Microscopic Imaging Homogeneous and Single Phase Superfluid Density in UTe_{2}.

Odd-parity superconductor UTe_{2} shows spontaneous time-reversal symmetry breaking and multiple superconducting phases, which imply chiral superconductivity, but only in a subset of samples. Here we microscopically observe a homogeneous superfluid density n_{s} on the surface of UTe_{2} and an enhanced superconducting transition temperature near the edges. We also detect vortex-antivortex pairs even at zero magnetic field, indicating the existence of a hidden internal field. The temperature dependence of n_{s}, determined independent of sample geometry, does not support point nodes along the b axis for a quasi-2D Fermi surface and provides no evidence for multiple phase transitions in UTe_{2}.

Absence of Spontaneous Magnetic Fields due to Time-Reversal Symmetry Breaking in Bulk Superconducting UTe_{2}.

We have investigated the low-temperature local magnetic properties in the bulk of molten salt-flux (MSF)-grown single crystals of the candidate odd-parity superconductor UTe_{2} by zero-field muon spin relaxation (µSR). In contrast to previous µSR studies of UTe_{2} single crystals grown by a chemical vapor transport method, we find no evidence of magnetic clusters or electronic moments fluctuating slow enough to cause a discernible relaxation of the zero-field µSR asymmetry spectrum. Consequently, our measurements on MSF-grown single crystals rule out the generation of spontaneous magnetic fields in the bulk that would occur near impurities or lattice defects if the superconducting state of UTe_{2} breaks time-reversal symmetry. This result suggests that UTe_{2} is characterized by a single-component superconducting order parameter.

Mapping tree density at a global scale.

The global extent and distribution of forest trees is central to our understanding of the terrestrial biosphere. We provide the first spatially continuous map of forest tree density at a global scale. This map reveals that the global number of trees is approximately 3.04 trillion, an order of magnitude higher than the previous estimate. Of these trees, approximately 1.39 trillion exist in tropical and subtropical forests, with 0.74 trillion in boreal regions and 0.61 trillion in temperate regions. Biome-level trends in tree density demonstrate the importance of climate and topography in controlling local tree densities at finer scales, as well as the overwhelming effect of humans across most of the world. Based on our projected tree densities, we estimate that over 15 billion trees are cut down each year, and the global number of trees has fallen by approximately 46% since the start of human civilization.

From clear lakes to murky waters - tracing the functional response of high-latitude lake communities to concurrent 'greening' and 'browning'.

Climate change and the intensification of land use practices are causing widespread eutrophication of subarctic lakes. The implications of this rapid change for lake ecosystem function remain poorly understood. To assess how freshwater communities respond to such profound changes in their habitat and resource availability, we conducted a space-for-time analysis of food-web structure in 30 lakes situated across a temperature-productivity gradient equivalent to the predicted future climate of subarctic Europe (temperature +3°C, precipitation +30% and nutrient +45 µg L-1 total phosphorus). Along this gradient, we observed an increase in the assimilation of pelagic-derived carbon from 25 to 75% throughout primary, secondary and tertiary consumers. This shift was overwhelmingly driven by the consumption of pelagic detritus by benthic primary consumers and was not accompanied by increased pelagic foraging by higher trophic level consumers. Our data also revealed a convergence of the carbon isotope ratios of pelagic and benthic food web endmembers in the warmest, most productive lakes indicating that the incorporation of terrestrial derived carbon into aquatic food webs increases as land use intensifies. These results, reflecting changes along a gradient characteristic of the predicted future environment throughout the subarctic, indicate that climate and land use driven eutrophication and browning are radically altering the function and fuelling of aquatic food webs in this biome.

Sex differences in national rates of repair of emergency abdominal aortic aneurysm.

