Search

ABSTRACT Level crossing rails are high risk areas due to the combination of the limited effectiveness of current inspection methods and high corrosion rates which often exist. This paper discusses [...]

The American Trial Using Tranexamic Acid (TXA) in Thrombocytopenia (A-TREAT, NCT02578901) demonstrated no superiority of TXA over placebo in preventing World Health Organization (WHO) grade 2 or higher bleeding in patients with severe thrombocytopenia requiring supportive platelet transfusion following myeloablative therapy for hematologic disorders. In this ancillary study, we sought to determine whether this clinical outcome could be explained on the basis of correlative assays of fibrinolysis. Plasma was collected from A-TREAT participants (n = 115) before the initiation of study drug (baseline) and when TXA was at steady-state trough concentration (follow-up). Global fibrinolysis was measured by 3 assays: euglobulin clot lysis time (ECLT), plasmin generation (PG), and tissue-type plasminogen activator (tPA)–challenged clot lysis time (tPA-CLT). TXA was quantified in follow-up samples by tandem mass spectrometry. Baseline samples did not demonstrate fibrinolytic activation by ECLT or tPA-CLT. Furthermore, neither ECLT nor levels of plasminogen activator inhibitor-1, tPA, plasminogen, alpha2-antiplasmin, or plasmin-antiplasmin complexes were associated with a greater risk of WHO grade 2+ bleeding. TXA trough concentrations were highly variable (range, 0.7-10 μg/mL) and did not correlate with bleeding severity, despite the fact that plasma TXA levels correlated strongly with pharmacodynamic assessments by PG (Spearman r, −0.78) and tPA-CLT (r, 0.74). We conclude that (1) no evidence of fibrinolytic activation was observed in these patients with thrombocytopenia, (2) trough TXA concentrations varied significantly between patients receiving the same dosing schedule, and (3) tPA-CLT and PG correlated well with TXA drug levels.

Hydrodynamics is a universal effective theory that describes the thermalization of chaotic many-body systems, and depends only on the symmetries of the underlying theory. Although the Navier–Stokes equations can describe classical liquids and gases, quantum fluids of ultracold atoms or quark–gluon plasma, they cannot yet describe the phases of matter where particle motion is kinematically constrained. Here we present the nonlinear fluctuating hydrodynamics of models with simultaneous charge/mass, dipole/centre of mass and momentum conservation. This hydrodynamic effective theory is unstable below four spatial dimensions: dipole-conserving fluids at rest are unstable to fluctuations, which drive the system to a dynamical universality class with qualitatively distinct features from conventional fluids. In one spatial dimension, our construction is reminiscent of the well-established renormalization group flow of the stochastic Navier–Stokes equations; however, the fixed point we find possesses subdiffusive scaling rather than the superdiffusive scaling of the Kardar–Parisi–Zhang universality class. We numerically simulate many-body classical dynamics in one- and two-dimensional models with dipole and momentum conservation, and find evidence for the predicted breakdown of hydrodynamics. Our theory provides a controlled example of how kinematic constraints lead to a rich landscape of dynamical universality classes in high-dimensional models.

The ability to forecast the biological productivity of the coastal ocean relies on the quantification of the physical processes that deliver nutrients to the euphotic zone. Here we explore these pathways using observations of the coupled biological and physical variability of waters offshore of the east coast of Tasmania in the summertime. The observations include an array of moored autonomous profilers deployed over an 18‐d period—providing continuous, full‐depth measurements of turbulent microstructure, temperature, velocity, and chlorophyll a(Chl a) fluorescence, complemented by shipboard nutrient measurements. Local upwelling was driven by the encroaching East Australian Current (EAC) extension onto the shelf and to a lesser extent the local winds. The interaction of the local winds and the encroaching boundary current was reflected in the shelf nutrient budget and led to a rapid increase in subsurface Chl a. Diffusive vertical fluxes had minimal impact on subsurface Chl ain the mid‐shelf and outer‐shelf. Upwelling‐favorable winds were too weak to drive significant vertical mixing, and mixing associated with the current‐driven Ekman transport was too deep compared to the euphotic zone depth. The observed subsurface Chl adid not reflect the satellite estimates of productivity. Since the EAC extension transports warm, low‐nutrient surface waters from the subtropics, satellite chlorophyll measurements decreased during the same period the depth‐averaged Chl aincreased. This seeming paradox illustrated how long duration, full water column sampling can elucidate the coupled biological and physical processes that aid our ongoing effort to forecast the biological state of the coastal ocean.

