The pace of change of summertime temperature extremes.

Summer temperature extremes can have large impacts on humans and the biosphere, and an increase in heat extremes is one of the most visible symptoms of climate change. Multiple mechanisms have been proposed that would predict faster warming of heat extremes than typical summer days, but it is unclear whether this is occurring. Here, we show that, in both observations and historical climate model simulations, the hottest summer days have warmed at the same pace as the median globally, in each hemisphere, and in the tropics from 1959 to 2023. In contrast, the coldest summer days have warmed more slowly than the median in the global average, a signal that is not simulated in any of 262 simulations across 28 CMIP6 models. The observed stretching of the cold tail indicates that observed summertime temperatures have become more variable despite the lack of hot day amplification. The interannual variability and trend in the warming of both hot and cold extremes compared to the median can be explained from a surface energy balance perspective based on changes in net surface radiation and evaporative fraction. Tropical hot day amplification is projected to emerge in the future (2024-2099, SSP3-7.0 scenario), while Northern Hemisphere heat extremes are expected to continue to follow the median.

Health-related quality of life in cutaneous T-cell lymphoma: A post hoc analysis of a phase 3 trial in mycosis fungoides and Sézary syndrome.

BACKGROUND: Mycosis fungoides (MF) and Sézary syndrome (SS) are common subtypes of cutaneous T-cell lymphoma that primarily affect the skin but may spread to the lymph nodes, viscera and blood. The symptom burden may compromise health-related quality of life (HRQL). The phase 3 MAVORIC study (ClinicalTrials.gov identifier NCT01728805) in patients with relapsed/refractory MF/SS reported improved HRQL with mogamulizumab compared with vorinostat. OBJECTIVES: Use baseline (pre-treatment) data from the MAVORIC study to describe the symptom burden of MF/SS and identify characteristics associated with worse HRQL. METHODS: Data were from 372 adults with stage IB-IVB histologically confirmed relapsed/ refractory MF or SS. Associations between demographic and medical history variables and worse HRQL (Skindex-29, ItchyQol and Functional Assessment of Cancer Therapy - General [FACT-G]) were determined by regression models. RESULTS: In the cohort of 372 adults, 70% were white; 42% were female; mean age was 63 (SD 13.0) years. Fifty-five per cent had MF and 45% had SS; 77% had advanced (stage IIB-IV) disease, involving the skin in all patients and the blood and/or nodes in 66%. HRQL scores showed impairment versus normative means (where available), with the greatest impact on Symptoms and Emotions in the Skindex-29, Functioning in the ItchyQol, and Functional Wellbeing in the FACT-G. In regression analysis, worse HRQL across all domains and total score was associated with being female and younger, worse mSWAT score and worse itch for the Skindex-29 (n = 352), and being female, younger, Black/African American, worse performance status and worse itch for the ItchyQol (n = 369). Associations across domains and total score were not found for the FACT-G. Associations between domains and demographic/medical history were seen for all instruments. CONCLUSIONS: The symptoms of advanced MF/SS compromise all HRQL domains. Treatment goals and therapeutic choice should be informed by individual patients' disease burden.

The chromatin landscape of high-grade serous ovarian cancer metastasis identifies regulatory drivers in post-chemotherapy residual tumour cells.

Disease recurrence following chemotherapy is a major clinical challenge in ovarian cancer (OC), but little is known regarding how the tumour epigenome regulates transcriptional programs underpinning chemoresistance. We determine the single cell chromatin accessibility landscape of omental OC metastasis from treatment-naïve and neoadjuvant chemotherapy-treated patients and define the chromatin accessibility profiles of epithelial, fibroblast, myeloid and lymphoid cells. Epithelial tumour cells display open chromatin regions enriched with motifs for the oncogenic transcription factors MEIS and PBX. Post chemotherapy microenvironments show profound tumour heterogeneity and selection for cells with accessible chromatin enriched for TP53, TP63, TWIST1 and resistance-pathway-activating transcription factor binding motifs. An OC chemoresistant tumour subpopulation known to be present prior to treatment, and characterised by stress-associated gene expression, is enriched post chemotherapy. Nuclear receptors RORa, NR2F6 and HNF4G are uncovered as candidate transcriptional drivers of these cells whilst closure of binding sites for E2F2 and E2F4 indicate post-treated tumour having low proliferative capacity. Delineation of the gene regulatory landscape of ovarian cancer cells surviving chemotherapy treatment therefore reveals potential core transcriptional regulators of chemoresistance, suggesting novel therapeutic targets for improving clinical outcome.

