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Gravitational lensing magnification of Type Ia supernovae (SNe Ia) allows information to be obtained about the distribution of matter on small scales. In this paper, we derive limits on the fraction |$\alpha$| of the total matter density in compact objects (which comprise stars, stellar remnants, small stellar groupings, and primordial black holes) of mass M > 0.03 |${\rm M}_{\odot }$| over cosmological distances. Using 1532 SNe Ia from the Dark Energy Survey Year 5 sample (DES-SN5YR) combined with a Bayesian prior for the absolute magnitude M , we obtain α < 0.12 at the 95 per cent confidence level after marginalization over cosmological parameters, lensing due to large-scale structure, and intrinsic non-Gaussianity. Similar results are obtained using priors from the cosmic microwave background, baryon acoustic oscillations, and galaxy weak lensing, indicating our results do not depend on the background cosmology. We argue our constraints are likely to be conservative (in the sense of the values we quote being higher than the truth), but discuss scenarios in which they could be weakened by systematics of the order of |$\Delta \alpha \sim 0.04$|⁠. [ABSTRACT FROM AUTHOR]

Thermal management is an intrinsic aspect of the electronics industry, and a flat plate pulsating heat pipe (FPPHP) consisting of multiple capillary channels machined on a flat plate, sealed using another plate, and filled with a working fluid is an ideal choice for flat heat sources. Typically, the FPPHP plate is divided into the evaporator section, where the heat source is attached, and a condenser section, where heat is dissipated all on the same side of the plate. In the present work, the studied FPPHPs have evaporator and condenser sections arranged in a novel antiparallel manner, with the former attached to the bottom half of the FPPHP plate and the latter on the upper half of the cover plate, suitable for many commercial compact electronic housings having space constraints. Two FPPHP configurations are investigated for thermal performance, one with a gasket (Configuration 1) and the other with O-rings (Configuration 2) between the FPPHP and the cover plates for tight sealing between the channels. The condenser section is air-cooled with multiple fins, and the optimum fin length is investigated for maximum thermal performance. A resistance model is presented with the overall thermal resistance between the evaporator and condenser section comprising plate resistance, fluid resistance, condenser resistance, and gasket/O-rings resistance. Configuration 1 has a lesser fluid resistance of a minimum of 55% at 100 W than Configuration 2, as it can hold a larger working fluid volume. However, the overall thermal resistance is lesser in Configuration 2 by 16% over Configuration 1 at higher heat inputs because of better working fluid pulsation. Further superhydrophilic treatment of the FPPHP surface decreases the thermal resistance by 16%, and the impact of the FPPHP material’s thermal conductivity, that is, aluminum FPPHP has a decreased thermal resistance of 20% over copper FPPHP, is reported. [ABSTRACT FROM AUTHOR]

We present a precise measurement of cosmological time dilation using the light curves of 1504 Type Ia supernovae from the Dark Energy Survey spanning a redshift range |$0.1\lesssim z\lesssim 1.2$|⁠. We find that the width of supernova light curves is proportional to |$(1+z)$|⁠ , as expected for time dilation due to the expansion of the Universe. Assuming Type Ia supernovae light curves are emitted with a consistent duration |$\Delta t_{\rm em}$|⁠ , and parametrizing the observed duration as |$\Delta t_{\rm obs}=\Delta t_{\rm em}(1+z)^b$|⁠ , we fit for the form of time dilation using two methods. First, we find that a power of |$b \approx 1$| minimizes the flux scatter in stacked subsamples of light curves across different redshifts. Secondly, we fit each target supernova to a stacked light curve (stacking all supernovae with observed bandpasses matching that of the target light curve) and find |$b=1.003\pm 0.005$| (stat) |$\pm \, 0.010$| (sys). Thanks to the large number of supernovae and large redshift-range of the sample, this analysis gives the most precise measurement of cosmological time dilation to date, ruling out any non-time-dilating cosmological models at very high significance. [ABSTRACT FROM AUTHOR]

We report constraints on a variety of non-standard cosmological models using the full 5-yr photometrically classified type Ia supernova sample from the Dark Energy Survey (DES-SN5YR). Both Akaike Information Criterion (AIC) and Suspiciousness calculations find no strong evidence for or against any of the non-standard models we explore. When combined with external probes, the AIC and Suspiciousness agree that 11 of the 15 models are moderately preferred over Flat- |$\Lambda$| CDM suggesting additional flexibility in our cosmological models may be required beyond the cosmological constant. We also provide a detailed discussion of all cosmological assumptions that appear in the DES supernova cosmology analyses, evaluate their impact, and provide guidance on using the DES Hubble diagram to test non-standard models. An approximate cosmological model, used to perform bias corrections to the data holds the biggest potential for harbouring cosmological assumptions. We show that even if the approximate cosmological model is constructed with a matter density shifted by |$\Delta \Omega _{\rm m}\sim 0.2$| from the true matter density of a simulated data set the bias that arises is subdominant to statistical uncertainties. Nevertheless, we present and validate a methodology to reduce this bias. [ABSTRACT FROM AUTHOR]

The residuals of the distance moduli of Type Ia supernovae (SNe Ia) relative to a Hubble diagram fit contain information about the inhomogeneity of the Universe, due to weak lensing magnification by foreground matter. By correlating the residuals of the Dark Energy Survey Year 5 SN Ia sample (DES-SN5YR) with extragalactic foregrounds from the DES Y3 Gold catalogue, we detect the presence of lensing at |$6.0 \sigma$| significance. This is the first detection with a significance level above |$5\sigma$|⁠. Constraints on the effective mass-to-light ratios and radial profiles of dark matter haloes surrounding individual galaxies are also obtained. We show that the scatter of SNe Ia around the Hubble diagram is reduced by modifying the standardization of the distance moduli to include an easily calculable de-lensing (i.e. environmental) term. We use the de-lensed distance moduli to recompute cosmological parameters derived from SN Ia, finding in Flat w cold dark matter a difference of |$\Delta \Omega _{\rm M} = +0.036$| and |$\Delta w = -0.056$| compared to the unmodified distance moduli, a change of |$\sim 0.3\sigma$|⁠. We argue that our modelling of SN Ia lensing will lower systematics on future surveys with higher statistical power. We use the observed dispersion of lensing in DES-SN5YR to constrain |$\sigma _8$|⁠ , but caution that the fit is sensitive to uncertainties at small scales. Nevertheless, our detection of SN Ia lensing opens a new pathway to study matter inhomogeneity that complements galaxy–galaxy lensing surveys and has unrelated systematics. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance was estimated to be associated with 4.95 million deaths worldwide in 2019. It is possible to frame the antimicrobial resistance problem as a feedback-control problem. If we could optimize this feedback-control problem and translate our findings to the clinic, we could slow, prevent, or reverse the development of high-level drug resistance. Prior work on this topic has relied on systems where the exact dynamics and parameters were known a priori. In this study, we extend this work using a reinforcement learning (RL) approach capable of learning effective drug cycling policies in a system defined by empirically measured fitness landscapes. Crucially, we show that it is possible to learn effective drug cycling policies despite the problems of noisy, limited, or delayed measurement. Given access to a panel of 15 β-lactam antibiotics with which to treat the simulated Escherichia coli population, we demonstrate that RL agents outperform two naive treatment paradigms at minimizing the population fitness over time. We also show thatRLagents approach the performance of the optimal drug cycling policy. Even when stochastic noise is introduced to the measurements of population fitness, we show that RL agents are capable of maintaining evolving populations at lower growth rates compared to controls. We further tested our approach in arbitrary fitness landscapes of up to 1,024 genotypes. We show that minimization of population fitness using drug cycles is not limited by increasing genome size. Our work represents a proof-of-concept for using AI to control complex evolutionary processes. [ABSTRACT FROM AUTHOR]

