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PT-112 is a novel immunogenic cell death (ICD)-inducing small molecule currently under Phase 2 clinical development, including in metastatic castration-resistant prostate cancer (mCRPC), an immunologically cold and heterogeneous disease state in need of novel therapeutic approaches. PT-112 has been shown to cause ribosome biogenesis inhibition and organelle stress followed by ICD in cancer cells, culminating in anticancer immunity. In addition, clinical evidence of PT-112-driven immune effects has been observed in patient immunoprofiling. Given the unmet need for immune-based therapies in prostate cancer, along with a Phase I study (NCT#02266745) showing PT-112 activity in mCRPC patients, we investigated PT-112 effects in a panel of human prostate cancer cell lines. PT-112 demonstrated cancer cell selectivity, inhibiting cell growth and leading to cell death in prostate cancer cells without affecting the non-tumorigenic epithelial prostate cell line RWPE-1 at the concentrations tested. PT-112 also caused caspase-3 activation, as well as stress features in mitochondria including ROS generation, compromised membrane integrity, altered respiration, and morphological changes. Moreover, PT-112 induced damage-associated molecular pattern (DAMP) release, the first demonstration of ICD in human cancer cell lines, in addition to autophagy initiation across the panel. Taken together, PT-112 caused selective stress, growth inhibition and death in human prostate cancer cell lines. Our data provide additional insight into mitochondrial stress and ICD in response to PT-112. PT-112 anticancer immunogenicity could have clinical applications and is currently under investigation in a Phase 2 mCRPC study. [ABSTRACT FROM AUTHOR]

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Exposure of the Hubble Space Telescope to space in low Earth orbit resulted in numerous hypervelocity impacts by cosmic dust (micrometeoroids) and anthropogenic particles (orbital debris) on the solar arrays and the radiator shield of the Wide Field and Planetary Camera 2, both subsequently returned to Earth. Solar cells preserve residues from smaller cosmic dust (and orbital debris) but give less reliable information from larger particles. Here, we present images and analyses from electron, ion and X-ray fluorescence microscopes for larger impact features (millimetre- to centimetre-scale) on the radiator shield. Validated by laboratory experiments, these allow interpretation of composition, probable origin and likely dimensions of the larger impactors. The majority (~90%) of impacts by grains greater than 50 μm in size were made by micrometeoroids, dominated by magnesium- and iron-rich silicates and iron sulfides, metallic iron-nickel and chromium-rich spinel similar to that in ordinary chondrite meteorites of asteroid origin. Our re-evaluation of the largest impact features shows substantially fewer large orbital debris impacts than reported by earlier authors. Mismatch to the NASA ORDEM and ESA MASTER models of particle populations in orbit may be partly due to model overestimation of orbital debris flux and underestimation of larger micrometeoroid numbers. This article is part of the theme issue 'Dust in the Solar System and beyond'. [ABSTRACT FROM AUTHOR]

The use of sodium bicarbonate (NaHCO3) supplementation to improve repeated high-intensity performance is recommended; however, most swimming performance studies examine time trial efforts rather than repeated swims with interspersed recovery that are more indicative of training sessions. The aim of this study, therefore, was to investigate the effects of 0.3 g.kg−1 BM NaHCO3 supplementation on sprint interval swimming (8 × 50 m) in regionally trained swimmers. Fourteen regionally competitive male swimmers (body mass (BM): 73 ± 8 kg) volunteered for this double-blind, randomised, crossover designed study. Each participant was asked to swim 8 × 50 m (front crawl) at a maximum intensity from a diving block, interspersed with 50 m active recovery swimming. After one familiarisation trial, this was repeated on two separate occasions whereby participants ingested either 0.3 g.kg−1 BM NaHCO3 or 0.05 g.kg−1 BM sodium chloride (placebo) in solution 60 min prior to exercise. Whilst there were no differences in time to complete between sprints 1–4 (p > 0.05), improvements were observed in sprint 5 (p = 0.011; ES = 0.26), 6 (p = 0.014; ES = 0.39), 7 (p = 0.005; ES = 0.60), and 8 (p = 0.004; ES = 0.79). Following NaHCO3 supplementation, pH was greater at 60 min (p < 0.001; ES = 3.09), whilst HCO3− was greater at 60 min (p < 0.001; ES = 3.23) and post-exercise (p = 0.016; ES = 0.53) compared to placebo. These findings suggest NaHCO3 supplementation can improve the latter stages of sprint interval swimming performance, which is likely due to the augmentation of pH and HCO3− prior to exercise and the subsequent increase in buffering capacity during exercise. [ABSTRACT FROM AUTHOR]

Background: We report a novel presentation of deficit in anterior pituitary function with variable immune deficiency (DAVID) syndrome in a healthy young girl presenting in Addisonian crisis with raised intracranial pressure. Nearly all cases of DAVID syndrome described in the literature have presented with recurrent infections and variable immunodeficiency. Pseudotumour cerebri has not been reported in DAVID syndrome to date. Case presentation: A four-year-old girl represented to hospital with vomiting, confusion and diplopia after ten days of tiredness, neck and abdominal pain, and headache. Her cranial nerve examination demonstrated a right abducens nerve palsy and papilloedema, and she was found to have ketotic hypoglycaemia and hypocortisolaemia secondary to adrenocorticotrophic hormone (ACTH) deficiency. Her neuroimaging was consistent with pseudotumour cerebri, and her lumbar puncture opening pressure confirmed raised intracranial pressure (30–40 cmH2O). Cerebrospinal fluid analysis was normal. The patient's symptoms improved with hydrocortisone replacement and acetazolamide, but the raised intracranial pressure recurred after acetazolamide was discontinued. She was subsequently found to have panhypogammaglobulinaemia, and DAVID syndrome was diagnosed. Genetic testing demonstrated a truncating mutation in the NFKB2 gene c.2557C > T, p.(Arg853*). Conclusions: This case demonstrates pseudotumour cerebri as a novel neurological presentation of DAVID syndrome, highlights the rare association between adrenal insufficiency and intracranial hypertension, and shows the challenges in diagnosing isolated ACTH deficiency. We emphasise that cortisol should be checked in pre-pubertal children with pseudotumour cerebri and a diagnosis of DAVID syndrome considered in those presenting with low cortisol and neurological symptoms. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The COVID-19 pandemic has had a significant impact on the delivery of elective orthopaedic care in the UK, leading to a hugely increased number of patients on waiting lists. The focus has therefore now turned to reducing the backlog. We sought to develop a clear, objective and reproducible system for prioritising elective hip arthroplasty. METHODS: The prioritisation scoring system was constructed using the Federation of Surgical Specialty Associations (FSSA) guidelines as a framework. This included current Oxford hip scores, review of imaging, waiting list duration and previous cancellations. The inter-rater and intra-rater reliability for the final prioritisation scores was tested using the Kappa statistic by two blinded surgeons independently reviewing a selection of patients on two separate occasions. RESULTS: A random sample of 20 scores from 125 of the 136 patients on the waiting list were included in the study. The level of prioritisation was assessed by two consultant surgeons. No statistically significant intra-rater or inter-rater reliability was demonstrated. CONCLUSIONS: Developing an equitable hip arthroplasty prioritisation system is an essential but challenging task. This scoring system was designed as an objective means of determining prioritisation for the elective arthroplasty waiting list within the FSSA categories of priority 3 and 4. Further refinement in light of the evolving guidelines will allow improved reliability. [ABSTRACT FROM AUTHOR]