Role of RNA structural plasticity in modulating HIV-1 genome packaging and translation.

HIV-1 transcript function is controlled in part by twinned transcriptional start site usage, where 5' capped RNAs beginning with a single guanosine (1G) are preferentially packaged into progeny virions as genomic RNA (gRNA) whereas those beginning with three sequential guanosines (3G) are retained in cells as mRNAs. In 3G transcripts, one of the additional guanosines base pairs with a cytosine located within a conserved 5' polyA element, resulting in formation of an extended 5' polyA structure as opposed to the hairpin structure formed in 1G RNAs. To understand how this remodeling influences overall transcript function, we applied in vitro biophysical studies with in-cell genome packaging and competitive translation assays to native and 5' polyA mutant transcripts generated with promoters that differentially produce 1G or 3G RNAs. We identified mutations that stabilize the 5' polyA hairpin structure in 3G RNAs, which promote RNA dimerization and Gag binding without sequestering the 5' cap. None of these 3G transcripts were competitively packaged, confirming that cap exposure is a dominant negative determinant of viral genome packaging. For all RNAs examined, conformations that favored 5' cap exposure were both poorly packaged and more efficiently translated than those that favored 5' cap sequestration. We propose that structural plasticity of 5' polyA and other conserved RNA elements place the 5' leader on a thermodynamic tipping point for low-energetic (~3 kcal/mol) control of global transcript structure and function.

Dose-related Mutagenic and Clastogenic Effects of Benzo[b]fluoranthene in Mouse Somatic Tissues Detected by Duplex Sequencing and the Micronucleus Assay.

Polycyclic aromatic hydrocarbons (PAHs) are common environmental pollutants that originate from the incomplete combustion of organic materials. We investigated the clastogenicity and mutagenicity of benzo[ b ]fluoranthene (BbF), one of 16 priority PAHs, in MutaMouse males after a 28-day oral exposure. BbF causes robust dose-dependent increases in micronucleus frequency in peripheral blood, indicative of chromosome damage. Duplex Sequencing (DS), an error-corrected sequencing technology, reveals that BbF induces dose-dependent increases in mutation frequencies in bone marrow (BM) and liver. Mutagenicity is increased in intergenic relative to genic regions, suggesting a role for transcription-coupled repair of BbF-induced DNA damage. At higher doses, the maximum mutagenic response to BbF is higher in liver, which has a lower mitotic index but higher metabolic capacity than BM; however, mutagenic potency is comparable between the two tissues. BbF induces primarily C:G>A:T mutations, followed by C:G>T:A and C:G>G:C, indicating that BbF metabolites mainly target guanines and cytosines. The mutation spectrum of BbF correlates with cancer mutational signatures associated with tobacco exposure, supporting its contribution to the carcinogenicity of combustion-derived PAHs in humans. Overall, BbF's mutagenic effects are similar to benzo[ a ]pyrene, a well-studied mutagenic PAH. Our work showcases the utility of DS for effective mutagenicity assessment of environmental pollutants. Synopsis: We used Duplex Sequencing to study the mutagenicity of benzo[ b ]fluoranthene across the mouse genome. Dose-dependent changes in mutation frequency and spectrum quantify its role in PAH-induced carcinogenicity.

Tree species explain only half of explained spatial variability in plant water sensitivity.

