Search

ObjectivesTo determine the incremental yield of prenatal exome sequencing (PES) over standard testing in fetuses with an isolated congenital heart abnormality (CHA), CHA associated with extra-cardiac malformations (ECMs) and CHA dependent upon anatomical subclassification.MethodsA systematic review of the literature was performed using MEDLINE, EMBASE, Web of Science and grey literature January 2010-February 2023. Studies were selected if they included greater than 20 cases of prenatally diagnosed CHA when standard testing (QF-PCR/chromosome microarray/karyotype) was negative. Pooled incremental yield was determined. PROSPERO CRD 42022364747.ResultsOverall, 21 studies, incorporating 1957 cases were included. The incremental yield of PES (causative pathogenic and likely pathogenic variants) over standard testing was 17.4% (95% CI, 13.5%-21.6%), 9.3% (95% CI, 6.6%-12.3%) and 35.9% (95% CI, 21.0%-52.3%) for all CHAs, isolated CHAs and CHAs associated with ECMs. The subgroup with the greatest yield was complex lesions/heterotaxy; 35.2% (95% CI 9.7%-65.3%). The most common syndrome was Kabuki syndrome (31/256, 12.1%) and most pathogenic variants occurred de novo and in autosomal dominant (monoallelic) disease causing genes (114/224, 50.9%).ConclusionThe likelihood of a monogenic aetiology in fetuses with multi-system CHAs is high. Clinicians must consider the clinical utility of offering PES in selected isolated cardiac lesions.What is already known?Congenital heart abnormalities are the most commonly occurring congenital anomalies and can be associated with chromosomal or monogenic conditions. With the increasing use of fetal sequencing, there is a need to define the association between monogenic conditions and specific cardiac abnormalities, particularly when isolated to facilitate triaging for prenatal sequencing.What does this study add?The incremental yield of prenatal exome sequencing over and above chromosome microarray for congenital heart abnormalities is 9.3% i

High-resolution Doppler spectroscopy provides an avenue to study the atmosphere of both transiting and non-transiting planets. This powerful method has also yielded some of the most robust atmospheric detections to date. Currently, high-resolution Doppler spectroscopy detects atmospheric signals by cross-correlating observed data with a model atmospheric spectrum. This technique has been successful in detecting various molecules such as H2O, CO, HCN and TiO, as well as several atomic species. Here we present an alternative method of performing high-resolution Doppler spectroscopy, using a technique known as Doppler tomography. We present an analysis of HD 179949 b using Doppler tomography and provide Doppler tomograms confirming previous detections of CO at 2.3 microns, and H2O at both 2.3 microns, and 3.5 microns within the atmosphere of HD 179949 b, showing significantly lower background noise levels when compared to cross-correlation methods applied to the same data. We also present a novel detection of H2O at 2.1 microns, as well as a tentative detection of CO on the night side of the planet at 2.3 microns. This represents the first observational evidence for molecular absorption in the night-side emission spectrum of an exoplanet using Doppler spectroscopy., Comment: Accepted for publication in the Monthly Notices of the Royal Astronomical Society. 16 pages, 14 figures, 7 tables

Long-period transiting exoplanets bridge the gap between the bulk of transit- and Doppler-based exoplanet discoveries, providing key insights into the formation and evolution of planetary systems. The wider separation between these planets and their host stars results in the exoplanets typically experiencing less radiation from their host stars; hence, they should maintain more of their original atmospheres, which can be probed during transit via transmission spectroscopy. Although the known population of long-period transiting exoplanets is relatively sparse, surveys performed by the Transiting Exoplanet Survey Satellite (TESS) and the Next Generation Transit Survey (NGTS) are now discovering new exoplanets to fill in this crucial region of the exoplanetary parameter space. This study presents the detection and characterisation of NGTS-30 b/TOI-4862 b, a new long-period transiting exoplanet detected by following up on a single-transit candidate found in the TESS mission. Through monitoring using a combination of photometric instruments (TESS, NGTS, and EulerCam) and spectroscopic instruments (CORALIE, FEROS, HARPS, and PFS), NGTS-30 b/TOI-4862 b was found to be a long-period (P = 98.29838 day) Jupiter-sized (0.928 RJ; 0.960 MJ) planet transiting a 1.1 Gyr old G-type star. With a moderate eccentricity of 0.294, its equilibrium temperature could be expected to vary from 274 K to 500 K over the course of its orbit. Through interior modelling, NGTS-30 b/TOI-4862 b was found to have a heavy element mass fraction of 0.23 and a heavy element enrichment (Zp/Z_star) of 20, making it metal-enriched compared to its host star. NGTS-30 b/TOI-4862 b is one of the youngest well-characterised long-period exoplanets found to date and will therefore be important in the quest to understanding the formation and evolution of exoplanets across the full range of orbital separations and ages., Comment: 18 pages, 14 figures, accepted for publication in A&A

Stellar activity and planetary effects induce radial velocity (RV) offsets and cause temporal distortions in the shape of the stellar line profile. Hence, accurately probing the stellar line profile offers a wealth of information on both the star itself and any orbiting planets. Typically, Cross-Correlation Functions (CCFs) are used as a proxy for the stellar line profile. The shape of CCFs, however, can be distorted by line blending and aliasing limiting the stellar and planetary physics that can be probed from them. Least-squares deconvolution (LSD) offers an alternative that directly fits the mean line profile of the spectrum to produce a high-precision profile. In this paper, we introduce our novel method ACID (Accurate Continuum fItting and Deconvolution) that builds on LSD techniques by simultaneously fitting the spectral continuum and line profile as well as performing LSD in effective optical depth. Tests on model data revealed ACID can accurately identify and correct the spectral continuum to retrieve an injected line profile. ACID was also applied to archival HARPS data obtained during the transit of HD189733b. The application of the Reloaded Rossiter-McLaughlin technique to both ACID profiles and HARPS CCFs shows ACID residual profiles improved the out-of-line RMS by over 5% compared to CCFs. Furthermore, ACID profiles are shown to exhibit a Voigt profile shape that better describes the expected profile shape of the stellar line profile. This improved representation shows that ACID better preserves the stellar and planetary physics encoded in the stellar line profile shape for slow rotating stars., Comment: 16 pages, 13 figures. Accepted for Publication in Monthly Notices of the Royal Astronomical Society

Funded by UK Research and Innovation (UKRI), the Constructing a Digital Environment Strategic Priorities Fund (CDE) programme aspired to support the development of a comprehensive ‘digital environment’ ecosystem that best served scientists, policymakers, businesses, and communities. Emphasising multi-disciplinary and inter-disciplinary collaboration, CDE supported a team of challenge-focused researchers from a variety of disciplines to bring to the fore current and future digital advances in sensors that are critical to addressing environmental concerns. From March 2023 to January 2024, the team worked together to develop frameworks that sought to optimise the benefits of both existing and emerging sensor network technologies and their related infrastructure. Central to the development of these frameworks was a co-creation writing retreat in July 2023, where we came together to discuss the environmental sensing ecosystems unmet needs and challenges around five themes: Values, Changes, Barriers, Tools, and Lessons. The resultant findings and call for action suggest that: A. Focusing on People, Places and Ethics when making decisions on the whole sensor systems lifecycle (sensor design, deployment, application, and uptake) can ensure that research is more holistic, relevant, ethically sound, innovative, and, at the same time, has the potential for real-world impact. B. There is a clear need for a better-enabled sensor ‘development and use’ ecosystem (i.e., frameworks, methodologies, designs, communities) that has strong foundations and support for collaborative and interdisciplinary research to drive ambition for responsible innovation and resilient research communities. Overall, the findings highlight the vast potential offered by increased sensor utilisation for science and society, as well as broader concerns around data practices and innovation and specific challenges to sensors and sensing for the environment. There is a greater need for responsible data sharing

The human immunoglobulin heavy chain (IGH) locus on chromosome 14 includes more than 40 functional copies of the variable gene (IGHV).

