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Abstract This study examined the moderating effect of self-compassion on the relationship between post-traumatic symptoms (PTS) and post-traumatic growth (PTG) among adults with trauma exposure. A sample of 413 participants (254 women, 155 men) aged 18 to 81 years (M = 33.8; SD = 12.9) completed questionnaires assessing trauma exposure, PTS, PTG, and self-compassion. The results indicated that women reported significantly higher PTS and lower self-compassion than men, while no significant gender differences were found for PTG. Correlational analyses revealed a significant positive association between PTS and PTG, and a significant negative association between PTS and self-compassion. Moderation analysis demonstrated that self-compassion significantly moderated the relationship between PTS and PTG, with higher levels of self-compassion linked to greater PTG, even at elevated levels of PTS. These findings underscore the importance of self-compassion as a protective factor in trauma recovery, promoting positive psychological transformation despite the presence of distress.

Abstract The composition of viral communities (i.e. viromes) can be dynamic and complex. Co-evolution may lead to virome host-specificity. However, eco-evolutionary factors may influence virome dynamics in wild host communities, potentially leading to disease emergence. Social bees are relevant models to address the drivers of virome composition: these important pollinators form multi-species assemblages, with high niche overlap and strong seasonality in their biotic interactions. We applied a microbial community approach to disentangle the role of host phylogeny and host ecology in shaping bee viromes, combining plant-pollinator networks with meta-transcriptomics, and small interfering RNAs as proxies for viral replication in pollinators and pollen. We identified over a hundred insect and plant viral sequences from ca. 4500 insect pollinator samples across three time points in one year. While host genetic distance drives the distribution of bee viruses, we find that plant-pollinator interactions and phenology drive plant virus communities collected by bees. This reveals the opportunities for virus spread in the bee assemblage. However, we show that transmission to multiple hosts is only realized for a fraction of insect viruses, with even fewer found to be actively replicating in multiple species, including the particularly virulent multi-host acute bee paralysis virus.

The genus Topiris Walker, 1863 is revised. This genus, previously neglected or deemed unrecognisable, comprised only Walker’s damaged and misrepaired type specimen of Topiris candidella Walker, 1863. Evidence is provided that this specimen was collected by Alfred Russel Wallace in 1855–56 in Sarawak, Malaysian Borneo. The mitogenome of this specimen was assembled using low coverage whole genome sequencing (genome skimming). The COI-5P portion of this mitogenome (658 bp) differs by 1–3 bp from two haplotypes sequenced from early 1990’s Brunei specimens. Another specimen recently discovered at NHMUK with an identical label to that of the type perfectly matches the Brunei specimens in its genitalia. Based on these four specimens, we present a fuller description of the morphology of T. candidella. Topiris includes the following additional species authored by Sterling and Lees: Topiris albidella sp. nov., T. albogrisella sp. nov., T. cinderella sp. nov., T. digiticosta sp. nov., T. lacteella sp. nov., T. madonna sp. nov., T. meyricki sp. nov., T. ochrotincta sp. nov., T. schneeweissella sp. nov., T. sericella sp. nov., and T. thunbergella sp. nov. The following new combinations are also established: T. salva (Meyrick, 1932), comb. nov. and T. sampitella (Lvovsky, 2014), comb. nov. The type of Athrypsiastis salva Meyrick is confirmed as lost and so a neotype and paraneotype of this species are designated. A published mitogenome of “Linoclostis gonatias” is shown to be correctly identified as T. salva, and references to L. gonatias, identified in some literature as a pest of Theaceae, are likely misidentified. The genus Topiris is divided into three groups, the candidella group, the salva group, and the albidella group, based on characters in the male genitalia. The candidella group and albidella group are supported sub-clades of Topiris. The phylogenetic placement of Topiris and Athrypsiastis within ‘core’ Xyloryctidae (as subtended by its type species, X. luteotactella) is confirmed by analysis of COI and seven nuclear genes, whereas the genera Eumenodora Meyrick, 1906 and Izatha Walker, 1864 do not fall within this clade. The morphology of Athrypsiastis phaeoleuca Meyrick, 1910 (the type species of Athrypsiastis; Xyloryctidae) is more fully described. The following new species authored by Sterling and Lees are described: Athrypsiastis cheesmanae sp. nov., A. edelweissella sp. nov., and A. penumbrella sp. nov. Two taxa are newly combined: Athrypsiastis halmaherella (Lvovsky, 2014), comb. nov. and Paralecta rosiflora (Meyrick, 1930), comb. nov.

Residual stress poses significant risks to the life management of key engineering components in nuclear fusion reactors. It is often induced within the narrow heat-affected zone (HAZ) during remote laser welding, essential for maintaining and assembling in-vessel components. Residual stress interacts with high temperatures, degrading mechanical properties and altering fracture mechanisms. Establishing a correlative methodology with microstructures to investigate these stresses and understand their effects on mechanical properties within the narrow HAZ is crucial for extending the reactor's lifetime. In this study, advanced residual stress measurements, including plasma-focused ion beam and digital image correlation, were employed to reveal heterogeneous stress distribution, discovering the peak tensile residual stress of 150 MPa at the interface of the fusion zone (FZ) and HAZ, and peak compressive residual stress of 550 MPa within HAZ. The residual stress effects on micro-hardness are quantitatively evaluated, showing a 25% hardening effect at HAZ/BM interface and a 10% softening effects at fusion line. The deformation mechanism is further analysed using tensile testing, where the residual stress effects were prominent in the low-stress field, reducing 6.5% strain evolution, while microstructures reinforced the material in the high-stress field. At elevated temperatures, the joint exhibited a significant reduction from 532 MPa to 345 MPa for yield strength and from 12 % to 8 % for elongation, with distinct fracture mechanisms observed through fractography compared to its behaviour at room temperature. These findings provide critical insights into enhancing laser welding processing and maintaining the structural integrity of in-service nuclear fusion reactor components.

Abstract Alzheimer’s disease (AD) ranks among the leading causes of morbidity and mortality worldwide. The objective was to evaluate the burden of AD and other dementias among the countries of the Middle East and North Africa (MENA) region by age and sex from 1990 to 2021. The data were sourced from the Global Burden of Disease (GBD) study 2021. The estimates are presented as counts and age-standardised rates per 100,000 accompanied by 95% uncertainty intervals (UIs). In 2021, AD and other dementias recorded an age-standardised prevalence of 772.7 per 100,000 in the MENA region (95% UI 671.2–877.6 per 100,000). This rate decreased by 4.9% in comparison to 1990, marking a statistically significant change. AD and other dementias also accounted for approximately 73.79 thousand deaths in the region in 2021, with the age-standardised rate decreasing by 8.6% compared to 1990. Moreover, the disability-adjusted life years (DALY) rate was 476.3 per 100,000 population (95% UI 225.6–1004.2), representing a 7.7% decrease from 1990 to 2021. Lebanon registered the highest point prevalence per 100,000 at 828.25, while the United Arab Emirates recorded the lowest at 652.43. The age-standardised point prevalence decreased from 1990 to 2021 in 13 of the MENA countries, while no significant changes were observed in eight of countries. Additionally, in 2021, women experienced higher prevalence rates, DALYs, compared to men. In the MENA region, age-standardised dementia prevalence rose with age in both sexes. The burden of dementia in MENA has decreased from 1990 to 2021, but it remains higher than global estimates. Furthermore, the findings indicate that dementia imposes a greater burden on the female population compared to males. To achieve a more accurate estimation of the burden of Alzheimer’s disease and other dementias, more systematic studies in low- to middle-income countries within the MENA region are required.

