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Background:The scale of the 2022 global mpox (formerly known as monkeypox) outbreak has been unprecedented. In less than 6 months, non-endemic countries have reported more than 67 000 cases of a disease that had previously been rare outside of Africa. Mortality has been reported as rare but hospital admission has been relatively common. We aimed to describe the clinical and laboratory characteristics and outcomes of individuals admitted to hospital with mpox and associated complications, including tecovirimat recipients. Methods:In this cohort study, we undertook retrospective review of electronic clinical records and pathology data for all individuals admitted between May 6, and Aug 3, 2022, to 16 hospitals from the Specialist and High Consequence Infectious Diseases Network for Monkeypox. The hospitals were located in ten cities in England and Northern Ireland. Inclusion criteria were clinical signs consistent with mpox and MPXV DNA detected from at least one clinical sample by PCR testing. Patients admitted solely for isolation purposes were excluded from the study. Key outcomes included admission indication, complications (including pain, secondary infection, and mortality) and use of antibiotic and anti-viral treatments. Routine biochemistry, haematology, microbiology, and virology data were also collected. Outcomes were assessed in all patients with available data. Findings:156 individuals were admitted to hospital with complicated mpox during the study period. 153 (98%) were male and three (2%) were female, with a median age of 35 years (IQR 30–44). Gender data were collected from electronic patient records, which encompassed full formal review of clincian notes. The prespecified options for data collection for gender were male, female, trans, non-binary, or unknown. 105 (71%) of 148 participants with available ethnicity data were of White ethnicity and 47 (30%) of 155 were living with HIV with a median CD4 count of 510 cells per mm3(IQR 349–828). Rectal or perianal pain (including proctitis) was the most common indication for hospital admission (44 [28%] of 156). Severe pain was reported in 89 (57%) of 156, and secondary bacterial infection in 82 (58%) of 142 individuals with available data. Median admission duration was 5 days (IQR 2–9). Ten individuals required surgery and two cases of encephalitis were reported. 38 (24%) of the 156 individuals received tecovirimat with early cessation in four cases (two owing to hepatic transaminitis, one to rapid treatment response, and one to patient choice). No deaths occurred during the study period. Interpretation:Although life-threatening mpox appears rare in hospitalised populations during the current outbreak, severe mpox and associated complications can occur in immunocompetent individuals. Analgesia and management of superimposed bacterial infection are priorities for patients admitted to hospital.

Anita Lynam,1 Charlotte Curtis,1 Brooklyn Stanley,2,3 Heath Heatley,3 Chloe Worthington,2,3 Emma-Jane Roberts,2,3 Christopher Price,2,3 Victoria Carter,2,3 John Dennis,1 Andrew McGovern,1 David Price2,3 1Momentum Data, Pendragon House, St. Albans, Hertfordshire, UK; 2Optimum Patient Care, Cambridge, UK; 3Observational and Pragmatic Research Institute, SingaporeCorrespondence: Andrew McGovern, Momentum Data, Pendragon House, St. Albans, Hertfordshire, UK, Email andy.mcgovern@momentumdata.co.ukIntroduction: Electronic medical records (EMRs) maintained in primary care in the UK and collected and stored in EMR databases offer a world-leading resource for observational clinical research. We aimed to profile one such database: the Optimum Patient Care Research Database (OPCRD).Methods and Participants: The OPCRD, incepted in 2010, is a growing primary care EMR database collecting data from 992 general practices within the UK. It covers over 16.6 million patients across all four countries within the UK, and is broadly representative of the UK population in terms of age, sex, ethnicity and socio-economic status. Patients have a mean duration of 11.7 years’ follow-up (SD 17.50), with a majority having key summary data from birth to last data entry. Data for the OPCRD are collected incrementally monthly and extracted from all of the major clinical software systems used within the UK and across all four coding systems (Read version 2, Read CTV3, SNOMED DM+D and SNOMED CT codes). Via quality-improvement programmes provided to GP surgeries, the OPCRD also includes patient-reported outcomes from a range of disease-specific validated questionnaires, with over 66,000 patient responses on asthma, COPD, and COVID-19. Further, bespoke data collection is possible by working with GPs to collect new research via patient-reported questionnaires.Findings to Date: The OPCRD has contributed to over 96 peer-reviewed research publications since its inception encompassing a broad range of medical conditions, including COVID-19.Conclusion: The OPCRD represents a unique resource with great potential to support epidemiological research, from retrospective observational studies through to embedded cluster-randomised trials. Advantages of the OPCRD over other EMR databases are its large size, UK-wide geographical coverage, the availability of up-to-date patient data from all major GP software systems, and the unique collection of patient-reported information on respiratory health.Keywords: primary care, electronic health records, medical records, datasets, demography, health outcomes