INTRODUCTION: Adolescence is a period of major transition in physical, cognitive, social and emotional development, and the peak time for the onset of mental health conditions, substance use disorders and sexual and reproductive health risks. Prevention and treatment during this time can improve health and well-being now and into the future. However, despite clinical guidelines recommending annual preventive health assessments for young people, health professionals cite lack of consultation time and adequate funding as key barriers. This trial aims to determine whether a specific fee-for-service ('rebate payment') for a young person's health assessment, is effective and cost-effective at increasing the detection and management of health risk behaviours and conditions among young people. METHODS AND ANALYSIS: This cluster randomised controlled trial will be conducted in Australian general practice. 42 general practices (clusters) will be randomly allocated 1:1 to either an intervention arm where general practitioners receive a rebate payment for each annual health assessment undertaken for 14-24-year-olds during a 2 year study period, or a control arm (no rebate). The rebate amount will be based on the Medical Benefits Schedule (Australia's list of health professional services subsidised by the Australian Government) currently available for similar age-based assessments. Our primary outcome will be the annual rate of risk behaviours and health conditions recorded in the patient electronic health record (eg, alcohol/drug use, sexual activity and mental health issues). Secondary outcomes include the annual rate of patient management activities related to health risks and conditions identified (eg, contraception prescribed, sexually transmitted infection tests ordered). A process evaluation will assess acceptability, adoption, fidelity and sustainability of the rebate; an economic evaluation will assess its cost-effectiveness. Analyses will be intention-to-treat. ETHICS

Introduction: Urine drug screens (UDS) have unproven clinical utility in emergency department (ED) chest pain presentations. A test with such limited clinical utility may exponentiate biases in care, but little is known about the epidemiology of UDS use for this indication. We hypothesized that UDS utilization varies nationally across race and gender.Methods: This was a retrospective observational analysis of adult ED visits for chest pain in the 2011–2019 National Hospital Ambulatory Medical Care Survey. We calculated the utilization of UDS across race/ethnicity and gender and then characterized predictors of use via adjusted logistic regression models.Results: We analyzed 13,567 adult chest pain visits, representative of 85.8 million visits nationally. Use of UDS occurred for 4.6% of visits (95% CI 3.9%-5.4%). White females underwent UDS at 3.3% of visits (95% CI 2.5%-4.2%), and Black females at 4.1% (95% CI 2.9%-5.2%). White males were tested at 5.8% of visits (95% CI 4.4%-7.2%), while Black males were tested at 9.3% of visits (95% CI 6.4%-12.2%). A multivariate logistic regression model including race, gender, and time period shows significantly increased odds of ordering UDS for Black patients (odds ratio [OR] 1.45 (95% CI 1.11-1.90, p = 0.007)) and male patients (OR 2.0 (95% CI 1.55-2.58, p < 0.001) as compared to White patients and female patients.Conclusion: We identified wide disparities in the utilization of UDS for the evaluation of chest pain. If UDS were used at the rate observed for White women, Black men would undergo nearly 50,000 fewer tests annually. Future research should weigh the potential of the UDS to magnify biases in care against the unproven clinical utility of the test.

Contains fulltext : 294860.pdf (Publisher’s version ) (Open Access)

OBJECTIVE: Loneliness is prevalent in people with HIV (PWH) and associated with adverse health-related consequences, including depression. Chronic inflammation has been linked to depression in PWH, though its association with loneliness is less well established. Simultaneous examination of inflammation, loneliness and depression is needed to clarify these relationships. This study investigated the relationship between loneliness and inflammation, and the effects of loneliness and inflammation on depression in PWH. METHODS: 82 PWH who were on suppressive ART (mean age [SD] = 53.2 [9.0]) completed the UCLA Loneliness Scale-Version 3 and the Center for Epidemiologic Studies Depression Scale as part of a comprehensive evaluation. Biomarkers of systemic inflammation (CRP, IL-6, CCL2/MCP-1, sCD14) and coagulation (D-dimer) were measured in blood using commercial immunoassays. RESULTS: Multivariable linear regression analyses revealed that higher D-dimer, CCL2/MCP-1, and sCD14 were significant predictors of loneliness (ps < .05) while accounting for relevant covariates. Stepwise multiple linear regression models that included loneliness, biomarkers, and their interactions as predictors of depressive symptoms revealed significant main effects of loneliness and CCL2/MCP-1 levels (ps < .05), and a significant loneliness by D-dimer interaction (p < .05) whereby higher D-dimer was associated with increased depressive symptoms only at higher levels of loneliness. CONCLUSIONS: Increased coagulation activity is associated with loneliness, and in the context of loneliness, may increase risk for depression. Increased inflammation was associated with depression suggesting potentially dissociable underlying biological processes. To the extent that these processes are modifiable, such findings could have important implications in the treatment of loneliness and depression in PWH.

Hospital-based transmission had a dominant role in Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV) epidemics1, 2, but large-scale studies of its role in the SARS-CoV-2 pandemic are lacking. Such transmission risks spreading the virus to the most vulnerable individuals and can have wider-scale impacts through hospital–community interactions. Using data from acute hospitals in England, we quantify within-hospital transmission, evaluate likely pathways of spread and factors associated with heightened transmission risk, and explore the wider dynamical consequences. We estimate that between June 2020 and March 2021 between 95,000 and 167,000 inpatients acquired SARS-CoV-2 in hospitals (1% to 2% of all hospital admissions in this period). Analysis of time series data provided evidence that patients who themselves acquired SARS-CoV-2 infection in hospital were the main sources of transmission to other patients. Increased transmission to inpatients was associated with hospitals having fewer single rooms and lower heated volume per bed. Moreover, we show that reducing hospital transmission could substantially enhance the efficiency of punctuated lockdown measures in suppressing community transmission. These findings reveal the previously unrecognized scale of hospital transmission, have direct implications for targeting of hospital control measures and highlight the need to design hospitals better equipped to limit the transmission of future high-consequence pathogens.