Purpose of Review: Due to the rarity and often discrete nature of hamate body fractures, timely diagnosis requires a high level of suspicion on the part of the clinician. Here, the authors have compiled the findings from 6 cohort studies and 33 case reports describing hamate body fractures in order to summarize the natural history, management, and outcomes of these infrequent injuries. Recent Findings: Fractures of the hamate body typically occur in the coronal plane through axial loading of the metacarpals or loading in the transverse plane by a compressive force. Standard radiographs of the wrist frequently miss hamate fractures. Oblique and carpal tunnel views can be obtained when a fracture of the hamate is suspected. Advanced imaging with high-resolution computed tomography should also be considered if radiographs are negative and high suspicion for fracture remains or for the purpose of pre-operative planning. Co-existing injuries often include subluxation or dislocation of the 4th and 5th metacarpals with or without fracture. Non-displaced injuries that are stable may be treated non-operatively with immobilization. Displaced or unstable fracture patterns typically require closed reduction and percutaneous pinning versus open reduction internal fixation in order to restore anatomical alignment and maximize outcomes. Summary: Hamate body fractures are uncommon fractures of the carpus. When appropriately treated, patients with hamate body fractures usually recover full pain-free range of motion and preserved grip strength. Complications are usually secondary to late presentation or noncompliance. [ABSTRACT FROM AUTHOR]

Their paper describes the term biocultural conservation, 'that wields the relationships between a culture and the natural world to strengthen conservation efforts', and highlights the relevance of Indigenous understandings of relationships to the natural world to deities, and how oral histories form an important repository for the ancestral memory of Indigenous Peoples that can transform conservation. Conservation biology and conservation biologist Conservation biology was defined by Michael [67], one of the "founding fathers" of the field, as the field of scientific study that 'addresses the biology of species, communities, and ecosystems that are perturbed, either directly or indirectly, by human activities or other agents'. From our perspective, the dominant thinking and practice of conservation biology has been afflicted by a scarcity mindset that permeates conservation decisions and has become embedded within conservation policy. [Extracted from the article]

A crucial aspect of mass mapping, via weak lensing, is quantification of the uncertainty introduced during the reconstruction process. Properly accounting for these errors has been largely ignored to date. We present a new method to reconstruct maximum a posteriori (MAP) convergence maps by formulating an unconstrained Bayesian inference problem with Laplace-type l 1-norm sparsity-promoting priors, which we solve via convex optimization. Approaching mass mapping in this manner allows us to exploit recent developments in probability concentration theory to infer theoretically conservative uncertainties for our MAP reconstructions, without relying on assumptions of Gaussianity. For the first time, these methods allow us to perform hypothesis testing of structure, from which it is possible to distinguish between physical objects and artefacts of the reconstruction. Here, we present this new formalism, and demonstrate the method on simulations, before applying the developed formalism to two observational data sets of the Abell 520 cluster. Initial reconstructions of the Abell 520 catalogues reported the detection of an anomalous 'dark core' – an overdense region with no optical counterpart – which was taken to be evidence for self-interacting dark matter. In our Bayesian framework, it is found that neither Abell 520 data set can conclusively determine the physicality of such dark cores at |$99{{\ \rm per\ cent}}$| confidence. However, in both cases the recovered MAP estimators are consistent with both sets of data. [ABSTRACT FROM AUTHOR]

The plumes naturally erupting from the icy satellite Enceladus were sampled by the Cassini spacecraft in high‐speed fly‐bys, which gave evidence of salt. This raises the question of how salt behaves under high‐speed impact, and how it can best be sampled in future missions to such plumes. We present the results of 35 impacts onto aluminum targets by a variety of salts (NaCl, NaHCO3, MgSO4, and MgSO4·7H2O) at speeds from 0.26 to 7.3 km s−1. Using SEM‐EDX, identifiable projectile residue was found in craters at all speeds. It was possible to distinguish NaCl and NaHCO3 from each other, and from the magnesium sulfates, but not to separate the hydrous from anhydrous magnesium sulfates. Raman spectroscopy on the magnesium sulfates and NaHCO3 residues failed to find a signal at low impact speeds (<0.5 km s−1) where there was insufficient projectile material deposited at the impact sites. At intermediate speeds (0.5 to 2–3 km s−1), identifiable Raman spectra were found in the impact craters, but not at higher impact speeds, indicating a loss of structure during the high speed impacts. Thus, intact capture of identifiable salt residues on solid metal surfaces requires impact speeds between 0.75 and 2 km s−1. [ABSTRACT FROM AUTHOR]

The future 'broadband platform' could be any device that is attached to the broadband-enabled home network. In this paper, we focus on the use of PCs and games consoles to provide a shared experience of streamed 3D interactive mixed media. We describe a demonstration application which is being developed to provide a better understanding of what can be achieved with streamed 3D interactive mixed media [ABSTRACT FROM AUTHOR]

