Current Transition Practice for Primary Immunodeficiencies and Autoinflammatory Diseases in Europe: a RITA-ERN Survey

background due to the absence of curative treatments for inborn errors of immunity (IEI), children born with IEI require long-term follow-up for disease manifestations and related complications that occur over the lifespan. effective transition from pediatric to adult services is known to significantly improve adherence to treatment and long-term outcomes. It is currently not known what transition services are available for young people with IEI in europe. objective to understand the prevalence and practice of transition services in europe for young people with IEI, encompassing both primary immunodeficiencies (PID) and systemic autoinflammatory disorders (AID). methods a survey was generated by the european reference network on immunodeficiency, autoinflammatory, and autoimmune diseases transition working group and electronically circulated, through professional networks, to pediatric centers across europe looking after children with IEI. results seventy-six responses were received from 52 centers, in 45 cities across 17 different countries. all services transitioned patients to adult services, mainly to specialist PID or AID centers, typically transferring up to ten patients to adult care each year. the transition process started at a median age of 16-18 years with transfer to the adult center occurring at a median age of 18-20 years. 75% of PID and 68% of AID centers held at least one joint appointment with pediatric and adult services prior to the transfer of care. approximately 75% of PID and AID services reported having a defined transition process, but few centers reported national disease-specific transition guidelines to refer to. conclusions transition services for children with IEI in europe are available in many countries but lack standardized guidelines to promote best practice

Intensity-modulated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): 2-year toxicity results from an open-label, randomised, phase 3, non-inferiority trial

Background Localised prostate cancer is commonly treated with external beam radiotherapy and moderate hypofractionation is non-inferior to longer schedules. Stereotactic body radiotherapy (SBRT) allows shorter treatment courses without impacting acute toxicity. We report 2-year toxicity findings from PACE-B, a randomised trial of conventionally fractionated or moderately hypofractionated radiotherapy versus SBRT. Methods PACE is an open-label, multicohort, randomised, controlled, phase 3 trial conducted at 35 hospitals in the UK, Ireland, and Canada. In PACE-B, men aged 18 years and older with a WHO performance status 0–2 and low-risk or intermediate-risk histologically-confirmed prostate adenocarcinoma (Gleason 4 + 3 excluded) were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group to control radiotherapy (CRT; 78 Gy in 39 fractions over 7·8 weeks or, following protocol amendment on March 24, 2016, 62 Gy in 20 fractions over 4 weeks) or SBRT (36·25 Gy in five fractions over 1–2 weeks). Androgen deprivation was not permitted. Co-primary outcomes for this toxicity analysis were Radiation Therapy Oncology Group (RTOG) grade 2 or worse gastrointestinal and genitourinary toxicity at 24 months after radiotherapy. Analysis was by treatment received and included all patients with at least one fraction of study treatment assessed for late toxicity. Recruitment is complete. Follow-up for oncological outcomes continues. The trial is registered with ClinicalTrials.gov, NCT01584258. Findings We enrolled and randomly assigned 874 men between Aug 7, 2012, and Jan 4, 2018 (441 to CRT and 433 to SBRT). In this analysis, 430 patients were analysed in the CRT group and 414 in the SBRT group; a total of 844 (97%) of 874 randomly assigned patients. At 24 months, RTOG grade 2 or worse genitourinary toxicity was seen in eight (2%) of 381 participants assigned to CRT and 13 (3%) of 384 participants assigned to SBRT (absolute difference 1·3% [95% CI –1·3 to 4·0]; p=0·39); RTOG grade 2 or worse gastrointestinal toxicity was seen in 11 (3%) of 382 participants in the CRT group versus six (2%) of 384 participants in the SBRT group (absolute difference –1·3% [95% CI –3·9 to 1·1]; p=0·32). No serious adverse events (defined as RTOG grade 4 or worse) or treatment-related deaths were reported within the analysis timeframe. Interpretation In the PACE-B trial, 2-year RTOG toxicity rates were similar for five fraction SBRT and conventional schedules of radiotherapy. Prostate SBRT was found to be safe and associated with low rates of side-effects. Biochemical outcomes are awaited

Clinical features and management of individuals admitted to hospital with monkeypox and associated complications across the UK: a retrospective cohort study.