Artificial intelligence (AI) is rapidly entering the field of medicine, but the role of patents in this process remains relatively opaque. Regulators report hundreds of machine learning (ML) medical devices that have passed regulatory oversight1, including systems involved in radiology, cardiology, ophthalmology, and many other fields. Major hospitals and academic medical systems have both developed and deployed AI/ML systems, and some AI tools have been embedded in electronic health records used by health systems covering millions of patients. Nevertheless, despite this wave of innovation in medical machine learning (MML), the influence of patents on that process has only been sketched rather than interrogated in detail.

Across the globe, planktonic consumer resource interactions are being altered by changing environmental conditions. Climate change is altering the distributions of both phytoplankton and zooplankton, thus modifying the base of the food web, which has consequences for the feeding environment of consumers and predators with knock on effects for population viability. In the Arctic, inflows of Atlantic waters are strengthening, which is increasing sea surface temperatures, weakening stratification and transporting temperate and sub-Arctic plankton species deeper into the Arctic interior. In other regions, increased sea ice melt is freshening and stratifying the water column, causing phenological shifts to phytoplankton blooms. These heterogenous alterations have direct effects to zooplankton feeding and the wider food web. Our knowledge of the responses of zooplankton feeding within the planktonic Arctic food web is limited due to the highly seasonal nature of the Arctic environment that adds to food web complexity. Untangling this complexity remains a challenge if we are to accurately predict and understand the functioning of marine food webs in the Arctic. In this thesis I aim to resolve the spatial and interannual feeding ecology the calanoid copepods Calanus in the Arctic. I use multivariate statistical techniques on an abundance Continuous Plankton Recorder dataset to define the feeding environment for Calanus and a dual biomarker approach of isotope analysis and DNA gut content analysis to estimate the feeding strategies of Calanus. These dietary descriptors are contextualised by environmental parameters derived from CTD casts, remote sensing databases and models. Changes to the food environment for Calanus were variable on both spatial and interannual scales, these include differences in net primary production, and in the phytoplankton assemblage. The drivers of these changes were factors that altered the strength of stratification, which impact nutrient delivery and primary production in the surface. Despite these changes, Calanus were consistently omnivorous, occupying the trophic level 2.5. In some regions, the smaller C. finmarchicus/glacialis had a slightly higher TP than the larger C. hyperboreus, likely due to the earlier termination of feeding by the latter. In water masses with low productivity and strong stratification, the niches of these two Calanus groups were separated, indicating different resource utilization. Whereas in highly productive regions, there was high niche overlap, suggesting the sharing of resources. The high plasticity of Calanus indicates that, providing the nutritional quality of dietary items is maintained, they should continue to transfer essential lipids to the rest of the food web despite the regionally specific changes in stratification and net primary production rates.

The ancient one-to-one relationship with the biological life cycle has gradually deteriorated due to the world undergoing a metamorphic process. Such a metamorphosis has affected ecological harmony, in terms of it being both an approach to studying the relationships between living beings and the environment, and a branch of knowledge protecting and promoting ecological balance. One of the crucial aspects of this phenomenon is the need to rethink and redefine the concept of life in an era that has been described as the “Anthropocene”. In introducing this special issue of the Journal, the paper aims to investigate the environmental question, which plays a crucial role in contemporary political thought, due to the survival of both nature and mankind being threatened. Since the 1950s, such a complex situation has resulted in two lines of thought whose views follow two opposed ideologies – anthropocentrism and anti-anthropocentrism.