BACKGROUND: The aim of this study was to assess the sex differences in both the rate and type of repair for emergency abdominal aortic aneurysm (AAA) in England. METHODS: Hospital Episode Statistics (HES) data sets from April 2002 to February 2015 were obtained. Clinical and administrative codes were used to identify patients who underwent primary emergency definitive repair of ruptured or intact AAA, and patients with a diagnosis of AAA who died in hospital without repair. These three groups included all patients with a primary AAA who presented as an emergency. Sex differences between repair rates and type of surgery (endovascular aneurysm repair (EVAR) versus open repair) over time were examined. RESULTS: In total, 15 717 patients (83·3 per cent men) received emergency surgical intervention for ruptured AAA and 10 276 (81·2 per cent men) for intact AAA; 12 767 (62·0 per cent men) died in hospital without attempted repair. The unadjusted odds ratio for no repair in women versus men was 2·88 (95 per cent c.i. 2·75 to 3·02). Women undergoing repair of ruptured AAA were older and had a higher in-hospital mortality rate (50·0 versus 41·0 per cent for open repair; 30·9 versus 23·5 per cent for EVAR). After adjustment for age, deprivation and co-morbidities, the odds ratio for no repair in women versus men was 1·34 (1·28 to 1·40). The in-hospital mortality rate after emergency repair of an intact AAA was also higher among women. CONCLUSION: Women who present as an emergency with an AAA are less likely to undergo repair than men. Although some of this can be explained by differences in age and co-morbidities, the differences persist after case-mix adjustment.

Quantum Oscillations in Flux-Grown SmB_{6} with Embedded Aluminum.

SmB_{6} is a candidate topological Kondo insulator that displays surface conduction at low temperatures. Here, we perform torque magnetization measurements as a means to detect de Haas-van Alphen (dHvA) oscillations in SmB_{6} crystals grown by aluminum flux. We find that dHvA oscillations occur in single crystals containing embedded aluminum, originating from the flux used to synthesize SmB_{6}. Measurements on a sample with multiple, unconnected aluminum inclusions show that aluminum crystallizes in a preferred orientation within the SmB_{6} cubic lattice. The presence of aluminum is confirmed through bulk susceptibility measurements, but does not show a signature in transport measurements. We discuss the ramifications of our results.

Enhanced Hybridization Sets the Stage for Electronic Nematicity in CeRhIn_{5}.

High magnetic fields induce a pronounced in-plane electronic anisotropy in the tetragonal antiferromagnetic metal CeRhIn_{5} at H^{*}≳30 T for fields ≃20° off the c axis. Here we investigate the response of the underlying crystal lattice in magnetic fields to 45 T via high-resolution dilatometry. At low fields, a finite magnetic field component in the tetragonal ab plane explicitly breaks the tetragonal (C_{4}) symmetry of the lattice revealing a finite nematic susceptibility. A modest a-axis expansion at H^{*} hence marks the crossover to a fluctuating nematic phase with large nematic susceptibility. Magnetostriction quantum oscillations confirm a Fermi surface change at H^{*} with the emergence of new orbits. By analyzing the field-induced change in the crystal-field ground state, we conclude that the in-plane Ce 4f hybridization is enhanced at H^{*}, in agreement with the in-plane lattice expansion. We argue that the nematic behavior observed in this prototypical heavy-fermion material is of electronic origin, and is driven by the hybridization between 4f and conduction electrons which carries the f-electron anisotropy to the Fermi surface.

Factors influencing attendance at structured education for Type 1 diabetes in south London.