Previous examinations of fully-convective M-dwarf stars have highlighted enhanced rates of nanoflare activity on these distant stellar sources. However, the specific role the convective boundary, which is believed to be present for spectral types earlier than M2.5V, plays on the observed nanoflare rates is not yet known. Here, we utilize a combination of statistical and Fourier techniques to examine M-dwarf stellar lightcurves that lie on either side of the convective boundary. We find that fully convective M2.5V (and later sub-types) stars have greatly enhanced nanoflare rates compared with their pre-dynamo mode transition counterparts. Specifically, we derive a flaring power-law index in the region of $3.00 \pm 0.20$, alongside a decay timescale of $200 \pm 100$~s for M2.5V and M3V stars, matching those seen in prior observations of similar stellar sub-types. Interestingly, M4V stars exhibit longer decay timescales of $450 \pm 50$~s, along with an increased power-law index of $3.10 \pm 0.18$, suggesting an interplay between the rate of nanoflare occurrence and the intrinsic plasma parameters, for example, the underlying Lundquist number. In contrast, partially convective (i.e., earlier sub-types from M0V to M2V) M-dwarf stars exhibit very weak nanoflare activity, which is not easily identifiable using statistical or Fourier techniques. This suggests that fully convective stellar atmospheres favor small-scale magnetic reconnection, leading to implications for the flare-energy budgets of these stars. Understanding why small-scale reconnection is enhanced in fully convective atmospheres may help solve questions relating to the dynamo behavior of these stellar sources., Comment: 16 pages, 5 figures, 5 tables. Accepted to ApJ

The photospheric unsigned magnetic flux has been shown to be highly correlated with radial velocity (RV) variations caused by solar surface activity. This activity indicator is therefore a prime candidate to unlock the potential of RV surveys to discover Earth twins orbiting Sun-like stars. We show for the first time how a precise proxy of the unsigned magnetic flux ($\Delta\alpha B^2$) can be obtained from Sun-as-a-star intensity spectra by harnessing the magnetic information contained in over 4000 absorption lines in the wavelength range from 380 to 690 nm. This novel activity proxy can thus be obtained from the same spectra from which RVs are routinely extracted. We derived $\Delta\alpha B^2$ from 500 randomly selected spectra from the HARPS-N public solar data set, which spans from 2015 to 2018. We compared our estimates with the unsigned magnetic flux values from the Solar Dynamics Observatory (SDO) finding excellent agreement (median absolute deviation: 4.9 per cent). The extracted indicator $\Delta\alpha B^2$ correlates with SDO's unsigned magnetic flux estimates on the solar rotational timescale (Pearson correlation coefficient 0.67) and on the three-year timescale of our data set (correlation coefficient 0.91). We find correlations of $\Delta\alpha B^2$ with the HARPS-N solar RV variations of 0.49 on the rotational timescale and 0.78 on the three-year timescale. The Pearson correlation of $\Delta\alpha B^2$ with the RVs is found to be greater than the correlation of the classical activity indicators with the RVs. For solar-type stars, $\Delta\alpha B^2$ therefore represents the best simultaneous activity proxy known to date., Comment: 17 pages, 10 figures, accepted for publication in MNRAS

Many cities are built on or near active faults, which pose seismic hazard and risk to the urban population. This risk is exacerbated by city expansion, which may obscure signs of active faulting. Here, we estimate the risk to Bishkek city, Kyrgyzstan, due to realistic earthquake scenarios based on historic earthquakes in the region and an improved knowledge of the active fault sources. We use previous literature and fault mapping, combined with new high-resolution digital elevation models to identify and characterise faults that pose a risk to Bishkek. We then estimate the hazard (ground shaking), damage to residential buildings and distribution of losses (economical cost and fatalities) using the Global Earthquake Model OpenQuake engine. We model historical events and hypothetical events on a variety of faults that could plausibly host significant earthquakes. This includes proximal, recognised, faults as well as a fault under folding in the north of the city that we identify using satellite DEMs. We find that potential earthquakes on faults nearest to Bishkek—Issyk Ata, Shamsi Tunduk, Chonkurchak and the northern fault—would cause the most damage to the city. An Mw 7.5 earthquake on the Issyk Ata fault could potentially cause 7900 ± 2600 completely damaged buildings, a further 16,400 ± 2000 damaged buildings and 2400 ± 1500 fatalities. It is vital to properly identify, characterise and model active faults near cities to reduce uncertainty as modelling the northern fault as a Mw 6.5 instead of Mw 6.0 would result in 37% more completely damaged buildings and 48% more fatalities.

Selection within natural communities has mainly been studied along large abiotic gradients, while the selection of individuals within populations should occur locally in response to biotic filters. To better leverage the role of the latter, we considered the hierarchal nature of environmental selection for the multiple dimensions of the trait space across biological levels, that is, from the species to the community and the ecosystem levels. We replicated a natural species richness gradient where communities included from two to 16 species within four wetlands (bog, fen, meadow, and marsh) contrasting in plant productivity. We sampled functional traits from individuals in each community and used hierarchical distributional modeling in order to analyze the independent variation of the mean and dispersion of functional trait space at ecosystem, community, and species levels. The plant productivity gradient observed between wetlands led to species turnover and selection of traits related to leaf nutrient conservation/acquisition strategy. Within wetlands, plant species richness drove trait variation across both communities and species. Among communities, variation of species richness correlated with the selection of individuals according to their use of vertical space and leaf adaptations to light conditions. Within species, intraspecific light-related trait variation in response to species richness was associated with stable population density for some species, while others reached low population density in more diverse communities. Within ecosystems, variation in biotic conditions selects individuals along functional dimensions that are independent of those selected across ecosystems. Within-species variations of light-related traits are related to demographic responses, linking biotic selection of individuals within communities to eco-evolutionary dynamics of species.

Comprehensive evidence-based guidelines for the practice of pancreas transplantation are yet to be established. The First World Consensus Conference on Pancreas Transplantation was convened for this purpose. A steering committee selected the participants and defined the questions to be addressed. A group of literature reviewers identified 597 studies to be included in summaries for guidelines production. Expert groups formulated the first draft of recommendations. Two rounds of discussion and voting occurred online, using the Delphi method (agreement rate ≥85%). After each round, critical responses of experts were reviewed, and recommendations were amended accordingly. Recommendations were finalized after live discussions. Each session was preceded by expert presentations and a summary of results of systematic literature review. Up to three voting rounds were allowed for each recommendation. To avoid potential conflicts of interest, deliberations on issues regarding the impact of pancreas transplantation on the management of diabetes were conducted by an independent jury. Recommendations on technical issues were determined by experts and validated using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Quality of evidence was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) methodology. Each recommendation received a GRADE rating (Grading of Recommendations, Assessment, Development and Evaluations).

The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts’ recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246.

Formal deliberations for the new collective quantified goal on climate finance began at COP26 in Glasgow. This Perspectives article aims to inform this process by discussing the potential size and nature of is post-2025 target. We argue that the climate finance system around the current target to mobilise US$100 billion per year to support developing countries has been fraught with difficulties, and that it would be ineffective to simply increase the climate finance target without addressing these difficulties. Therefore, we identify and discuss five priority elements for negotiations: the relation to Article 2.1(c) of the Paris Agreement; the adaptation-mitigation balance; financial instruments; mobilising private finance; and new and additional finance. To increase transparency, accountability, and trust in climate finance under the UNFCCC and to simultaneously allow for the mobilisation of finance at scale, we suggest setting a sub-target for grants. In combination with additional (sub)target(s), this could define an overall new collective quantified goal that is better suited to serve the challenging dual role of mobilising finance at scale and transferring resources to developing countries. Key policy insights Ambiguous definitions of climate finance and the US$100 billion target allow for multiple interpretations, reducing transparency and trust between countries. Climate finance targets can be interpreted in a dual and sometimes contrasting way: mobilising investment at scale and transferring resources from developed to developing countries. Recognising this duality may help to find common ground for a post-2025 climate finance target. Increasing the climate finance target may prove ineffective without further clarity on private finance mobilisation, the relation to Art. 2.1(c), and other priority elements. More detailed assessments of needs, priorities, costs, and support are needed to inform the post-2025 target and assess climate finance provision effectiv, Funding Agencies|German Federal Ministry of Economic Cooperation and Development (BMZ)