Spatiotemporal patterns of plant water uptake, loss, and storage exert a first-order control on photosynthesis and evapotranspiration. Many studies of plant responses to water stress have focused on differences between species because of their different stomatal closure, xylem conductance, and root traits. However, several other ecohydrological factors are also relevant, including soil hydraulics, topographically driven redistribution of water, plant adaptation to local climatic variations, and changes in vegetation density. Here, we seek to understand the relative importance of the dominant species for regional-scale variations in woody plant responses to water stress. We map plant water sensitivity (PWS) based on the response of remotely sensed live fuel moisture content to variations in hydrometeorology using an auto-regressive model. Live fuel moisture content dynamics are informative of PWS because they directly reflect vegetation water content and therefore patterns of plant water uptake and evapotranspiration. The PWS is studied using 21,455 wooded locations containing U.S. Forest Service Forest Inventory and Analysis plots across the western United States, where species cover is known and where a single species is locally dominant. Using a species-specific mean PWS value explains 23% of observed PWS variability. By contrast, a random forest driven by mean vegetation density, mean climate, soil properties, and topographic descriptors explains 43% of observed PWS variability. Thus, the dominant species explains only 53% (23% compared to 43%) of explainable variations in PWS. Mean climate and mean NDVI also exert significant influence on PWS. Our results suggest that studies of differences between species should explicitly consider the environments (climate, soil, topography) in which observations for each species are made, and whether those environments are representative of the entire species range.

The association of P2 and lean % estimates from commercial measurement systems with computed tomography determined composition within Australian pork abattoirs.

Pork carcasses were obtained from three abattoirs in Australia (n = 345) where technologies enabled collection of post slaughter measures of P2 fat depth (mm) (Hennessy Grading Probe (HGP), AutoFom III, PorkScan Lite) and estimates of carcass lean % (HGP, AutoFom III, PorkScan Plus). Computed tomography (CT) was used to scan carcasses and determine lean and fat %, with the strength of associations with abattoir measurement devices determined. The AutoFom III lean % demonstrated the strongest associations with whole carcass CT lean % (R2 0.63, RMSE 1.73) and fat % (R2 0.68, RMSE 1.80) and with section (fore, loin, belly and hind) CT composition. The association of P2 from AutoFom III was lower in comparison, however remained superior to other commercial devices (PorkScan Lite and HGP). Porkscan Plus lean % demonstrated moderate associations with whole carcass and section CT lean and fat %, with R2 values generally less than half those of the AutoFom III. The HGP demonstrated weakest associations with CT lean and fat % using either lean % or P2 outputs, which is likely related to data being collected from only the P2 measurement site. This is the first experiment to compare the strength of associations between multiple pork abattoir measurement devices and CT lean and fat % in Australia. P2 is the current industry standard for the assessment of lean yield in pork, however demonstrates weaker associations with carcass CT composition than devices capable of capturing multiple measures across the carcass like AutoFom III and PorkScan Plus.

After a period of forced abstinence, rats treated with the norepinephrine neurotoxin DSP-4 still exhibit preserved food-seeking behavior and prefrontal cortex fos-expressing neurons.

Aims: Relapse is a common characteristic of compulsive behaviors like addiction, where individuals tend to return to drug use or overeating after a period of abstinence. PFC (prefrontal cortex) neuronal ensembles are required for drug and food-seeking behaviors and are partially regulated by Norepinephrine (NE). However, the contributions of neuromodulators, such as the adrenergic system, in food-seeking behavior are not fully understood. Main methods: To investigate this, we trained male and female rats to press a lever in an operant chamber to obtain banana-flavored food pellets for ten days. We then administered DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride), a neurotoxin that diminishes norepinephrine levels in the brain. The rats were kept in their home cages for ten more days before being returned to the operant chambers to measure food-seeking behavior. Key findings: Despite receiving DSP-4, the PFC neuronal ensembles measured by Fos and food-seeking behavior did not differ between groups, but rather sex. Significance: Although both NE and Fos expressing neurons are implicated in food-seeking, they do not seem to be involved in a cue-contextual induced re-exposure response.