The ever-changing nature of cancer poses the most difficult challenge oncologists face today. Cancer's remarkable adaptability has inspired many to work toward understanding the evolutionary dynamics that underlie this disease in hopes of learning new ways to fight it. Eco-evolutionary dynamics of a tumor are not accounted for in most standard treatment regimens, but exploiting them would help us combat treatment-resistant effectively. Here, we outline several notable efforts to exploit these dynamics and circumvent drug resistance in cancer. [ABSTRACT FROM AUTHOR]

Background: To report our recommended methodology for extracting and then confirming research uncertainties - areas where research has failed to answer a research question - derived from previously published literature during a broad scope Priority Setting Partnership (PSP) with the James Lind Alliance (JLA).Methods: This process was completed in the UK as part of the PSP for "Common Conditions Affecting the Hand and Wrist", comprising of health professionals, patients and carers and reports the data (uncertainty) extraction phase of this. The PSP followed the robust methodology dictated by the JLA and sought to identify knowledge gaps, termed "uncertainties" by the JLA. Published Cochrane Systematic Reviews, Guidelines and Protocols, NICE (National Institute for Health and Care Excellence) Guidelines, and SIGN (Scottish Intercollegiate Guidelines Network) Guidelines were screened for documented "uncertainties". A robust method of screening, internally verifying and then checking uncertainties was adopted. This included independent screening and data extraction by multiple researchers and use of a PRISMA flowchart, alongside steering group consensus processes. Selection of research uncertainties was guided by the scope of the Common Conditions Affecting the Hand and Wrist PSP which focused on "common" hand conditions routinely treated by hand specialists, including hand surgeons and hand therapists limited to identifying questions concerning the results of intervention, and not the basic science or epidemiology behind disease.Results: Of the 2358 records identified (after removal of duplicates) which entered the screening process, 186 records were presented to the PSP steering group for eligibility assessment; 79 were deemed within scope and included for the purpose of research uncertainty extraction (45 full Cochrane Reviews, 18 Cochrane Review protocols, 16 Guidelines). These yielded 89 research uncertainties, which were compared to the stakeholder survey, and added to the longlist where necessary; before derived uncertainties were checked against non-Cochrane published systematic reviews.Conclusions: In carrying out this work, beyond reporting on output of the Common Conditions Affecting the Hand and Wrist PSP, we detail the methodology and processes we hope can inform and facilitate the work of future PSPs and other evidence reviews, especially those with a broader scope beyond a single disease or condition. [ABSTRACT FROM AUTHOR]

It is well known that the axial dipole part of Earth's magnetic field reverses polarity, so that the magnetic North Pole becomes the South Pole and vice versa. The timing of reversals is well documented for the past 160 Myr, but the conditions that lead to a reversal are still not well understood. It is not known if there are reliable 'precursors' of reversals (events that indicate that a reversal is upcoming) or what they might be. We investigate if machine learning (ML) techniques can reliably identify precursors of reversals based on time-series of the axial magnetic dipole field. The basic idea is to train a classifier using segments of time-series of the axial magnetic dipole. This training step requires modification of standard ML techniques to account for the fact that we are interested in rare events—a reversal is unusual, while a non-reversing field is the norm. Without our tweak, the ML classifiers lead to useless predictions. Perhaps even more importantly, the usable observational record is limited to 0–2 Ma and contains only five reversals, necessitating that we determine if the data are even sufficient to reliably train and validate an ML algorithm. To answer these questions we use several ML classifiers (linear/non-linear support vector machines and long short-term memory networks), invoke a hierarchy of numerical models (from simplified models to 3-D geodynamo simulations), and two palaeomagnetic reconstructions (PADM2M and Sint-2000). The performance of the ML classifiers varies across the models and the observational record and we provide evidence that this is not an artefact of the numerics, but rather reflects how 'predictable' a model or observational record is. Studying models of Earth's magnetic field via ML classifiers thus can help with identifying shortcomings or advantages of the various models. For Earth's magnetic field, we conclude that the ability of ML to identify precursors of reversals is limited, largely due to the small amount and low frequency resolution of data, which makes training and subsequent validation nearly impossible. Put simply: the ML techniques we tried are not currently capable of reliably identifying an axial dipole moment (ADM) precursor for geomagnetic reversals. This does not necessarily imply that such a precursor does not exist, and improvements in temporal resolution and length of ADM records may well offer better prospects in the future. [ABSTRACT FROM AUTHOR]

In this review, we consider the role of cell-cell fusion in cancer development and progression through an evolutionary lens. We begin by summarizing the origins of fusion proteins (fusogens), of which there are many distinct classes that have evolved through convergent evolution. We then use an evolutionary framework to highlight how the persistence of fusion over generations and across different organisms can be attributed to traits that increase fitness secondary to fusion; these traits map well to the expanded hallmarks of cancer. By studying the tumor microenvironment, we can begin to identify the key selective pressures that may favor higher rates of fusion compared to healthy tissues. The paper concludes by discussing the increasing number of research questions surrounding fusion, recommendations for how to answer them, and the need for a greater interest in exploring cell fusion and evolutionary principles in oncology moving forward. [Display omitted] • Cell-cell fusion is a known phenomenon that characterizes human physiology as well as the pathological hallmarks of cancer. • Many of the known biochemical pathways that up-regulate fusion (via fusogen production) have been previously associated with tumorigenesis. • Several of these triggers of cell-cell fusion are key components of the tumor microenvironment (TME). • There is growing evidence that cell-cell fusion enables cancer hallmarks, and could become a cancer hallmark in its own right. [ABSTRACT FROM AUTHOR]