AIM: To investigate the factors influencing uptake of structured education for people with Type 1 diabetes in our local population in order to understand why such uptake is low. METHODS: We conducted a cross-sectional database study of adults with Type 1 diabetes in two south London boroughs, analysed according to Dose Adjustment For Normal Eating (DAFNE) attendance or non-attendance. Demographics, glycaemic control and service use, with subset analysis by ethnicity, were compared using univariate analysis. An exploratory regression model was used to identify influencing factors. RESULTS: The analysis showed that 73% of adults had not attended the DAFNE programme. For non-attenders vs attenders, male gender (59 vs 48%; P = 0.002), older age (39 vs 35 years; P < 0.001), non-white ethnicity (30 vs 20%; P = 0.001) and coming from an area of social deprivation (index of multiple deprivation score 31 vs 28; P < 0.001) were associated with non-attendance. The difference in gender (88% men vs 70% women; P < 0.001) and age (43 vs 34 years) persisted in the non-white group. Regression analysis showed that higher baseline HbA1c level (odds ratio 1.96; P = 0.004), younger age (odds ratio 0.98; P = 0.001) and lower social deprivation (odds ratio 0.52; P = 0.001) was associated with attendance. CONCLUSION: Socio-economic status and factors perceived as indicating greater severity of disease (HbA1c ) influence attendance at DAFNE. More work is necessary to understand the demography of non-attenders to aid future service design and alternative engagement strategies for these groups.

Patterns of Use and Short-Term Outcomes of Minimally Invasive Surgery for Malignant Pheochromocytoma: A Population-Level Study.

BACKGROUND: Malignant pheochromocytoma is rare, and there is a scarcity of data on the use of minimally invasive surgery (MIS) for treatment. The aims of this study were to analyze patterns of use of MIS for malignant pheochromocytoma in the U.S. and compare short-term outcomes to those of open adrenalectomy. METHODS: Patients with malignant pheochromocytoma undergoing MIS, including laparoscopy, robotic assisted, laparoscopy converted to open, or open adrenalectomy, were culled from the National Cancer Database, from 1998 to 2011. Data were examined using simple summary statistics, Χ2 and student's t tests, Mann-Whitney test, and logistic regression. RESULTS: A total of 36 MIS and 67 open adrenalectomies were identified in 2010-2011. No significant differences were observed between the two treatment groups in demographic characteristics or comorbidities. Preoperative diagnosis of malignancy was made in 52.8% of MIS and 48.5% of open patients (p=NS). MIS and open adrenalectomies did not differ with respect to lymph node metastases, vascular invasion, extra-adrenal-extension, and distant metastases (all p=NS). MIS tended to more often be used to perform partial adrenalectomy (38.9 vs. 20.4% open, p=0.061); surgical margins, 30-day readmission and mortality rates were similar to open adrenalectomy (all p=NS). Tumors removed via MIS were smaller (48.7 vs. 73.3 mm open, p=0.003) and associated with a shorter length of stay. CONCLUSIONS: A significant proportion of patients with malignant pheochromocytomas underwent MIS, with short-term outcomes which are comparable to those of open surgery. Further studies focused on long-term survival and recurrence are needed to assess the role of MIS in the management of these rare tumors.

Climatic suitability of Aedes albopictus in Europe referring to climate change projections: comparison of mechanistic and correlative niche modelling approaches.

The Asian tiger mosquito, Aedes albopictus, is capable of transmitting a broad range of viruses to humans. Since its introduction at the end of the 20th century, it has become well established in large parts of southern Europe. As future expansion as a result of climate change can be expected, determining the current and projected future climatic suitability of this invasive mosquito in Europe is of interest. Several studies have tried to detect the potential habitats for this species, but differing data sources and modelling approaches must be considered when interpreting the findings. Here, various modelling methodologies are compared with special emphasis on model set-up and study design. Basic approaches and model algorithms for the projection of spatio-temporal trends within the 21st century differ substantially. Applied methods range from mechanistic models (e.g. overlay of climatic constraints based on geographic information systems or rather process-based approaches) to correlative niche models. We conclude that spatial characteristics such as introduction gateways and dispersal pathways need to be considered. Laboratory experiments addressing the climatic constraints of the mosquito are required for improved modelling results. However, the main source of uncertainty remains the insufficient knowledge about the species' ability to adapt to novel environments.