Dynamic correction of dual-energy x-ray absorptiometry images improves chain speed prediction of lamb composition in abattoirs.

A prototype, on-line Dual Energy X-ray Absorptiometer (DXA) has shown high precision of the prediction of carcass composition for the purpose of improved sheep meat grading in the Australian lamb supply chain, albeit with small inaccuracies over time. These inaccuracies were present across hours, and more significantly across days, which were unacceptable for any accreditation of this device as an objective carcass measurement tool in Australia. This inaccuracy demanded the creation of a novel image-processing algorithm for the prototype DXA. This DXA was tested for repeatability of predictions of lamb carcass composition over minutes, hours, and days, using two developed image processing algorithms. There was high immediate repeatability for both algorithms when predicting lean muscle % in 40 lamb carcasses, with a maximum CV of 0.65% over five repeated scans. There was a decrease in the CV of the prediction of lean muscle % of 30 lambs scanned three times over a 48-h period from 5.93 to 1.19% when the superior algorithm was used. The inaccuracies of lean muscle % predictions were associated with increases in the unattenuated space pixel values in DXA images. Improvements of the current algorithm are required to demonstrate repeatability over time for the purpose of accreditation within the Australian sheep meat industry, and for possible expansion of this technology into international supply chains.

Improved cut weight predictions from DEXA scans of lamb carcasses enables more accurate allocation of cuts to processing plans.

The value of precise dual energy X-ray absorptiometry (DEXA) cut weight predictions to lamb allocation to cut plans is unknown. Lambs (n = 191) varying in carcase weight (HSCW) and GR (tissue depth over the 12th rib) were DEXA scanned and boned out to weigh retail cuts. Cut weights were predicted using HSCW; HSCW + GR; HSCW + DEXA and HSCW + DEXA image components in GLM models. DEXA improved cut weight predictions in most cuts (P < 0.05). A dataset of 10,000 carcases was then simulated using the associations between HSCW, GR and cut weights, before being truncated to 4500 lambs representing onel day's HSCW distribution. A lamb Carcase Optimisation Tool scenario was developed with 2-3 cut options per carcase section and cut weight thresholds applied to several cuts. Processing costs, market values and actual cut weights were input into the Optimiser to determine carcase allocation to cut options for optimised profits. This scenario was repeated using the predicted cut weights to determine the cut misallocations caused. DEXA-predicted cut weights produced 16.7% and 8.0% less misallocations than HSCW and GR. DEXA produced 20.8% and 14.3% less misallocations than HSCW and GR in shortloins, and 25.5% and 12.9% less in hindquarters. While cut misallocations have little direct impact on total profits, as product is over and under-valued when misallocated, reducing cut misallocations will improve processor compliance when sorting carcases into cut plans- reducing their need to retrim, downgrade and repackage product or the erosion of customer confidence caused by supplying product not meeting market specifications.

Point-of-care diagnostics for sexually transmitted infections among migrants in Greece.

SETTING: Sexually transmitted infections (STIs) can impact individuals of any demographic. The most common pathogens causing STIs are Chlamydia trachomatis, Neisseria gonorrhea and Trichomonas vaginalis; these can be treated with specific antibiotics. OBJECTIVE: To compare the GeneXpert CT/NG test-and-treat algorithm to the syndromic approach algorithm and their impact on antibiotic prescription for gonorrhoea and chlamydia STIs. DESIGN: A retrospective observational study on women aged ≥18 years who accessed the Médecins Sans Frontières Day Care Centre in Athens with complaints related to urogenital infections between January 2021 and March 2022. Women with abnormal vaginal discharge, excluding clinically diagnosed candidiasis, were eligible for Xpert CT/NG testing. RESULTS: Of the 450 women who accessed care, 84 were eligible for Xpert CT/NG testing, and only one was positive for chlamydia, therefore resulting in saving 81 doses of ceftriaxone and azithromycin, and 19 doses of metronidazole. The cost of Xpert CT/NG testing, including treatment was €4,606.37, while full antibiotic treatment would have costed €536.76. CONCLUSION: The overall cost of the Xpert CT/NG test-and-treat algorithm was higher than the syndromic approach. However, quality of care should be weighed against the potential benefits of testing and syndromic treatment to determine the best option for each patient; we therefore advocate for decreasing the costs.