Abstract Background In the oral cavity, host-microbe interactions (HMI) continuously occur and greatly impact oral health. In contrast to the well-studied disease-associated HMI during, for example, periodontitis, HMI that are essential in maintaining oral health have been rarely investigated, especially in a human-relevant context. The aim of this study was to extensively characterize homeostatic HMI between saliva-derived biofilms and a reconstructed human gingiva (RHG). RHG was reconstructed following the structure of native gingiva, composed of a multilayered epithelium formed by keratinocytes and a fibroblast-populated compartment. To mimic the oral environment, RHG were inoculated with pooled human saliva resuspended in different saliva substitute media and incubated for 2 or 4 days. The co-cultured biofilms were retrieved and characterized by viable bacterial counting and compositional profiling (16S rRNA gene sequencing). RHG was investigated for metabolic activity (MTT assay), tissue histology (hematoxylin and eosin staining), epithelial proliferation (Ki67 staining), antimicrobial peptide expression, and cytokine secretion. Results Viable biofilms were detected up to day 4 of co-culturing. Bacterial counts indicated biofilm growth from the inoculation to day 2 and maintained thereafter at a similar level until day 4. All biofilms shared similar composition throughout 4 days, independent of co-culture time and different saliva substitute media used during inoculation. Biofilms were diverse with Streptococcus, Haemophilus, and Neisseria being the dominating genera. While supporting biofilm development, RHG displayed no significant changes in metabolic activity, tissue histology, or epithelial proliferation. However, in the presence of biofilms, the antimicrobial peptides elafin and human β-defensin-2 were upregulated, and the secretion of cytokines IL-6, CXCL1, CXCL8, CCL5, and CCL20 increased. Conclusion This model mimicked homeostatic HMI where a healthy gingiva supported a viable, diverse, and stable microbial community, incorporating bacterial genera found on native gingiva. The gingiva model maintained its tissue integrity and exerted protective responses in the presence of biofilms over time. This study adds to the evidence that shows the important role of the host in maintaining homeostatic HMI that are essential for oral health. Video Abstract

Abstract Esports is a fast-growing worldwide phenomenon encompassing hundreds of millions of competitive players. It is well-established that different game genres require distinct cognitive skills, but the biomechanical implications of playing different game genres have received little attention. This is the first study to quantify gamers’ kinematic behaviour across genres, demonstrating the importance of physical demands on performance and equipment in esports. The purpose of this study was to investigate whether the right upper limb kinematic behaviour differs among players across game genres. 63 esports players played a First Person Shooter (FPS), Multiplayer Online Battle Arena (MOBA), or Adventure game for 10 min. Three tri-axial accelerometers, positioned on each participant’s right upper limb (hand, forearm, arm), recorded kinematic data during gameplay. Hand acceleration magnitude, direction change, distance travelled (sum of all hand displacements over 10-min of gameplay), and displacement area (size and shape) were calculated in addition to hand, forearm, and arm acceleration ratios. There was a marked difference in movement patterns across players of different game genres. FPS players displayed greater hand acceleration magnitude (0.96 m.s−2 ± 0.07 SEM), moved their hand through a greater distance (38.96 m ± 2.47 SEM), and over a larger displacement area (119.13 cm2 ± 16.05 SEM) compared to MOBA and Adventure players. MOBA players exhibited greater hand acceleration magnitude (0.73 m.s−2 ± 0.05 SEM), changed direction more (2335 ± 172 SEM) and covered more distance (29.25 m ± 1.80 SEM) compared to Adventure players within a smaller overall area (70.49 cm2 ± 9.91 SEM). These findings have the potential to impact the design of gaming equipment and the training volumes of gamers across different game genres, so as to mitigate injury risk and improve overall gaming performance.

Abstract Globally, the number of refugees and displaced individuals has surpassed 100 million for the first time in history. Refugees are more likely than non-refugee populations to experience psychological distress and develop mental disorders. Early Adolescent Skills for Emotion (EASE), developed by the World Health Organization, is a potentially scalable task-sharing intervention targeting symptoms of internalizing disorders such as depression and anxiety for 10–15 years old and their caregiver. Prior to this study a randomized controlled trial in Amman, Jordan was conducted showing effectiveness of EASE reducing caregiver distress and inconsistent disciplinary parenting as well as reducing internalizing problems in adolescence. This study aims to explore individual and contextual barriers and facilitators for scaling the EASE intervention for Syrian refugees in Jordan. Ten semi-structured interviews and four focus group discussions were conducted between October 2020 and February 2023 with five key mental health and psychosocial support (MHPSS) informants, eight EASE providers, 11 adolescents, and 12 caregivers. Purposeful quota sampling technique was used to recruit participants with attention to sex and age and number of interviews and focus group discussions determined through empirical saturation. Inductive and deductive codes were utilized in a six-step thematic analysis. Participants reported a beneficial impact of EASE sessions in terms of reducing experienced anxiety levels, improved communication between adolescents and caregivers, reduced feelings of anger and jealousy, and improved familial relationships. Individual participation was hampered by transportation issues, scheduling conflicts, gender-mixed groups, and competing responsibilities. Scale-up facilitators included; increased mental health awareness, perceived low cost of EASE, feasibility of delivery by non-specialists, and an intervention engaging both adolescents and caregivers. Barriers included location, online sessions, sustainability, general implementation issues caused by individual barriers, and some concerns about non-specialists. Results add nuances not detected in the previous randomized control trial in Jordan and provide important context for understanding effectiveness results. Future research should investigate the cost-effectiveness of EASE along with stepped-care implementation models to provide EASE within existing health systems.

Abstract Peatlands are prevalent across northern regions, including bogs, fens, marshes, meadows, and select tundra wetlands that all vary in size (e.g., 0.01 s to 10 s km2) and shape (e.g., circular to elongated). However, our best remotely sensed products describing the regional-scale distribution of peatland extents are constrained to 1 km2 pixels, often representing notable sub-pixel heterogeneity and local-scale uncertainties. Here we develop a new 20 m spatial resolution wall-to-wall ~1.5 million km2 peatland map of Alaska, using peat cores, ground observations, and sub-meter resolution image interpretation. Ground-data were used to train machine learning classifiers to detect peatlands using a fusion of Sentinel-1 (Dual-polarized Synthetic Aperture Radar), Sentinel-2 (Multi-Spectral Imager), and derivatives from the Arctic Digital Elevation Model (ArcticDEM), that were spatially constrained by a peatland suitability model. Statewide peatland mapping (overall agreement:85%) identified peatlands to cover 4.6, 10.4, and 5.3% of polar, boreal, and maritime ecoregions, respectively, and 7.3% of the total terrestrial land area. This new dataset will improve the representation of peatland carbon, nutrient, and fire dynamics across Alaska.

Abstract Background To investigate the global, regional, and national burden of the diseases attributable to excess body weight (EBW) from 1990 to 2019, stratified by age, sex, underlying cause, and sociodemographic index (SDI). Methods Using the Comparative Risk Assessment approach of the Global Burden of Disease (GBD) study 2019, the burden of diseases attributable to EBW was reported for the period from 1990 to 2019. For adults, EBW was defined as a body mass index (BMI) exceeding 25 kg/m2, while for children aged 1 to 19 years, EBW was determined according to the standards set by the International Obesity Taskforce. The burden was reported in terms of numbers, proportions, and age-standardised rates per 100,000, accompanied by corresponding 95% uncertainty intervals (UIs). Results In 2019, there were an estimated 5.0 million deaths (95% UI: 3.2–7.1) and 160.3 million DALYs (106.0–218.9) attributable to EBW worldwide. The age-standardised DALY rate attributable to EBW increased by 18.0% (2.2–42.3) from 1990 to 2019, with notable regional variations. Southeast Asia and South Asia exhibited the highest age-standardised DALY rates. Conversely, the age-standardised death rate due to EBW showed no significant change, with an increase of 4.9% (-7.3 to 24.6) over the same period. Significant regional variations were again observed, particularly in Southeast Asia and South Asia, which recorded the highest age-standardised death rates. Moreover, a non-linear association was observed between the SDI and the regional age-standardised DALY rate of diseases attributable to EBW. Conclusions The global burden of EBW has increased over the past three decades. This trend aligns with socio-demographic indices and is influenced by the physical activity levels and dietary habits of these populations.

Abstract Eye-movement metrics like fixation location and duration are increasingly being used in infancy research. We tested whether fixation durations during meaningful social stimulus viewing involve common or different familial influences than fixation durations during viewing of abstract stimulus. We analysed the duration of fixations, and the allocation of fixations to face and motion, from 536 dizygotic and monozygotic 5-month-old twins in: naturalistic scenes including low- and high-level social features, and abstract scenes only having low-level features. We observed significant genetic influences in both conditions (h 2 naturalistic = 0.30, 95% confidence interval (CI) 0.14 to 0.44; h 2 abstract = 0.25, 95% CI 0.09 to 0.39), while shared environmental influences were negligible. Although some genetic influences were shared between the two conditions, unique genetic factors were linked to naturalistic scene viewing, indicating that fixation durations index different phenomena dependent on the context. Heritability for face looking was moderate (h 2 = 0.19, 95% CI 0.03 to 0.34), and no familial influences were found for motion looking. Exploratory polygenic score analyses revealed no significant associations with fixation measures. This study underscores the dissociable genetic influences on infants’ visual exploration of abstract versus naturalistic stimuli and the importance of considering context when interpreting eye-tracking data.