Background: The COVID-19 pandemic interrupted the delivery of face-to-face pain services including pain management programmes in the United Kingdom with considerable negative impact on patients with chronic musculoskeletal pain. We aimed to develop and implement a remotely delivered pain management programme (PMP) using video-conferencing technology that contains all the core components of a full programme: the ‘virtual PMP’ (vPMP). By reporting on the process of this development, we endeavour to help address the paucity of literature on the development of remote pain management programmes.Methods: The vPMP was developed by an inter-disciplinary group of professionals as a quality improvement (QI) project. The Model for Improvement Framework was employed with patient involvement at the design phase and at subsequent improvements. Improvement was measured qualitatively with frequent and repeated qualitative data collection leading to programme change. Quantitative patient demographic comparisons were made with a patient cohort who had been on a face-to-face PMP pathway.Results: Sixty-one patients on the PMP waiting list were contacted and 43 met the criteria for the programme. Fourteen patients participated in three vPMP cycles. Patient involvement and comprehensive stakeholder consultation were essential to a robust design for the first vPMP. Continued involvement of patient partners during the QI process led to rapid resolution of implementation problems. The most prominent issues that needed action were technical challenges including training needs, participant access to physical and technological resources, participant fatigue and concerns about adequate communication and peer support.Conclusion: This report demonstrates how a remotely delivered PMP, fully in line with national guidance, was rapidly developed and implemented in a hospital setting for patients with chronic musculoskeletal pain. We also discuss the relevance of our findings to the issues of cost, patient experience, patient preferences and inequities of access in delivering telerehabilitation for chronic pain.

High resolution shipboard observations reveal the complex processes controlling the evolution and subduction of a cold and salty, dense filament in the Bay of Bengal (BoB). The filament, likely formed through coastal upwelling, was advected offshore by the mesoscale velocity field, and was brought adjacent to a shallow, low salinity mixed layer by mesoscale strain. The front that formed on the Eastern edge of the dense filament was observed to undergo both restratification and steepening, creating barrier layers, in response to evolving mesoscale and submesoscale convergence and divergences. Measurements and analyses indicate that the development of both small‐scale instabilities such as symmetric instability (SI) and slightly larger scale ageostrophic secondary circulation (ASC), acted in concert to subduct and stir surface heat into the interior. These mechanisms also drive the generation of temperature inversions from O(1 km) lateral temperature variability at the surface, demonstrating the need for model parameterizations at such spatial scales. Our results highlight the importance of submesoscale dynamics in creating and warming barrier layers, facilitating vertical heat exchanges, and setting sea surface temperature in the Bay of Bengal, a critical input to coupled atmosphere/ocean models of the southwest monsoon. Such complex dynamics should be considered in regions where salinity governs stratification and compensated waters stir. Improving predictions for the monsoon seasons in the Bay of Bengal depends on the accuracy of the ocean's surface temperatures, which involve both one‐dimensional and three‐dimensional processes that impact the vertical structure of the upper ocean. In this study, we observed a cold and salty water mass that upwelled near the coast of India drift into the center of the Bay where it met ambient low salinity water to create surface lateral density gradients. High‐resolution shipboard observations revealed evidence of small‐scale physical processes as well as features typical of regions where the vertical structure is governed by salinity. The observations document the complexity of upper ocean heat content on scales less than 10 km, with impacts for sea surface temperature and couple ocean ‐atmosphere forecasting of the southwest monsoon. The subduction of a dense filament in the Bay of Bengal suggests the role of submesoscale processes in setting upper ocean heat contentBarrier layers form at edges of fronts, sequestering heat from the surface and creating shallow mixed layers with lateral scales O(10 km)Small‐scale lateral temperature variability is exchanged vertically through instabilities, encouraging formation of temperature inversions The subduction of a dense filament in the Bay of Bengal suggests the role of submesoscale processes in setting upper ocean heat content Barrier layers form at edges of fronts, sequestering heat from the surface and creating shallow mixed layers with lateral scales O(10 km) Small‐scale lateral temperature variability is exchanged vertically through instabilities, encouraging formation of temperature inversions