Background: Cerebral cavernous malformations, also known as cavernous angiomas, are blood vessel abnormalities comprised of clusters of grossly enlarged and hemorrhage-prone capillaries. The prevalence in the general population, including asymptomatic cases, is estimated to be 0.5%. Some patients develop severe symptoms, including seizures and focal neurological deficits, whereas others remain asymptomatic. The causes of this remarkable presentation heterogeneity within a primarily monogenic disease remain poorly understood. Methods: We established a chronic mouse model of cerebral cavernous malformations, induced by postnatal ablation of Krit1 with Pdgfb-CreERT2 , and examined lesion progression in these mice with T2-weighted 7T magnetic resonance imaging (MRI). We also established a modified protocol for dynamic contrast-enhanced MRI and produced quantitative maps of gadolinium tracer gadobenate dimeglumine. After terminal imaging, brain slices were stained with antibodies against microglia, astrocytes, and endothelial cells. Results: These mice develop cerebral cavernous malformations lesions gradually over 4 to 5 months of age throughout the brain. Precise volumetric analysis of individual lesions revealed nonmonotonous behavior, with some lesions temporarily growing smaller. However, the cumulative lesional volume invariably increased over time and after about 2 months followed a power trend. Using dynamic contrast-enhanced MRI, we produced quantitative maps of gadolinium in the lesions, indicating a high degree of heterogeneity in lesional permeability. MRI properties of the lesions were correlated with cellular markers for endothelial cells, astrocytes, and microglia. Multivariate comparisons of MRI properties of the lesions with cellular markers for endothelial and glial cells revealed that increased cell density surrounding lesions correlates with stability, whereas denser vasculature within and surrounding the lesions may correlate with high permeability. Conclusions: Our results lay a foundation for better understanding individual lesion properties and provide a comprehensive preclinical platform for testing new drug and gene therapies for controlling cerebral cavernous malformations.

The application of carbonate clumped isotope (Δ47) thermometry in deep-time is often limited by modification of the original temperature signal by thermal resetting. New modeling approaches to estimate the initial isotopic composition of partially reset calcites and maximal burial temperatures, however, open promising avenues in temperature reconstruction. Such approaches strongly depend on laboratory-derived kinetic parameters of calcite materials, which may differ in their microstructure, water content and distribution, and minor and trace element composition, and thus may have different resetting kinetics. The rostra of belemnites, an extinct group of mollusks with a wide temporal and spatial occurrence in the Mesozoic, have been extensively used for deep-time paleoclimate reconstructions using oxygen isotope geochemistry. Belemnites are also important targets for clumped isotope-based temperature reconstructions, but often are found to have reset Δ47 compositions. Here, we present results from heating experiments on belemnite rostral calcite and optical calcite and provide belemnite-specific kinetic parameters for clumped isotope resetting. We show that belemnite calcite is altered faster and at lower temperatures than optical calcite and all other calcites reported in previous studies. We suggest that fast initial resetting results from oxygen isotope exchange of belemnite calcite with internal skeletal water present as fluid inclusions or organic-derived water, a process completed within 2–4 min at the experimental temperatures used here. Extrapolation to geological timescales using different solid-state bond reordering models shows that belemnite calcite resetting starts at lower burial temperatures than brachiopod, spar, and optical calcites. This susceptibility to thermal resetting results in a measurable (+3 ◦C) increase of the apparent Δ47 temperature even under shallow to moderate burial conditions (i.e., 40–50 ◦C for 106–107 years timescales). Following the overprint to higher apparent Δ47 temperatures during burial, the belemnite Δ47 may further reequilibrate during exhumation resulting in a decrease of apparent Δ47 temperatures. Such “retrograde resetting” is similar to what is observed for carbonatites and marbles during cooling, and may cause underestimation of the thermal resetting a sample experienced during its geological history. Overall, our results demonstrate the importance of material-specific kinetic parameters and we urge caution when interpreting Δ47-derived temperatures of biogenic carbonates from deep-time archives., Swiss National Science Foundation project number 200021_169849, AF from Juan de la Cierva Fellowship (IJC2019040065-I), Spanish Ministry of Science and Innovation, European Development Fund and the European Social Fund, The European Commission, Horizon 2020 (ICECAP; grant no. 101024218), The Research Council of Norway Centre of Excellence funding scheme, Project number 223272. EBSD data for the WA-CB-11 brachiopod provided by the authors of Henkes et al. (2014), US National Science Foundation (EAR-1226832)