Formal deliberations for the new collective quantified goal on climate finance began at COP26 in Glasgow. This Perspectives article aims to inform this process by discussing the potential size and nature of is post-2025 target. We argue that the climate finance system around the current target to mobilise US$100 billion per year to support developing countries has been fraught with difficulties, and that it would be ineffective to simply increase the climate finance target without addressing these difficulties. Therefore, we identify and discuss five priority elements for negotiations: the relation to Article 2.1(c) of the Paris Agreement; the adaptation-mitigation balance; financial instruments; mobilising private finance; and new and additional finance. To increase transparency, accountability, and trust in climate finance under the UNFCCC and to simultaneously allow for the mobilisation of finance at scale, we suggest setting a sub-target for grants. In combination with additional (sub)target(s), this could define an overall new collective quantified goal that is better suited to serve the challenging dual role of mobilising finance at scale and transferring resources to developing countries. Key policy insights Ambiguous definitions of climate finance and the US$100 billion target allow for multiple interpretations, reducing transparency and trust between countries. Climate finance targets can be interpreted in a dual and sometimes contrasting way: mobilising investment at scale and transferring resources from developed to developing countries. Recognising this duality may help to find common ground for a post-2025 climate finance target. Increasing the climate finance target may prove ineffective without further clarity on private finance mobilisation, the relation to Art. 2.1(c), and other priority elements. More detailed assessments of needs, priorities, costs, and support are needed to inform the post-2025 target and assess climate finance provision effectiv, Funding Agencies|German Federal Ministry of Economic Cooperation and Development (BMZ)

BACKGROUND: Recurrent vulvovaginal candidiasis (RVVC) affects up to 5% of women. No comprehensive systematic review of treatments for RVVC has been published. OBJECTIVES: The primary objective was to assess the effectiveness and safety of pharmacological and non-pharmacological treatments for RVVC. The secondary objective was to assess patient preference of treatment options. SEARCH METHODS: We conducted electronic searches of bibliographic databases, including CENTRAL, MEDLINE, Embase, and CINAHL (search date 6 October 2021). We also handsearched reference lists of identified trials and contacted authors of identified trials, experts in RVVC, and manufacturers of products for vulvovaginal candidiasis. SELECTION CRITERIA: We considered all published and unpublished randomised controlled trials evaluating RVVC treatments for at least six months, in women with four or more symptomatic episodes of vulvovaginal candidiasis in the past year. We excluded women with immunosuppressive disorders or taking immunosuppressant medication. We included women with diabetes mellitus and pregnant women. Diagnosis of RVVC must have been confirmed by presence of symptoms and a positive culture and/or microscopy. We included all drug and non-drug therapies and partner treatment, assessing the following primary outcomes: • number of clinical recurrences per participant per year (recurrence defined as clinical signs and positive culture/microscopy); • proportion of participants with at least one clinical recurrence during the treatment and follow-up period; and • adverse events. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed titles and abstracts to identify eligible trials. Duplicate data extraction was completed independently by two authors. We assessed risk of bias as described in the Cochrane Handbook for Systematic Reviews of Interventions. We used the fixed-effects model for pooling and expressed the results as risk ratio (RR) with 95% confidence intervals (CI). Whe

ObjectiveGiven the aging population of people with HIV (PWH), along with increasing rates of binge drinking among both PWH and the general older adult population, this study examined the independent and interactive effects of HIV, binge drinking, and age on neurocognition.MethodParticipants were 146 drinkers stratified by HIV and binge drinking status (i.e., ≥4 drinks for women and ≥5 drinks for men within approximately 2 h): HIV+/Binge+ (n = 30), HIV-/Binge+ (n = 23), HIV+/Binge- (n = 55), HIV-/Binge- (n = 38). All participants completed a comprehensive neuropsychological battery measuring demographically-corrected global and domain-specific neurocognitive T scores. ANCOVA models examined independent and interactive effects of HIV and binge drinking on neurocognitive outcomes, adjusting for overall alcohol consumption, lifetime substance use, sex, and age. Subsequent multiple linear regressions examined whether HIV/Binge group moderated the relationship between age and neurocognition.ResultsHIV+/Binge+ participants had worse global neurocognition, processing speed, delayed recall, and working memory than HIV-/Binge- participants (p's < .05). While there were significant main effects of HIV and binge drinking, their interaction did not predict any of those neurocognitive outcomes (p's > .05). Significant interactions between age and HIV/Binge group showed that HIV+/Binge+ participants demonstrated steeper negative relationships between age and neurocognitive outcomes of learning, delayed recall, and motor skills compared to HIV-/Binge- participants (p's < .05).ConclusionsResults showed adverse additive effects of HIV and binge drinking on neurocognitive functioning, with older adults demonstrating the most vulnerability to these effects. Findings support the need for interventions to reduce binge drinking, especially among older PWH.

Contains fulltext : 252184.pdf (Publisher’s version ) (Open Access), We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57.

Contains fulltext : 252184.pdf (Publisher’s version ) (Open Access), We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57.

AIM: Exclusive enteral nutrition (EEN) is recommended as a first-line therapy for active luminal paediatric Crohn's disease, by many contemporary consensus guidelines. However, EEN protocols vary internationally. A key enabler for the use of EEN therapy has been identified as the standardisation of protocols. The aim of this study was to develop an optimal care pathway for use of EEN in children with active luminal Crohn's disease. METHODS: A working group of 11 paediatric gastroenterology dietitians and one paediatric gastroenterologist from Australia and New Zealand was convened to develop a standard optimal care pathway. Seven key areas were identified; clinical indications, workup assessments, EEN prescription, monitoring, food reintroduction, partial enteral nutrition and maintenance enteral nutrition. Recent literature was reviewed, assessed according to the National Health and Medical Research Council guidelines, and consensus statements were developed and voted on. Consensus opinion was used where literature gaps existed. RESULTS: A total of nineteen consensus statements from the seven key areas were agreed upon. The consensus statements informed the optimal care pathway for children with active luminal undertaking EEN in Australia and New Zealand. CONCLUSION: This study developed an EEN optimal care pathway to facilitate standardisation of clinical care for children with active luminal Crohn's disease, and hopefully improve clinical outcomes and identify areas for future research.