Abstract Epilepsy is characterized by recurrent, unpredictable seizures that impose significant challenges in daily management and treatment. One emerging area of interest is the identification of seizure cycles, including multiday patterns, which may offer insights into seizure prediction and treatment optimization. This study investigated multiday seizure cycles in a Tetanus Toxin (TT) rat model of epilepsy. Six TT-injected rats were observed over a 40-day period, with continuous EEG monitoring to record seizure events. Wavelet transform analysis revealed significant multiday cycles in seizure occurrences, with periods ranging from 4 to 7 days across different rats. Synchronization Index (SI) analysis demonstrated variable phase locking, with some rats showing strong synchronization of seizures with specific phases of the cycle. Importantly, the study revealed that these seizure cycles are dynamic and evolve over time, with some rats exhibiting shifts in cycle periods during the recording period. This suggests that the underlying neural mechanisms driving these cycles may change as the epileptic state progresses. The identification of stable and evolving multiday rhythms in seizure activity, independent of external factors, highlights a potential intrinsic biological basis for seizure timing. These findings offer promising avenues for improving seizure forecasting and designing personalized, timing-based therapeutic interventions in epilepsy. Future research should explore the underlying neural mechanisms and clinical applications of multiday seizure cycles.

Abstract Objective This research reports the incidence, mortality, and disability-adjusted life years (DALYs) associated with urinary tract infections (UTIs) in the Middle East and North Africa (MENA) region, stratified by sex, age, and Socio-demographic Index (SDI) from 1990 to 2021. Methods Data were sourced from the Global Burden of Disease 2021 study, encompassing all 21 countries in the region. Metrics such as absolute counts, age-standardised rates, and percentage changes from 1990 to 2021 are presented with 95% uncertainty intervals (UIs). Results In 2019, the MENA region recorded an incidence rate of 4,033.4 per 100,000 (95% UIs: 3,553.7–4,548.7) and 7,687 deaths (95% UIs: 6,663–8,969). The DALY rate was 41.3 per 100,000 (95% UIs: 36.1–47.2), which was highest among older adults, reaching a peak in the 80–89 age range, and increasing with age, particularly from the 50 + age groups. A non-linear relationship was identified between the burden of UTIs and the SDI, with higher-than-expected rates in lower SDI countries such as Syria and Lebanon. Conclusion Despite a substantial increase in the total number of UTI cases and DALYs in the region from 1990 to 2021, the age-standardised rates remained stable. The larger burden in lower SDI countries highlights the urgent need for targeted public health interventions. Improving healthcare access and antibiotic stewardship is crucial to mitigating the growing burden of UTIs, particularly among older populations in the region.

Abstract Objective To examine the burden of benign prostatic hyperplasia (BPH) in the Middle East and North Africa (MENA) region from 1990 to 2021 by age and sociodemographic index (SDI). Methods Data were sourced from the Global Burden of Disease (GBD) 2021 database. We analysed the incidence, prevalence, and years lived with disability (YLDs) attributable to BPH across the MENA region and its constituent countries. Results In 2021, the MENA region had an estimated 4.7 million prevalent cases of BPH, with an age-standardised prevalence rate of 2168.6 per 100,000. BPH contributed to 93.6 thousand YLDs, with an age-standardised YLD rate of 42.8 per 100,000. The highest prevalence and incidence rates were observed in Jordan, Qatar, and Iran, while Egypt and Yemen recorded the lowest rates. The burden of BPH was found to increase with age, peaking in the 65–69 age range. Conclusion This study reveals an increasing burden of BPH in the MENA region, primarily due to aging populations. These findings underscore the need for tailored public health policies and strategies to enhance early detection, prevention, and management of BPH, thereby reducing its impact on healthcare systems and individuals.

Abstract Background Synergists reduce insecticide metabolism in mosquitoes by competing with insecticides for the active sites of metabolic enzymes, such as cytochrome P450s (CYPs). This increases the availability of the insecticide at its specific target site. The combination of both insecticides and synergists increases the toxicity of the mixture. Given the demonstrated resistance to the classical insecticides in numerous Anopheles spp., the use of synergists is becoming increasingly pertinent. Tropical plants synthesize diverse phytochemicals, presenting a repository of potential synergists. Methods Extracts prepared from medicinal plants found in Jamaica were screened against recombinant Anopheles gambiae CYP6M2 and CYP6P3, and Anopheles funestus CYP6P9a, CYPs associated with anopheline resistance to pyrethroids and several other insecticide classes. The toxicity of these extracts alone or as synergists, was evaluated using bottle bioassays with the insecticide permethrin. RNA sequencing and in silico modelling were used to determine the mode of action of the extracts. Results Aqueous extracts of Piper amalago var. amalago inhibited CYP6P9a, CYP6M2, and CYP6P3 with IC50s of 2.61 ± 0.17, 4.3 ± 0.42, and 5.84 ± 0.42 μg/ml, respectively, while extracts of Kalanchoe pinnata, inhibited CYP6M2 with an IC50 of 3.52 ± 0.68 μg/ml. Ethanol extracts of P. amalago var. amalago and K. pinnata displayed dose-dependent insecticidal activity against An. gambiae, with LD50s of 368.42 and 282.37 ng/mosquito, respectively. Additionally, An. gambiae pretreated with K. pinnata (dose: 1.43 μg/mosquito) demonstrated increased susceptibility (83.19 ± 6.14%) to permethrin in a bottle bioassay at 30 min compared to the permethrin only treatment (0% mortality). RNA sequencing demonstrated gene modulation for CYP genes in anopheline mosquitoes exposed to 715 ng of ethanolic plant extract at 24 h. In silico modelling showed good binding affinity between CYPs and the plants’ secondary metabolites. Conclusion This study demonstrates that extracts from P. amalago var. amalago and K. pinnata, with inhibitory properties, IC50

Abstract Prostate cancer ranks among the most prevalent malignancies affecting males globally. This study sought to document the incidence, deaths and disability-adjusted life-years (DALYs) that were due to prostate cancer in the Middle East and North Africa (MENA) region, and its 21 countries, from 1990 to 2021. We analysed publicly accessible data from the Global Burden of Disease 2021 study to present findings on the incidence, deaths, and disability-adjusted life years (DALYs) associated with prostate cancer. These metrics were reported as counts and age-standardised rates, each accompanied by 95% uncertainty intervals. In 2021, the age-standardised incidence of prostate cancer in the region was 27.4 per 100,000 population, representing a 125.1% increase from 1990. The age-standardised mortality rate was 10.1, and the age-standardised DALY rate was 173.6, neither of which showed significant increases since 1990. Qatar recorded the highest age-standardised DALY rate in 2021, while Algeria had the lowest. The largest number of incident cases, deaths, and DALYs in 2021 were found in the 65–69, 80–84, and 70–74 age groups, respectively. Additionally, from 1990 to 2021, the burden of prostate cancer largely increased with the socio-demographic index (SDI) at the regional level. The burden of prostate cancer in the MENA region rose markedly between 1990 and 2021. Further studies into the underlying causes of this increasing incidence are essential to devise effective strategies for the early detection and prevention of the disease.

Synchrotron sourced Fourier transform infrared (SS FTIR) microspectroscopy was employed to investigate the biological effects on the neuron-like pheochromocytoma (PC 12) cells after exposure to synchrotron sourced terahertz (SS THz) radiation. Over 10 min of exposure, the PC 12 cells received a total energy of 600 J m2, with a total incident power density of ∼1.0 W m−2 (0.10 mW cm−2) at the beam extraction port (BEP) of the THz beamline at the Australian Synchrotron. To investigate the metabolic response of PC 12 cells after synchrotron THz radiation exposure, we utilized the FTIR microscope at the Infrared Microspectroscopy IRM beamline, which offers high photon flux and diffraction-limited spatial resolution enabling the detection of functional group variations in biological molecules at a single-cell level. Principal component analysis (PCA) based on the SS FTIR spectral data revealed a distinct separation of SS THz-exposed and control (non-exposed) cells. According to the PCA loadings, the key changes in the exposed cells involved lipid and protein compositions as indicated by the stretching vibrations of CH2/CH3 groups and amide I/II bands, respectively. An increase in lipids, such as cholesterol, or notable changes in their compositions and in some protein secondary structures were observed in the SS THz-exposed cells. The PCA analysis further suggests that PC 12 cells might maintain cell membrane stability after SS THz irradiation through higher volumes of cholesterol and cell morphology via regulation of the synthesis of cytoskeleton proteins such as actin-related proteins. The outcome of this study re-emphasized the exceptional SS FTIR capability to perform single-cell analysis directly, providing (i) unique biological information on cell variability within the population as well as between different groups, and (ii) evidence of molecular changes in the exposed cells that could lead to a deeper understanding of the effect of THz exposure at a single-cell level.