High selenium (Se) forages grow on seleniferous soils in many parts of the world and upon Se-contaminated rangelands such as in the Western Phosphate Resource Area in the western United States. When consumed in large enough amounts or for extended durations, animals can be poisoned, developing acute or chronic selenosis. Naïve livestock will indiscriminately consume forage with increased concentrations of Se if available. However, most animals upon ingesting a sublethal Se dose will become averted to Se-rich plants and select forages with decreased Se concentrations. The purpose of this study was to determine Se concentrations in feed that cause reduced feed intake and decreased body weight (BW) gain in growing lambs (6 to 8 mo of age). Lambs (n = 5) were randomly divided into four groups and were fed a control pellet (< 1 ppm Se) at 1.5% of their BW and had free choice to a custom Se alfalfa pellet containing < 1 (control), 10, 20, or 40 ppm Se for 8 wk. During the 8 wk period the lambs gained 32.9 ± 4.1, 27.8 ± 1.8, 18.9 ± 9.2, and 7.4 ± 2.8% (mean ±SD) of their initial BW in the < 1 (control), 10, 20, or 40 ppm Se groups, respectively. After the 8 wk were completed, the lambs were fed only the custom Se alfalfa pellets, with < 1 (control), 10, 20, or 40 ppm Se, free choice for four additional weeks. As Se concentration in the pellets fed increased, the feed intake and BW gains significantly decreased. Lambs in the control and 10 ppm Se groups ate approximately 2-fold more than the lambs in the 40 ppm Se group, which lost over 3% of their initial BW. Understanding the concentration of Se in forages and how it affects appetite and BW gain allows range managers to better manage seleniferous or Se-contaminated ranges to safely use sheep on these types of rangelands. Additional work is needed to better understand the management of other livestock species grazing on high Se-containing ranges and pastures. [ABSTRACT FROM AUTHOR]

MicroRNA (miRNA)-based therapies are an emerging class of targeted therapeutics with many potential applications. Ewing Sarcoma patients could benefit dramatically from personalized miRNA therapy due to inter-patient heterogeneity and a lack of druggable (to this point) targets. However, because of the broad effects miRNAs may have on different cells and tissues, trials of miRNA therapies have struggled due to severe toxicity and unanticipated immune response. In order to overcome this hurdle, a network science-based approach is well-equipped to evaluate and identify miRNA candidates and combinations of candidates for the repression of key oncogenic targets while avoiding repression of essential housekeeping genes. We first characterized 6 Ewing sarcoma cell lines using mRNA sequencing. We then estimated a measure of tumor state, which we term network potential, based on both the mRNA gene expression and the underlying protein-protein interaction network in the tumor. Next, we ranked mRNA targets based on their contribution to network potential. We then identified miRNAs and combinations of miRNAs that preferentially act to repress mRNA targets with the greatest influence on network potential. Our analysis identified TRIM25, APP, ELAV1, RNF4, and HNRNPL as ideal mRNA targets for Ewing sarcoma therapy. Using predicted miRNA-mRNA target mappings, we identified miR-3613-3p, let-7a-3p, miR-300, miR-424-5p, and let-7b-3p as candidate optimal miRNAs for preferential repression of these targets. Ultimately, our work, as exemplified in the case of Ewing sarcoma, describes a novel pipeline by which personalized miRNA cocktails can be designed to maximally perturb gene networks contributing to cancer progression. Author summary: Precision medicine in cancer aims to find the right treatment, for the right patient, at the right time. Substantial variation between patient tumors, even of the same disease site, has limited the application of precision medicine in the clinic. In this study, we present novel computational tools for the identification of targets for cancer therapy using widely available sequencing data. We used a network-science based approach that leveraged multiple types of 'omic data to identify functionally relevant disease targets. Further, we developed algorithms to identify potential miRNA-based therapies that inhibit these predicted disease targets. We applied this pipeline to a novel Ewing Sarcoma transcriptomics data-set as well as publicly available patient data from the St. Jude Cloud. We identified a number of promising therapeutic targets for this rare disease, including EWSR1, the proposed driver of Ewing Sarcoma development. These novel data and methods will provide researchers with new tools for the development of precision medicine treatments in a variety of cancer systems. [ABSTRACT FROM AUTHOR]

Personal protective equipment (PPE) is crucially important to the safety of both patients and medical personnel, particularly in the event of an infectious pandemic. As the incidence of Coronavirus Disease 2019 (COVID-19) increases exponentially in the United States and many parts of the world, healthcare provider demand for these necessities is currently outpacing supply. In the midst of the current pandemic, there has been a concerted effort to identify viable ways to conserve PPE, including decontamination after use. In this study, we outline a procedure by which PPE may be decontaminated using ultraviolet (UV) radiation in biosafety cabinets (BSCs), a common element of many academic, public health, and hospital laboratories. According to the literature, effective decontamination of N95 respirator masks or surgical masks requires UV-C doses of greater than 1 Jcm−2, which was achieved after 4.3 hours per side when placing the N95 at the bottom of the BSCs tested in this study. We then demonstrated complete inactivation of the human coronavirus NL63 on N95 mask material after 15 minutes of UV-C exposure at 61 cm (232 μWcm−2). Our results provide support to healthcare organizations looking for methods to extend their reserves of PPE. [ABSTRACT FROM AUTHOR]

• Serum amyloid A (SAA) can modulate autophagy through multiple entry points in cancer cells. • SAA can modulate autophagy positively or negatively, depending on cell type and cellular context. • SAA receptor-binding can modulate autophagy in cancer by activating the PI3K/Akt/mTOR and the MAPK signaling pathways. • SAA can regulate autophagy through its role as a pro-inflammatory cytokine. • Regulation of autophagy by SAA can influence treatment outcomes, highlighting SAA as a potenital target for cancer treatment. Chronic inflammation, systemic or local, plays a vital role in tumour progression and metastasis. Dysregulation of key physiological processes such as autophagy elicit unfavourable immune responses to induce chronic inflammation. Cytokines, growth factors and acute phase proteins present in the tumour microenvironment regulate inflammatory responses and alter crosstalk between various signalling pathways involved in the progression of cancer. Serum amyloid A (SAA) is a key acute phase protein secreted by the liver during the acute phase response (APR) following infection or injury. However, cancer and cancer-associated cells produce SAA, which when present in high levels in the tumour microenvironment contributes to cancer initiation, progression and metastasis. SAA can activate several signalling pathways such as the PI3K and MAPK pathways, which are also known modulators of the intracellular degradation process, autophagy. Autophagy can be regarded as having a double edged sword effect in cancer. Its dysregulation can induce malignant transformation through metabolic stress which manifests as oxidative stress, endoplasmic reticulum (ER) stress and DNA damage. On the other hand, autophagy can promote cancer survival during metabolic stress, hypoxia and senescence. Autophagy has been utilised to promote the efficiency of chemotherapeutic agents and can either be inhibited or induced to improve treatment outcomes. This review aims to address the known mechanisms that regulate autophagy as well as illustrating the role of SAA in modulating these pathways and its clinical implications for cancer therapy. [ABSTRACT FROM AUTHOR]