Understanding the true nature of extra-terrestrial water and organic matter that were present at the birth of our solar system, and their subsequent evolution, necessitates the study of pristine astromaterials. In this study, we have studied both the water and organic contents from a dust particle recovered from the surface of near-Earth asteroid 25143 Itokawa by the Hayabusa mission, which was the first mission that brought pristine asteroidal materials to Earth's astromaterial collection. The organic matter is presented as both nanocrystalline graphite and disordered polyaromatic carbon with high D/H and 15N/14N ratios (δD = + 4868 ± 2288‰; δ15N = + 344 ± 20‰) signifying an explicit extra-terrestrial origin. The contrasting organic feature (graphitic and disordered) substantiates the rubble-pile asteroid model of Itokawa, and offers support for material mixing in the asteroid belt that occurred in scales from small dust infall to catastrophic impacts of large asteroidal parent bodies. Our analysis of Itokawa water indicates that the asteroid has incorporated D-poor water ice at the abundance on par with inner solar system bodies. The asteroid was metamorphosed and dehydrated on the formerly large asteroid, and was subsequently evolved via late-stage hydration, modified by D-enriched exogenous organics and water derived from a carbonaceous parent body. [ABSTRACT FROM AUTHOR]

Purpose: Rating of perceived exertion (RPE) is a reliable method of assessing exercise intensity during isolated arm and leg cycling. The aim of this study was to assess the validity and reproducibility of perceptually regulated exercise responses during combined arm + leg cycling. Methods: Twelve males (age; 24.6 ± 5.3 years, height; 1.81 ± 0.7 m, mass; 83.1 ± 8.4 kg) initially undertook incremental exercise tests to volitional exhaustion for arm cycling (133 ± 14 W) and leg cycling (253 ± 32 W). On three subsequent occasions, participants undertook combined arm + leg cycling trials using two modified Monark ergometers involving three bouts of exercise at RPE 9, 13 and 17, in that order. Heart rate (HR), oxygen uptake ( V ˙ O 2 ) and pulmonary ventilation ( V ˙ E ) were recorded continuously. Results: No significant differences were observed for HR (P = 0.086), V ˙ O 2 (P = 0.525) and V ˙ E (P = 0.899) between trials, whilst significant differences were observed between each level of RPE (all P < 0.001). For % peak V ˙ O 2 , the ICC increased with successive trials for all RPE levels. For % maximal HR the ICC generally decreased with successive trials. Conclusion: RPE can be used as a reliable frame of reference for the production of exercise intensity during combined arm + leg cycling without any formal familiarisation. Since combined arm + leg cycling elicits a greater energy expenditure than arm or leg work alone, this novel mode of non-weight bearing exercise might prove effective for aerobic conditioning and weight control. [ABSTRACT FROM AUTHOR]

Background: It is unknown how the novel Coronavirus SARS‐CoV‐2, the cause of the current acute respiratory illness COVID‐19 pandemic that has infected millions of people, affects people with intellectual and developmental disability (IDD). The aim of this study is to describe how individuals with IDD have been affected in the first 100 days of the COVID‐19 pandemic. Methods: Shortly after the first COVID‐19 case was reported in the USA, our organisation, which provides continuous support for over 11 000 individuals with IDD, assembled an outbreak committee composed of senior leaders from across the health care organisation. The committee led the development and deployment of a comprehensive COVID‐19 prevention and suppression strategy, utilising current evidence‐based practice, while surveilling the global and local situation daily. We implemented enhanced infection control procedures across 2400 homes, which were communicated to our employees using multi‐faceted channels including an electronic resource library, mobile and web applications, paper postings in locations, live webinars and direct mail. Using custom‐built software applications enabling us to track patient, client and employee cases and exposures, we leveraged current public health recommendations to identify cases and to suppress transmission, which included the use of personal protective equipment. A COVID‐19 case was defined as a positive nucleic acid test for SARS‐CoV‐2 RNA. Results: In the 100‐day period between 20 January 2020 and 30 April 2020, we provided continuous support for 11 540 individuals with IDD. Sixty‐four per cent of the individuals were in residential, community settings, and 36% were in intermediate care facilities. The average age of the cohort was 46 ± 12 years, and 60% were male. One hundred twenty‐two individuals with IDD were placed in quarantine for exhibiting symptoms and signs of acute infection such as fever or cough. Sixty‐six individuals tested positive for SARS‐CoV‐2, and their average age was 50. The positive individuals were located in 30 different homes (1.3% of total) across 14 states. Fifteen homes have had single cases, and 15 have had more than one case. Fifteen COVID‐19‐positive individuals were hospitalised. As of 30 April, seven of the individuals hospitalised have been discharged back to home and are recovering. Five remain hospitalised, with three improving and two remaining in intensive care and on mechanical ventilation. There have been three deaths. We found that among COVID‐19‐positive individuals with IDD, a higher number of chronic medical conditions and male sex were characteristics associated with a greater likelihood of hospitalisation. Conclusions: In the first 100 days of the COVID‐19 outbreak in the USA, we observed that people with IDD living in congregate care settings can benefit from a coordinated approach to infection control, case identification and cohorting, as evidenced by the low relative case rate reported. Male individuals with higher numbers of chronic medical conditions were more likely to be hospitalised, while most younger, less chronically ill individuals recovered spontaneously at home. [ABSTRACT FROM AUTHOR]

The presence and accessibility of a sub‐ice‐surface saline ocean at Enceladus, together with geothermal activity and a rocky core, make it a compelling location to conduct further, in‐depth, astrobiological investigations to probe for organic molecules indicative of extraterrestrial life. Cryovolcanic plumes in the south polar region of Enceladus enable the use of remote in situ sampling and analysis techniques. However, efficient plume sampling and the transportation of captured organic materials to an organic analyzer present unique challenges for an Enceladus mission. A systematic study, accelerating organic ice‐particle simulants into soft inert metal targets at velocities ranging 0.5–3.0 km s−1, was carried out using a light gas gun to explore the efficacy of a plume capture instrument. Capture efficiency varied for different metal targets as a function of impact velocity and particle size. Importantly, organic chemical compounds remained chemically intact in particles captured at speeds up to ~2 km s−1. Calibration plots relating the velocity, crater, and particle diameter were established to facilitate future ice‐particle impact experiments where the size of individual ice particles is unknown. [ABSTRACT FROM AUTHOR]