Cross‐shore velocities in the coastal ocean typically vary with depth. The direction and magnitude of transport experienced by meroplanktonic larvae will therefore be influenced by their vertical position. To quantify how swimming behavior and vertical position in internal waves influence larval cross‐shore transport in the shallow (~ 20 m), stratified coastal waters off Southern California, we deployed swarms of novel, subsurface larval mimics, the Mini‐Autonomous Underwater Explorers (M‐AUEs). The M‐AUEs were programmed to maintain a specified depth, and were deployed near a mooring. Transport of the M‐AUEs was predominantly onshore, with average velocities up to 14 cm s−1. To put the M‐AUE deployments into a broader context, we simulated > 500 individual high‐frequency internal waves observed at the mooring over a 14‐d deployment; in each internal wave, we released both depth‐keeping and passive virtual larvae every meter in the vertical. After the waves' passage, depth‐keeping virtual larvae were usually found closer to shore than passive larvae released at the same depth. Near the top of the water column (3–5‐m depth), ~ 20% of internal waves enhanced onshore transport of depth‐keeping virtual larvae by ≥ 50 m, whereas only 1% of waves gave similar enhancements to passive larvae. Our observations and simulations showed that depth‐keeping behavior in high‐frequency internal waves resulted in enhanced onshore transport at the top of the water column, and reduced offshore dispersal at the bottom, compared to being passive. Thus, even weak depth‐keeping may allow larvae to reach nearshore adult habitats more reliably than drifting passively.

Tissue-resident memory T (TRM) cells are non-recirculating cells that exist throughout the body. Although TRMcells in various organs rely on common transcriptional networks to establish tissue residency, location-specific factors adapt these cells to their tissue of lodgment. Here we analyze TRMcell heterogeneity between organs and find that the different environments in which these cells differentiate dictate TRMcell function, durability and malleability. We find that unequal responsiveness to TGFβ is a major driver of this diversity. Notably, dampened TGFβ signaling results in CD103−TRMcells with increased proliferative potential, enhanced function and reduced longevity compared with their TGFβ-responsive CD103+TRMcounterparts. Furthermore, whereas CD103−TRMcells readily modified their phenotype upon relocation, CD103+TRMcells were comparatively resistant to transdifferentiation. Thus, despite common requirements for TRMcell development, tissue adaptation of these cells confers discrete functional properties such that TRMcells exist along a spectrum of differentiation potential that is governed by their local tissue microenvironment.

Coastal physical processes are essential for the cross‐shore transport of meroplanktonic larvae to their benthic adult habitats. To investigate these processes, we released a swarm of novel, trackable, subsurface vehicles, the Mini‐Autonomous Underwater Explorers (M‐AUEs), which we programmed to mimic larval depth‐keeping behavior. The M‐AUE swarm measured a sudden net onshore transport of 30–70 m over 15–20 min, which we investigated in detail. Here, we describe a novel transport mechanism of depth‐keeping plankton revealed by these observations. In situ measurements and models showed that, as a weakly nonlinear internal wave propagated through the swarm, it deformed surface‐intensified, along‐isopycnal background velocities downward, accelerating depth‐keeping organisms onshore. These higher velocities increased both the depth‐keepers' residence time in the wave and total cross‐shore displacement, leading to wave‐induced transports twice those of fully Lagrangian organisms and four times those associated with the unperturbed background currents. Our analyses also show that integrating velocity time series from virtual larvae or mimics moving with the flow yields both larger and more accurate transport estimates than integrating velocity time series obtained at a point (Eulerian). The increased cross‐shore transport of organisms capable of vertical swimming in this wave/background‐current system is mathematically analogous to the increase in onshore transport associated with horizontal swimming in highly nonlinear internal waves. However, the mechanism described here requires much weaker swimming speeds (mm s−1vs. cm s−1) to achieve significant onshore transports, and meroplanktonic larvae only need to orient themselves vertically, not horizontally.

The meroplanktonic larvae of many invertebrate and vertebrate species rely on physical transport to move them across the shelf to their adult habitats. One potential mechanism for cross‐shore larval transport is Stokes drift in internal waves. Here, we develop theory to quantify the Stokes velocities of neutrally buoyant and depth‐keeping organisms in linear internal waves in shallow water. We apply the analyses to theoretical and measured internal wave fields, and compare results with a numerical model. Near the surface and bottom boundaries, both neutrally buoyant and depth‐keeping organisms were transported in the direction of the wave's phase propagation. However, neutrally buoyant organisms were transported in the opposite direction of the wave's phase at mid depths, while depth‐keeping organisms had zero net transport there. Weakly depth‐keeping organisms had Stokes drifts between the perfectly depth‐keeping and neutrally buoyant organisms. For reasonable wave amplitudes and phase speeds, organisms would experience horizontal Stokes speeds of several centimeters per second—or a few kilometers per day in a constant wave field. With onshore‐polarized internal waves, Stokes drift in internal waves presents a predictable mechanism for onshore transport of meroplanktonic larvae and other organisms near the surface, and offshore transport at mid depths.