CONTEXTE: Les infections sexuellement transmissibles (STI, pour l'anglais « sexually transmitted infections ¼) touchent tous les individus. Les agents pathogènes les plus courants à l'origine des STI sont Chlamydia trachomatis, Neisseria gonorrhea et Trichomonas vaginalis, et ils peuvent être traités avec des antibiotiques spécifiques. OBJECTIF: Comparer l'algorithme test-and-treat du GeneXpert CT/NG à l'algorithme de l'approche syndromique et leur impact sur la prescription d'antibiotiques pour les STI à gonorrhée et à chlamydia. MÉTHODE: Une étude observationnelle rétrospective sur les femmes âgées de ≥18 ans qui ont accédé au centre de soins de jour de Médecins Sans Frontières à Athènes avec des plaintes relatives aux infections urogénitales entre janvier 2021 et mars 2022. Les femmes présentant des pertes vaginales anormales, à l'exclusion des candidoses cliniquement diagnostiquées, étaient éligibles pour le test GeneXpert CT/NG. RÉSULTATS: Sur les 450 femmes qui ont eu accès aux soins, 84 étaient éligibles au test GeneXpert CT/NG et une seule était positive à la chlamydia, ce qui a permis d'économiser 81 doses de ceftriaxone et d'azithromycine, et 19 doses de métronidazole. Le coût du test GeneXpert CT/NG, traitement compris, s'est élevé à €4 606,37, tandis qu'un traitement antibiotique complet aurait coûté €536,76. CONCLUSION: Le coût global de l'algorithme GeneXpert CT/NG test-and-treat était plus élevé que celui de l'approche syndromique. Cependant, la qualité des soins doit être mise en balance avec les avantages potentiels des tests et du traitement syndromique afin de déterminer la meilleure option pour chaque patient, et nous plaidons par conséquent en faveur d'une diminution des coûts.

Initial experience using middle meningeal artery embolisation for patients with recurrent and high-recurrence-risk chronic subdural haematoma.

Recurrence rates following surgical management of chronic subdural haematoma (CSDH) range from 5 to 33 %. There is growing evidence which suggests middle meningeal artery embolisation (MMAe) may reduce recurrence rates when used as surgical adjunct or standalone treatment. In this study we described our experience of this new procedure in the our UK institution. Patients with recurrent CSDH or CSDH at high risk of recurrence were selected for MMAe on a case-by-case basis following MDT discussion. A departmental database was used to identify patients treated. 26 CSDH were embolised in 20 patients; 9 CSDH were de-novo and 17 were recurrent. 10/26 CSDH were treated with MMAe only. No procedural mortality, access site or thrombo-embolic complications occurred. One patient experienced symptomatic collection growth 12 h following MMAe and required surgical drainage. 15 (75 %) of patients were living at home at follow-up (mean 14 months). On imaging follow-up 15/18 showed CSDH volume reduction or resolution, 1/18 remained stable requiring no further treatment, 2/18 patients suffered recurrent CSDH requiring treatment. In both recurrent cases incomplete embolisation was noted on procedural imaging (posterior division of MMA not embolised). Persistent posterior MMA division filling was significantly associated with collection recurrence (p = 0.002). Our results suggest MMAe as a stand-alone or adjuvant therapy can be performed safely in a UK neuroscience setting and is associated with high rates of symptomatic CSDH size reduction or resolution in problematic CSDH that have either recurred or are prone to recurrence.

Occupational health screening during Gurkha Central Selection: a retrospective cohort study.