Formal deliberations for the new collective quantified goal on climate finance began at COP26 in Glasgow. This Perspectives article aims to inform this process by discussing the potential size and nature of is post-2025 target. We argue that the climate finance system around the current target to mobilise US$100 billion per year to support developing countries has been fraught with difficulties, and that it would be ineffective to simply increase the climate finance target without addressing these difficulties. Therefore, we identify and discuss five priority elements for negotiations: the relation to Article 2.1(c) of the Paris Agreement; the adaptation-mitigation balance; financial instruments; mobilising private finance; and new and additional finance. To increase transparency, accountability, and trust in climate finance under the UNFCCC and to simultaneously allow for the mobilisation of finance at scale, we suggest setting a sub-target for grants. In combination with additional (sub)target(s), this could define an overall new collective quantified goal that is better suited to serve the challenging dual role of mobilising finance at scale and transferring resources to developing countries. Key policy insights Ambiguous definitions of climate finance and the US$100 billion target allow for multiple interpretations, reducing transparency and trust between countries. Climate finance targets can be interpreted in a dual and sometimes contrasting way: mobilising investment at scale and transferring resources from developed to developing countries. Recognising this duality may help to find common ground for a post-2025 climate finance target. Increasing the climate finance target may prove ineffective without further clarity on private finance mobilisation, the relation to Art. 2.1(c), and other priority elements. More detailed assessments of needs, priorities, costs, and support are needed to inform the post-2025 target and assess climate finance provision effectiv, Funding Agencies|German Federal Ministry of Economic Cooperation and Development (BMZ)

To push the radial velocity (RV) exoplanet detection threshold, it is crucial to find more reliable radial velocity extraction methods. The Least-Squares Deconvolution (LSD) technique has been used to infer the stellar magnetic flux from spectropolarimetric data for the past two decades. It relies on the assumption that stellar absorption lines are similar in shape. Although this assumption is simplistic, LSD provides a good model for intensity spectra and likewise an estimate for their Doppler shift. We present the Multi-Mask Least-Squares Deconvolution (MM-LSD) RV extraction pipeline which extracts the radial velocity from two-dimensional echelle-order spectra using LSD with multiple tailored masks after continuum normalisation and telluric absorption line correction. The flexibility of LSD allows to exclude spectral lines or pixels at will, providing a means to exclude variable lines or pixels affected by instrumental problems. The MM-LSD pipeline was tested on HARPS-N data for the Sun and selected well-observed stars with 5.7 < Vmag < 12.6. For FGK-type stars with median signal-to-noise above 100, the pipeline delivered RV time series with on average 12 per cent lower scatter as compared to the HARPS-N RV extraction pipeline based on the Cross-Correlation Function technique. The MM-LSD pipeline may be used as a standalone RV code, or modified and extended to extract a proxy for the magnetic field strength.

Formal deliberations for the new collective quantified goal on climate finance began at COP26 in Glasgow. This Perspectives article aims to inform this process by discussing the potential size and nature of is post-2025 target. We argue that the climate finance system around the current target to mobilise US$100 billion per year to support developing countries has been fraught with difficulties, and that it would be ineffective to simply increase the climate finance target without addressing these difficulties. Therefore, we identify and discuss five priority elements for negotiations: the relation to Article 2.1(c) of the Paris Agreement; the adaptation-mitigation balance; financial instruments; mobilising private finance; and new and additional finance. To increase transparency, accountability, and trust in climate finance under the UNFCCC and to simultaneously allow for the mobilisation of finance at scale, we suggest setting a sub-target for grants. In combination with additional (sub)target(s), this could define an overall new collective quantified goal that is better suited to serve the challenging dual role of mobilising finance at scale and transferring resources to developing countries. Key policy insights Ambiguous definitions of climate finance and the US$100 billion target allow for multiple interpretations, reducing transparency and trust between countries. Climate finance targets can be interpreted in a dual and sometimes contrasting way: mobilising investment at scale and transferring resources from developed to developing countries. Recognising this duality may help to find common ground for a post-2025 climate finance target. Increasing the climate finance target may prove ineffective without further clarity on private finance mobilisation, the relation to Art. 2.1(c), and other priority elements. More detailed assessments of needs, priorities, costs, and support are needed to inform the post-2025 target and assess climate finance provision effectiv, Funding Agencies|German Federal Ministry of Economic Cooperation and Development (BMZ)

Formal deliberations for the new collective quantified goal on climate finance began at COP26 in Glasgow. This Perspectives article aims to inform this process by discussing the potential size and nature of is post-2025 target. We argue that the climate finance system around the current target to mobilise US$100 billion per year to support developing countries has been fraught with difficulties, and that it would be ineffective to simply increase the climate finance target without addressing these difficulties. Therefore, we identify and discuss five priority elements for negotiations: the relation to Article 2.1(c) of the Paris Agreement; the adaptation-mitigation balance; financial instruments; mobilising private finance; and new and additional finance. To increase transparency, accountability, and trust in climate finance under the UNFCCC and to simultaneously allow for the mobilisation of finance at scale, we suggest setting a sub-target for grants. In combination with additional (sub)target(s), this could define an overall new collective quantified goal that is better suited to serve the challenging dual role of mobilising finance at scale and transferring resources to developing countries. Key policy insights Ambiguous definitions of climate finance and the US$100 billion target allow for multiple interpretations, reducing transparency and trust between countries. Climate finance targets can be interpreted in a dual and sometimes contrasting way: mobilising investment at scale and transferring resources from developed to developing countries. Recognising this duality may help to find common ground for a post-2025 climate finance target. Increasing the climate finance target may prove ineffective without further clarity on private finance mobilisation, the relation to Art. 2.1(c), and other priority elements. More detailed assessments of needs, priorities, costs, and support are needed to inform the post-2025 target and assess climate finance provision effectiv, Funding Agencies|German Federal Ministry of Economic Cooperation and Development (BMZ)

Human immunoglobulin heavy chain (IGH) locus on chromosome 14 includes more than 40 functional copies of the variable gene (IGHV), which are critical for the structure of antibodies that identify and neutralize pathogenic invaders as a part of the adaptive immune system. Because of its highly repetitive sequence composition, the IGH locus has been particularly difficult to assemble or genotype when using standard short-read sequencing technologies. Here, we introduce ImmunoTyper-SR, an algorithmic tool for the genotyping and CNV analysis of the germline IGHV genes on Illumina whole-genome sequencing (WGS) data using a combinatorial optimization formulation that resolves ambiguous read mappings. We have validated ImmunoTyper-SR on 12 individuals, whose IGHV allele composition had been independently validated, as well as concordance between WGS replicates from nine individuals. We then applied ImmunoTyper-SR on 585 COVID patients to investigate the associations between IGHV alleles and anti-type I IFN autoantibodies, which were previously associated with COVID-19 severity.

To push the radial velocity (RV) exoplanet detection threshold, it is crucial to find more reliable radial velocity extraction methods. The Least-Squares Deconvolution (LSD) technique has been used to infer the stellar magnetic flux from spectropolarimetric data for the past two decades. It relies on the assumption that stellar absorption lines are similar in shape. Although this assumption is simplistic, LSD provides a good model for intensity spectra and likewise an estimate for their Doppler shift. We present the Multi-Mask Least-Squares Deconvolution (MM-LSD) RV extraction pipeline which extracts the radial velocity from two-dimensional echelle-order spectra using LSD with multiple tailored masks after continuum normalisation and telluric absorption line correction. The flexibility of LSD allows to exclude spectral lines or pixels at will, providing a means to exclude variable lines or pixels affected by instrumental problems. The MM-LSD pipeline was tested on HARPS-N data for the Sun and selected well-observed stars with 5.7 < Vmag < 12.6. For FGK-type stars with median signal-to-noise above 100, the pipeline delivered RV time series with on average 12 per cent lower scatter as compared to the HARPS-N RV extraction pipeline based on the Cross-Correlation Function technique. The MM-LSD pipeline may be used as a standalone RV code, or modified and extended to extract a proxy for the magnetic field strength., Comment: Accepted for publication in MNRAS. Code available on github: https://github.com/florian-lienhard/MM-LSD. 16 pages, 15 figures