Abstract Background Gene signatures derived from transcriptomic-causal networks offer potential for tailoring clinical care in cancer treatment by identifying predictive and prognostic biomarkers. This study aimed to uncover such signatures in metastatic colorectal cancer (CRC) patients to aid treatment decisions. Methods We constructed transcriptomic-causal networks and integrated gene interconnectivity into overall survival (OS) analysis to control for confounding genes. This integrative approach involved germline genotype and tumor RNA-seq data from 1165 metastatic CRC patients. The patients were enrolled in a randomized clinical trial receiving either cetuximab or bevacizumab in combination with chemotherapy. An external cohort of paired CRC normal and tumor samples, along with protein-protein interaction databases, was used for replication. Results We identify promising predictive and prognostic gene signatures from pre-treatment gene expression profiles. Our study discerns sets of genes, each forming a signature that collectively contribute to define patient subgroups with different prognosis and response to the therapies. Using an external cohort, we show that the genes influencing OS within the signatures, such as FANCI and PRC1, are upregulated in CRC tumor vs. normal tissue. These signatures are highly associated with immune features, including macrophages, cytotoxicity, and wound healing. Furthermore, the corresponding proteins encoded by the genes within the signatures interact with each other and are functionally related. Conclusions This study underscores the utility of gene signatures derived from transcriptomic-causal networks in patient stratification for effective therapies. The interpretability of the findings, supported by replication, highlights the potential of these signatures to identify patients likely to benefit from cetuximab or bevacizumab.

The Kjell Henriksen Observatory (KHO) is the world’s largest optical observatory for auroral and airglow measurements, operated by the University Centre in Svalbard (UNIS). KHO is a unique site that lies underneath the dayside cusp, a funnel-shaped region where particles from the Sun can directly enter the Earth’s upper atmosphere, including the ionosphere. Building on the pioneering observations of its predecessor—the Auroral Station in Adventdalen, Svalbard—KHO has played a pivotal role in advancing our understanding of phenomena in the polar atmosphere. The Auroral Station and KHO have amassed climatological measurements over Svalbard for an impressive 40-year period. KHO’s diverse instrumentation, combined with other co-located optical and radar infrastructure, and in situ measurements from satellites and sounding rockets, has paved the way for impactful multi-instrument studies. Serving as an accessible testbed for instrument development, new types of instruments have recently been installed, both at KHO and on satellites. Beyond its scientific contributions, KHO has become an integral part of the Longyearbyen community, with students, visitors, and locals participating in tours and educational initiatives. This connection underscores KHO’s multi-functional role, not only as a centre for excellent research but also as a vital hub for public outreach and engagement.

The goal of the Paris Agreement is to keep global temperature rise well below 2°C. In this agreement—and its antecedents negotiated in Copenhagen and Cancun—the fear of crossing a dangerous climate threshold is supposed to serve as the catalyst for cooperation among countries. However, there are deep uncertainties about the location of the threshold for dangerous climate change, and recent evidence indicates this threshold uncertainty is a major impediment to collective action. Early warning signals of approaching climate thresholds are a potential remedy to this threshold uncertainty problem, and initial experimental evidence suggests such early detection systems may improve the prospects of cooperation. Here, we provide a direct experimental assessment of this early warning signal hypothesis. Using a catastrophe avoidance game, we show that large initial—and subsequently unreduced—threshold uncertainty undermines cooperation, consistent with earlier studies. An early warning signal that reduced uncertainty to within 10% (but not 30%) of the threshold value catalysed cooperation and reduced the probability of catastrophe occurring, albeit not reliably so. Our findings suggest early warning signals can trigger action to avoid a dangerous threshold, but additional mechanisms may be required to foster the cooperation needed to ensure the threshold is not breached.

Summary: Monoclonal antibodies have potential as rapidly developable agents for treatment and prevention of emerging viruses. The ACTIV-2 trial randomized persons with mild-moderate COVID-19 to the monoclonal antibody combination tixagevimab/cilgavimab via intramuscular injection (600 mg IM) or infusion (300 mg IV) versus placebo. We present final safety and laboratory outcomes; primary outcomes were previously reported. The analyzed IM group included 214 participants, and the IV group, 106 participants. Adverse events were not different between treatment and placebo. The half-life of both components was >90 days for IM or 75 days for IV. New anti-drug antibodies were about 3 times more likely in active vs. placebo recipients. SARS-CoV-2 neutralizing antibodies increased 157-fold at 7 days and 127-fold at 1 month (IM-treated) but were less robust in IV participants. These data can inform future development of monoclonal antibodies against SARS-CoV-2 and other viruses, even if this intervention is of low utility for contemporary SARS-CoV-2 variants.

Background. Perihilar cholangiocarcinoma (phCCA) has excellent outcomes following liver transplantation (LT). Neoadjuvant radiation-based locoregional therapy is standard-of-care. Gemcitabine and cisplatin (gem/cis) combination systemic therapies have improved outcomes in advanced settings, but their efficacy pre-LT has not been studied. Methods. We review our experience following neoadjuvant gem/cis alone versus radiation-based approaches. Patients with phCCA undergoing LT at a single center between January 2008 and February 2023 were identified retrospectively. Neoadjuvant therapy was categorized as gem/cis systemic therapy (ST) alone, or any ST and radiotherapy (RT). Outcomes were posttransplant overall survival (OS), recurrence-free survival (RFS), waitlist time, and pathologic tumor response. Results. During study period, 27 phCCA patients underwent LT. One patient decompensated with neoadjuvant therapy and was excluded. Median age was 61 y (interquartile range, 53–68 y) and 14 (54%) were male. Of 26 patients, 12 (46%) received ST and 14 (54%) RT. Six RT patients received gem/cis ST. Median waitlist time was 199 d (interquartile range, 98–405 d) and did not differ by neoadjuvant regimen. Explanted tumors were predominantly T1 stage, without lymphovascular invasion or nodal involvement. Neither pathologic features nor percent tumor necrosis differed by regimen. OS probabilities at 1 and 3 y were 84% and 55% for the cohort. There was no significant difference in OS and RFS when stratified by regimen. Conclusions. Post-LT OS, RFS, waitlist time, and tumor response were similar in the 2 groups. Patients with phCCA who do not undergo RT may still be considered for LT under appropriate institution-based protocols that adhere to other established criteria.

A recently introduced quantitative susceptibility mapping (QSM) technique, χ-separation, offers the capability to separate paramagnetic (χpara) and diamagnetic (χdia) susceptibility distribution within the brain. In-vivo high-resolution mapping of iron and myelin distribution, estimated by χ-separation, could provide a deeper understanding of brain substructures, assisting the investigation of their functions and alterations. This can be achieved using 7T MRI, which benefits from a high signal-to-noise ratio and susceptibility effects. However, applying χ-separation at 7T presents difficulties due to the requirement of an R2 map, coupled with issues such as high specific absorption rate (SAR), large B1 transmit field inhomogeneities, and prolonged scan time. To address these challenges, we developed a novel deep neural network, R2PRIMEnet7T, designed to convert a 7T R2* map into a 3T R2′ map. Building on this development, we present a new pipeline for χ-separation at 7T, enabling us to generate high-resolution χ-separation maps from multi-echo gradient-echo data. The proposed method is compared with alternative pipelines, such as an end-to-end network and linearly-scaled R2′, and is validated against χ-separation maps at 3T, demonstrating its accuracy. The 7T χ-separation maps generated by the proposed method exhibit similar contrasts to those from 3T, while 7T high-resolution maps offer enhanced clarity and detail. Quantitative analysis confirms that the proposed method surpasses the alternative pipelines. The proposed method results well delineate the detailed brain structures associated with iron and myelin. This new pipeline holds promise for analyzing iron and myelin concentration changes in various neurodegenerative diseases through precise structural examination.

