB risks could be integrated into a risk-based herd testing programme to improve the targeting o

The eClinical Care Pathway Framework: A novel structure for creation of online complex clinical care pathways and its application in the management of sexually transmitted infections.

Despite considerable international eHealth impetus, there is no guidance on the development of online clinical care pathways. Advances in diagnostics now enable self-testing with home diagnosis, to which comprehensive online clinical care could be linked, facilitating completely self-directed, remote care. We describe a new framework for developing complex online clinical care pathways and its application to clinical management of people with genital chlamydia infection, the commonest sexually transmitted infection (STI) in England.Using the existing evidence-base, guidelines and examples from contemporary clinical practice, we developed the eClinical Care Pathway Framework, a nine-step iterative process. Step 1: define the aims of the online pathway; Step 2: define the functional units; Step 3: draft the clinical consultation; Step 4: expert review; Step 5: cognitive testing; Step 6: user-centred interface testing; Step 7: specification development; Step 8: software testing, usability testing and further comprehension testing; Step 9: piloting. We then applied the Framework to create a chlamydia online clinical care pathway (Online Chlamydia Pathway).Use of the Framework elucidated content and structure of the care pathway and identified the need for significant changes in sequences of care (Traditional: history, diagnosis, information versus Online: diagnosis, information, history) and prescribing safety assessment. The Framework met the needs of complex STI management and enabled development of a multi-faceted, fully-automated consultation.The Framework provides a comprehensive structure on which complex online care pathways such as those needed for STI management, which involve clinical services, public health surveillance functions and third party (sexual partner) management, can be developed to meet national clinical and public health standards. The Online Chlamydia Pathway's standardised method of collecting data on demographics and sexual behaviour, with potential for interoperability with surveillance systems, could be a powerful tool for public health and clinical management.UKCRC Translational Infection Research (TIR) Initiative supported by the Medical Research Council, eSTI2 Consortium (Grant Number G0901608)

Shake a tail feather: the evolution of the theropod tail into a stiff aerodynamic surface

Theropod dinosaurs show striking morphological and functional tail variation; e.g., a long, robust, basal theropod tail used for counterbalance, or a short, modern avian tail used as an aerodynamic surface. We used a quantitative morphological and functional analysis to reconstruct intervertebral joint stiffness in the tail along the theropod lineage to extant birds. This provides new details of the tail's morphological transformation, and for the first time quantitatively evaluates its biomechanical consequences. We observe that both dorsoventral and lateral joint stiffness decreased along the non-avian theropod lineage (between nodes Theropoda and Paraves). Our results show how the tail structure of non-avian theropods was mechanically appropriate for holding itself up against gravity and maintaining passive balance. However, as dorsoventral and lateral joint stiffness decreased, the tail may have become more effective for dynamically maintaining balance. This supports our hypothesis of a reduction of dorsoventral and lateral joint stiffness in shorter tails. Along the avian theropod lineage (Avialae to crown group birds), dorsoventral and lateral joint stiffness increased overall, which appears to contradict our null expectation. We infer that this departure in joint stiffness is specific to the tail's aerodynamic role and the functional constraints imposed by it. Increased dorsoventral and lateral joint stiffness may have facilitated a gradually improved capacity to lift, depress, and swing the tail. The associated morphological changes should have resulted in a tail capable of producing larger muscular forces to utilise larger lift forces in flight. Improved joint mobility in neornithine birds potentially permitted an increase in the range of lift force vector orientations, which might have improved flight proficiency and manoeuvrability. The tail morphology of modern birds with tail fanning capabilities originated in early ornithuromorph birds. Hence, these capabilities should have been present in the early Cretaceous, with incipient tail-fanning capacity in the earliest pygostylian birds

Alignment of the CMS muon system with cosmic-ray and beam-halo muons

This is the Pre-print version of the Article. The official published version of the Paper can be accessed from the link below - Copyright @ 2010 IOPThe CMS muon system has been aligned using cosmic-ray muons collected in 2008 and beam-halo muons from the 2008 LHC circulating beam tests. After alignment, the resolution of the most sensitive coordinate is 80 microns for the relative positions of superlayers in the same barrel chamber and 270 microns for the relative positions of endcap chambers in the same ring structure. The resolution on the position of the central barrel chambers relative to the tracker is comprised between two extreme estimates, 200 and 700 microns, provided by two complementary studies. With minor modifications, the alignment procedures can be applied using muons from LHC collisions, leading to additional significant improvements.This work is supported by FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR(Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTDS (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)