Formal deliberations for the new collective quantified goal on climate finance began at COP26 in Glasgow. This Perspectives article aims to inform this process by discussing the potential size and nature of is post-2025 target. We argue that the climate finance system around the current target to mobilise US$100 billion per year to support developing countries has been fraught with difficulties, and that it would be ineffective to simply increase the climate finance target without addressing these difficulties. Therefore, we identify and discuss five priority elements for negotiations: the relation to Article 2.1(c) of the Paris Agreement; the adaptation-mitigation balance; financial instruments; mobilising private finance; and ‘new and additional’ finance. To increase transparency, accountability, and trust in climate finance under the UNFCCC and to simultaneously allow for the mobilisation of finance at scale, we suggest setting a sub-target for grants. In combination with additional (sub)target(s), this could define an overall new collective quantified goal that is better suited to serve the challenging dual role of mobilising finance at scale and transferring resources to developing countries. Key policy insights Ambiguous definitions of climate finance and the US$100 billion target allow for multiple interpretations, reducing transparency and trust between countries. Climate finance targets can be interpreted in a dual and sometimes contrasting way: mobilising investment at scale and transferring resources from developed to developing countries. Recognising this duality may help to find common ground for a post-2025 climate finance target. Increasing the climate finance target may prove ineffective without further clarity on private finance mobilisation, the relation to Art. 2.1(c), and other priority elements. More detailed assessments of needs, priorities, costs, and support are needed to inform the post-2025 target and assess climate finance provision eff

While transgender and gender non-binary (trans/nb) individuals are disproportionately affected by HIV, pre-exposure prophylaxis (PrEP) uptake remains low in this underserved population. We conducted four focus groups with 37 trans/nb individuals in San Diego and Los Angeles to assess barriers and facilitators of PrEP usage. Transcripts were coded for qualitative themes. Although overall PrEP awareness was high, participants reported limited knowledge and misinformation about PrEP. Barriers to PrEP use included: structural access (e.g., discrimination from health care providers, lack of trans-inclusive services, financial barriers), mental health struggles limiting ability to access PrEP, and concerns about potential side effects, drug-drug interactions with hormone therapy, and lack of other STI protection. Facilitators of PrEP usage included: increased PrEP availability, prior experience taking daily medications, and motivation to have active and healthy lives without fear of contracting HIV. Addressing both structural and psychosocial/behavioral factors in trans-affirming health care environments is crucial to designing inclusive, effective PrEP interventions.

While transgender and gender non-binary (trans/nb) individuals are disproportionately affected by HIV, pre-exposure prophylaxis (PrEP) uptake remains low in this underserved population. We conducted four focus groups with 37 trans/nb individuals in San Diego and Los Angeles to assess barriers and facilitators of PrEP usage. Transcripts were coded for qualitative themes. Although overall PrEP awareness was high, participants reported limited knowledge and misinformation about PrEP. Barriers to PrEP use included: structural access (e.g., discrimination from health care providers, lack of trans-inclusive services, financial barriers), mental health struggles limiting ability to access PrEP, and concerns about potential side effects, drug-drug interactions with hormone therapy, and lack of other STI protection. Facilitators of PrEP usage included: increased PrEP availability, prior experience taking daily medications, and motivation to have active and healthy lives without fear of contracting HIV. Addressing both structural and psychosocial/behavioral factors in trans-affirming health care environments is crucial to designing inclusive, effective PrEP interventions.

Direct oral anticoagulants are now commonplace, and reversal agents are recently becoming available. Andexanet alfa (AnXa), approved by the United States Food and Drug Administration in 2018, is a novel decoy molecule that reverses factor Xa inhibitors in patients with major hemorrhage. We present a case of a 70-year-old man taking rivaroxaban with hemodynamic instability from a ruptured abdominal aortic aneurysm. He received AnXa prior to endovascular surgery, and intraoperatively he could not be heparinized for graft placement. Consideration should be given to the risks and benefits of AnXa administration in patients who require anticoagulation after hemorrhage has been controlled.

Direct oral anticoagulants are now commonplace, and reversal agents are recently becoming available. Andexanet alfa (AnXa), approved by the United States Food and Drug Administration in 2018, is a novel decoy molecule that reverses factor Xa inhibitors in patients with major hemorrhage. We present a case of a 70-year-old man taking rivaroxaban with hemodynamic instability from a ruptured abdominal aortic aneurysm. He received AnXa prior to endovascular surgery, and intraoperatively he could not be heparinized for graft placement. Consideration should be given to the risks and benefits of AnXa administration in patients who require anticoagulation after hemorrhage has been controlled.

ObjectiveGiven the aging population of people with HIV (PWH), along with increasing rates of binge drinking among both PWH and the general older adult population, this study examined the independent and interactive effects of HIV, binge drinking, and age on neurocognition.MethodParticipants were 146 drinkers stratified by HIV and binge drinking status (i.e., ≥4 drinks for women and ≥5 drinks for men within approximately 2 h): HIV+/Binge+ (n = 30), HIV-/Binge+ (n = 23), HIV+/Binge- (n = 55), HIV-/Binge- (n = 38). All participants completed a comprehensive neuropsychological battery measuring demographically-corrected global and domain-specific neurocognitive T scores. ANCOVA models examined independent and interactive effects of HIV and binge drinking on neurocognitive outcomes, adjusting for overall alcohol consumption, lifetime substance use, sex, and age. Subsequent multiple linear regressions examined whether HIV/Binge group moderated the relationship between age and neurocognition.ResultsHIV+/Binge+ participants had worse global neurocognition, processing speed, delayed recall, and working memory than HIV-/Binge- participants (p's < .05). While there were significant main effects of HIV and binge drinking, their interaction did not predict any of those neurocognitive outcomes (p's > .05). Significant interactions between age and HIV/Binge group showed that HIV+/Binge+ participants demonstrated steeper negative relationships between age and neurocognitive outcomes of learning, delayed recall, and motor skills compared to HIV-/Binge- participants (p's < .05).ConclusionsResults showed adverse additive effects of HIV and binge drinking on neurocognitive functioning, with older adults demonstrating the most vulnerability to these effects. Findings support the need for interventions to reduce binge drinking, especially among older PWH.

To date, only 18 exoplanets with radial velocity (RV) semi-amplitude <2 m s−1 have had their masses directly constrained. The biggest obstacle to RV detection of such exoplanets is variability intrinsic to stars themselves, e.g. nuisance signals arising from surface magnetic activity such as rotating spots and plages, which can drown out or even mimic planetary RV signals. We use Kepler-37 – known to host three transiting planets, one of which, Kepler-37d, should be on the cusp of RV detectability with modern spectrographs – as a case study in disentangling planetary and stellar activity signals. We show how two different statistical techniques – one seeking to identify activity signals in stellar spectra, and another to model activity signals in extracted RVs and activity indicators – can each enable a detection of the hitherto elusive Kepler-37d. Moreover, we show that these two approaches can be complementary, and in combination, facilitate a definitive detection and precise characterisation of Kepler-37d. Its RV semi-amplitude of 1.22 ± 0.31 m s−1 (mass 5.4 ± 1.4 M⊕) is formally consistent with TOI-178b’s 1.05+0.25−0.30 m s−1, the latter being the smallest detected RV signal of any transiting planet to date, though dynamical simulations suggest Kepler-37d’s mass may be on the lower end of our 1σ credible interval. Its consequent density is consistent with either a water-world or that of a gaseous envelope (⁠∼0.4% by mass) surrounding a rocky core. Based on RV modelling and a re-analysis of Kepler-37 TTVs, we also suggest that the putative (non-transiting) planet Kepler-37e should be stripped of its ‘confirmed’ status.