Assessing volcanic hazard in regions of distributed volcanism is challenging because of the uncertain location of future vents. A statistical‐mechanical strategy to forecast such locations was recently proposed: here, we further develop and test it with analog models. We stress a gelatin block laterally and with surface excavations, and observe air‐filled crack trajectories. We use the observed surface arrivals to sample the distributions of parameters describing the stress state of the gelatin block, combining deterministic crack trajectory simulations with a Monte Carlo approach. While the individual stress parameters remain unconstrained, we effectively retrieve their ratio and successfully forecast the arrival points of subsequent cracks. Plain Language Summary: In regions of distributed volcanism, eruption locations (vents) are scattered over a large area. Forecasting the new eruption locations over such regions is critically important, as many are densely populated. One of the main difficulties is dealing with few known past eruptions, that is, the data available to constrain forecast models are scarce. Thus, we develop a forecast strategy by applying extension or compression to blocks of gelatin with surface excavations and observing the propagation of air‐filled cracks. Such models, if properly scaled, are an analog for magma propagation in the Earth's crust. We use the surface arrival points of some observed cracks to retrieve the statistical distributions of a few parameters controlling the stress field. Next, we use such distributions to forecast the arrival points of other observed cracks. Although we could not retrieve all the stress parameters accurately, the forecasts we perform are reliable. Our strategy may help retrieving the state of stress in volcanic regions and forecast the location of future vents. Key Points: We stress a gelatin block by excavating its surface and imposing lateral strain, then observe air‐filled cracks trajectoriesWe numerically simulate the trajectories and retrieve the stress state of the gelatin, then we forecast new crack arrivals at the surfaceOur strategy correctly retrieves the ratio between lateral extension and excavation depth and leads to effective forecasts of eruptive vents [ABSTRACT FROM AUTHOR]

We combine data from ALMA and MUSE to study the resolved (∼300 pc scale) star formation relation (star formation rate, SFR, versus molecular gas surface density) in cluster galaxies. Our sample consists of nine Fornax cluster galaxies, including spirals, ellipticals, and dwarfs, covering a stellar mass range of ∼108.8–1011 M⊙. CO(1-0) and extinction corrected Hα were used as tracers for the molecular gas mass and SFR, respectively. We compare our results with Kennicutt and Bigiel et al. Furthermore, we create depletion time maps to reveal small-scale variations in individual galaxies. We explore these further in FCC290, using the 'uncertainty principle for star formation' (Kruijssen & Longmore) to estimate molecular cloud lifetimes, which we find to be short (<10 Myr) in this galaxy. Galaxy-averaged depletion times are compared with other parameters such as stellar mass and cluster-centric distance. We find that the star formation relation in the Fornax cluster is close to those from Kennicutt and Bigiel et al. but overlaps mostly with the shortest depletion times predicted by Bigiel et al. This slight decrease in depletion time is mostly driven by dwarf galaxies with disturbed molecular gas reservoirs close to the virial radius. In FCC90, a dwarf galaxy with a molecular gas tail, we find that depletion times are a factor ≳10 higher in its tail than in its stellar body. [ABSTRACT FROM AUTHOR]

The quality control of intracellular proteins is achieved by degrading misfolded proteins which cannot be refolded by molecular chaperones. In eukaryotes, such degradation is handled primarily by the ubiquitin-proteasome system. However, it remained unclear whether and how protein quality control deploys various deubiquitinases. To address this question, we screened deletions or mutation of the 20 deubiquitinase genes in Saccharomyces cerevisiae and discovered that almost half of the mutations slowed the removal of misfolded proteins whereas none of the remaining mutations accelerated this process significantly. Further characterization revealed that Ubp6 maintains the level of free ubiquitin to promote the elimination of misfolded cytosolic proteins, while Ubp3 supports the degradation of misfolded cytosolic and ER luminal proteins by different mechanisms. [ABSTRACT FROM AUTHOR]

In this paper, a plasmonic “ac Wheatstone bridge” circuit is proposed and theoretically modeled for the first time. The bridge circuit consists of three metallic nanoparticles, shaped as rectangular prisms, with two nanoparticles acting as parallel arms of a resonant circuit and the third bridging nanoparticle acting as an optical antenna providing an output signal. Polarized light excites localized surface plasmon resonances in the two arms of the circuit, which generate an optical signal dependent on the phase-sensitive excitations of surface plasmons in the antenna. The circuit is analyzed using a plasmonic coupling theory and numerical simulations. The analyses show that the plasmonic circuit is sensitive to phase shifts between the arms of the bridge and has the potential to detect the presence of single molecules. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to assess the feasibility of conducting a large, multicentre randomised controlled trial (RCT) comparing needle fasciotomy with limited fasciectomy for treatment of Dupuytren's contractures. Design: The design of this study is a parallel, two-arm, multicentre, randomised feasibility trial with embedded QuinteT Recruitment Intervention. Participants: Patients aged 18 years or over who were referred from primary to secondary care for treatment of a hand with Dupuytren's contractures of one or more fingers of more than 30° at the metacarpophalangeal (MCP) and/or proximal interphalangeal (PIP) joints and well-defined cord(s). Patients were excluded if they had undergone previous Dupuytren's contracture surgery on the same hand. Methods: Potential participants were screened for eligibility. Recruited participants randomised (1:1) to treatment with either needle fasciotomy or limited fasciectomy and followed-up for up to 6 months after treatment. Data on recruitment rates, completion of follow-up, and procedure costs were collected. Four patient reported outcome measures (PROMs) and objective outcome measures were collected before intervention and 6 weeks and 6 months afterwards. Results: One hundred and fifty-three of 267 (57%) primary-care referrals for Dupuytren's contractures met the eligibility criteria for the study. Seventy-one of the 153 (46%) agreed to participate and were randomly allocated to treatment with needle fasciotomy or limited fasciectomy. Sixty-seven of these underwent their allocated treatment, two were crossovers from limited fasciectomy to needle fasciotomy, and two (both allocated limited fasciectomy) received no treatment. Fifty-nine participants (85%) completed 6-month follow-up PROMs. Participants felt the MYMOP, PEM and URAM PROMs allowed them to better describe how their treatment affected their hand function than the DASH PROM. The estimated costs of limited fasciectomy (in an operating theatre) and needle fasciotomy (in a clinic room) were £777 and £111 respectively. Conclusion: A large RCT comparing treatment of Dupuytren's contractures by needle fasciotomy and limited fasciectomy is feasible. Data from this study will help determine the number of sites and duration of recruitment required to complete an adequately powered RCT and will assist the selection of PROMs in future studies on the treatment of Dupuytren's contractures. (Level 1 feasibility study). Trial registration: Trial registered with ISRCTN (registration number: ISRCTN11164292), date assigned - 28/08/2015. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer is often diagnosed in advanced stages, when survival is poor. Treatment advances have been made, but are inconsistently implemented. Our purpose was to project the maximum life expectancy gains that could be achieved in women with stage IIIC epithelial ovarian cancer if the implementation of available chemotherapy regimens could be optimized. Methods: We used a microsimulation model to estimate life expectancy benefits associated with “optimized” implementation of four post-operative chemotherapy options: standard intravenous chemotherapy; intraperitoneal + intravenous chemotherapy; bevacizumab + intravenous chemotherapy; and hyperthermic intraperitoneal chemotherapy + intravenous chemotherapy. Optimized implementation was defined as follows. Patients triaged to primary cytoreductive surgery received intraperitoneal + intravenous chemotherapy if optimally or completely cytoreduced, and bevacizumab + intravenous chemotherapy if suboptimally cytoreduced. Patients triaged to neoadjuvant chemotherapy received hyperthermic intraperitoneal chemotherapy at interval cytoreductive surgery if optimally or completely cytoreduced, and standard IV chemotherapy if suboptimally cytoreduced. Life expectancy associated with optimized implementation was compared with that of current utilization practices, estimated using published literature and the National Cancer Database. Effects of model uncertainty were evaluated in sensitivity analyses. Results: Life expectancy associated with optimized implementation vs. current practice was 76.7 vs. 64.5 months (life expectancy gain = 12.2 months). Providing intraperitoneal + intravenous chemotherapy to all eligible patients was the largest driver of life expectancy gains, due to both the potential benefit conferred by intraperitoneal + intravenous chemotherapy and the proportion of eligible women who do not receive intraperitoneal + intravenous chemotherapy in current practice. Conclusion: Population-level life expectancy in stage IIIC epithelial ovarian cancer could be substantially improved through greater uptake of available chemotherapy regimens. [ABSTRACT FROM AUTHOR]