Until recently, mass-mapping techniques for weak gravitational lensing convergence reconstruction have lacked a principled statistical framework upon which to quantify reconstruction uncertainties, without making strong assumptions of Gaussianity. In previous work, we presented a sparse hierarchical Bayesian formalism for convergence reconstruction that addresses this shortcoming. Here, we draw on the concept of local credible intervals (cf. Bayesian error bars) as an extension of the uncertainty quantification techniques previously detailed. These uncertainty quantification techniques are benchmarked against those recovered via Px-MALA – a state-of-the-art proximal Markov chain Monte Carlo (MCMC) algorithm. We find that, typically, our recovered uncertainties are everywhere conservative (never underestimate the uncertainty, yet the approximation error is bounded above), of similar magnitude and highly correlated with those recovered via Px-MALA. Moreover, we demonstrate an increase in computational efficiency of |$\mathcal {O}(10^6)$| when using our sparse Bayesian approach over MCMC techniques. This computational saving is critical for the application of Bayesian uncertainty quantification to large-scale stage IV surveys such as LSST and Euclid. [ABSTRACT FROM AUTHOR]

Weak lensing convergence maps – upon which higher order statistics can be calculated – can be recovered from observations of the shear field by solving the lensing inverse problem. For typical surveys this inverse problem is ill-posed (often seriously) leading to substantial uncertainty on the recovered convergence maps. In this paper we propose novel methods for quantifying the Bayesian uncertainty in the location of recovered features and the uncertainty in the cumulative peak statistic – the peak count as a function of signal-to-noise ratio (SNR). We adopt the sparse hierarchical Bayesian mass-mapping framework developed in previous work, which provides robust reconstructions and principled statistical interpretation of reconstructed convergence maps without the need to assume or impose Gaussianity. We demonstrate our uncertainty quantification techniques on both Bolshoi N -body (cluster scale) and Buzzard V-1.6 (large-scale structure) N -body simulations. For the first time, this methodology allows one to recover approximate Bayesian upper and lower limits on the cumulative peak statistic at well-defined confidence levels. [ABSTRACT FROM AUTHOR]

Background: Up to 15 per cent of colorectal cancers present with peritoneal metastases (CPM). Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS + HIPEC) aims to achieve macroscopic tumour resection combined with HIPEC to destroy microscopic disease. CRS + HIPEC is a major operation with significant morbidity and effects on quality of life (QoL). Improving patient selection is crucial to maximize patient outcomes while minimizing morbidity and mortality. The aim of this study was to identify prognostic factors for patients with CPM undergoing CRS + HIPEC. Methods: A systematic search of MEDLINE, Embase and Cochrane Library electronic databases was performed using terms for colorectal cancer, peritoneal metastasis and CRS + HIPEC. Included studies focused on the impact of prognostic factors on overall survival following CRS + HIPEC in patients with CPM. Results: Twenty‐four studies described 3128 patients. Obstruction or perforation of the primary tumour (hazard ratio (HR) 2·91, 95 per cent c.i. 1·5 to 5·65), extent of peritoneal metastasis as described by the Peritoneal Carcinomatosis Index (PCI) (per increase of 1 PCI point: HR 1·07, 1·02 to 1·12) and the completeness of cytoreduction (CC score above zero: HR 1·75, 1·18 to 2·59) were associated with reduced overall survival after CRS + HIPEC. Conclusion: Primary tumour obstruction or perforation, PCI score and CC score are valuable prognostic factors in the selection of patients with CPM for CRS + HIPEC. [ABSTRACT FROM AUTHOR]

The aim of the study was to determine whether climatic limits for achieving heat balance at rest are affected by spinal cord injury (SCI). Twenty-three men [8 ablebodied (AB), 8 with paraplegia (PP), and 7 with tetraplegia (TP)] rested in 37°C and 20% relative humidity (RH) for 20 min. With the ambient temperature held constant, RH was increased by 5% every 7 min, until gastrointestinal temperature (Tgi) showed a clear inflection or increased by >1°C. Tgi, skin temperatures, perceptual responses, and metabolic energy expenditure were measured throughout. Metabolic heat production [AB: 123 (21) W, PP: 111 (15) W, TP: 103 (29) W; means (SD)] and required rate of evaporative cooling for heat balance [Ereq; AB: 113 (20) W, PP: 107 (17) W, TP: 106 (29) W] were similar between groups (P = 0.22 and P = 0.79). Compared with AB, greater increases in Tgi were observed in TP (P = 0.01), with notable increases in mean skin temperature (Tsk) for TP and PP (P = 0.01). A Tgi inflection point was demonstrated by seven AB, only three of eight PP, and no TP. Despite metabolic heat production (and Ereq) being similar between groups, evaporative heat loss was not large enough to obtain heat balance in TP, linked to a shortfall in evaporative cooling potential. Although PP possess a greater sweating capacity, the continual increase in Tgi and Tsk in most PP, although lower than for TP, implies that latent heat loss for PP is also insufficient to attain heat balance. NEW & NOTEWORTHY In the absence of convective heat loss, at temperatures around 37°C evaporative heat loss is insufficient to attain heat balance at rest in individuals with paraplegia and tetraplegia. This finding was directly linked to a shortfall in evaporative cooling potential compared with required evaporative cooling. In this environment, individuals with both paraplegia and tetraplegia cannot subjectively determine the magnitude of their thermal strain; thus perceptual responses should not be relied upon for this population group. [ABSTRACT FROM AUTHOR]