Background & Aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress, and novel therapeutic response in PC to develop a biomarker-driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome, and functional characteristics of 61 novel PC patient–derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient-derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors, including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, cosegregates with response to platinum (P <.001) and PARP inhibitor therapy (P <.001) in vitro and in vivo. We generated a novel signature of replication stress that predicts response to ATR (P <.018) and WEE1 inhibitor (P <.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P <.001) but was not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR-proficient PC and after platinum therapy.

We present the discovery and characterisation of two transiting planets observed by \textit{TESS} in the light curves of the young and bright (V=9.67) star HD73583 (TOI-560). We perform an intensive spectroscopic and photometric space- and ground-based follow-up in order to confirm and characterise the system. We found that HD73583 is a young ($\sim 500$~Myr) active star with a rotational period of $12.08 \pm 0.11 $\,d, and a mass and radius of $ 0.73 \pm 0.02 M_\odot$ and $0.65 \pm 0.02 R_\odot$, respectively. HD73583 b ($P_b=6.3980420 _{ - 0.0000062 }^{+0.0000067}$ d) has a mass and radius of $10.2 _{-3.1}^{+3.4} M_\oplus$ and$2.79 \pm 0.10 R_\oplus$, respectively, that gives a density of $2.58 _{-0.81}^{ 0.95} {\rm g\,cm^{-3}}$. HD73583 c ($P_c= 18.87974 _{-0.00074 }^{+0.00086}$) has a mass and radius of $9.7_{-1.7} ^ {+1.8} M_\oplus$ and $2.39_{-0.09}^{+0.10} R_\oplus$, respectively, this translates to a density of $3.88 _{-0.80}^{+0.91} {\rm g\,cm^{-3}}$. Both planets are consistent with worlds made of a solid core surrounded by a volatile envelope. Because of their youth and host star brightness, they both are excellent candidates to perform transmission spectroscopy studies. We expect ongoing atmospheric mass-loss for both planets caused by stellar irradiation. We estimate that the detection of evaporating signatures on H and He would be challenging, but doable with present and future instruments., Comment: Accepted for publication in MNRAS

To date, only 18 exoplanets with radial velocity (RV) semi-amplitudes $<2$ m/s have had their masses directly constrained. The biggest obstacle to RV detection of such exoplanets is variability intrinsic to stars themselves, e.g. nuisance signals arising from surface magnetic activity such as rotating spots and plages, which can drown out or even mimic planetary RV signals. We use Kepler-37 - known to host three transiting planets, one of which, Kepler-37d, should be on the cusp of RV detectability with modern spectrographs - as a case study in disentangling planetary and stellar activity signals. We show how two different statistical techniques - one seeking to identify activity signals in stellar spectra, and another to model activity signals in extracted RVs and activity indicators - can enable detection of the hitherto elusive Kepler-37d. Moreover, we show that these two approaches can be complementary, and in combination, facilitate a definitive detection and precise characterisation of Kepler-37d. Its RV semi-amplitude of $1.22\pm0.31$ m/s (mass $5.4\pm1.4$ $M_\oplus$) is formally consistent with TOI-178b's $1.05^{+0.25}_{-0.30}$ m/s, the latter being the smallest detected RV signal of any transiting planet to date, though dynamical simulations suggest Kepler-37d's mass may be on the lower end of our $1\sigma$ credible interval. Its consequent density is consistent with either a water-world or that of a gaseous envelope ($\sim0.4\%$ by mass) surrounding a rocky core. Based on RV modelling and a re-analysis of Kepler-37 TTVs, we also argue that the putative (non-transiting) planet Kepler-37e should probably be stripped of its 'confirmed' status., Comment: Accepted for publication in MNRAS. 22 pages, 10 figures, 13 tables

State of the art radial velocity (RV) exoplanet searches are limited by the effects of stellar magnetic activity. Magnetically active spots, plage, and network regions each have different impacts on the observed spectral lines, and therefore on the apparent stellar RV. Differentiating the relative coverage, or filling factors, of these active regions is thus necessary to differentiate between activity-driven RV signatures and Doppler shifts due to planetary orbits. In this work, we develop a technique to estimate feature-specific magnetic filling factors on stellar targets using only spectroscopic and photometric observations. We demonstrate linear and neural network implementations of our technique using observations from the solar telescope at HARPS-N, the HK Project at the Mt. Wilson Observatory, and the Total Irradiance Monitor onboard SORCE. We then compare the results of each technique to direct observations by the Solar Dynamics Observatory (SDO). Both implementations yield filling factor estimates that are highly correlated with the observed values. Modeling the solar RVs using these filling factors reproduces the expected contributions of the suppression of convective blueshift and rotational imbalance due to brightness inhomogeneities. Both implementations of this technique reduce the overall activity-driven RMS RVs from 1.64 m/s to 1.02 m/s, corresponding to a 1.28 m/s reduction in the RMS variation. The technique provides an additional 0.41 m/s reduction in the RMS variation compared to traditional activity indicators., Comment: 16 pages, 6 figures, accepted by The Astrophysical Journal

Major faults of the Tien Shan, Central Asia, have long repeat times, but fail in large (urn:x-wiley:23335084:media:ess2922:ess2922-math-0001 7+) earthquakes. In addition, there may be smaller, buried faults off the major faults which are not properly characterized or even recognized as active. These all pose hazard to cities along the mountain range front such as Almaty, Kazakhstan. Here, we explore the seismic hazard and risk for Almaty from specific earthquake scenarios. We run three historical-based earthquake scenarios (1887 Verny urn:x-wiley:23335084:media:ess2922:ess2922-math-0002 7.3, 1889 Chilik urn:x-wiley:23335084:media:ess2922:ess2922-math-0003 8.0 and 1911 Chon-Kemin urn:x-wiley:23335084:media:ess2922:ess2922-math-0004 8.0) on the current population and four hypothetical scenarios for near-field faulting. By making high-resolution Digital Elevation Models (DEMs) from SPOT and Pleiades stereo optical satellite imagery, we identify fault splays near and under Almaty. We assess the feasibility of using DEMs to estimate city building heights, aiming to better constrain future exposure datasets. Both Pleiades and SPOT-derived DEMs find accurate building heights of the majority of sampled buildings within error; Pleiades tri-stereo estimates 80% of 15 building heights within one sigma and has the smallest average percentage difference to field-measured heights (14%). A moderately sized urn:x-wiley:23335084:media:ess2922:ess2922-math-0005 6.5 earthquake rupture occurring on a blind thrust fault, under folding north of Almaty is the most damaging scenario explored here due to the modeled fault stretching under Almaty, with estimated 12,300urn:x-wiley:23335084:media:ess2922:ess2922-math-00065,000 completely damaged buildings, 4,100 urn:x-wiley:23335084:media:ess2922:ess2922-math-0007 3,500 fatalities and an economic cost of 4,700 urn:x-wiley:23335084:media:ess2922:ess2922-math-0008 2,700 Million US dollars (one sigma uncertainty). This highlights the importance o