Many software programmers may be guilty of software piracy without even knowing it, writes Andrew Lucas. The law states that computer programs are protected by copyright as a literary work […]

In the present work, transient liquid phase bonding (TLP) of stainless steel 316 L to Ti-6Al-4 V using simultaneously both Cu and Ni interlayers was performed and effect of bonding temperature (950 to 1050 °C) on microstructure and mechanical properties of the joints was studied. The joint zones were analyzed using scanning electron microscopy (SEM) equipped with energy dispersive spectroscopy (EDS). Microhardness and shear strength tests were also applied to evaluate the mechanical properties of the joints. The results showed that various eutectic phases and intermetallic compounds were formed at the interface; however, diversity of intermetallics was different in the joint zone for each specimen which can be due to the bonding temperature and type of eutectic phase transformation. The more increase of bonding temperature to higher than 1000 °C, the more deterioration in mechanical properties of the bonded joints is led so that the shear strength decreased from 385 MPa (maximum value) to 257 MPa.

Policy-makers often need to rely on experts with disparate fields of expertise when making policy choices in complex, multi-faceted, dynamic environments such as those dealing with ecosystem services. For policy-makers wishing to make evidence-based decisions which will best support pollinator abundance and pollination services, one of the problems faced is how to access the information and evidence they need, and how to combine it to formulate and evaluate candidate policies. This is even more complex when multiple factors provide influence in combination. The pressures affecting the survival and pollination capabilities of honey bees (Apis mellifera), wild bees, and other pollinators are well documented, but incomplete. In order to estimate the potential effectiveness of various candidate policy choices, there is an urgent need to quantify the effect of various combinations of factors on the pollination ecosystem service. Using high-quality experimental evidence is the most robust approach, but key aspects of the system may not be amenable to experimentation or may be prohibitive based on cost, time and effort. In such cases, it is possible to obtain the required evidence by using structured expert elicitation, a method for quantitatively characterizing the state of knowledge about an uncertain quantity. Here we report and discuss the outputs of the novel use of a structured expert elicitation, designed to quantify the probability of good pollinator abundance given a variety of weather, disease, and habitat scenarios.Evaluación de la respuesta de la abundancia de polinizadores a las presiones ambientales mediante el uso de elicitación experta estructuradaA menudo los legisladores dependen de expertos en diversas áreas de conocimiento para tomar decisiones sobre legislación en entornos complejos, multifacéticos y dinámicos tales como los que tienen que ver con los servicios ecosistémicos. Los legisladores que quieren tomar decisiones basadas en evidencias que respalden mejor los servicios de polinización y la abundancia de polinizadores, se enfrentan al problema de cómo acceder a la información y a las evidencias que necesitan, y de cómo combinar éstas para formular y evaluar futuras leyes. Esto es aún más complejo cuando hay múltiples factores que influyen de manera combinada. Las presiones que afectan a la supervivencia y a la capacidad polinizadora de las abejas de la miel (Apis mellifera), a las abejas silvestres y a otros polinizadores están bien documentadas, pero de manera incompleta. Para estimar la efectividad potencial de varias opciones posibles de legislación, es necesario cuantificar el efecto combinado de varios factores sobre el servicio ecosistémico de polinización. El uso de una evidencia experimental de alta calidad es el enfoque más sólido, pero algunos aspectos clave del sistema podrían no ser susceptibles de experimentación o ser prohibitivos debido al coste, el tiempo y el esfuerzo. En tales casos, es posible obtener la evidencia requerida mediante el uso de la elicitación experta estructurada, un método para caracterizar cuantitativamente el estado del conocimiento sobre una cantidad incierta. En este estudio informamos y discutimos los resultados del uso novedoso de una elicitación experta estructurada, diseñada para cuantificar la probabilidad de una abundancia de polinizadores adecuada teniendo en cuenta una variedad de escenarios climáticos, de enfermedades y de hábitat.

The aim of this study was to determine the prevalence and type of autoantibodies in a general Australian population cohort.

Introduction:Major advances in carrier-mediated agents (CMAs), which include nanoparticles and conjugates, have revolutionized drug delivery capabilities over the past decade. While providing numerous advantages such as increased exposure duration, greater solubility and delivery to tumor sites over their small molecule counterparts, there is substantial variability in how individual CMA formulations affect the pharmacology, pharmacokinetics and pharmacodynamics (efficacy and toxicity) of these agents.Areas covered:CMA formulations are complex in nature compared to their small molecule counterparts and consist of multiple components and variables that can affect the pharmacological profile. This review provides an overview of factors that affect the pharmacologic profiles observed in CMA-formulated chemotherapy, primarily in liposomal formulations, that are currently in preclinical or early clinical development.Expert opinion:Despite the numerous advantages that CMA formulations provide, their clinical use is still in its infancy. It is critical that we understand the mechanisms and effects of CMAs in navigating biological barriers and how these factors affect their biodistribution and delivery to tumors. Future studies are warranted to better understand the complex pharmacology and interaction between CMA carriers and biological systems, such as the mononuclear phagocyte system and tumor microenvironment.