The report of a detection of an absorption profile centred at 78 MHz in the continuum radio background spectrum by the EDGES experiment and its interpretation as the redshifted 21 cm signal of cosmological origin has become one of the most debated results of observational cosmology in recent times. The cosmological 21 cm has long been proposed to be a powerful probe for observing the early Universe and tracing its evolution over cosmic time. Even though the science case is well established, measurement challenges posed on the technical ground are not fully understood to the level of claiming a successful detection. EDGES’s detection has naturally motivated a number of experimental attempts worldwide to corroborate the findings. In this paper, we present a precision cross-correlation spectrometer HYPEREION purpose-designed for a precision radio background measurement between 50–120 MHz to detect the absorption profile reported by the EDGES experiment. HYPEREION implements a pre-correlation signal processing technique that self-calibrates any spurious additive contamination from within the system and delivers a differential measurement of the sky spectrum and a reference thermal load internal to the system. This ensures an unambiguous “zero-point” of absolute calibration of the purported absorption profile. We present the system design, measurement equations of the ideal system, systematic effects in the real system, and finally, an assessment of the real system output for the detection of the absorption profile at 78 MHz in the continuum radio background spectrum.

Recent research into Rh and Ce0.80Gd0.20O1.90-impregnated La0.20Sr0.25Ca0.45TiO3 fuel electrodes for solid oxide fuel cells has demonstrated the high-stability of these material sets to a variety of harsh operating conditions at small scales (button cells with 1 cm2 active area), as well as full commercial scales (100 cm2 cells) in short stacks (5 cells) and full micro-combined heat and power systems (60 cells). In this work, the authors present a comprehensive evaluation of the ability of these novel titanate-based materials to function as fuel electrodes in solid oxide electrolysis cells (SOECs). Short-term and durability testing of button cell scale SOECs, under CO2 and steam electrolysis conditions, highlighted the limited stability of lanthanum strontium manganite-based air electrodes with lanthanum strontium cobaltite ferrite-based air electrodes offering improved degradation. Upscaling of this optimized cell chemistry to a 16 cm2 active area SOEC and testing under CO2, CO2/steam and steam electrolysis conditions demonstrated encouraging performance over a period of ~600 hours.

This study investigated the extraction and properties of an arabinogalactan polysaccharide from frost grape (FGP) as a potential alternative to gum arabic (GA). Collection date, solvent:feed ratio (S:F), chip size, C-18 filtration, ultrafiltration, freeze drying versus spray drying, methanol pre-extraction, and water absorption were examined. Sugar composition, elemental analysis, dietary fiber content, emulsification activity index (EAI), emulsification stability index (ESI), and viscosity were used to evaluate the extracts. Exudates collected in March from live stems were viscous with high percentage solids and FGP, while May collections were watery with low percentage solids and FGP. Frost grape stems were collected, chipped, and classified by size. The extraction system utilized pressure or vacuum to increase contact between the chips and extraction water. A S:F ratio of ca. 24% gave an excellent yield of FGP. Chips between 1.8 and 3.8 mm gave the highest mass yields. Pre-extracting the chips with methanol and C-18 filtration of the water extract both yielded a lighter product. The EAI for the FGP was higher than that for GA; however, its ESI was lower. Ultrafiltration of the crude extract separated glucose, fructose, and sucrose from the FGP. FGP with glucose, fructose, and sucrose adsorbed water and became darker.