Rationale & Objective: Equations for estimated glomerular filtration rate (eGFR) have previously included a coefficient for African American race. We evaluated and compared risk of incident stroke and dementia between old and new equations of eGFR for African American and non-African American participants. Study Design: Prospective observational study. Setting & Participants: Baseline values were collected from 6,814 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort between 2000 and 2002. Participants were followed up until 2018. The analytic sample consisted of 6,646 participants (mean [SD] age 62 [10] years; 53% female; 39% White, 27% African American, 12% Chinese American, and 22% Hispanic/Latino). Exposure: eGFR equation from 2021 based on serum creatinine and cystatin C levels without race. Outcome: Incident stroke and dementia. Analytical Approach: Cox proportional regression adjusting for demographic, lifestyle, and clinical variables was performed to estimate associations between different eGFR measures and risk of incident stroke and dementia. Results: During a median follow-up period of 17 years, 349 (5.3%) participants experienced an incident stroke event, and 574 (8.6%) participants experienced incident dementia. In the fully adjusted model, overall participants with eGFR 90 mL/min/1.73 m2 were at significantly increased risk of dementia (HR, 95% CI: 1.73, 1.21-2.45). A lower eGFR was not significantly associated with incident stroke (1.30, 0.75-2.24). African American participants tended to be reclassified to a lower group of eGFR in the new equations, whereas non-African American participants were reclassified to a higher group of eGFR. When comparing older versus newer equations of eGFR in African American and non-African American participants in association with incident stroke and dementia, differences were minimal. Limitations: Incident dementia was ascertained through International Classification of Diseases (Ninth and Tenth Revisions) codes. Conclusions: Our findings illustrate participants with 2021 eGFR 90 mL/min/1.73 m2 have higher risk of dementia in both African American and non-African American participants, but not of stroke. Plain Language Summary: Existing research has established that declined kidney function is associated with stroke and dementia. Kidney function is commonly estimated using inputs of blood proteins alongside demographic inputs of age, sex at birth, and race. Inclusion of race to estimate kidney function has gained increased scrutiny given its problematic nature of being a societal construct rather than an inherent biological trait that affects function of the kidneys. Recommendations were recently made to remove race from this estimation, and data were lacking on the relationship between new estimates of kidney function with outcomes such as stroke and dementia. Our research provides updated risk estimates for stroke and dementia using the new estimation for kidney function in a large multiethnic cohort.

Aquaculture has traditionally focused on supporting human food production, but there is a growing need for aquaculture associated with environmental restoration. For example, the in situ and ex situ rearing of corals for coral reef restoration is now implemented worldwide, but its success is limited by the lack of reef herbivores to combat the phase shift from coral-to-macroalgae-dominance on reefs, especially in the Caribbean. Laboratory-based aquaculture of some reef herbivores is possible but labor-intensive and insufficient to supply the numbers needed for large-scale restoration. We examined whether this bottleneck could be alleviated by the semi-wild mariculture of the Caribbean King Crab (MaguiMithrax spinosissimus)in saltwater quarries for subsequent use in coral reef restoration in the Florida Keys, Florida (USA).We surveyed the physico-chemical characteristics of 16 saltwater quarries in the Florida Keys relative to conditions in the wild and, in four quarries where crabs occurred, we examined crab population dynamics in comparison to that in the wild. Water chemistry and the availability of food (macroalgae) and crevice shelters were suitable for crab mariculture down to depths of at least 6 m. Herbivore competitors and predators were few in quarries, and there was no difference in the population size structure, fecundity, predatory mortality, or health of crabs in quarries compared to that in the wild. Therefore, the low-cost semi-wild mariculture of large numbers M. spinosissimus is feasible in saltwater quarries and could alleviate a logistical bottleneck to herbivore restoration on Caribbean coral reefs.

The ability to cope with stress is imperative for performance in competitive gaming, yet there is a lack of research examining the impact of gaming and esports participation on physiological stress. One way to measure physiological stress is via heart rate variability (HRV). The current literature examining HRV during competitive gaming is limited, with most studies focusing on multiplayer online battle arena games. To better understand the physiological demands of gaming, investigation into the stress imposed on players during gameplay of various game genres is required. In this study, we compared the physiological stress incurred on players who played either a competitive (sports) or a non-competitive (action-adventure) video game. Forty participants played either a sports or action-adventure game, whilst having their heart rate and heart rate variability monitored. Results showed that, compared to a pre-gaming baseline, playing either game increased heart rate, lowered RR intervals, and reduced both vagally mediated time and frequency domain vmHRV. Playing the sport game for 10 min induced higher heart rate and lower RR intervals compared to playing the action-adventure game. However, 10 min of game play was not enough to identify meaningful differences in vmHRV based on game genre played. These findings advance our understanding of the impact of video gaming on heart rate and heart rate variability, providing a useful method for coaches and players to index player stress and recovery.

Abstract Serpentinization, a consequence of water‐rock interaction in mafic and ultramafic rocks, refers to the hydrothermal alteration of olivine and pyroxene with serpentine as the typical product. Magnetite is produced in variable amounts during this serpentinization process. Here, we conducted a systematic rock magnetic study on the serpentinite of Ocean Drilling Program (ODP) Hole 1070A from the Iberia Abyssal Plain. From bottom to top, three units are distinguished rock‐magnetically: (a) serpentinized peridotite dominated by single‐domain (SD) ± multidomain (MD) magnetite particles; (b) gabbro with SD ± vortex state magnetite; (c) breccia dominated by MD ± vortex and SD ± vortex state maghemite/hematite and magnetite. Samples of the three units are highly serpentinized with serpentinization degrees >60%. The magnetite content increases exponentially with the degree of serpentinization. Two phases of serpentinization are proposed: (a) massive serpentinization that occurred before mantle exhumation and (b) maghemitization‐serpentinization that occurred near or at the seafloor after the final exhumation of mantle peridotites. The latter reduces the magnetization of the breccia unit significantly. Serpentinized peridotite associated with strong magnetization is the dominant contributor to the marine magnetic anomalies in ocean to continent transition areas.

Studying lists of associatively related words often produces false recognition of non-studied critical lures (CL). This false memory illusion can be found both when word lists are directly related to a CL as in the DRM paradigm (e.g., water, bridge, run, for the CL river), and when words are indirectly related to CLs via non-presented mediators (e.g., faucet[water], London[bridge], jog[run], for the CL river). Mediated false memory is strong evidence for activation-monitoring processes over gist extraction as mediated lists lack a consistent gist theme. In the present study, we evaluated whether context details (font color) of studied lists are attributed to CLs when they are falsely recognized. Participants studied directly related and mediated word lists presented in one of two font colors, followed by a source test which required specification of the font color for recognized test items. When CLs were falsely recognized, participants were able to correctly identify the font color of the CL’s origin list for both list types at a higher rate than incorrect identification. Because mediated false recognition reflects implicit activation, this pattern indicates activation processes may include both semantic and perceptual source details.

ABSTRACT Group A Streptococcus (GAS) is a human-adapted pathogen responsible for a variety of diseases. The GAS M1UK lineage has contributed significantly to the recently reported increases in scarlet fever and invasive infections. However, the basis for its evolutionary success is not yet fully understood. During the transition to systemic disease, the M1 serotype is known to give rise to spontaneous mutations in the control of virulence two-component regulatory system (CovRS) that confer a fitness advantage during invasive infections. Mutations that inactivate CovS function result in the de-repression of key GAS virulence factors such as streptolysin O (SLO), a pore-forming toxin and major trigger of inflammasome/interleukin-1β-dependent inflammation. Conversely, expression of the streptococcal cysteine protease SpeB, which is required during initial stages of colonization and onset of invasive disease, is typically lost in such mutants. In this study, we identified and characterized a novel covS single nucleotide polymorphism detected in three separate invasive M1UK isolates. The resulting CovSAla318Val mutation caused a significant upregulation of SLO resulting in increased inflammasome activation in human THP-1 macrophages, indicating an enhanced inflammatory potential. Surprisingly, SpeB production was unaffected. Site-directed mutagenesis was performed to assess the impact of this mutation on virulence and global gene expression. We found that the CovSAla318Val mutation led to subtle, virulence-specific changes of the CovRS regulon compared to previously characterized covS mutations, highlighting an unappreciated level of complexity in CovRS-dependent gene regulation. Continued longitudinal surveillance is warranted to determine whether this novel covS mutation will expand in the M1UK lineage.IMPORTANCEThe M1UK lineage of GAS has contributed to a recent global upsurge in scarlet fever and invasive infections. Understanding how GAS can become more virulent is critical for infection control and identifying new treatment approaches. The two-component CovRS system, comprising the sensor kinase CovS and transcription factor CovR, is a central regulator of GAS virulence genes. In the M1 serotype, covRS mutations are associated with an invasive phenotype. Such mutations have not been fully characterized in the M1UK lineage. This study identified a novel covS mutation in invasive Australian M1UK isolates that resulted in a more nuanced virulence gene regulation compared to previously characterized covS mutations. A representative isolate displayed upregulated SLO production and triggered amplified interleukin-1β secretion in infected human macrophages, indicating an enhanced inflammatory potential. These findings underscore the need for comprehensive analyses of covRS mutants to fully elucidate their contribution to M1UK virulence and persistence.