[Mosquitoes as vectors for exotic pathogens in Germany]. / Stechmücken als Überträger exotischer Krankheitserreger in Deutschland.

As a result of intensified globalization of international trade and of substantial travel activities, mosquito-borne exotic pathogens are becoming an increasing threat for Europe. In Germany some 50 different mosquito species are known, several of which have vector competence for pathogens. During the last few years a number of zoonotic arboviruses that are pathogenic for humans have been isolated from mosquitoes in Germany including Usutu, Sindbis and Batai viruses. In addition, filarial worms, such as Dirofilaria repens have been repeatedly detected in mosquitoes from the federal state of Brandenburg. Other pathogens, in particular West Nile virus, are expected to emerge sooner or later in Germany as the virus is already circulating in neighboring countries, e.g. France, Austria and the Czech Republic. In upcoming years the risk for arbovirus transmission might increase in Germany due to increased occurrence of new so-called "invasive" mosquito species, such as the Asian bush mosquito Ochlerotatus japonicus or the Asian tiger mosquito Aedes albopictus. These invasive species are characterized by high vector competence for a broad range of pathogens and a preference for human blood meals. For risk assessment, a number of mosquito and pathogen surveillance projects have been initiated in Germany during the last few years; however, mosquito control strategies and plans of action have to be developed and put into place to allow early and efficient action against possible vector-borne epidemics.

The clinical characteristics at diagnosis of type 2 diabetes in a multi-ethnic population: the South London Diabetes cohort (SOUL-D).

AIMS/HYPOTHESIS: This study aimed to investigate the clinical features of newly diagnosed type 2 diabetes in an urban multi-ethnic cohort. METHODS: A population-based cross-sectional design was used. People diagnosed with type 2 diabetes in the preceding 6 months were recruited from primary care practices in three adjacent inner-city boroughs of South London, serving a population in which 20% of residents are of black African or Caribbean ethnicity. Sociodemographic and biomedical data were collected by standardised clinical assessment and from medical records. Multiple logistic regression methods were used to report associations between ethnicity and diabetes-complication status. RESULTS: From 96 general practices, 1,506 patients were recruited. Their mean age was 55.6 (± 11.07) years, 55% were men, 60% were asymptomatic at diagnosis and 51%, 38% and 11% were of white, black and South Asian/other ethnicity, respectively. Compared with white participants, black and South Asian/other participants were: younger (mean age 58.9 [± 10.09], 52.4 [± 11.19] and 51.5 [± 10.42] years, respectively; p < 0.0001); less likely to have neuropathy (10.1%, 3.6% and 4.4%; p < 0.0001) or report coronary artery disease (12.7%, 4.8% and 7.3%; p < 0.0001). In logistic regression, compared with white participants, black participants had lower levels of macrovascular complications (OR 0.52, 95% CI 0.32, 0.84; p = 0.01). Male sex was independently associated with microvascular disease (OR 1.69, 95% CI 1.26, 2.28; p < 0.0001). CONCLUSIONS/INTERPRETATION: The prevalence of complications at time of diagnosis was lower than expected, especially in black and South Asian/other ethnic groups. However, in multi-ethnic inner-city populations, onset of type 2 diabetes occurred almost 10 years earlier in non-white populations than in white participants, predicating a prolonged morbidity.

Collagen type XI α1 facilitates head and neck squamous cell cancer growth and invasion.