OBJECTIVE: The selection process to the British Army's Brigade of Gurkhas is rigorous, demanding and competitive. The ethos of recruitment to the Gurkhas is grounded in an overarching tenant: that selection is free, fair and transparent. The aim of this study was to retrospectively review reasons for potential recruits (PRs) to be deemed medically unsuitable or deferred suitability on medical grounds for selection to the Brigade of Gurkhas. METHODS: A retrospective review was conducted by extracted data from published post-exercise reports for the past four years to ascertain numbers of PRs deemed medically fit, medically unsuitable or deferred suitability on medical grounds. The International Classification of Disease version 11 (ICD-11) codes were retrospectively assigned to code medical reasons for non-progression. Rates of medical non-progression were compared by year. RESULTS: A total of 3154 PRs were analysed between 2018 and 2021. There was no significant difference between PRs deemed medically fit and those deemed medically suitable or deferred on medical grounds over the study period (p=0.351). There was a significant difference in the ratio of PRs deferred on medical grounds and those deemed medically unsuitable over the study period (p<0.05). CONCLUSION: Selection to the Gurkhas is extremely competitive. These data demonstrate that, overall, reasons for medical deferral or unsuitability have remained constant despite the impact of a global pandemic. These data reinforce the central tenant of Gurkha selection; that it continues to be free, fair, and transparent.

The perspective of current and retired world class, elite and national athletes on the inclusion and eligibility of transgender athletes in elite sport.

There has been limited empirical study allowing athletes to voice their opinions on transgender participation in elite sport. This study surveyed 175 national, elite and world class athletes eligible to compete in the female category regarding transgender inclusion and eligibility. The study compared current Olympic versus current Olympic Recognised sports, elite versus world class, and current versus retired Olympic sport athletes. Most athletes favoured biological sex categorisation (58%) and considered it unfair for trans women to compete in the female category, except for precision sports. This view was held most strongly by world class athletes regarding their own sport (77% unfair, 15% fair). For trans men inclusion in the male category, most athletes considered it fair, except for Olympic sport athletes regarding contact sports (49% unfair, 27% fair) and sports heavily reliant on physical capacity (53% unfair, 29% fair). Notwithstanding those views, athletes (81%) believed sporting bodies should improve inclusivity for transgender athletes. Opinion varied somewhat according to career stage, competitive level and sport type. Nevertheless, athletes in the present study favoured categorisation by biological sex and did not support trans women eligibility for the female category in sports reliant on performance-related biological factors that differ between sexes.

Are There Sensitive Periods for Skill Development in Male Adolescent Basketball Players?

PURPOSE: Although spurts in physical capacities during adolescence are well known, little is known about the existence of such spurts in sport-specific skill development, especially during the period of rapid growth in stature. Our aims were to examine the timing, intensity, and sequence of basketball-specific skill spurts aligned with biological (years from peak height velocity (PHV)) rather than chronological age. We then defined putative sensitive periods (windows of optimal development) for each skill aligned to the adolescent growth spurt. METHODS: Altogether, 160 adolescent male basketballers aged 11-15 yr were tested biannually over 3 consecutive years. The years from attainment of PHV was estimated, and six skill tests were aligned to each year from PHV in 3-month intervals. Skill velocities were estimated using a nonsmooth polynomial model. RESULTS: Maximal gains in slalom dribble occurred 12 months before PHV attainment (intensity, 0.18 m·s -1 ·yr -1 ), whereas in speed shot shooting (intensity, 9.91 pts·yr -1 ), passing (intensity, 19.13 pts·yr -1 ), and slalom sprint (intensity, 0.19 m·s -1 ·yr -1 ), these skill spurts were attained 6 months before PHV attainment. The mean gains in control dribble (intensity, 0.10 m·s -1 ·yr -1 ) and defensive movement (intensity, 0.12 m·s -1 ·yr -1 ) peaks coincided with attainment of PHV. We identified different sized windows for optimal development for each skill. CONCLUSIONS: Peak spurts in skill development, for most basketball skills, were attained at the same time as PHV. The multiple peaks observed within the defined windows of optimal development suggest that there is room for skill improvement even if gains might be greater earlier rather than later in practice. Our findings highlight the need to make coaches aware of where their players are relative to the attainment of PHV because different skills appear to develop differently relative to PHV. Such knowledge may help in designing more relevant training regimes that incorporate the athlete's current growth status so that skill development can be maximized.