IntroductionGlaucoma, optic neuritis (ON), and non-arteritic anterior ischemic optic neuropathy (NAION) produce distinct patterns of retinal ganglion cell (RGC) damage. We propose a booster Variational Autoencoder (bVAE) to capture spatial variations in RGC loss and generate latent space (LS) montage maps that visualize different degrees and spatial patterns of optic nerve bundle injury. Furthermore, the bVAE model is capable of tracking the spatial pattern of RGC thinning over time and classifying the underlying cause.MethodsThe bVAE model consists of an encoder, a display decoder, and a booster decoder. The encoder decomposes input ganglion cell layer (GCL) thickness maps into two display latent variables (dLVs) and eight booster latent variables (bLVs). The dLVs capture primary spatial patterns of RGC thinning, while the display decoder reconstructs the GCL map and creates the LS montage map. The bLVs add finer spatial details, improving reconstruction accuracy. XGBoost was used to analyze the dLVs and bLVs, estimating normal/abnormal GCL thinning and classifying diseases (glaucoma, ON, and NAION). A total of 10,701 OCT macular scans from 822 subjects were included in this study.ResultsIncorporating bLVs improved reconstruction accuracy, with the image-based root-mean-square error (RMSE) between input and reconstructed GCL thickness maps decreasing from 5.55 ± 2.29 µm (two dLVs only) to 4.02 ± 1.61 µm (two dLVs and eight bLVs). However, the image-based structural similarity index (SSIM) remained similar (0.91 ± 0.04), indicating that just two dLVs effectively capture the main GCL spatial patterns. For classification, the XGBoost model achieved an AUC of 0.98 for identifying abnormal spatial patterns of GCL thinning over time using the dLVs. Disease classification yielded AUCs of 0.95 for glaucoma, 0.84 for ON, and 0.93 for NAION, with bLVs further increasing the AUCs to 0.96 for glaucoma, 0.93 for ON, and 0.99 for NAION.ConclusionThis study presents a novel approach to visualizing and quantifying GCL thinning patterns in optic neuropathies using the bVAE model. The combination of dLVs and bLVs enhances the model’s ability to capture key spatial features and predict disease progression. Future work will focus on integrating additional image modalities to further refine the model’s diagnostic capabilities.

Background. Hepatocellular carcinoma (HCC) has a rising incidence and mortality in North America. Liver transplantation (LT) with adjunctive therapies offers excellent outcomes. However, HCC recurrences are associated with high mortality. We investigate whether adjuvant systemic therapy can reduce recurrence, as shown with other malignancies. Methods. Medical records of patients undergoing LT for HCC at a single center between January 2016 and December 2022 were retrospectively reviewed. Patients were stratified into 3 groups: (1) recipients of adjuvant sorafenib, (2) nonrecipients at high recurrence risk, and (3) nonrecipients at low risk by explant pathology features. The outcomes were overall survival (OS) and recurrence-free survival (RFS). Adjuvant sorafenib recipients were also propensity score matched 1:2 to nonadjuvant recipients based on recurrence risk features. Results. During the study period, 273 patients with HCC underwent LT and 16 (5.9%) received adjuvant sorafenib therapy. Adjuvant sorafenib recipients were demographically similar to nonrecipients and, on explant pathology, had greater tumor burden, lymphovascular invasion, and poorer differentiation (all P

Statins are first-line treatments in the primary and secondary prevention of cardiovascular disease. Clinical studies show statins act independently of lipid-lowering mechanisms to decrease C-reactive protein (CRP), an inflammation marker. We aim to elucidate genetic loci associated with CRP statin response.CRP statin response is the change in log-CRP between off-treatment and on-treatment measurements. Cohort-level Genome-Wide Association Studies (GWAS) of CRP response were performed using 1000 Genomes imputed data, testing ∼10 million common genetic variants. GWAS meta-analysis combined results from seven cohorts and clinical trials totalling 14,070 statin-treated individuals of European ancestry within the GIST consortium. Secondary analyses included statin-by-placebo interaction analyses, and lookups in African ancestry cohorts.Our GWAS identified two genome-wide significant (P

Background: Unhealthy alcohol use is a leading cause of preventable mortality and a risk factor for an array of social and health problems. The Intervention in Small primary care Practices to Implement Reduction in unhealthy alcohol use (INSPIRE) study is part of a nationwide campaign to improve the identification and treatment of patients engaging in unhealthy alcohol use. Methods: We conducted a single arm, pragmatic study consisting of seventeen primary care practices in the Chicago metropolitan area, Wisconsin, and California across two waves with a 6-month latent period, a 12-month intervention period, followed by a 6-month sustainability period. Enrolled practices were independent, Federally Qualified Health Centers, network-based, and academic health centers. INSPIRE utilized the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework to examine implementation feasibility, fidelity, and performance of clinicians on practice adoption of screening, brief intervention, referral to treatment (SBIRT) and medication for unhealthy alcohol use (MAUD) activities in primary care clinics. Results: Seventeen eligible primary care practices were enrolled over the course of 21 months beginning in March of 2020 through December of 2021. There was a pause in recruitment from March of 2020 through July of 2020 due to the Covid-19 pandemic. The majority of enrolled practices were small (

Tobacco smoking is increasing in many low-and-middle-income countries, but data about initiation and cessation patterns are sparse, particularly in rural areas. We investigated changes in smoking status and their determinants in rural South Africa. Participants enrolled in the Vukuzazi population cohort in rural KwaZulu-Natal, South Africa completed a baseline tobacco behavioural survey during 1 May 2018 to 31 March 2020. A follow-up survey was conducted during 4 May 2021 to 18 November 2022 among all participants aged ≥15 years who reported current and former smoking at baseline (to detect cessation and relapse) and in a random selection of participants aged 15-29 years who reported never smoking at baseline (to detect initiation). We fit regression models to estimate smoking initiation (from never to current or former smoking), cessation (from current to former smoking) and relapse (from former to current smoking) between baseline and follow-up, and to investigate the sociodemographic and behavioural variables associated with each outcome. Of those recruited, 52% (754/1448) participated in the follow-up survey, which occurred a median of 3.0 years (IQR: 2.6-3.2) from baseline. Initiation, cessation and relapse occurrence was 12.0% (95% CI: 8.4-16.8), 12.9% (95% CI: 10.0-16.5) and 10.9% (95% CI: 4.4-24.2), respectively. Males had significantly higher odds of initiation than females (adjusted odds ratio [AOR] 12.81, 95% confidence interval [CI]: 3.54-46.36). Moderate/heavy smoking (≥10 products per day; AOR 0.27, 95% CI: 0.08-0.93 relative to light smoking

Honey bees balance colony populations against available food resources by adjusting brood rearing during nutritionally-stressed periods. Workers limit colony populations primarily through brood cannibalism of eggs and young larvae but often resume brood rearing when conditions improve. However, extended brood cannibalism reduces brood and removes brood signals that mediate brood rearing, such as E-β-ocimene, a volatile pheromone produced by eggs, young larvae, prepupae and ovipositing queens. We examined the effects of pollen supplementation on ocimene signaling in nutritionally-stressed colonies. Pollen-deprived colonies showed declines in ocimene emissions that coincided with sustained brood cannibalism of pheromone-producing brood. In contrast, pollen-supplemented colonies reared more brood and released more ocimene. Twelve day old workers that completed adult development in pollen-deprived colonies had less well developed hypopharyngeal glands and fat bodies than workers that matured in pollen-supplemented colonies. Given that ocimene emissions increased once brood rearing resumed, we considered the possibility that ocimene may help suppress brood cannibalism and support egg retention in nutritionally stressed nuc colonies. Broodless nucleus frames were treated with synthetic ocimene releases equivalent to 3,744 L2-L3 larvae. All ocimene-supplemented nucs retained large numbers of eggs and young larvae four days after initial treatment. By contrast, half of the unsupplemented nucs cannibalized all of their eggs and L1 larvae. Most of the remaining unsupplemented nuc colonies retained fewer eggs and L1 larvae than ocimene supplemented nuc colonies. E-B-ocimene may prime nutritionally stressed workers to increase brood rearing during dearth periods by projecting the presence of healthy eggs and young larvae.