Abstract The formulation for the 3D triangular displacement discontinuity boundary element method with frictional constraints is described in detail. Its accuracy in comparison to analytical solutions is then quantified. We show how this can be used to approximate stress intensity factors at the crack tips. Using this method, we go on to quantify how slip is reduced on fault surfaces with topography, where the asperities are approximated as a sinusoidal waveform, i.e. corrugations. We use stress boundary conditions (compressive) orientated such that frictional contacts shear. We show that slip reductions relative to planar faults for 2D line and 3D penny-shaped crack models are comparable within 10% when slip is perpendicular to the corrugations. Using the 3D model, we then show how slip is reduced more when corrugation wavelengths are doubled compared to the reduction due to corrugation misalignment with the slip direction. When slip is parallel with the corrugation alignment we show that reducing the out-of-plane stress, from the normal traction acting on the fault when planar to that resolved on a perpendicular plane, has the same effect as halving the length of the corrugation waveform in terms of slip reduction for a given amplitude. Highlights • 3D displacement discontinuity method friction and stress intensity formulations. • Quantifies how slip reduction changes due to boundary conditions and fault shape. • Shear fractures can open even when pore pressure doesn't exceed confining stress. [ABSTRACT FROM AUTHOR]

We investigate whether barred galaxies are statistically more likely to harbour radial molecular gas flows and what effect those flows have on their global properties. Using 46 galaxies from the ALMA-MaNGA QUEnching and STar formation (ALMaQUEST) survey, we identify galaxies hosting optical bars using a combination of the morphological classifications in Galaxy Zoo 2 and HyperLEDA. In order to detect radial molecular gas flows, we employ full 3D kinematic modelling of the ALMaQUEST 12CO(1–0) data cubes. By combining our bar classifications with our radial bar-driven flow detections, we find that galaxies classed as barred are statistically more likely to host large-scale radial gas motions compared to their un-barred and edge-on galaxy counterparts. Moreover, the majority of barred galaxies require multicomponent surface brightness profiles in their best-fitting models, indicative of the presence of resonance systems. We find that galaxies classed as barred with radial bar-driven flows ('barred + radial flow' subset) have significantly suppressed global star-formation efficiencies compared to barred galaxies without radial bar-driven flows and galaxies in the other morphological sub-samples. Our 'barred + radial flow' subset galaxies also possess consistently centrally concentrated molecular gas distributions, with no indication of depleted gas mass fractions, suggesting that gas exhaustion is not the cause of their suppressed star formation. Furthermore, these objects have higher median gas mass surface densities in their central 1 kpc, implying that central gas enhancements do not fuel central starbursts in these objects. We propose that dynamical effects, such as shear caused by large-scale inflows of gas, act to gravitationally stabilize the inner gas reservoirs. [ABSTRACT FROM AUTHOR]

Modified long-chain alkanes are often used to functionalize graphene and MoS2 noncovalently, with the goal of controlling the substrate electronic structure or interactions with the environment. Alkyl chain adsorption enthalpy is lower on MoS2 than on graphite; the decreased molecule–substrate interaction strength suggests utility for monolayer structures that increase stability through other means. Previously, we have found that diyne phospholipid monolayers on HOPG are more stable toward solution processing than monolayers of single-chain amphiphiles. Here, we show that this is also true for assembly on MoS2, but that the additional stability appears to arise from edge-on adsorption, producing monolayers in which alkyl chains form two stacked layers on the substrate. [ABSTRACT FROM AUTHOR]

Objective For patients with advanced stage epithelial ovarian cancer (EOC), substantial emphasis has been placed on diagnostic tests that can discern which of two treatment options – primary cytoreductive surgery (PCS) or neoadjuvant chemotherapy followed by interval cytoreductive surgery (NACT + ICS) – optimizes patient-level outcomes. Our goal was to project potential life expectancy (LE) gains that could be achieved by use of such a test. Methods We developed a microsimulation model to project LE for patients with stage IIIC EOC. We compared: a “standard-of-care” strategy, in which patients were triaged to PCS vs. NACT + ICS based on current clinical practice; and a “test” strategy, in which patients were triaged based on results of a hypothetical test. We identified those test performance characteristics for which the test strategy outperformed the standard-of-care strategy, from a LE standpoint. Effects of parameter uncertainty were evaluated in sensitivity analysis. Results Even with a perfect test, the LE gain was modest (LE with test vs. standard-of-care strategy = 67.6 vs. 66.4 months; LE gain = 1.2 months). In order to outperform the standard-of-care, the test had to have a high probability of correctly identifying “resectable” patients at PCS (i.e. those for whom complete or optimal cytoreduction would be possible); this test property was more important than correct triage of unresectable patients to NACT + ICS. Results were sensitive to the proportion of patients whose underlying disease was resectable at PCS. Conclusion Diagnostic tests that are designed to triage patients with advanced stage EOC will likely have only a modest effect on LE. [ABSTRACT FROM AUTHOR]

Abstract: Spruce beetle populations (Dendroctonus rufipennis) (Coleoptera: Scolytinae) in Engelmann spruce (Picea engelmannii) stands were monitored at twelve sites for 6 years in northern Colorado using pheromone‐baited Lindgren funnel traps. During the trapping period, over 30,000 beetles were captured, and beetle abundance data were used to construct empirical models of trap capture phenology based on day of year, accumulation of thermal units and thermal day thresholds, with the goal of informing future regional trapping efforts and producing a simple model for use by forest managers. Ordinal day models outperformed thermal accumulation and thermal threshold models in both predictive power and parsimony. Mean date of earliest capture was Day 153 (June 2) and ranged from Day 126 to Day 161 (May 6–June 10), and mean date of final capture was Day 243 (August 31) and ranged from Day 220 to Day 286 (August 8–October 13). A two‐parameter logistic function was the most parsimonious of several ordinal day models, accounting for 81% of the variance in cumulative trap capture across all sites and dates. The model predicts 50% of trap captures to occur by Day 181 (June 30). This model has application as a decision support tool for forest ecosystem managers concerned with the timing of trap deployment or D. rufipennis mitigation treatments. [ABSTRACT FROM AUTHOR]