We present a systematic derivation of the effective action for interacting vortices in a nonrelativistic two-dimensional superfluid described by the Gross-Pitaevskii equation by integrating out longitudinal fluctuations of the order parameter. There are no logarithmically divergent coefficients in the equations of motion. Our analysis is valid in a dilute limit of vortices where the intervortex spacing is large compared to the core size, and where number fluctuations of atoms in vortex cores are suppressed. We analyze sound-induced corrections to the dynamics of a vortex-antivortex pair and show that there is no instability to annihilation, suggesting that sound-mediated interactions are not strong enough to ruin an inverse energy cascade in two-dimensional zero-temperature superfluid turbulence. [ABSTRACT FROM AUTHOR]

This study sought to examine nevirapine hypersensitivity (NVP HSR) phenotypes and their relationship with differing major histocompatibility complex (MHC) Class I and Class II alleles and the associated CD4and CD8T-cell NVP-specific responses and their durability over time.

We compute the direct-current resistivity of a scale-invariant, d-dimensional strange metal with dynamic critical exponent z and hyperscaling-violating exponent θ, weakly perturbed by a scalar operator coupled to random-field disorder that locally breaks a Z2 symmetry. Independent calculations via Einstein-Maxwell dilaton holography and memory matrix methods lead to the same results. We show that random-field disorder has a strong effect on resistivity and leads to a short relaxation time for the total momentum. In the course of our holographic calculation, we use a nontrivial dilaton coupling to the disordered scalar, allowing us to study a strongly coupled scale-invariant theory with θ ≠ 0. Using holography, we are also able to determine the disorder strength at which perturbation theory breaks down. Curiously, for locally critical theories, this breakdown occurs when the resistivity is proportional to the entropy density, up to a possible logarithmic correction. [ABSTRACT FROM AUTHOR]

The Wnt-dependent, β-catenin-independent pathway modulates cell movement and behavior. A downstream regulator of this signaling pathway is Dishevelled (Dvl), which, among other multiple interactions, binds to the Frizzled receptor and the plasma membrane via phosphatidic acid (PA) in a mechanism proposed to be pH-dependent. While the Dvl DEP domain is central to the β-catenin-independent Wnt signaling function, the mechanism underlying its physical interaction with the membrane remains elusive. In this report, we elucidate the structural and functional basis of PA association to the Dvl2 DEP domain. Nuclear magnetic resonance, molecular-dynamics simulations, and mutagenesis data indicated that the domain interacted with the phospholipid through the basic helix 3 and a contiguous loop with moderate affinity. The association suggested that PA binding promoted local conformational changes in helix 2 and β-strand 4, both of which are compromised to maintain a stable hydrophobic core in the DEP domain. We also show that the Dvl2 DEP domain bound PA in a pH-dependent manner in a mechanism that resembles deprotonation of PA. Collectively, our results structurally define the PA-binding properties of the Dvl2 DEP domain, which can be exploited for the investigation of binding mechanisms of other DEP domain-interacting proteins.

We study (2+1)-dimensional conformal field theories (CFTs) with a globally conserved U(1) charge, placed in a chemical potential which is periodically modulated along the spatial direction x with zero average: μ(x)=V cos(kx). The dynamics of such theories depends only on the dimensionless ratio V/k, and we expect that they flow in the infrared to new CFTs whose universality class changes as a function of V/k. We compute the frequency-dependent conductivity of strongly coupled CFTs using holography of the Einstein-Maxwell theory in four-dimensional anti-de Sitter space. We compare the results with the corresponding computation of weakly coupled CFTs, perturbed away from the CFT of free, massless Dirac fermions (which describes graphene at low energies). We find that the results of the two computations have significant qualitative similarities. However, differences do appear in the vicinities of an infinite discrete set of values of V/k: the universality class of the infrared CFT changes at these values in the weakly coupled theory, by the emergence of new zero modes of Dirac fermions which are remnants of local Fermi surfaces. The infrared theory changes continuously in holography, and the classical gravitational theory does not capture the physics of the discrete transition points between the infrared CFTs. We briefly note implications for a nonzero average chemical potential. [ABSTRACT FROM AUTHOR]