Aims: To assess whether glycaemic control is associated with a lifelong increased risk of fracture in people with newly diagnosed Type 1 diabetes. Methods: People with newly diagnosed Type 1 diabetes between 1 January 1995 and 10 May 2016 were identified in The Health Improvement Network database. Longitudinal HbA1c measurements from diagnosis to fracture or study end or loss to follow‐up were collected. A Cox proportional hazards model with HbA1c included as a time‐dependent variable was fitted to these data. Results: Some 5368 people with newly diagnosed Type 1 diabetes were included. The estimated adjusted hazard ratio (aHR) for HbA1c was statistically significant [aHR 1.007; 95% confidence interval (CI) 1.002–1.011 (mmol/mol) and aHR 1.07; 95% CI 1.03–1.12 (%)]. An incremental higher risk of fracture was observed with increasing levels of HbA1c. Conclusions: In people with newly diagnosed Type 1 diabetes, higher HbA1c is associated with an increased risk for fractures. What's new?: Type 1 diabetes is associated with an increased incidence of fractures. The effect of glycemia is unknown, because change of glycaemic control over time has never been considered.HbA1c was associated with an increased fracture risk in people with newly diagnosed Type 1 diabetes (7% increments for each per cent increase in HbA1c).This information may be considered in fracture risk assessment, and even in prompting early anti‐osteoporotic intervention in the context of Type 1 diabetes, especially when another established risk factor is present. [ABSTRACT FROM AUTHOR]

The article provides information about the Parliamentary and Scientific Committee in Great Britain. An informal all-party group formed in 1939, membership of the Committee is open to all members of the House of Lords and the House of Commons. It receives no subsidy from the government or from any political party and its revenue came from the voluntary subscriptions of the peers and members of Parliament. The committee sought to be the center in the Parliament for any scientific or technological question which may have a useful bearing on the activities of the Parliament or government.

Introduction: Five billion people worldwide do not have timely access to surgical care. Cinterandes is one of the only mobile surgical units in low- and middle-income countries. This paper examines the methodology that Cinterandes uses to deliver mobile surgery.Methods: Founding and core staff were interviewed, four missions were participated in, and internal documents and records were analysed between 1 May and 1 July 2014.Results: Cinterandes performed 7641 operations over the last 20 years (60% gastrointestinal/laparoscopic), travelling 300,000 km to remote areas of Ecuador. The mobile surgery programme was initiated by a local Ecuadorian surgeon in 1980. Funding was acquired from businesses, private hospitals, and individuals, to fund a low-cost surgical truck, simple equipment, and running costs. The mobile surgical unit is a 24-foot modified Isuzu truck containing a preparation room with general equipment storage and running water, together with an operating room including the operating table, anaesthetic and surgical equipment. Mission structure includes: patient identification by a network of local medical personnel in remote regions; pre-operative assessment at 1 week by core team via teleconsultations; four-day surgical missions; post-operative recovery in tents or a local clinic; post-operative follow-up care by local personnel and remote teleconsultations. The permanent core team includes seven members; lead surgeon, lead anaesthetist, operating-room technician, medical coordinator, driver, general coordinator, and receptionist. Additional support members include seven regular surgeons, residents, medical students, and volunteers.Conclusion: Surgery is a very effective way to gain the trust of the community, due to immediate results. Trust opens doors to other programmes (e.g. family medicine). Surgery can be incorporated with all other aspects of health care, which can in turn be incorporated with all other aspects of human development, education, food production and nutrition, housing, work and productivity, communication, and recreation. [ABSTRACT FROM AUTHOR]

From staffing and supply shortages to furloughs and layoffs, few expected—let alone had a plan for managing—the COVID-19 pandemic. The crisis allowed nursing professional development to demonstrate its value like never before. This article explores the impact of the pandemic on nursing professional development practice at the micro (unit), meso (organization), and macro (national) levels of our specialty. From staffing and supply shortages to furloughs and layoffs, few expected—let alone had a plan for managing—the COVID-19 pandemic. The crisis allowed nursing professional development to demonstrate its value like never before. This article explores the impact of the pandemic on nursing professional development practice at the micro (unit), meso (organization), and macro (national) levels of our specialty. [[J Contin Educ Nurs. 2020;51(8):349–351.] [ABSTRACT FROM AUTHOR]

Summary: Bacterial genes for molybdenum‐containing and tungsten‐containing enzymes are often differentially regulated depending on the metal availability in the environment. Here, we describe a new family of transcription factors with an unusual DNA‐binding domain related to excisionases of bacteriophages. These transcription factors are associated with genes for various molybdate and tungstate‐specific transporting systems as well as molybdo/tungsto‐enzymes in a wide range of bacterial genomes. We used a combination of computational and experimental techniques to study a member of the TF family, named TaoR (for tungsten‐containing aldehyde oxidoreductase regulator). In Desulfovibrio vulgaris Hildenborough, a model bacterium for sulfate reduction studies, TaoR activates expression of aldehyde oxidoreductase aor and represses tungsten‐specific ABC‐type transporter tupABC genes under tungsten‐replete conditions. TaoR binding sites at aor promoter were identified by electrophoretic mobility shift assay and DNase I footprinting. We also reconstructed TaoR regulons in 45 Deltaproteobacteria by comparative genomics approach and predicted target genes for TaoR family members in other Proteobacteria and Firmicutes. [ABSTRACT FROM AUTHOR]

Summary: Background: Low and high birthweight is known to increase the risk of acute and longer‐term adverse outcomes, such as stillbirth, infant mortality, obesity, type 2 diabetes and cardiovascular diseases. Gestational dyslipidaemia is associated with a numbers of adverse birth outcomes, but evidence regarding birthweight is still inconsistent to reliably inform clinical practice and treatment recommendations. Objective: The aim of this study was to explore the relationship between maternal gestational dyslipidaemia and neonatal health outcomes, namely, birthweight, metabolic factors and inflammatory parameters. Methods: We searched systematically Embase, MEDLINE, PubMed, CINAHL Plus and Cochrane Library up to 1 August 2016 (with an updated search in MEDLINE at the end of July 2017) for longitudinal studies that assessed the association of maternal lipid levels during pregnancy with neonatal birthweight, or metabolic and inflammatory parameters up to 3 years old. Results: Data from 46 publications including 31,402 pregnancies suggest that maternal high triglycerides and low high‐density‐lipoprotein cholesterol levels throughout pregnancy are associated with increased birthweight, higher risk of large for gestational age and macrosomia and lower risk of small‐for‐gestational age. The findings were consistent across the studied populations, but stronger associations were observed in women who were overweight or obese prior to pregnancy. Conclusions: This meta‐analysis suggested that the potential under‐recognized adverse effects of intrauterine exposure to maternal dyslipidaemia may warrant further investigation into the relationship between maternal dyslipidaemia and birthweight in large prospective cohorts or in randomized trials. [ABSTRACT FROM AUTHOR]