Rayless goldenrod (Isocoma spp.) and white snakeroot (Ageratina altissima) poison livestock, wildlife and humans. The suggested toxin for both plants is tremetone, a mixture of benzofuran ketones. However, plant tremetone concentrations often do not correlate with poisoning, and they have not been identified in contaminated milk that poisons nursing neonates. This suggests there may be unidentified metabolites or toxins. Previous studies using various cell culture and large animal models have been inconsistent with varying animal response that often require large doses. The objective of this work is to document the toxicity of rayless goldenrod in California white leghorn chicks, a susceptible small animal model, that would require relatively small amounts of plant material or purified toxins. Four groups of 15 chicks were gavaged with finely ground I. pluriflora at rates of 0, 1%, 2% or 3% of their bodyweight per day for 7 days. After 7 exposure days the chicks were euthanized, necropsied and tissues were collected, fixed and examined microscopically. Myocyte damage was evaluated using clinical signs, weight gain, serum biochemical changes, and histologic lesions and scores. The 3% group had focally extensive myocyte degeneration and necrosis most severely affecting leg muscles (semitendinosus, iliotibialis, peroneus longus and gastrocnemius). This was supported by serum biochemical changes and reduced weight gains. These findings indicate young chicks are a sensitive model of toxicity that may be useful to better identify the rayless goldenrod and white snakeroot toxins, including those unidentified toxins of transmammary poisoning. Skeletal muscle of a chick poisoned with rayless goldenrod. Skeletal necrosis (arrows) and hypereosinophilia (h) as well as monocytic inflammation (arrow heads) are visible. These changes indicate that chicks are a sensitive small animal model of rayless goldenrod toxicity. [Display omitted] [ABSTRACT FROM AUTHOR]

We present stress concentration factors at the edges of 3D voids in uniaxial compression. Variations in these stress concentration factors due to Poisson's ratio of the host material, void shape, and void-void proximity are explicitly quantified. Voids loaded by a vertical compressive stress are hypothesised to fail in one or two ways: (1) tension crack development due to tensile stress concentrations at the void poles; or (2) compressive stress concentrations at the void sides causing the void wall to fail in shear. The stress concentration factors in this study are found using the numerical displacement discontinuity method. Equations are provided to assess the proximity of a void to the two hypothesised modes of failure. For 3D voids thinned in an axis that lies parallel to the compressive stress these have increasingly high stress concentrations at their sides. Changes in stress concentrations due to the Poisson's ratio of the matrix are minor, apart from for the intermediate stress at the void sides. Void shape, void separation, and void alignment are critical factors in the concentration of stresses. This suggests a significant departure from strength predictions for porous material that are based solely on scalar values of porosity. [ABSTRACT FROM AUTHOR]

We consider the dispersion on the supernova distance-redshift relation due to peculiar velocities and gravitational lensing, and the sensitivity of these effects to the amplitude of the matter power spectrum. We use the Method-of-the-Moments (MeMo) lensing likelihood developed by Quartin et al., which accounts for the characteristic non-Gaussian distribution caused by lensing magnification with measurements of the first four central moments of the distribution of magnitudes. We build on the MeMo likelihood by including the effects of peculiar velocities directly into the model for the moments. In order to measure the moments from sparse numbers of supernovae, we take a new approach using Kernel density estimation to estimate the underlying probability density function of the magnitude residuals. We also describe a bootstrap re-sampling approach to estimate the data covariance matrix. We then apply the method to the joint light-curve analysis (JLA) supernova catalogue. When we impose only that the intrinsic dispersion in magnitudes is independent of redshift, we find σ8 = 0.44-0.44+0.63 at the one standard deviation level, although we note that in tests on simulations, this model tends to overestimate the magnitude of the intrinsic dispersion, and underestimate σ8. We note that the degeneracy between intrinsic dispersion and the effects of σ8 is more pronounced when lensing and velocity effects are considered simultaneously, due to a cancellation of redshift dependence when both effects are included. Keeping the model of the intrinsic dispersion fixed as a Gaussian distribution of width 0.14 mag, we find σ8 = 1.07-0.76+0.50. [ABSTRACT FROM AUTHOR]

In this paper we investigate how observational effects could possibly bias cosmological inferences from peculiar velocity measurements. Specifically, we look at how bulk flow measurements are compared with theoretical predictions. Usually bulk flow calculations try to approximate the flow that would occur in a sphere around the observer. Using the Horizon Run 2 simulation we show that the traditional methods for bulk flow estimation can overestimate the magnitude of the bulk flow for two reasons: when the survey geometry is not spherical (the data do not cover the whole sky), and when the observations undersample the velocity distributions. Our results may explain why several bulk flow measurements found bulk flow velocities that seem larger than those expected in standard Λ cold dark matter cosmologies. We recommend a different approach when comparing bulk flows to cosmological models, in which the theoretical prediction for each bulk flow measurement is calculated specifically for the geometry and sampling rate of that survey. This means that bulk flow values will not be comparable between surveys, but instead they are comparable with cosmological models, which is the more important measure. [ABSTRACT FROM AUTHOR]

Although statins may increase glycaemia in type 2 diabetes, available data are from single-dose intervention trials or studies with no adjustment for concomitant changes in blood glucose-lowering therapy. To provide real-life data covering common statin types and doses, glycated haemoglobin ( HbA1c) data from patients in the Fremantle Diabetes Study phases I ( FDS1) and II ( FDS2) and data on stable diabetes treatment before and after statin initiation were analysed. Intensity of statin therapy was categorized as low, moderate or high based on within-group dose regimens with similar serum LDL cholesterol-lowering effects. In pooled analyses of 335 eligible patients in FDS1 and FDS2, there was no change in HbA1c in the low-intensity group (0.04% or 0.4 mmol/mol; n = 159; p = .40), but a mean 0.22% (2.4 mmol/mol) increase in the moderate-intensity group (n = 185; p = .022) and a larger mean increase of 1.05% (11.5 mmol/mol) increase in the high-intensity group (n = 11; p = .023). These real-life data suggest a dose-response relationship between statin treatment intensity and glycaemia that has potential clinical implications. [ABSTRACT FROM AUTHOR]