BACKGROUND: Although it is well established that the extracellular matrix affects tumour progression, not much is known about the various components and their effect on head and neck squamous cell carcinoma (HNSCC) progression. Levels of collagen type XI α1 (colXIα1), a minor fibrillar collagen, have been shown to be increased in tumour compared with normal tissue in several cancers, including colorectal, breast, and non-small cell lung cancer. Currently, the functional significance of colXIα1 is not understood. METHODS: We examined the expression levels of colXIα1 mRNA and elucidated the functional role of colXIα1 in HNSCC. Cell proliferation, invasion, and migration were examined with and without colXIα1 knockdown with siRNA in HNSCC cells. RESULTS: Our data demonstrate that colXIα1 expression is increased in tumour samples compared with levels in normal adjacent tissue in 16/23 HNSCC patients. In addition, colα11 is increased in HNSCC cell lines compared with normal immortalised epithelial cells and is increased in tumour-derived fibroblasts compared with normal fibroblasts. Using an siRNA approach, we demonstrate that colXIα1 contributes to proliferation, migration, and invasion of HNSCC. CONCLUSION: Our cumulative findings suggest that colXIα1 contributes to HNSCC tumorigenesis and may serve as a potential therapeutic target.

Risk of kidney stones with surgical intervention in living kidney donors.

A kidney stone in a person with a solitary kidney requires urgent attention, which may result in surgical and/or hospital attention. We conducted a matched retrospective cohort study to determine if living kidney donors compared to healthy nondonors have a higher risk of: (i) kidney stones with surgical intervention, and (ii) hospital encounters for kidney stones. We reviewed all predonation charts for living kidney donations from 1992 to 2009 at five major transplant centers in Ontario, Canada, and linked this information to healthcare databases. We selected nondonors from the healthiest segment of the general population and matched 10 nondonors to every donor. Of the 2019 donors and 20 190 nondonors, none had evidence of kidney stones prior to cohort entry. Median follow-up time was 8.4 years (maximum 19.7 years; loss to follow-up <7%). There was no difference in the rate of kidney stones with surgical intervention in donors compared to nondonors (8.3 vs. 9.7 events/10 000 person-years; rate ratio 0.85; 95% confidence interval [CI] 0.47-1.53). Similarly there was no difference in the rate of hospital encounters for kidney stones (12.1 vs. 16.1 events/10 000 person-years; rate ratio 0.75; 95% CI 0.45-1.24). These interim results are reassuring for the safety of living kidney donation.

Systematic review and meta-analysis of additional technologies to enhance angioplasty for infrainguinal peripheral arterial occlusive disease.

BACKGROUND: There are several additional techniques designed to enhance conventional percutaneous transluminal balloon angioplasty (PTA). This systematic review assessed current evidence on the clinical effectiveness of additional techniques for infrainguinal peripheral arterial occlusive disease (PAD). METHODS: Relevant electronic databases, including MEDLINE, were searched in May 2011. The population comprised participants with symptomatic PAD undergoing endovascular treatment for disease distal to the inguinal ligament. Interventions were additional techniques compared with conventional PTA. Main outcome measures were restenosis and need for reintervention. Randomized clinical trials (RCTs) of clinical effectiveness were assessed for quality and data were extracted. Where appropriate, meta-analysis was undertaken to produce risk ratios (RRs). RESULTS: Forty RCTs were selected. Meta-analysis showed a significant benefit in reducing restenosis rates at 6 months for self-expanding stents (RR 0.49) and drug-coated balloons (RR 0.40), and at 12 months for endovascular brachytherapy (RR 0.63). There was also evidence that use of a stent-graft significantly reduced restenosis compared with PTA, as did drug-eluting stents compared with bare-metal stents. Meta-analysis showed that use of drug-coated balloons was associated with significantly lower reintervention rates than PTA alone at 6 months (RR 0.24) and 24 months (RR 0.27) of follow-up. There was also evidence of significantly lower reintervention rates for self-expanding stents at 6 months. Other techniques did not show significant treatment effects for restenosis or reintervention. CONCLUSION: The conclusions of this review should be tempered by small sample sizes, lack of clinical outcome measures and differing outcome definitions, making direct comparison across trials difficult. However, self-expanding stents, drug-eluting stents and drug-coated balloons appeared to be the most promising technologies worthy of future study.

Cost-effectiveness analysis of enhancements to angioplasty for infrainguinal arterial disease.