Agronomic and weed management practices employed by growers in the production of snap bean (Phaseolus vulgaris) for the processing industry are poorly characterized. To address this knowledge gap, records of agronomic and weed management practices from 358 snap bean fields were obtained from collaborating processors. These fields encompassed three production regions in the United States: the Northwest (NW), Midwest (MW), and Northeast (NE). The obtained records were formatted to be more suitable for presentation or analysis. Forty cultivars were used across all three regions, primarily of green round podded type (∼90% of all fields). However, it was common for only relatively few cultivars to be widespread in each region. Seeding rates were substantially higher (by more than 100,000 plants/ha on average) in the NW region. Crop row widths were also narrower in the NW region compared with other regions. Planting and harvest occurred across a wide range of dates in all three production regions, with the NW having a delay of ∼10 days. The most common crop in rotation with snap bean was usually some type of corn, although the NW region had more variability in crop rotation. Spring tillage and irrigation were commonly used practices across all regions. Weed management was dominated by the use of interrow cultivation and a narrow spectrum of preemergence and postemergence herbicides. However, interrow cultivation was not used as much in the NW compared with the other two regions. Snap bean grown in the NW production region showed a departure in agronomic and weed management practices compared with the MW and NE production regions.

The DAF-2/insulin/insulin-like growth factor signaling (IIS) pathway plays an evolutionarily conserved role in regulating reproductive development, life span, and stress resistance. In Caenorhabditis elegans, DAF-2/IIS signaling is modulated by an extensive array of insulin-like peptides (ILPs) with diverse spatial and temporal expression patterns. However, the release dynamics and specific functions of these ILPs in adapting to different environmental conditions remain poorly understood. Here, we show that the ILP, insulin-3 (INS-3), plays a crucial role in modulating the response to various environmental stressors in C. elegans. ins-3 mutants display increased resistance to heat, oxidative stress, and starvation; however, this advantage is countered by slower reproductive development under favorable conditions. We find that ins-3 expression is downregulated in response to environmental stressors, whereas, the neurohormone tyramine, which is released during the acute flight response, increases ins-3 expression. We show that tyramine induces intestinal calcium (Ca2+) transients through the activation of the TYRA-3 receptor. Our data support a model in which tyramine negatively impacts environmental stress resistance by stimulating the release of INS-3 from the intestine via the activation of a TYRA-3-Gαq-IP3 pathway. The release of INS-3 systemically activates the DAF-2 pathway, resulting in the inhibition of cytoprotective mechanisms mediated by DAF-16/FOXO. These studies offer mechanistic insights into a brain-gut communication pathway that weighs adaptive strategies to respond to acute and long-term stressors.

IntroductionHaemodynamic atrioventricular delay (AVD) optimisation has primarily focussed on signals that are not easy to acquire from a pacing system itself, such as invasive left ventricular catheterisation or arterial blood pressure (ABP). In this study, standard clinical central venous pressure (CVP) signals are tested as a potential alternative.MethodsSixteen patients with a temporary pacemaker after cardiac surgery were studied. AV delay optimisation was performed by alternating between a reference AVD of 120ms and tested settings ranging from 40 to 280ms, with 8 replicates for each setting. Alongside (a) the raw data, three methods of correcting for respiration were tested: (b) limiting analysis to a respiratory cycle, (c) asymmetric least squares (ALS) and (d) discrete wavelet transform (DWT). The utility of a quality control step was tested.ResultsCVP signals were a mirror image of the systolic ABP signals: The four R values were -0.674, -0.692, -0.631, -0.671 respectively (all pConclusionsCentral venous pressure signals could be used to optimise AVD, because they have a reliable inverse relationship with ABP when pacemaker settings undergo protocolised testing. However, protocols need careful design to circumvent spontaneous biological variability.

Cognitive flexibility requires both the encoding of task-relevant and the ignoring of task-irrelevant stimuli. While the neural coding of task-relevant stimuli is increasingly well understood, the mechanisms for ignoring task-irrelevant stimuli remain poorly understood. Here, we study how task performance and biological constraints jointly determine the coding of relevant and irrelevant stimuli in neural circuits. Using mathematical analyses and task-optimized recurrent neural networks, we show that neural circuits can exhibit a range of representational geometries depending on the strength of neural noise and metabolic cost. By comparing these results with recordings from primate prefrontal cortex (PFC) over the course of learning, we show that neural activity in PFC changes in line with a minimal representational strategy. Specifically, our analyses reveal that the suppression of dynamically irrelevant stimuli is achieved by activity-silent, sub-threshold dynamics. Our results provide a normative explanation as to why PFC implements an adaptive, minimal representational strategy.

ObjectiveTo assess the burden of dietary iron deficiency in the Middle East and North Africa (MENA) region, focusing on prevalence and years lived with disability (YLD) in 2021 and their changes since 1990.MethodsData from the Global Burden of Disease (GBD) 2021 study were utilised to report counts and age-standardised rates for prevalence and YLD related to dietary iron deficiency. All estimates were accompanied by 95% uncertainty intervals (UIs).ResultsIn 2021, the age-standardised prevalence of dietary iron deficiency in the MENA region was 14368.2 per 100,000, representing a 26% decline since 1990. The highest age-standardised prevalence rates were observed in Yemen (30146.5), Sudan (19296.9), and Morocco (15,303) per 100,000 population. Prevalence was notably highest among children under 5 years old and women of reproductive age, with a gradual decline in older age groups. The greatest reductions in prevalence were seen among older age groups, indicating an age-related downward trend from 1990 to 2021.ConclusionDespite some improvements, dietary iron deficiency remains a significant public health concern in the MENA region, particularly in countries with lower socio-demographic indices (SDI). Targeted interventions are essential, especially for vulnerable groups such as children and women.

Hypereutrophic Grand Lake St Marys (GLSM) is a large (52 km2), shallow (mean depth ~ 1.5 m) reservoir in an agricultural watershed of western Ohio (USA). GLSM suffers from extensive cyanobacterial harmful algal blooms (cHABs) that persist much of the year, resulting in total microcystin concentrations that are often above safe contact levels. Over two summers (2020 and 2021), two phosphorus (P) binding agents (alum and lanthanum/bentonite clay Phoslock, respectively), in conjunction with a P-binding algaecide (SeClear) in 2021, were applied to a 3.24-ha enclosure to mitigate cHAB activity and create a ‘safe’ recreational space for the public. We evaluated these applications by comparing total phosphorus (TP), total microcystin, total chlorophyll, and phycocyanin concentrations within the enclosure and the adjacent lake. Some evidence for short-term reductions in TP, microcystin, chlorophyll, and phycocyanin concentrations were observed following each P binding treatment, but all parameters rapidly returned to or exceeded pre-application levels within 2–3 weeks after treatment. These results suggest that in-lake chemical treatments to mitigate cHABs are unlikely to provide long-lasting benefits in these semi-enclosed areas of large, shallow, hypereutrophic systems, and resources may be better applied toward reducing external nutrient loads (P and nitrogen) from the watershed.

Levayer and colleagues assessed integrity issues in randomized controlled trials (RCTs) in four spine journals using baseline p-values from categorical variables, concluding that there was no evidence of ‘systemic fraudulent behaviour’. We used their published dataset to assess the accuracy of reported p-values and whether observed and expected distributions of frequency counts and p-values were consistent. In 51 out of 929 (5.5%) baseline variables, the sum of frequencies did not agree with the reported number of participants. For one-third of reported p-values (172 out of 522), we could not calculate a matching p-value using a range of statistical tests. Sparse data were common: for 22% (74 out of 332) of variables in which the reported p-value matched the p-value calculated from a chi-square test, the expected cells were smaller than recommended for the use of chi-square tests. There were 20–25% more two-arm trials with differences in frequency counts of 1 or 2 between-groups than expected. There were small differences between observed and expected distributions of baseline p-values, but these depended on analysis methods. In summary, incorrectly reported p-values and incorrect statistical test usage were common, and there were differences between observed and expected distributions of baseline p-values and frequency counts, raising questions about the integrity of some RCTs in these journals.

This proof-of-concept study evaluated an optimization strategy for the Community Case Detection Tool (CCDT) aimed at improving community-level mental health detection and help-seeking among children aged 6–18 years. The optimization strategy, CCDT+, combined data-driven supervision with motivational interviewing techniques and behavioural nudges for community gatekeepers using the CCDT. This mixed-methods study was conducted from January to May 2023 in Palorinya refugee settlement in Uganda. We evaluated (1) the added value of the CCDT+ in improving the accuracy of detection and mental health service utilization compared to standard CCDT, and (2) implementation outcomes of the CCDT+. Of the 1026 children detected, 801 (78%) sought help, with 656 needing mental health care (PPV = 0.82; 95% CI: 0.79, 0.84). The CCDT+ significantly increased detection accuracy, with 2.34 times higher odds compared to standard CCDT (95% CI: 1.41, 3.83). Additionally, areas using the CCDT+ had a 2.05-fold increase in mental health service utilization (95% CI: 1.09, 3.83). The CCDT+ shows promise as an embedded quality-optimization process for the detection of mental health problems among children and enhance help-seeking, potentially leading to more efficient use of mental health care resources.