Aims To validate the findings, in a usual care setting, of glycaemic intervention trials, which have shown that tight control in patients with recently diagnosed type 2 diabetes protects against death during post-study monitoring, but that it may be deleterious in long-duration diabetes with vascular complications. Methods A subset of 531 patients with type 2 diabetes from the community-based observational Fremantle Diabetes Study Phase 1, who attended ≥5 annual reviews (mean follow-up 15.9 years), were categorized by baseline diabetes duration [<1 year (Group 1); 1 to <5 years (Group 2); and ≥5 years (Group 3)]. Glycated haemoglobin ( HbA1c) trajectories over the first 5 years were determined [low, medium and high; equivalent to mean HbA1c ≤6.6% (<49 mmol/mol), 6.7-8.0% (50-64 mmol/mol) and ≥8.0% (>64 mmol/mol), respectively]. Kaplan-Meier analysis was used to assess survival by duration and HbA1c trajectory. Cox proportional hazards modelling identified predictors of all-cause death. Results There was greater mortality in patients with a medium versus those with a low trajectory in Group 1: hazard ratio ( HR) 1.99 [95% confidence interval ( CI) 1.003-3.94; p = 0.049], and in patients with a high versus a low trajectory in Group 2: HR 2.02 (95% CI 1.11-3.71; p = 0.022). In Group 3, both medium [ HR 0.57 (95% CI 0.35-0.92; p = 0.022)] and high [ HR 0.56 (95% CI 0.32-0.96); p = 0.035] trajectories were independently and inversely associated with death. Conclusions In community-based patients with newly or recently diagnosed type 2 diabetes, poor glycaemic control was an adverse prognostic indicator. Tight control was independently associated with death in patients with diabetes duration ≥5 years. These data parallel intervention trial findings and support individualization of HbA1c targets. [ABSTRACT FROM AUTHOR]

Posaconazole is an antifungal therapy reported to cause incident hypertension. Hypokalemia is also a known side effect. The combination of hypertension and hypokalemia suggests mineralocorticoid excess. We present the case of a 15-year-old adolescent male with hypertensive urgency while on prophylactic posaconazole therapy for a combined immunodeficiency. We identify the mechanism of posaconazole-induced hypertension to be inhibition of the 11β-hydroxylase enzyme, resulting in elevated levels of the mineralocorticoid receptor activator deoxycorticosterone. Loss of function of the 11β-hydroxylase enzyme is responsible for a rare form of congenital adrenal hyperplasia and can be associated with life-threatening adrenal crisis. [ABSTRACT FROM AUTHOR]

The article presents answers to a clinical quiz on several topics including synthetic cannabinoid (SC)-induced acute kidney injury (AKI); mechanism of SC-induced AKI; and urine drug screen for tetrahydrocannabinol.

In type 1 diabetes ( T1D), insulin replacement therapy should ideally replicate endogenous insulin secretion, but achieving this goal requires frequent adjustments to insulin delivery based on glucose levels and trends, carbohydrate intake and physical activity. An overriding concern for people taking insulin is hypoglycaemia, which remains the most feared consequence of insulin therapy and limits therapy intensification options. Although fully automated systems that achieve consistent euglycaemia in T1D remain an elusive goal, improvements in continuous glucose monitoring ( CGM) sensors and control algorithms have enabled semi-automated systems that lower the risk of hypoglycaemia, especially nocturnal hypoglycaemia. The present review focuses on an important advance in insulin delivery systems: the use of CGM data to stop insulin delivery in the presence of hypoglycaemia. Although conceptually simple, this strategy represents a critical step in the journey toward a fully closed-loop artificial pancreas; the next steps in this journey are also discussed. [ABSTRACT FROM AUTHOR]

Membrane-bound and soluble proteins of the secretory pathway are commonly glycosylated in the endoplasmic reticulum. These adducts have many biological functions, including, notably, their contribution to the maturation of glycoproteins. N-linked glycans are of oligomeric structure, forming configurations that provide blueprints to precisely instruct the folding of protein substrates and the quality control systems that scrutinize it. O-linked mannoses are simpler in structure and were recently found to have distinct functions in protein quality control that do not require the complex structure of N-linked glycans. Together, recent studies reveal the breadth and sophistication of the roles of these glycan-directed modifications in protein biogenesis. [ABSTRACT FROM AUTHOR]

The initial shear layer characteristics of a jet play an important role in the initiation and development of instabilities and hence radiated noise. Particle image velocimetry has been utilized to study the initial shear layer development of supersonic free and impinging jets. Microjet control employed to reduce flow unsteadiness and jet noise appears to affect the development of the shear layer, particularly near the nozzle exit. Velocity field measurements near the nozzle exit show that the initially thin, uncontrolled shear layer develops at a constant rate while microjet control is characterized by a rapid nonlinear thickening that asymptotes downstream. The shear layer linear growth rate with microjet control, in both the free and the impinging jet, is diminished. In addition, the thickened shear layer with control leads to a reduction in azimuthal vorticity for both free and impinging jets. Linear stability theory is used to compute unstable growth rates and convection velocities of the resultant velocity profiles. The results show that while the convection velocity is largely unaffected, the unstable growth rates are significantly reduced over all frequencies with microjet injection. For the case of the impinging jet, microjet control leads to near elimination of the impingement tones and an appreciable reduction in broadband levels. Similarly, for the free jet, significant reduction in overall sound pressure levels in the peak radiation direction is observed. [ABSTRACT FROM AUTHOR]

The author discusses hematuria as blood in the urine or the presence of 5 or more blood cells (RBCs) per high-power field. Topics discussed include the cause/source of hematuria such as nephrolithiasis if there is acute flank pain radiating to the groin, with either microscopic or gross hematuria, vascular complications as the most common cause hematuria in the neonate which include renal vein thrombosis and acute tubular necrosis from decreased kidney perfusion.

Selenium-accumulator plants are reputed to be unpalatable to large ungulates. Elk (Cervus canadensis) populations in southeastern Idaho overlap with populations of Se-rich plants, but there is no information on the influence of plant Se concentration on elk dietary preferences. The objective of this study was to determine, under controlled conditions, the preference of elk for feeds varying in Se concentrations. Seven yearling female elk (128 ± 5 kg) were purchased from a commercial elk farm in southeastern Idaho and adapted to low-Se alfalfa pellets. Three feeding trials using pellets with predetermined Se concentrations were conducted. Alfalfa pellets were commercially made with the addition of Symphyotrichum ascendens (western aster) so that the pellets contained 0.4, 5, 20, 50, or 100 mg/kg (DM basis) Se. In trial 1, 5 Se-containing alfalfa pellets (0.4, 5, 20, 50, and 100 mg/kg Se) were offered for 10 d; trial 2 used 4 Se-containing alfalfa pellet choices (0.4, 20, 50, and 100 mg/kg), and trial 3 used 3 pellet choices (0.4, 50, and 100 mg/kg) for 6 d. In trial 1, consumption of the control pellets by elk was greater than each of the other pellet choices (P < 0.001). Similarly, consumption of the 5-mg/kg Se pellet differed from control pellet and all other Se-containing pellets (P < 0.0001). There were no differences (P > 0.50) in consumption of the 20-, 50-, or 100-mg/kg Se pellets. In trial 2, elk consumed more (P < 0.0001) of the control pellet than the 20-, 50-, and 100-mg/kg Se pellets. Similarly, elk consumed more (P < 0.0001) of the 20-mg/kg Se pellet than the 50- and 100-mg/ kg Se pellets. There were no differences (P > 0.99) in elk consumption of the 50- and 100-mg/kg Se pellets. In trial 3, elk consumption of the control and 50- and 100-mg/kg Se pellets differed (P ≤ 0.03) from one another each day except that on d 1 and 2, where elk consumption of the 50- and 100-mg/kg Se pellets did not differ (P ≥ 0.32). Elk clearly discriminated against pellets with the highest Se concentrations when they were given pellets with differing Se concentrations. These results suggest that elk are not likely to select forages with high Se concentrations, particularly when high-Se plants are present in a rangeland situation with numerous other forage choices. [ABSTRACT FROM AUTHOR]