Due to growing evidence of extensive trauma associated with high exposure to traumatizing events, including posttraumatic stress disorder (PTSD) and maladaptive coping strategies among practicing journalists, the drive to prepare journalism students to cope with the emotional and psychological stress of reporting trauma and human suffering has grown significantly among scholars in recent years. This special issue proposes a new pathway to an educational agenda in response to this persistent work-related problem in journalism practice.

This article provides a summary history and critique of the Queensland experience of restorative justice for adult offenders, with a focus on policy development and program implementation. It aims to identify key lessons to improve policy and implementation that may be transferrable to similar jurisdictions. Public source material was analysed to identify significant moments of change, including the launch of programs, the political rhetoric and commentary, as well as key activity data (e.g. referral rates). Results identified a significant lack of program uptake, with limited referral rates hindering the utilisation of restorative justice as an effective diversionary mechanism for adult offending in Queensland. In terms of both diversion and prevention, the study was restricted by a lack of data, indicating a significant practice and research gap, hence the need for enhanced research, increased application and greater transparency. Combined with a review of the literature, the results suggest the need for a greater focus on the welfare needs of victims and offenders to improve client and program outcomes, and reduce reoffending.

Young protostellar discs are likely to be both self-gravitating, and to support grain growth to sizes where the particles decoupled from the gas. This combination could lead to short-wavelength fragmentation of the solid component in otherwise non-fragmenting gas discs, forming Earth-mass solid cores during the Class 0/I stages of Young Stellar Object evolution. We use three-dimensional smoothed particle hydrodynamics simulations of two-fluid discs, in the regime where the Stokes number of the particles St>1, to study how the formation of solid clumps depends on the disc-to-star mass ratio, the strength of gravitational instability, and the Stokes number. Gravitational instability of the simulated discs is sustained by local cooling. We find that the ability of the spiral structures to concentrate solids increases with the cooling time, and decreases with the Stokes number, while the relative dynamical temperature between gas and dust of the particles decreases with the cooling time and the disc-to-star mass ratio, and increases with the Stokes number. Dust collapse occurs in a subset of high disc mass simulations, yielding clumps whose mass is close to linear theory estimates, namely 1-10 Earth masses. Our results suggest that if planet formation occurs via this mechanism, the best conditions correspond to near the end of the self-gravitating phase, when the cooling time is long and the Stokes number close to unity., Accepted for publication in MNRAS, 20 pages

Modern multivariate machine learning and statistical methodologies estimate parameters of interest while leveraging prior knowledge of the association between outcome variables. The methods that do allow for estimation of relationships do so typically through an error covariance matrix in multivariate regression which does not scale to other types of models. In this article we proposed the MinPEN framework to simultaneously estimate regression coefficients associated with the multivariate regression model and the relationships between outcome variables using mild assumptions. The MinPen framework utilizes a novel penalty based on the minimum function to exploit detected relationships between responses. An iterative algorithm that generalizes current state of the art methods is proposed as a solution to the non-convex optimization that is required to obtain estimates. Theoretical results such as high dimensional convergence rates, model selection consistency, and a framework for post selection inference are provided. We extend the proposed MinPen framework to other exponential family loss functions, with a specific focus on multiple binomial responses. Tuning parameter selection is also addressed. Finally, simulations and two data examples are presented to show the finite sample properties of this framework., 35 pages 5 Figures