In recent years the evidence base for psychological interventions in low- and -middle-income countries (LMIC) has rapidly accrued, demonstrating that task-shifting models result in desired outcomes. Next, it is important to look at how this evidence translates into practice. In doing so, this paper argues that the field of global mental health might benefit from applying a system theory or system science perspective. Systems thinking aims to understand how different components are connected and interdependent within a larger emergent entity. At present much of the research efforts into psychological interventions in LMIC are focusing on single interventions, with little focus on how these interventions sit in, or influence, a larger system. Adopting systems theory and system dynamics tools can help in; (i) better analyzing and understanding the key drivers of mental health problems and services, (ii) optimizing mental health services; and (iii) understanding the organization of people, institutions and resources required for rolling out and scaling-up mental health services. This paper reflects on some of these merits of a systems perspective, as well as provides some examples.

Background Gait analysis is traditionally conducted using marker-based methods yet markerless motion capture is emerging as an alternative. Initial studies have begun to evaluate the reliability of markerless motion capture yet the evaluation of different clothing conditions across sessions and complete evaluation of the lower limb and pelvis reliability have yet to be considered. The aim of this study was to evaluate the inter-trial, inter-session and inter-session-clothing variation and root mean square differences between tight- or loose-fitting clothing during walking. Method Twenty-two healthy adult participants walked along an indoor walkway whilst eight video cameras recorded their gait in either tight- or loose-fitting clothing. A commercial markerless motion capture system (Theia3D) provided gait kinematics for evaluation. Results Reliability results showed average inter-trial variation of

BackgroundCampylobacter is associated with environmental enteric dysfunction (EED) and malnutrition in children. Campylobacter infection could be a linchpin between livestock fecal exposure and health outcomes in low-resource smallholder settings.MethodsWe followed a birth cohort of 106 infants in rural smallholder households in eastern Ethiopia up to 13 months of age. We measured anthropometry, surveyed sociodemographic determinants, and collected stool and urine samples. A short survey was conducted during monthly visits, infant stool samples were collected, and Campylobacter spp. was quantified using genus-specific qPCR. In month 13, we collected stool and urine samples to assay for EED biomarkers. We employed regression analyses to assess the associations of household determinants with Campylobacter colonization, EED, and growth faltering.ResultsThe Campylobacter load in infant stools increased with age. The mean length-for-age Z-score (LAZ) decreased from −0.45 at 3–4 months of age to −2.06 at 13 months, while the prevalence of stunting increased from 3 to 51%. The prevalence of EED at 13 months of age was 56%. A higher Campylobacter load was associated with more frequent diarrhea. Prelacteal feeding significantly increased Campylobacter load in the first month of life. Over the whole follow-up period, Campylobacter load was increased by keeping chickens unconfined at home and unsanitary disposal of infant stools while decreased by mothers’ handwashing with soap. Longitudinally, Campylobacter load was positively associated with food insecurity, introduction of complementary foods, and raw milk consumption. There were no significant associations between Campylobacter load, EED, and LAZ.ConclusionThis study found that most determinants associated with increased Campylobacter infection were related to suboptimal feeding practices and hygiene. The findings related to livestock-associated risks were inconclusive. Although stunting, EED, and Campylobacter prevalence rates all increased to high levels by the end of the first year of life, no significant association between them was identified. While additional research is needed to investigate whether findings from this study are replicable in other populations, community efforts to improve infant and young child feeding practices and food hygiene, and water, sanitation, and hygiene (WaSH) at the household level, could reduce (cross-)contamination at the point of exposure.

Objectives Platform trials were used successfully in adult populations during the COVID-19 pandemic. By testing multiple treatments within a single trial, platform trials can help identify the most effective treatments (and any interactions between treatments) for patients more quickly and with less burden for patients and their families. The aim of this qualitative research was to inform the design of the first adaptive platform trial for paediatric intensive care in the UK with young people, parents/carers and paediatric intensive care unit (PICU) staff.Design Qualitative semistructured focus group study. Data were analysed using reflexive thematic analysis.Participants Young people, parents/carers, and PICU medical, nursing and research staff.Setting The UK.Results A total of 86 participants (18 young people; 15 parents/carers; 53 PICU staff) took part in 1 of 10 focus groups between May and September 2023. Participants viewed the proposed PICU platform trial and use of research without prior consent to be acceptable. Findings provide insight into how the PICU platform trial should be designed and operationalised, including having a broad and inclusive population eligible for inclusion onto the platform trial, with different inclusion and exclusion criteria for each domain; starting the trial with no more than three domains and prioritising the outcomes of Child quality of life and Survival (all participants). Optimal governance structure and suggestions about how any challenges to the success of the full trial can be overcome are also presented.Conclusions Young people, parents/carers and PICU staff viewed the proposed PICU platform trial to be acceptable. These key stakeholders supported us with the design of an adaptive platform trial for PICU that has a rigorous methodology, yet can be operationalised in a family-centred way, to provide high-quality evidence that can support clinical decision-making and guide the treatment of critically ill children. Our findings have informed the PICU platform trial protocol.

Grape phylloxera, Daktulosphaira vitifoliae (Fitch), is an economically significant pest of grapevines. Identification of phylloxera genotypes is an important aspect of management as genotypes differ in virulence and susceptibility to control using resistant rootstocks. Microsatellite markers developed on polyacrylamide gel systems have been the most widely used molecular method for phylloxera genotype identification, but this approach has been superseded by fluorescent capillary-based genotyping. The current study presents new laboratory methods for amplifying a standard set of eight phylloxera microsatellite markers using PCR-incorporated fluorescently labelled primers, genotyped on an ABI capillary platform. Comparison of allele size data scored on (i) polyacrylamide, (ii) capillary, and (iii) high-throughput sequencing (HTS) platforms revealed that the capillary genotyping most closely matched the HTS allele sizes, while alleles of loci originally scored on a polyacrylamide platform differ in size by up to three base pairs, mostly due to the presence of previously uncharacterised DNA sequence indels. Seven common clonal lineages of phylloxera known from Australia are proposed as reference samples for use in calibrating genotyping systems between platforms and laboratories to ensure universal scoring of allele sizes, providing a critical link for accurately matching previous phylloxera genotype studies with current research.

This article explores Ephesians, asking how the theme of the new creation is developed in Ephesians. Rather than specifying matters like authorship, date, and recipients, it takes a broad view of the situation of the letter so that the focus can be on exploring the theme. It argues that the new creation idea is developed in three main ways. First, while Ephesians has a decidedly realized eschatology, there are hints throughout the letter of the consummation when the whole Earth is freed from corruption and reconciled under one head, Jesus Christ. Second, particularly in chapters 1–3, the writer of Ephesians focuses on realized aspects of eschatology to strengthen the readers’ understanding of their identity in Christ and their status as people of the new creation. The writer does this to strengthen the readers to assume the posture of the new creation while living in a fallen world beset with sin and under spiritual powers. In Ephesians 4–6, the writer describes this new creation virtues the readers are to embody as they contend for God in the world. Finally, the article explores the missional appeal of the letter. The writer challenges the readers to embody the new creation ethic and join God’s mission that calls all humankind to believe in the gospel and become people of the new creation.

Support to improve teacher wellbeing is scarce in almost all contexts, but especially so in low- and middle-income settings in which teachers face both professional and personal challenges (Kirk and Winthrop 2007; Mendenhall, Gomez, and Varni 2018). In this field note, we discuss War Child's development of Coaching-Observing-Reflecting-Engaging (CORE) for Teachers, an intervention that focuses on improving teachers' wellbeing. CORE is grounded in acceptance and commitment therapy and in the social-emotional framework of the Collaborative for Academic, Social, and Emotional Learning. It also draws from current research, including Jennings and Greenberg's (2009) prosocial classroom model. CORE aims to have a positive influence on classroom climate by providing teachers with the skills and knowledge they need to create an enabling, impactful, and safe learning environment for their students. In this field note, we outline the background on the development of the CORE intervention, including a literature review, the development of a theory of change, and field testing conducted in Chocó, Colombia. Having been field tested and adapted, CORE now is ready for further studies to determine feasibility and effectiveness.