Purpose Surgical site infection (SSI) caused by Propionibacterium acnes is an infrequent but devastating complication after spinal fusion. The purpose of this study was to identify risk factors for SSI with Propionibacterium acnes after spinal fusion for juvenile and adolescent idiopathic scoliosis (JIS and AIS). Methods A case-control study was performed. Each case was matched 2:1 for age, gender and diagnosis. Retrospective chart review was performed to obtain relevant demographic, surgical and clinical data for all cases and controls. Statistical analysis included paired t-test and McNemar test, as well as exact logistic regression and robust regression models. Results This study included ten infection cases (eight AIS, two JIS) and 20 controls (16 AIS, four JIS). In total, six infected cases presented within two weeks of the index procedure (acute infection) and four infected cases presented more than one year from the index procedure (delayed infection). The most common presentation for acute infections was wound drainage, while back pain was more common in delayed infections. All infections were successfully treated with surgical irrigation and debridement and postoperative antibiotics. Hardware was removed for patients with delayed infections. The strongest risk factor for infection was increased requirement for blood transfusion, but it did not reach statistical significance. Conclusion SSI with Propionibacterium acnes is an important complication after spinal fusion for idiopathic scoliosis. These infections can be successfully treated, but larger studies are needed to further identify risk factors and establish standardized guidelines for the treatment and prevention of this complication. [ABSTRACT FROM AUTHOR]

Abstract: Musculoskeletal modeling and marker‐based motion capture techniques are commonly used to quantify the motions of body segments, and the forces acting on them during human gait. However, when these techniques are applied to analyze the gait of people with lower limb loss, the clinically relevant interaction between the residual limb and prosthesis socket is typically overlooked. It is known that there is considerable motion and loading at the residuum‐socket interface, yet traditional gait analysis techniques do not account for these factors due to the inability to place tracking markers on the residual limb inside of the socket. In the present work, we used a global optimization technique and anatomical constraints to estimate the motion and loading at the residuum‐socket interface as part of standard gait analysis procedures. We systematically evaluated a range of parameters related to the residuum‐socket interface, such as the number of degrees of freedom, and determined the configuration that yields the best compromise between faithfully tracking experimental marker positions while yielding anatomically realistic residuum‐socket kinematics and loads that agree with data from the literature. Application of the present model to gait analysis for people with lower limb loss will deepen our understanding of the biomechanics of walking with a prosthesis, which should facilitate the development of enhanced rehabilitation protocols and improved assistive devices. [ABSTRACT FROM AUTHOR]

Knowledge of Earth's past mantle structure is inherently unknown. This lack of knowledge presents problems in many areas of Earth science, including in mantle circulation modelling (MCM). As a mathematical model of mantle convection, MCMs require boundary and initial conditions. While boundary conditions are readily available from sources such as plate reconstructions for the upper surface, and as free slip at the core-mantle boundary, the initial condition is not known. MCMs have historically 'created' an initial condition using long 'spin up' processes using the oldest available plate reconstruction period available. While these do yield good results when models are run to present day, it is difficult to infer with confidence results from early in a model's history. Techniques to overcome this problem are now being studied in geodynamics, such as by assimilating the known internal structure (e.g. from seismic tomography) of Earth at present day backwards in time. One such method is to use an iterative process known as the forward-adjoint method. While this is an efficient means of solving this inverse problem, it still strains all but the most cutting edge computational systems. In this study we endeavour to profile the effectiveness of this method using synthetic test cases as our known data source. We conclude that savings in terms of computational expense for forward-adjoint models can be achieved by streamlining the time-stepping of the calculation, as well as determining the most efficient method of updating initial conditions in the iterative scheme. Furthermore, we observe that in the models presented, there exists an upper limit on the time interval over which solutions will practically converge, although this limit is likely to be linked to Rayleigh number. [ABSTRACT FROM AUTHOR]

Australia has a thriving Psycho-Oncology research and clinical community. In this article, the Australian health system in which Psycho-Oncology is embedded is described. Clinical Psycho-Oncology services are outlined, in terms of their composition, processes and reach. The development of the internationally ground-breaking Australian Psychosocial guidelines for the care of adults with cancer is described. Two large Psycho-Oncology organisations which are strongly linked to mainstream Oncology organisations are discussed: the Australian Psycho-Oncology Society (OzPos, a primarily clinician-led and focused organisation) and the Psycho-Oncology Co-operative Research Group (PoCoG, a national cancer clinical trial group). OzPos is a special interest group within the Clinical Oncology Society of Australia, while PoCoG is one of 14 cancer clinical trial groups funded by the national government. It is these strong connections with major multidisciplinary cancer organisations, and a culture of collaboration and co-operation, that have made Psycho-Oncology grow and thrive in Australia. Examples of large collaborative programs of Psycho-Oncology research are provided, as well as the mechanisms used to achieve these outcomes. [ABSTRACT FROM AUTHOR]

The mineralogy of comet 81P/Wild 2 particles, collected in aerogel by the Stardust mission, has been determined using synchrotron Fe-K X-ray absorption spectroscopy with in situ transmission XRD and X-ray fluorescence, plus complementary microRaman analyses. Our investigation focuses on the terminal grains of eight Stardust tracks: C2112,4,170,0,0; C2045,2,176,0,0; C2045,3,177,0,0; C2045,4,178,0,0; C2065,4,187,0,0; C2098,4,188,0,0; C2119,4,189,0,0; and C2119,5,190,0,0. Three terminal grains have been identified as near pure magnetite Fe3O4. The presence of magnetite shows affinities between the Wild 2 mineral assemblage and carbonaceous chondrites, and probably resulted from hydrothermal alteration of the coexisting FeNi and ferromagnesian silicates in the cometary parent body. In order to further explore this hypothesis, powdered material from a CR2 meteorite ( NWA 10256) was shot into the aerogel at 6.1 km s−1, using a light-gas gun, and keystones were then prepared in the same way as the Stardust keystones. Using similar analysis techniques to the eight Stardust tracks, a CR2 magnetite terminal grain establishes the likelihood of preserving magnetite during capture in silica aerogel. [ABSTRACT FROM AUTHOR]