Lightning strikes are pervasive, however, their distributions vary both spatially and in time, resulting in a complex pattern of lightning-ignited wildfires. Over the last decades, lightning-ignited wildfires have become an increasing threat in south-east Australia. Lightning in combination with drought conditions preceding the fire season can increase probability of sustained ignitions. In this study, we investigate spatial and seasonal patterns in cloud-to-ground lightning strikes in the island state of Tasmania using data from the Global Position and Tracking System (GPATS) for the period January 2011 to June 2019. The annual number of lightning strikes and the ratio of negative to positive lightning (78:22 overall) were considerably different from one year to the next. There was an average of 80 lightning days per year, however, 50% of lightning strikes were concentrated over just four days. Most lightning strikes were observed in the west and north of the state consistent with topography and wind patterns. We searched the whole population of lightning strikes for those most likely to cause wildfires up to 72 h before fire detection and within 10 km of the ignition point derived from in situ fire ignition records. Only 70% of lightning ignitions were matched up with lightning records. The lightning ignition efficiency per stroke/flash was also estimated, showing an annual average efficiency of 0.24% ignition per lightning stroke with a seasonal maximum during summer. The lightning ignition efficiency as a function of different fuel types also highlighted the role of buttongrass moorland (0.39%) in wildfire incidents across Tasmania. Understanding lightning climatology provides vital information about lightning characteristics that influence the probability that an individual stroke causes ignition over a particular landscape. This research provides fire agencies with valuable information to minimize the potential impacts of lightning-induced wildfires through ea

BACKGROUND AND OBJECTIVES: Women's ability to negotiate condom use helps prevent sexually transmissible infections (STIs) and unintended pregnancies. The aim of this study was to assess the relationship between substance use, risk perception and the certainty of using condoms in several hypothetical situations. METHOD: This is a secondary analysis from the Australian Contraceptive ChOice pRoject (ACCORd) cluster randomised controlled trial. Descriptive statistics and logistic regression were used for the analysis. RESULTS: At baseline, contraceptive questions were answered by 698 women attending 57 general practices in Melbourne, Australia. Condom use was reported by 47%. Of those using condoms as the sole form of contraception (n = 137), 20% used them inconsistently. Dual protection was used by 58% of women (188/325). Condoms and the pill were more frequently used than condoms and longer-acting contraceptives. Women were less likely to be confident negotiating condom use when using substances. DISCUSSION: Substance use and the concurrent use of other forms of contraception impact use of condoms. Even when condoms are the sole form of contraception with willing partners, use is inconsistent, leaving women at risk of pregnancy and STI.

Decades of neuroscientific findings have elucidated the highly specialized brain areas involved in reading, especially along the ventral occipitotemporal stream where the critical step of recognizing words occurs. We report on a 14-year-old female with temporary dyslexia after a left ventral occipitotemporal ischemic stroke. Our longitudinal multimodal findings show that the resolution of the reading impairment was associated with heightened activity in the left posterior superior and inferior temporal gyri. Our findings highlight the role of the left inferior temporal gyrus in reading and the importance of perilesional and ipsilateral cortical areas for functional recovery after childhood stroke.

State of the art radial velocity (RV) exoplanet searches are limited by the effects of stellar magnetic activity. Magnetically active spots, plage, and network regions each have different impacts on the observed spectral lines, and therefore on the apparent stellar RV. Differentiating the relative coverage, or filling factors, of these active regions is thus necessary to differentiate between activity-driven RV signatures and Doppler shifts due to planetary orbits. In this work, we develop a technique to estimate feature-specific magnetic filling factors on stellar targets using only spectroscopic and photometric observations. We demonstrate linear and neural network implementations of our technique using observations from the solar telescope at HARPS-N, the HK Project at the Mt. Wilson Observatory, and the Total Irradiance Monitor onboard SORCE. We then compare the results of each technique to direct observations by the Solar Dynamics Observatory (SDO). Both implementations yield filling factor estimates that are highly correlated with the observed values. Modeling the solar RVs using these filling factors reproduces the expected contributions of the suppression of convective blueshift and rotational imbalance due to brightness inhomogeneities. Both implementations of this technique reduce the overall activity-driven RMS RVs from 1.64 m/s to 1.02 m/s, corresponding to a 1.28 m/s reduction in the RMS variation. The technique provides an additional 0.41 m/s reduction in the RMS variation compared to traditional activity indicators.

We present the discovery and characterisation of two transiting planets observed by \textit{TESS} in the light curves of the young and bright (V=9.67) star HD73583 (TOI-560). We perform an intensive spectroscopic and photometric space- and ground-based follow-up in order to confirm and characterise the system. We found that HD73583 is a young ($\sim 500$~Myr) active star with a rotational period of $12.08 \pm 0.11 $\,d, and a mass and radius of $ 0.73 \pm 0.02 M_\odot$ and $0.65 \pm 0.02 R_\odot$, respectively. HD73583 b ($P_b=6.3980420 _{ - 0.0000062 }^{+0.0000067}$ d) has a mass and radius of $10.2 _{-3.1}^{+3.4} M_\oplus$ and$2.79 \pm 0.10 R_\oplus$, respectively, that gives a density of $2.58 _{-0.81}^{ 0.95} {\rm g\,cm^{-3}}$. HD73583 c ($P_c= 18.87974 _{-0.00074 }^{+0.00086}$) has a mass and radius of $9.7_{-1.7} ^ {+1.8} M_\oplus$ and $2.39_{-0.09}^{+0.10} R_\oplus$, respectively, this translates to a density of $3.88 _{-0.80}^{+0.91} {\rm g\,cm^{-3}}$. Both planets are consistent with worlds made of a solid core surrounded by a volatile envelope. Because of their youth and host star brightness, they both are excellent candidates to perform transmission spectroscopy studies. We expect ongoing atmospheric mass-loss for both planets caused by stellar irradiation. We estimate that the detection of evaporating signatures on H and He would be challenging, but doable with present and future instruments., Comment: Accepted for publication in MNRAS

To date, only 18 exoplanets with radial velocity (RV) semi-amplitudes $<2$ m/s have had their masses directly constrained. The biggest obstacle to RV detection of such exoplanets is variability intrinsic to stars themselves, e.g. nuisance signals arising from surface magnetic activity such as rotating spots and plages, which can drown out or even mimic planetary RV signals. We use Kepler-37 - known to host three transiting planets, one of which, Kepler-37d, should be on the cusp of RV detectability with modern spectrographs - as a case study in disentangling planetary and stellar activity signals. We show how two different statistical techniques - one seeking to identify activity signals in stellar spectra, and another to model activity signals in extracted RVs and activity indicators - can enable detection of the hitherto elusive Kepler-37d. Moreover, we show that these two approaches can be complementary, and in combination, facilitate a definitive detection and precise characterisation of Kepler-37d. Its RV semi-amplitude of $1.22\pm0.31$ m/s (mass $5.4\pm1.4$ $M_\oplus$) is formally consistent with TOI-178b's $1.05^{+0.25}_{-0.30}$ m/s, the latter being the smallest detected RV signal of any transiting planet to date, though dynamical simulations suggest Kepler-37d's mass may be on the lower end of our $1\sigma$ credible interval. Its consequent density is consistent with either a water-world or that of a gaseous envelope ($\sim0.4\%$ by mass) surrounding a rocky core. Based on RV modelling and a re-analysis of Kepler-37 TTVs, we also argue that the putative (non-transiting) planet Kepler-37e should probably be stripped of its 'confirmed' status., Comment: Accepted for publication in MNRAS. 22 pages, 10 figures, 13 tables