BACKGROUND: The aim was to perform an economic evaluation of the cost-effectiveness of endovascular enhancements to percutaneous transluminal balloon angioplasty (PTA) with bail-out bare metal stents for infrainguinal peripheral arterial disease. METHODS: The following interventions were considered: PTA with no bail-out stenting, PTA with bail-out drug-eluting stents, drug-coated balloons, primary bare metal stents, primary drug-eluting stents, endovascular brachytherapy, stent-grafts and cryoplasty. A discrete-event simulation model was developed to assess the relative cost-effectiveness of the interventions from a health service perspective over a lifetime. Populations of patients with intermittent claudication (IC) and critical leg ischaemia (CLI) were modelled separately. Univariable and probabilistic sensitivity analyses were undertaken. Effectiveness was measured by quality-adjusted life-years (QALYs). RESULTS: For both patient populations, the use of drug-coated balloons dominated all other options by having both lower lifetime costs and greater effectiveness. For willingness-to-pay thresholds between £0 and £100,000 per additional QALY, the probability of drug-coated balloons being cost-effective was at least 58.3 per cent for patients with IC and at least 72.2 per cent for patients with CLI. Sensitivity analyses showed that the results were robust to different assumptions regarding the clinical benefits attributable to the interventions. CONCLUSION: The use of drug-coated balloons represents a cost-effective alternative to the use of PTA with bail-out bare metal stents.

Signalling by adhesion receptors.

Over the past twenty years, intensive research has enabled us to identify components of specific signalling pathways downstream of an array of adhesion and growth-factor receptors. The first Gordon Research Conference on 'Signalling by Adhesion Receptors', which took place in Newport, Rhode Island, USA (23-28 July 2000), focused on these findings.

N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility.

The Wiskott-Aldrich syndrome protein (WASP) family of molecules integrates upstream signalling events with changes in the actin cytoskeleton. N-WASP has been implicated both in the formation of cell-surface projections (filopodia) required for cell movement and in the actin-based motility of intracellular pathogens. To examine N-WASP function we have used homologous recombination to inactivate the gene encoding murine N-WASP. Whereas N-WASP-deficient embryos survive beyond gastrulation and initiate organogenesis, they have marked developmental delay and die before embryonic day 12. N-WASP is not required for the actin-based movement of the intracellular pathogen Listeria but is absolutely required for the motility of Shigella and vaccinia virus. Despite these distinct defects in bacterial and viral motility, N-WASP-deficient fibroblasts spread by using lamellipodia and can protrude filopodia. These results imply a crucial and non-redundant role for N-WASP in murine embryogenesis and in the actin-based motility of certain pathogens but not in the general formation of actin-containing structures.

Characterization of tissue types in basal cell carcinoma images via generative modeling and concept vectors.

The promise of machine learning methods to act as decision support systems for pathologists continues to grow. However, central to their successful adoption must be interpretable implementations so that people can trust and learn from them effectively. Generative modeling, most notable in the form of adversarial generative models, is a naturally interpretable technique because the quality of the model is explicit from the quality of images it generates. Such a model can be further assessed by exploring its latent space, using human-meaningful concepts by defining concept vectors. Motivated by these ideas, we apply for the first time generative methods to histological images of basal cell carcinoma (BCC). By simultaneously learning to generate and encode realistic image patches, we extract feature rich latent vectors that correspond to various tissue morphologies, namely BCC, epidermis, keratin, papillary dermis and inflammation. We show that a logistic regression model trained on these latent vectors can achieve high classification accuracies across 6 binary tasks (86-98%). Further, by projecting the latent vectors onto learned concept vectors we can generate a score for the absence or degree of presence for a given concept, providing semantically accurate "conceptual summaries" of the various tissues types within a patch. This can be extended to generate multi-dimensional heat maps for whole-image specimens, which characterizes the tissue in a similar way to a pathologist. We additionally find that accurate concept vectors can be defined using a small labeled dataset.