The size, shape, and arrangement of tentacles in scleractinian coral polyps are likely to affect particle capture yet have not been investigated in a systematic way. Morphometric measurements of tentacles of several coral species found in the Caribbean Sea were taken from macro-photographs, and from these, models were constructed in three postures: straight, upstream-facing, and downstream-facing. These models were placed in a flume to video the flow paths of particles around them. Video analysis indicates tentacles, and their specific postures, have a dramatic effect on micro-flow patterns. The expanded soft tissue tentacles, and their specific postures, greatly increase probability of particle capture by direct impaction, inertial impaction, and gravitational deposition. All tentacle postures cause increased retention time relative to freestream travel in their immediate proximity, as well as increasing both contact with the tentacle surface, and tumbling of particles. Straight and upstream-facing tentacles deflect particles downward to their base, while downstream-facing tentacles deflect particles upwards. When results from individual tentacles are considered in geometric combination, the secondary radial symmetry of the tentacular whorls in simple coral polyps appears to be an optimal strategy to filter suspended particulate material in an oscillating and omni-directional flow environment. In meandrine corals, the hedgerows of straight and curved tentacles appear to draw particles downward, retain them, and direct them onto the oral feeding areas below the thecal ridges. The size, shape, and arrangement of tentacles are thus of key importance in understanding suspension feeding in scleractinian corals.

Purpose of Review Chronic liver disease is a major cause of morbidity and mortality amongst people living with HIV (PLWH). Emerging data suggests that gut microbial translocation may play a role in driving and modulating liver disease, a bi-directional relationship termed the gut–liver axis. While it is recognized that PLWH have a high degree of dysbiosis and gut microbial translocation, little is known about the gut–liver axis in PLWH. Recent Findings Recent studies have shown that microbial translocation can directly lead to hepatic inflammation, and have linked gut microbial signatures, dysbiosis, and translocation to liver disease in PLWH. Additionally, multiple trials have explored interventions targeting the microbiome in PLWH. Summary Emerging research supports the interaction between the gut microbiome and liver disease in PLWH. This offers new opportunities to expand our understanding of the pathophysiology of liver disease in this population, as well as to explore possible clinical interventions.

Anxiety disorders are a prevalent and severe problem that are often developed early in life and can disrupt the daily lives of affected individuals for many years into adulthood. Given the persistent negative aspects of anxiety, accurate and early assessment is critical for long term outcomes. Currently, the most common method for anxiety assessment is through point-in-time measures like the GAD-7. Unfortunately, this survey and others like it can be subject to recall bias and do not fully capture the variability in an individual’s day-to-day symptom experience. The current work aims to evaluate how point-in-time assessments like the GAD-7 relate to daily measurements of anxiety in a teenage population. To evaluate this relationship, we leveraged data collected at four separate three week intervals from 30 teenagers over the course of a year. The specific items of interest were a single item anxiety severity measure collected three times per day and end-of-month GAD-7 assessments. Within this sample, 40% of individuals reported clinical levels of generalized anxiety disorder symptoms at some point during the study. The first component of analysis was a visual inspection assessing how daily anxiety severity fluctuated around end-of-month reporting via the GAD-7. The second component was a between-subjects comparison assessing whether individuals with similar GAD-7 scores experienced similar symptom dynamics across the month as represented by latent features derived from a deep learning model. With this approach, similarity was operationalized by hierarchical clustering of the latent features. The aim clearly indicated that an individual’s daily experience of anxiety varied widely around what was captured by the GAD-7. Additionally, when hierarchical clustering was applied to the three latent features derived from the (LSTM) encoder (r=0.624 for feature reconstruction), it was clear that individuals with similar GAD-7 outcomes were experiencing different symptom dynamics. Upon further inspection of the latent features, the LSTM model appeared to rely as much on anxiety variability over the course of the month as it did on anxiety severity (p

Background: Palliative care (PC) focuses on listening to patient preferences, goals, and values to help health care providers educate, support, and collaborate during challenging disease processes, demanding treatments, and difficult decision-making. Method: A recently developed Phases and Transitions Model for Serious Illness helps guide nursing students in initiating therapeutic conversations about PC. Each phase and transition shows unique characteristics of illness and treatment to clarify the importance of introducing PC for that phase. Interventions in education, support, and treatment help students guide patients and families through the trajectory of serious illness. Results: The Phases and Transitions Model for Serious Illness and PC interventions provide a clear and practical structure to educate and empower nursing students to engage in PC conversations. Conclusion: Nursing educators can integrate this new model to broaden the perspective of PC as an everyday nursing practice for patients who have a serious illness. [ J Nurs Educ . 2023;62(5):279–284.]