Walking (and talking) the plank: dual-task performance costs in a virtual balance-threatening environment.

We evaluated the effects of engaging in extemporaneous speech in healthy young adults while they walked in a virtual environment meant to elicit low or high levels of mobility-related anxiety. We expected that mobility-related anxiety imposed by a simulated balance threat (i.e., virtual elevation) would impair walking behavior and lead to greater dual-task costs. Altogether, 15 adults (age = 25.6 ± 4.7 yrs, 7 women) walked at their self-selected speed within a VR environment that simulated a low (ground) and high elevation (15 m) setting while speaking extemporaneously (dual-task) or not speaking (single-task). Likert-scale ratings of cognitive and somatic anxiety, confidence, and mental effort were evaluated and gait speed, step length, and step width, as well as the variability of each, was calculated for every trial. Silent speech pauses (> 150 ms) were determined from audio recordings to infer the cognitive costs of extemporaneous speech planning at low and high virtual elevation. Results indicated that the presence of a balance threat and the inclusion of a concurrent speech task both perturbed gait kinematics, but the virtual height illusion led to increased anxiety and mental effort and a decrease in confidence. The extemporaneous speech pauses were longer on average when walking, but no effects of virtual elevation were reported. Trends toward interaction effects arose in self-reported responses, with participants reporting more comfort walking at virtual heights if they engaged in extemporaneous speech. Walking at virtual elevation and while talking may have independent and significant effects on gait; both effects were robust and did not support an interaction when combined (i.e., walking and talking at virtual heights). The nature of extemporaneous speech may have distracted participants from the detrimental effects of walking in anxiety-inducing settings.

The impacts of rising vapour pressure deficit in natural and managed ecosystems.

An exponential rise in the atmospheric vapour pressure deficit (VPD) is among the most consequential impacts of climate change in terrestrial ecosystems. Rising VPD has negative and cascading effects on nearly all aspects of plant function including photosynthesis, water status, growth and survival. These responses are exacerbated by land-atmosphere interactions that couple VPD to soil water and govern the evolution of drought, affecting a range of ecosystem services including carbon uptake, biodiversity, the provisioning of water resources and crop yields. However, despite the global nature of this phenomenon, research on how to incorporate these impacts into resilient management regimes is largely in its infancy, due in part to the entanglement of VPD trends with those of other co-evolving climate drivers. Here, we review the mechanistic bases of VPD impacts at a range of spatial scales, paying particular attention to the independent and interactive influence of VPD in the context of other environmental changes. We then evaluate the consequences of these impacts within key management contexts, including water resources, croplands, wildfire risk mitigation and management of natural grasslands and forests. We conclude with recommendations describing how management regimes could be altered to mitigate the otherwise highly deleterious consequences of rising VPD.

Enhancing emotion regulation with an in situ socially assistive robot among LGBTQ+ youth with self-harm ideation: protocol for a randomised controlled trial.