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 mm (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

Enabling planetary science across light-years. Ariel Definition Study Report

Ariel, the Atmospheric Remote-sensing Infrared Exoplanet Large-survey, was adopted as the fourth medium-class mission in ESA's Cosmic Vision programme to be launched in 2029. During its 4-year mission, Ariel will study what exoplanets are made of, how they formed and how they evolve, by surveying a diverse sample of about 1000 extrasolar planets, simultaneously in visible and infrared wavelengths. It is the first mission dedicated to measuring the chemical composition and thermal structures of hundreds of transiting exoplanets, enabling planetary science far beyond the boundaries of the Solar System. The payload consists of an off-axis Cassegrain telescope (primary mirror 1100 mm x 730 mm ellipse) and two separate instruments (FGS and AIRS) covering simultaneously 0.5-7.8 micron spectral range. The satellite is best placed into an L2 orbit to maximise the thermal stability and the field of regard. The payload module is passively cooled via a series of V-Groove radiators; the detectors for the AIRS are the only items that require active cooling via an active Ne JT cooler. The Ariel payload is developed by a consortium of more than 50 institutes from 16 ESA countries, which include the UK, France, Italy, Belgium, Poland, Spain, Austria, Denmark, Ireland, Portugal, Czech Republic, Hungary, the Netherlands, Sweden, Norway, Estonia, and a NASA contribution

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Rapid and highly variable warming of lake surface waters around the globe

In this first worldwide synthesis of in situ and satellite-derived lake data, we find that lake summer surface water temperatures rose rapidly (global mean = 0.34°C decade-1) between 1985 and 2009. Our analyses show that surface water warming rates are dependent on combinations of climate and local characteristics, rather than just lake location, leading to the counterintuitive result that regional consistency in lake warming is the exception, rather than the rule. The most rapidly warming lakes are widely geographically distributed, and their warming is associated with interactions among different climatic factors - from seasonally ice-covered lakes in areas where temperature and solar radiation are increasing while cloud cover is diminishing (0.72°C decade-1) to ice-free lakes experiencing increases in air temperature and solar radiation (0.53°C decade-1). The pervasive and rapid warming observed here signals the urgent need to incorporate climate impacts into vulnerability assessments and adaptation efforts for lakes

Automated recording of home cage activity and temperature of individual rats housed in social groups: The Rodent Big Brother project

Measuring the activity and temperature of rats is commonly required in biomedical research. Conventional approaches necessitate single housing, which affects their behavior and wellbeing. We have used a subcutaneous radiofrequency identification (RFID) transponder to measure ambulatory activity and temperature of individual rats when group-housed in conventional, rack-mounted home cages. The transponder location and temperature is detected by a matrix of antennae in a baseplate under the cage. An infrared high-definition camera acquires side-view video of the cage and also enables automated detection of vertical activity. Validation studies showed that baseplate-derived ambulatory activity correlated well with manual tracking and with side-view whole-cage video pixel movement. This technology enables individual behavioral and temperature data to be acquired continuously from group-housed rats in their familiar, home cage environment. We demonstrate its ability to reliably detect naturally occurring behavioral effects, extending beyond the capabilities of routine observational tests and conventional monitoring equipment. It has numerous potential applications including safety pharmacology, toxicology, circadian biology, disease models and drug discovery

Global data set of long-term summertime vertical temperature profiles in 153 lakes

Climate change and other anthropogenic stressors have led to long-term changes in the thermal structure, including surface temperatures, deepwater temperatures, and vertical thermal gradients, in many lakes around the world. Though many studies highlight warming of surface water temperatures in lakes worldwide, less is known about long-term trends in full vertical thermal structure and deepwater temperatures, which have been changing less consistently in both direction and magnitude. Here, we present a globally-expansive data set of summertime in-situ vertical temperature profiles from 153 lakes, with one time series beginning as early as 1894. We also compiled lake geographic, morphometric, and water quality variables that can influence vertical thermal structure through a variety of potential mechanisms in these lakes. These long-term time series of vertical temperature profiles and corresponding lake characteristics serve as valuable data to help understand changes and drivers of lake thermal structure in a time of rapid global and ecological change

Global data set of long-term summertime vertical temperature profiles in 153 lakes

Measurement(s) : temperature of water, temperature profile Technology Type(s) : digital curation Factor Type(s) : lake location, temporal interval Sample Characteristic - Environment : lake, reservoir Sample Characteristic - Location : global Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.14619009Climate change and other anthropogenic stressors have led to long-term changes in the thermal structure, including surface temperatures, deepwater temperatures, and vertical thermal gradients, in many lakes around the world. Though many studies highlight warming of surface water temperatures in lakes worldwide, less is known about long-term trends in full vertical thermal structure and deepwater temperatures, which have been changing less consistently in both direction and magnitude. Here, we present a globally-expansive data set of summertime in-situ vertical temperature profiles from 153 lakes, with one time series beginning as early as 1894. We also compiled lake geographic, morphometric, and water quality variables that can influence vertical thermal structure through a variety of potential mechanisms in these lakes. These long-term time series of vertical temperature profiles and corresponding lake characteristics serve as valuable data to help understand changes and drivers of lake thermal structure in a time of rapid global and ecological change