Background Clostridium difficile infection ( CDI) is the commonest nosocomial cause of diarrhoea. Faecal microbiota transplantation ( FMT) is an approved treatment for recurrent or refractory CDI but there is uncertainty about its use. Aim To evaluate the efficacy of FMT in treating recurrent and refractory CDI and investigate outcomes from modes of delivery and preparation. Methods A systematic review and meta-analysis was performed. MEDLINE, EMBASE, CINAHL, Cochrane Library, trial registers and conference proceedings were searched. Studies on FMT in recurrent and refractory CDI were included. The primary outcome was clinical resolution with subgroup analyses of modes of delivery and preparation. Random effects meta-analyses were used to combine data. Results Thirty seven studies were included; seven randomised controlled trials and 30 case series. FMT was more effective than vancomycin ( RR: 0.23 95% CI 0.07-0.80) in resolving recurrent and refractory CDI. Clinical resolution across all studies was 92% (95% CI 89%-94%). A significant difference was observed between lower GI and upper GI delivery of FMT 95% (95% CI 92%-97%) vs 88% (95% CI 82%-94%) respectively ( P=.02). There was no difference between fresh and frozen FMT 92% (95% CI 89%-95%) vs 93% (95% CI 87%-97%) respectively ( P=.84). Administering consecutive courses of FMT following failure of first FMT resulted in an incremental effect. Donor screening was consistent but variability existed in recipient preparation and volume of FMT. Serious adverse events were uncommon. Conclusion Faecal microbiota transplantation is an effective treatment for recurrent and refractory Clostridium difficile infection, independent of preparation and route of delivery. [ABSTRACT FROM AUTHOR]

Daily growth rings were examined in the otoliths of wild juvenile sockeye salmon Oncorhynchus nerka to determine whether infection by ectoparasitic sea lice Caligus clemensi and Lepeophtheirus salmonis was associated with reduced host body growth, an important determinant of survival. Over 98% of the sea lice proved to be C. clemensi and the fish that were highly infected grew more slowly than uninfected individuals. Larger fish also grew faster than smaller fish. Finally, there was evidence of an interaction between body size and infection status, indicating the potential for parasite-mediated growth divergence. [ABSTRACT FROM AUTHOR]

Purpose: We developed an eight-lesson internet-delivered CBT (iCBT) program targeting anxiety and depression in early-stage cancer and cancer survivors. To explore the acceptability of the program, we showed volunteers the first two lessons and asked for their views.Methods: Focus groups (n = 3) and individual interviews (n = 5) were undertaken with 15 participants (11 survivors) with mainly breast (11 of the 15) cancer, who had reviewed intervention materials. Participants were asked to consider the acceptability of the iCBT program content and implementation design (timing, duration). Semi-structured questions guided discussion. Thematic analysis was conducted of participant reactions to the acceptability and/or suitability of materials created for use in a psychological intervention. We took a data-driven (inductive) approach to semantic theme development across the data set.Results: Participants reported high acceptability of the internet delivery format, good engagement and user-friendly material. Participants were broadly supportive of combining depression and anxiety iCBT resources for early-stage cancer patients and survivors. Participants further indicated that a separate course would be needed to address the needs of patients with advanced stage disease.Conclusions: Participants welcomed the general development of an internet-delivered CBT intervention program to treat patients with clinical depression and/or anxiety. Furthermore, the sessions reviewed were highly acceptable to all participants. Study findings informed researchers on the development of iCBT resources for the cancer community. [ABSTRACT FROM AUTHOR]

Introduction Component-resolved diagnostics using specific IgE to 2 S albumins has shown to be a valuable new option in diagnostic procedure. Ana o 3 is a 2 S albumin from cashew. The aim of this study was to investigate the role of Ana o 3-specific serum IgE in the diagnosis of cashew allergy and to identify cut-off levels to replace oral food challenges. Moreover, the value of additional determination of total IgE has been investigated. Methods In a multicentre study, we analysed specific IgE to cashew extract and Ana o 3 as well as total IgE in children with suspected cashew allergy using the Immuno CAP- FEIA and a standardized diagnostic procedure including oral challenges where indicated. Results A total of 61 patients were included in the study. Forty-two were allergic to cashew, and 19 were tolerant. In receiver operating curves, Ana o 3 discriminates between allergic and tolerant children better than cashew-specific IgE with an area under the curve of 0.94 vs 0.78. The ratio of Ana o 3-specific IgE to total IgE did not further improve the diagnostic procedure. Probability curves for Ana o 3-specific IgE have been calculated, and a 95% probability could be estimated at 2.0 kU/l. Conclusion Specific IgE to Ana o 3 is a valuable tool for the diagnosis of cashew allergy. Considering its positive predictive value, it might allow to make a considerable number of oral challenges superfluous. [ABSTRACT FROM AUTHOR]

A unit for measuring cycle times and displaying the numerical frequency at which they occur is described. A block diagram of the electrical circuit is given. The unit has been used for determining and displaying operator cycle times in repetitive work. [ABSTRACT FROM AUTHOR]

Consumption of central nervous system tissue (CNST) from cattle with bovine spongiform encephalopathy (BSE) is thought to cause the human neurological disease, variant Creutzfeldt-Jacob disease. To identify points of cross-contamination of beef carcasses with CNST, 55 young beef cattle were slaughtered and processed through a federally inspected multispecies abattoir. The objectives of this study were to evaluate CNST spread following the placement of a plug in the penetration site of the skull after captive bolt stunning, to evaluate cross-contamination of carcasses before and after splitting, to compare the effects of hot water pasteurization (84°C for 10 s) versus cold water wash (10°C for 30 s) for reducing CNST on the carcass, and to examine other possible sources of cross-contamination in the abattoir. Results indicated that the use of a plastic plug reduced CNST contamination near the bolt penetration site. This study also confirmed that carcass splitting resulted in an increase in CNST contamination at various areas of the carcass. Hot water pasteurization appeared to be an effective means of removing CNST contamination from carcasses in most of the areas sampled. [ABSTRACT FROM AUTHOR]