Introduction Remotely delivered pain management programmes have been offered in place of in-person programmes by many chronic pain services since the onset of the COVID-19 pandemic. There is a lack of evidence regarding the acceptability of these programmes. In this evaluation, we have explored patients’ acceptability of a remotely delivered pain management programme for patients with persistent musculoskeletal pain.Methods Qualitative data were collected using focus groups with participants who had previously attended the remote pain management programme. Data were analysed using abductive analysis.Results Three focus groups were conducted with a total of 13 participants. The programmme was either entirely acceptable, had some acceptable components or was not acceptable to patients. Factors leading to the programme being acceptable include learning to manage pain from home, receiving high quality care from home, enhancing the potential of rehabilitation using technology, enabling attendance on a pain management programme from home, overcoming social distancing requirements of COVID-19 using technology, and virtual peer support. Factors leading to the programme not being acceptable include having an inappropriate home environment for virtual therapy, communication challenges with virtual therapy, technological issues and concerns regarding the quality of care.Conclusions There is a spectrum of acceptability with respect to the remote programme. The factors that influence this are dynamic, individual and situational. Hybrid programmes have the potential to enhance access to pain management programmes and improve patient experience and programme outcomes in the future.

Failed back surgery syndrome or “failed back syndrome” refers to persistent pain after spinal surgery. This opinion piece will discuss the back ground and scale of failed back surgery syndrome. There will be a description of the medical and psychological factors that have been reported as predictors of poor outcome from spinal surgery. The management of failed back surgery syndrome will be discussed with a personal viewpoint based on working with this patient group for fifteen years. It will be argued that failed back surgery syndrome and failed back syndrome are now redundant terms and are not useful for either patient or healthcare provider, and so should be discarded.Key words Failed back surgery syndrome, failed back syndrome

Background:We previously reported the results of the A-TREAT study (American Trial Using Tranexamic Acid in Thrombocytopenia: NCT02578901). This randomized double-blind placebo-controlled trial demonstrated that TXA administration is not superior to placebo in preventing WHO grade 2 or higher bleeding in severely thrombocytopenic patients requiring supportive platelet transfusion following myeloablative therapy for hematologic disorders (Gernsheimer T., ASH 2020Plenary Session).

Background Abacavir hypersensitivity in genetically susceptible individuals implicates an abacavir-specific T-cell response to either the parent drug or a metabolite generated in vivo. We have analysed the cytokine profile in antigen-presenting cells and the T-lymphocytes that are involved in the pathological immune response to abacavir.Methods In this study, we compared abacavir-specific cytokine responses in cultured peripheral blood mononuclear cells (PBMCs) from HIV-infected abacavir hypersensitive, tolerant and naive individuals. Cells were cultured in the presence or absence of abacavir. Cytokine expression was determined by microarray analysis, enzyme-linked immunosorbent assays and flow cytometry.Results We demonstrated using in vitromodels of immune activation that the production of interferon-?was specifically induced by abacavir treatment in PBMCs obtained from hypersensitive patients carrying the HLA-B*5701allele (median 123.86 compared with -30.83 for tolerant controls, P=0.001).Conclusion These results provide further insight into the immunological and metabolic basis of abacavir hypersensitivity syndrome. In vitroassays could assist in the identification of susceptible loci by providing a surrogate marker for the hypersensitivity reaction. Such a marker could be studied in unexposed individuals to shed further light on the immunopathogenesis of the abacavir hypersensitivity syndrome.

: The aim of this paper is to take the reader through the decisions made in designing a holonic system architecture to support customised packing of gift boxes with personal grooming (Gillette) products. The paper highlights issues that cause a divergence between a theoretical model of a holonic system and the approach that was actually encoded.

Fractalkine (CX3CL1) is synthesized as a type I transmembrane protein. Its unique CX3C chemokine domain is attached to a 241-amino acid mucin stalk, a 19-amino acid transmembrane domain, and a 37-amino acid intracellular domain of unknown function. A soluble form of fractalkine can be generated by proteolytic cleavage at the base of the mucin stalk. Novel monoclonal and polyclonal antibodies that specifically recognize only the amino- or carboxyl-terminal ends of the human fractalkine molecule have revealed that epithelial cells are the predominant cell type expressing transmembrane forms of fractalkine in human skin, the tonsil, and the large intestine. Using these specific anti-fractalkine reagents we do not detect high-level expression of fractalkine on endothelial cells in normal or inflamed colon samples obtained from patients with Crohn’s disease or ulcerative colitis. In contrast to previous reports we do not detect fractalkine expression by Langerhans cells or immature dendritic cells in mucosal-associated lymphoid tissues in vivo. We show that the reagent used in previous studies, an anti-fractalkine N-terminal peptide antisera, cross-reacts with human CD84. Finally we discuss potential roles for fractalkine in constitutive leukocyte trafficking based on its observed pattern of expression in epithelia.