Sixteen meat and bone meal (MBM) samples were obtained and selected from various company plants to provide a wide range in pepsin nitrogen digestibility values. Pepsin digestibility was determined using either 0.02 or 0.002% pepsin. Amino acid (AA) digestibility of the 16 MBM samples was then determined using a precision-fed cecectomized rooster assay. The 0.02% pepsin digestibility values were numerically higher than the 0.002% pepsin values. The values varied from 77 to 93% for 0.02% pepsin and from 67 to 91% for 0.002% pepsin. The rooster AA digestibility results showed a wide range of values among MBM samples mostly due to the 4 samples having lowest and highest AA digestibility. A precision-fed broiler chick ileal AA digestibility assay confirmed that there were large differences in AA digestibility among the MBM samples having the lowest and highest rooster digestibility values. Correlation analyses between pepsin and AA digestibility values showed that the correlation values (r) were highly significant (P < 0.0001) for all AA when all 16 MBM samples were included in the analysis. However, when the MBM samples with the 2 lowest and the 2 highest rooster digestibility values were not included in the correlation analyses, the correlation coefficient values (r) were generally very low and not significant (P > 0.05). The results indicated that the pepsin nitrogen digestibility assay is only useful for detecting large differences in AA digestibility among MBM. There also was no advantage for using 0.02 versus 0.002% pepsin. [ABSTRACT FROM AUTHOR]

The article describes the case of an 8 day old term male infant presented for evaluation of puffy hand and feet. He was assessed to be dehydrated and was given a does of IV hydrocortisone following concerns for congenital adrenal hyperplasia. A diagnostic voiding cystourethrogram (VCUG) indiated posterior urethral valves (PUVs) and pine cone bladder with multiple diverticulum and was prescribed ampicillin for 14 days. He underwent fulguration of the PUV on the 9th day.

Human papillomavirus (HPV) vaccination is proven to reduce the risk of HPV-associated cancers and lesions. Factors associated with HPV vaccine receipt or rejection have been studied, but specific maternal characteristics driving uptake among teens requires further investigation. The aim of this study was to examine maternal characteristics influencing teen vaccine uptake and intent to vaccinate. Cross-sectional analysis We analyzed data on 27,320 teens aged 13-17 using the 2020 National Immunization Survey-Teen. We constructed regression models to determine the associations, via relative risk, between child vaccination status and maternal characteristics. Compared with mothers with less education, those with a college degree were significantly more likely to have their children receive HPV vaccination (RR = 1.18; 95% CI, 1.11-1.26). Compared to mothers under 35 years, those aged 35-44 (RR 1.07; 95% CI 1.01-1.14) and over 45 (RR = 1.13; 95% CI, 1.07-1.21) were more likely to provide HPV vaccination to their child. Among children not previously vaccinated (n = 12,098; N = 5,752,355), educated mothers were significantly less likely to report intent to vaccinate their child in the next year. There was no significant difference in vaccination rates in mothers who were married compared with never married (RR = 0.99; 95% CI, 0.97-1.02). Maternal education was the strongest predictor of teens receiving the HPV vaccine. Among mothers with teens not previously vaccinated, intent to obtain the HPV vaccine for their child was higher among mothers with less education compared with college-level educated mothers. Understanding maternal characteristics driving HPV vaccine hesitancy can inform targeted approaches to improve vaccine uptake in children. Additionally, adequate and consistent health messaging on the safety, efficacy, and benefits of HPV vaccination from health providers and public health agencies could increase uptake among adolescents and teens of vaccine-hesitant mothers. [ABSTRACT FROM AUTHOR]

Davis TME, Singh B, Choo KE, Ibrahim J, Sulaiman SA, Kadir ZA, Ismail R (University of Western Australia, Fremantle Hospital, Fremantle, Western Australia, Australia. Universiti Sains Malaysia, Kubang Kerian, Kota Bharu; General Hospital, Kota Bharu, Kuala Krai Hospital, Kuala Krai; Kelantan, Malaysia) Dynamic assessment of parathyroid function in acute malaria. J Intern Med 1998; 243: 349–54. Objectives To investigate the dynamic parathyroid response to rapidly induced, sustained hypocalcaemia in patients with acute malaria and in healthy volunteers. Design Serum intact parathormone (PTH) concentrations were measured on samples taken before and during a variable-rate tri-sodium citrate infusion designed to ‘clamp’ the whole blood ionised calcium concentration 0.20 mmol L-1 below baseline for 120 min. Subjects Six Malaysian patients aged 17–42 years with acute malaria, four of whom were restudied in convalescence, and 12 healthy controls aged 19–36 years. Main outcome measures Whole-blood ionised calcium and serum intact PTH concentrations. Results The mean (SD baseline ionised calcium was lower in the malaria patients than in controls (1.09 ± 0.06 vs. 1.18 ± 0.03 mmol L-1, respectively; P = 0.01) but PTH concentrations were similar (3.0 ± 1.8 vs. 3.3 ± 1.3 pmol L-1; P = 0.33). Target whole-blood ionised calcium concentrations were achieved more rapidly in the controls than the patients (within 15 vs. 30 min) despite significantly more citrate being required in the patients (area under the citrate infusion-time curve 0.95 (0.25 vs. 0.57 ± 0.09 mmol kg-1; P < 0.01). The ratio of the change in serum PTH to that in ionised calcium (δPTH/δCa2+), calculated to adjust for differences in initial rate of fall of ionised calcium, was similar during the first 5 min of the clamp (132 ± 75 × 10-6 vs. 131 ± 43 × 10-6 in patients and controls, respectively, P > 0.05), as were steady-state serum PTH levels during the second hour (7.0 ± 2.2 pmol L-1 in each case). Convalescent patients had normal basal ionised calcium levels but the lowest serum intact PTH levels before and during the clamp, consistent with an increase in skeletal PTH sensitivity after treatment. Conclusions There is a decreased ionised calcium ‘set point’ for basal PTH secretion but a normal PTH response to acute hypocalcaemia in malaria. Skeletal resistance may attenuate the effects of the PTH response but patients with malaria appear relatively resistant to the calcium chelating effects of citrated blood products. [ABSTRACT FROM AUTHOR]