In this study, we examined whether the proportion of tubal factor infertility (TFI) that is attributable to Chlamydia trachomatis, the population excess fraction (PEF), can be estimated from serological data using finite mixture modeling. Whole-cell inclusion immunofluorescence serum antibody titers were recorded among infertile women seen at St. Michael's Hospital in Bristol, United Kingdom, during the period 1985-1995. Women were classified as TFI cases or controls based on laparoscopic examination. Finite mixture models were used to identify the number of component titer distributions and the proportion of serum samples in each, from which estimates of PEF were derived. Four titer distributions were identified. The component at the highest titer was found only in samples from women with TFI, but there was also an excess of the second-highest titer component in TFI cases. Minimum and maximum estimates of the PEF were 28.0% (95% credible interval: 6.9, 50.0) and 46.8% (95% credible interval: 23.2, 64.1). Equivalent estimates based on the standard PEF formula from case-control studies were 0% and over 65%. Finite mixture modeling can be applied to serological data to obtain estimates of the proportion of reproductive damage attributable to C. trachomatis. Further studies using modern assays in contemporary, representative populations should be undertaken. [ABSTRACT FROM AUTHOR]

Pelvic inflammatory disease (PID) and more specifically salpingitis (visually confirmed inflammation) is the primary cause of tubal factor infertility and is an important risk factor for ectopic pregnancy. The risk of these outcomes increases following repeated episodes of PID. We developed a homogenous discrete-time Markov model for the distribution of PID history in the UK. We used a Bayesian framework to fully propagate parameter uncertainty into the model outputs. We estimated the model parameters from routine data, prospective studies, and other sources. We estimated that for women aged 35–44 years, 33·6% and 16·1% have experienced at least one episode of PID and salpingitis, respectively (diagnosed or not) and 10·7% have experienced one salpingitis and no further PID episodes, 3·7% one salpingitis and one further PID episode, and 1·7% one salpingitis and ⩾2 further PID episodes. Results are consistent with numerous external data sources, but not all. Studies of the proportion of PID that is diagnosed, and the proportion of PIDs that are salpingitis together with the severity distribution in different diagnostic settings and of overlap between routine data sources of PID would be valuable. [ABSTRACT FROM PUBLISHER]

We investigated how a target's porosity affects the outcome of a collision, with respect to the impactor's fate. Laboratory impact experiments using peridot projectiles were performed at a speed range between 0.3 and 3.0 km s-1, on to high-porosity water-ice (40 per cent) and fine-grained calcium carbonate (70 per cent) targets. We report that the amount of implanted material in the target body increases with increasing target's porosity, while the size frequency distribution of the projectile's ejecta fragments becomes steeper. A supplementary Raman study showed no sign of change of the Raman spectra of the recovered olivine projectile fragments indicate minimal physical change. [ABSTRACT FROM AUTHOR]

The Gulf Sturgeon, Acipenser oxyrinchus desotoi, is an anadromous species of Acipenseridae and native to North America. It currently inhabits and spawns in the upper reaches of seven natal rivers along the northern coast of the Gulf of Mexico from the Suwannee River, Florida, to the Pearl River, Louisiana, during spring to autumn. Next to the Alligator Gar (Atractosteus spatula), the Gulf Sturgeon is currently the largest fish species occurring in U.S. Gulf Coast rivers, attaining a length of 2.35 m and weights exceeding 135 kg, but historically attained a substantially larger size. Historically, the spawning populations existed in additional rivers from which the species has been wholly or nearly extirpated, such as the Mobile and Ochlockonee rivers, and possibly the Rio Grande River. Most Gulf Sturgeon populations were decimated by unrestricted commercial fishing between 1895-1910. Subsequently most populations remained unrecovered or extirpated due to continued harvest until the 1970s-1980s, and the construction of dams blocking access to ancestral upriver spawning grounds. Late 20th Century harvest bans and net bans enacted by the several Gulf Coast states have stabilized several populations and enabled the Suwannee River population to rebound substantially and naturally. Hatchery supplementation has not been necessary in this regard to date. Sturgeon are resilient and adaptable fishes with a geological history of 150 million years. Research undertaken since the 1970s has addressed many aspects of Gulf Sturgeon life history, reproduction, migration, population biology, habitat requirements, and other aspects of species biology. However, many knowledge gaps remain, prominently including the life history of early developmental stages in the first year of life. Natural population recovery is evident for the Suwannee River population, but seems promising as well for at least four other populations. The Pascagoula and Pearl River populations face a challenging future due a combination of natural and anthropogenic factors. These two populations, and perhaps the Escambia River population, are particularly vulnerable to periodic mass mortality due to major stochastic events including hurricanes, flooding, hypoxia, and toxic spills. The present manuscript provides a comprehensive synthesis of knowledge regarding the Gulf Sturgeon at the organismal and population levels, identifying knowledge gaps as priorities for future research. Topics not treated in the present synthesis include morphology, internal biology, physiology, and endocrinology. Topics only briefly treated include parasites and diseases, contaminants, and sturgeon aquaculture. [ABSTRACT FROM AUTHOR]

The in situ absolute calibration of the JET real-time protection imaging system has been performed for the first time by means of radiometric light source placed inside the JET vessel and operated by remote handling. High accuracy of the calibration is confirmed by cross-validation of the near infrared (NIR) cameras against each other, with thermal IR cameras, and with the beryllium evaporator, which lead to successful protection of the JET first wall during the last campaign. The operation temperature ranges of NIR protection cameras for the materials used on JET are Be 650-1600 ◦C, W coating 600-1320 ◦C, and W 650-1500 ◦C. [ABSTRACT FROM AUTHOR]

Recent improvements in software tools and methodology have allowed us to perform a more comprehensive in-vessel calibration for all mid-infrared camera systems at JET. A comparison of experimental methods to calculate the non-uniformity correction is described as well as the linearity for the different camera systems. Measurements of the temperature are assessed for the different diagnostics. [ABSTRACT FROM AUTHOR]