Interviews Andrew Lucas, director of music for Saint Albans Cathedral Choir about trends in choral singing in Great Britain. Decrease of male singers from the cathedral choir system; Advantage of a separate girls' choir; Effect of the attitude of parents towards the boarding school system.

The heterogeneous pool of tissue-resident lymphocytes in solid organs mediates infection responses and supports tissue integrity and repair. Their vital functions in normal physiology suggest an important role in solid organ transplantation; however, their detailed examination in this context has not been performed. Here, we report the fate of multiple lymphocyte subsets, including T, B, and innate lymphoid cells, after murine liver and heart transplantation. In major histocompatibility complex (MHC)-matched transplantation, donor lymphocytes are retained in liver grafts and peripheral lymphoid organs of heart and liver transplant recipients. In MHC-mismatched transplantation, increased infiltration of the graft by recipient cells and depletion of donor lymphocytes occur, which can be prevented by removal of recipient T and B cells. Recipient lymphocytes fail to recreate the native organs’ phenotypically diverse tissue-resident lymphocyte composition, even in MHC-matched models. These post-transplant changes may leave grafts vulnerable to infection and impair long-term graft function.

Comments on conservationists' judgments about which species are worthy of protection. How animals qualify for protection; Inconsistencies in conservationists' efforts to protect certain species.

Asian summer monsoon has a planetary‐scale, westward propagating “quasi‐biweekly” mode of variability with a 10–25 day period. Six years of moored observations at 18°N, 89.5°E in the north Bay of Bengal (BoB) reveal distinct quasi‐biweekly variability in sea surface salinity (SSS) during summer and autumn, with peak‐to‐peak amplitude of 3–8 psu. This large‐amplitude SSS variability is not due to variations of surface freshwater flux or river runoff. We show from the moored data, satellite SSS, and reanalyses that surface winds associated with the quasi‐biweekly monsoon mode and embedded weather‐scale systems, drive SSS and coastal sea level variability in 2015 summer monsoon. When winds are calm, geostrophic currents associated with mesoscale ocean eddies transport Ganga‐Brahmaputra‐Meghna river water southward to the mooring, salinity falls, and the ocean mixed layer shallows to 1–10 m. During active (cloudy, windy) spells of quasi‐biweekly monsoon mode, directly wind‐forced surface currents carry river water away to the east and north, leading to increased salinity at the moorings, and rise of sea level by 0.1–0.5 m along the eastern and northern boundary of the bay. During July–August 2015, a shallow pool of low‐salinity river water lies in the northeastern bay. The amplitude of a 20‐day oscillation of sea surface temperature (SST) is two times larger within the fresh pool than in the saltier ocean to the west, although surface heat flux is nearly identical in the two regions. This is direct evidence that spatial‐temporal variations of BoB salinity influences sub‐seasonal SST variations, and possibly SST‐mediated monsoon air‐sea interaction. The north Bay of Bengal (BoB) is characterized by 1–10 m deep layer of river water, very stable density stratification, and deep isothermal layer warmed by penetration of sunlight below the thin mixed layer. Thermodynamic structure of the upper ocean influences intraseasonal active‐break cycles of the summer monsoon and promotes intensification of postmonsoon tropical cyclones by inhibiting storm‐induced cooling of sea surface temperature. Hence, it is important to understand the space‐time variability of surface salinity in this basin. The quasi‐biweekly (10–25 day) oscillation is a prominent mode of the Asian summer monsoon, seen in winds, cloudiness, rainfall and surface heat flux. Six years of mooring observations at 18°N in the north BoB show large amplitude (2–8 psu) changes in surface salinity on quasi‐biweekly timescales in summer and autumn. Using moored observations, satellite data and reanalyses, we show that changes in surface winds associated with quasi‐biweekly monsoon mode and its embedded low‐pressure systems drive large changes in surface salinity and coastal sea level. We show that the response of SST to subseasonal variations of surface heat flux is enhanced in the presence of a thin layer of river water. These observations have important implications for regional air‐sea interaction on subseasonal timescales. Moored observations show large amplitude quasi‐biweekly variability of surface salinity in the north Bay of BengalMesoscale eddies and shallow wind‐driven monsoon currents lead to lateral dispersal of river waterShallow, fresh layer enhances sea surface temperature response to surface heat flux on subseasonal timescales Moored observations show large amplitude quasi‐biweekly variability of surface salinity in the north Bay of Bengal Mesoscale eddies and shallow wind‐driven monsoon currents lead to lateral dispersal of river water Shallow, fresh layer enhances sea surface temperature response to surface heat flux on subseasonal timescales