INTRODUCTION: Purrble, a socially assistive robot, was codesigned with children to support in situ emotion regulation. Preliminary evidence has found that LGBTQ+ youth are receptive to Purrble and find it to be an acceptable intervention to assist with emotion dysregulation and their experiences of self-harm. The present study is designed to evaluate the impact of access to Purrble among LGBTQ+ youth who have self-harmful thoughts, when compared with waitlist controls. METHODS AND ANALYSIS: The study is a single-blind, randomised control trial comparing access to the Purrble robot with waitlist control. A total of 168 LGBTQ+ youth aged 16-25 years with current self-harmful ideation will be recruited, all based within the UK. The primary outcome is emotion dysregulation (Difficulties with Emotion Regulation Scale-8) measured weekly across a 13-week period, including three pre-deployment timepoints. Secondary outcomes include self-harm (Self-Harm Questionnaire), anxiety (Generalised Anxiety Disorder-7) and depression (Patient Health Questionnaire-9). We will conduct analyses using linear mixed models to assess primary and secondary hypotheses. Intervention participants will have unlimited access to Purrble over the deployment period, which can be used as much or as little as they like. After all assessments, control participants will receive their Purrble, with all participants keeping the robot after the end of the study. After the study has ended, a subset of participants will be invited to participate in semistructured interviews to explore engagement and appropriation of Purrble, considering the young people's own views of Purrble as an intervention device. ETHICS AND DISSEMINATION: Ethical approval was received from King's College London (RESCM-22/23-34570). Findings will be disseminated in peer review open access journals and at academic conferences. TRIAL REGISTRATION NUMBER: NCT06025942.

Associations between age-related differences in occipital alpha power and the broadband parameters of the EEG power spectrum: A cross-sectional cohort study.

In adulthood, neurological structure and function are often affected by aging, with negative implications for daily life as well as laboratory-based tasks. Some of these changes include decreased efficiency modulating cortical activity and lower signal-to-noise ratios in neural processing (as inferred from surface electroencephalography). To better understand mechanisms influencing age-related changes in cortical activity, we explored the effects of aging on narrow-band alpha power (7.5-12.5 Hz) and broadband/aperiodic components that span a wider range (1.5-30.5 Hz) over the occipital region during eyes-open and eyes-closed wakeful rest in 19 healthy young adults (18-35 years) and 21 community-dwelling older adults (59+ years). Older adults exhibited a smaller change in alpha power across conditions compared to younger adults. Older adults also showed flatter aperiodic slopes in both conditions. These changes in narrow-band alpha are consistent with previous work and suggest that older adults may have a reduced ability to modulate state-specific activity. Differences in the aperiodic slope suggest age-related changes in the signal-noise-ratio in cortical oscillations. However, the relationship between narrow-band alpha modulation and the aperiodic slope was unclear, warranting further investigation into how these variables relate to each other in the aging process. In summary, aging is associated with a broadband flattening of the EEG power spectrum and reduced state-specific modulation of narrow-band alpha power, but these changes appear to be (at least partially) independent of each other. The present findings suggest that separate mechanisms may underlie age-related differences in aperiodic power and narrow-band oscillations.

Intrauterine growth restriction in piglets modulates postnatal immune function and hepatic transcriptional responses independently of energy intake.

Introduction: Insufficient prenatal nutrition can affect fetal development and lead to intrauterine growth restriction (IUGR). The aim of this study was to investigate hepatic transcriptional responses and innate immune function in piglets suffering from IUGR compared to normal-sized piglets at 3 days of age and explore whether the provision of an energy-rich supplement at birth could modulate these parameters. Methods: A total of 68 piglets were included in the study. Peripheral blood mononuclear cells were harvested for LPS stimulation, and organs were harvested post-mortem to quantify relative weights. Liver tissue was utilized for RNA sequencing coupled with gene-set enrichment analysis. Results: IUGR resulted in increased expression of genes such as PDK4 and substantial alterations in transcriptional pathways related to metabolic activity (e.g., citric acid and Krebs cycles), but these changes were equivalent in piglets given an energy-rich supplement or not. Transcriptomic analysis and serum biochemistry suggested altered glucose metabolism and a shift toward oxidation of fatty acids. IUGR piglets also exhibited suppression of genes related to innate immune function (e.g., CXCL12) and pathways related to cell proliferation (e.g., WNT and PDGF signaling). Moreover, they produced less IL-1ß in response to LPS stimulation and had lower levels of blood eosinophils than normal-sized piglets. Discussion: Taken together, our results indicate that IUGR results in early-life alterations in metabolism and immunity that may not be easily restored by the provision of exogenous energy supplementation.