The land‐sea breeze is resonant with the inertial response of the ocean at the critical latitude of 30°N/S. 1‐D vertical numerical experiments were undertaken to study the key drivers of enhanced diapycnal mixing in coastal upwelling systems driven by diurnal‐inertial resonance near the critical latitude. The effect of the land boundary was implicitly included in the model through the “Craig approximation” for first‐order cross‐shore surface elevation gradient response. The model indicates that for shallow water depths (<∼100 m), bottom shear stresses must be accounted for in the formulation of the “Craig approximation,” as they serve to enhance the cross‐shore surface elevation gradient response, while reducing shear and mixing at the thermocline. The model was able to predict the observed temperature and current features during an upwelling/mixing event in 60 m water depth in St Helena Bay (∼32.5°S, southern Benguela), indicating that the locally forced response to the land‐sea breeze is a key driver of diapycnal mixing over the event. Alignment of the subinertial Ekman transport with the surface inertial oscillation produces shear spikes at the diurnal‐inertial frequency; however their impact on mixing is secondary when compared with the diurnal‐inertial resonance phenomenon. The amplitude of the diurnal anticyclonic rotary component of the wind stress represents a good diagnostic for the prediction of diapycnal mixing due to diurnal‐inertial resonance. The local enhancement of this quantity over St Helena Bay provides strong evidence for the importance of the land‐sea breeze in contributing to primary production in this region through nutrient enrichment of the surface layer. Winds near the coast often have a daily cycle known as the land‐sea breeze. Near latitudes of 30°N/S ubiquitous rotating ocean currents also have a daily frequency and therefore become enhanced by daily winds at these latitudes. The ocean currents result in vertical mixing of subsurface and surface water layers, bringing subsurface nutrients to the surface where they stimulate phytoplankton growth. In this study we use a simple model of the ocean (composed of the vertical dimension only) to study the key drivers of vertical mixing due to the land‐sea breeze. We show how vertical mixing is reduced in shallow water (<∼100 m) near the coast, where currents are slowed down by friction at the seabed. We find that vertical mixing can be predicted by a parameter computed from wind speed and direction over time. This parameter is shown to be enhanced over St Helena Bay on the west coast of South Africa, where phytoplankton blooms are known to be particularly prevalent. The results suggest that the land‐sea breeze is likely to be an important contributor to phytoplankton bloom development in this region. Similar processes are likely to be at play in other coastal regions. Land‐sea breeze driven vertical mixing is studied using a 1‐D model including the land boundary effectThe land boundary effect dampens vertical mixing, particularly when bottom friction is nonnegligibleThe diurnal anticyclonic rotary component of the wind stress provides a diagnostic for diapycnal mixing

Hydrodynamics is a theory of long-range excitations controlled by equations of motion that encode the conservation of a set of currents (energy, momentum, charge, etc.) associated with explicitly realized global symmetries. If a system possesses additional weakly broken symmetries, the low-energy hydrodynamic degrees of freedom also couple to a few other "approximately conserved" quantities with parametrically long relaxation times. It is often useful to consider such approximately conserved operators and corresponding new massive modes within the low-energy effective theory, which we refer to as quasihydrodynamics. Examples of quasihydrodynamics are numerous, with the most transparent among them hydrodynamics with weakly broken translational symmetry. Here, we show how a number of other theories, normally not thought of in this context, can also be understood within a broader framework of quasihydrodynamics: in particular, the Müller-Israel-Stewart theory and magnetohydrodynamics coupled to dynamical electric fields. While historical formulations of quasihydrodynamic theories were typically highly phenomenological, here, we develop a holographic formalism to systematically derive such theories from a (microscopic) dual gravitational description. Beyond laying out a general holographic algorithm, we show how the Müller-Israel-Stewart theory can be understood from a dual higher-derivative gravity theory and magnetohydrodynamics from a dual theory with two-form bulk fields. In the latter example, this allows us to unambiguously demonstrate the existence of dynamical photons in the holographic description of magnetohydrodynamics. [ABSTRACT FROM AUTHOR]

Environmental changes influencing the interaction between the maturing immune system and pathogen exposure are implicated in the rising rates of allergic disease. There is emerging evidence that differences in innate immune function contribute to the development of allergy. Consequently, associated genetic factors may be critical for the difference in immune ontogeny, seen in allergic children.

Focuses on the life and works of Christopher Dearnley, organist of Saint Paul's Cathedral in London, England. Family and education background; Achievements of Dearnley as a writer, scholar, composer and editor; Efforts to recognize talents of other people.