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Abstract A plausible, but largely unexplored reason for many weed biocontrol agents failing to establish or being ineffective, could involve abiotically induced changes to an invasive plants’ biochemical phenotype and consequent enhanced herbivore resistance. Considerable literature demonstrates that chemically altered plant phenotypes can impair insect life history performance. Heather beetle, (Lochmaea suturalis), introduced to control invasive heather (Calluna vulgaris) in New Zealand (NZ) was difficult to establish and displays variable effectiveness. Using UHPLC-MS non-targeted metabolomics, we analysed primary and secondary metabolites of C. vulgaris from its native range (Scotland) and it’s introduced range (NZ), between which, differences in soil nutrients and ultraviolet light exist. We also explored secondary metabolite variation between sites within each range. New Zealand samples had the highest number of amplified metabolites, most notably defensive phenylpropanoids, supporting the concept of abiotically induced upregulation of key biosynthetic pathways. Analysis of secondary metabolite variation within each range revealed differences between sites but found little correlation of phenylpropanoid levels being influenced by variable soil nutrients. These results validate questions about the possibility of abiotically altered biochemical phenotypes in invasive plants, influencing weed biocontrol agent establishment and effectiveness, and show the potential for metabolomics in assisting future, or retrospectively analysing biological control programmes.

Abstract Background Colorectal cancer is a public health issue and was the third leading cause of cancer-related death worldwide in 2022. Early diagnosis can improve prognosis, making screening a central part of colorectal cancer management. Blood-based screening, diagnosis and follow-up of colorectal cancer patients are possible with the study of cell-free circulating tumor DNA. This study aimed to identify novel DNA methylation biomarkers of colorectal cancer that can be used for the follow-up of patients with colorectal cancer. Methods A DNA methylation profile was established in the Gene Expression Omnibus (GEO) database (n = 507) using bioinformatics analysis and subsequently confirmed using The Cancer Genome Atlas (TCGA) database (n = 348). The in silico profile was then validated on local tissue and cell-free DNA samples using methylation-specific digital PCR in colorectal cancer patients (n = 35) and healthy donors (n = 35). Results The DNA methylation of COL25A1 and METAP1D was predicted to be a colorectal cancer biomarker by bioinformatics analysis (ROC AUC = 1, 95% CI [0.999–1]). The two biomarkers were confirmed with tissue samples, and the combination of COL25A1 and METAP1D yielded 49% sensitivity and 100% specificity for cell-free DNA. Conclusion Bioinformatics analysis of public databases revealed COL25A1 and METAP1D DNA methylation as clinically applicable liquid biopsies DNA methylation biomarkers. The specificity implies an excellent positive predictive value for follow-up, and the high sensitivity and relative noninvasiveness of a blood-based test make these biomarkers compatible with colorectal cancer screening. However, the clinical impact of these biomarkers in colorectal cancer screening and follow-up needs to be established in further prospective studies.

Introduction Diabetic kidney disease (DKD) is a common cause of chronic kidney disease with around 25-40% of patients with diabetes being affected. The course of DKD is variable and estimated glomerular filtration rate (eGFR) and albuminuria, the currently used clinical markers, are not able to accurately predict the individual disease trajectory, in particular in early stages of the disease. The aim of this study was to assess the association of urine levels of selected protein biomarkers with the progression of DKD at an early stage of disease. Methods We measured 22 protein biomarkers using the Mesoscale Discovery platform in 461 urine samples of the PROVALID cohort, an observational study of patients with type 2 diabetes mellitus followed at the primary health care level for a minimum of four years. Odds ratios (OR) were estimated for the effect of marker values above median on fast progression using unadjusted and adjusted logistic regression models. RNA expression at the single cell level in kidney biopsy samples obtained from a cohort of young persons with type 2 diabetes mellitus was in addition determined for markers showing significant associations with disease progression. Results Increased urinary levels of epidermal growth factor (EGF) were linked to lower odds of fast progression (defined as annual eGFR decline greater than 2.58 ml/min per 1.73 m2) with an odds ratio (OR) of 0.60 (95% CI 0.46, 0.78). The association with outcome was even stronger when adjusting for a set of 14 baseline clinical parameters including age, biological sex, eGFR, body mass index, albuminuria, and HbA1c. Elevated urinary levels of fatty acid binding protein 3 (FABP3) and vascular cell adhesion molecule 1 (VCAM1) were each significantly associated with fast progression with an OR of 1.44 (95% CI 1.11, 1.87) and an OR of 1.41 (95% CI 1.08, 1.83), respectively. Enriched expression of EGF and FABP3 was observed in distal convoluted tubular cells and VCAM1 in parietal epithelial cells at single cell level from biopsies of patients with early DKD. Conclusion In summary we show that lower urinary levels of EGF and higher urinary levels of FABP3 and VCAM1 are significantly associated with DKD progression in early-stage disease.

Abstract Background Effective physician-patient communication is crucial to compassionate healthcare, particularly when conveying life-altering diagnoses such as those associated with congenital heart diseases. Despite its importance, medical practitioners often face challenges in communicating effectively. Because of these gaps, we aim to introduce a simulation-based training protocol to improve pediatric cardiology trainee’s communication skills. This study will be conducted in collaboration with associations supporting caregivers of children with congenital heart disease. It strives to demonstrate how specific training programs can efficiently foster humanistic, patient-centered care in standard medical practice. Methods This multicenter, open-label randomized controlled trial will be conducted in pediatric cardiac units and simulation centers of across 10 universities in France. The study population comprises pediatric cardiologists in training (including pediatric cardiac fellows or specialist assistants). The SIMUL-CHD intervention will consist of simulation-based training with standardized patients, focusing on improving communication skills for pediatric cardiology trainees during diagnostic counselling. Patients and caregivers have been recruited from a National Patient Association named “Petit Cœur de Beurre”. The primary outcome is the quality of physicians’ communication skills. The evaluation committee, which will review video recordings of the sessions, will be blinded to which participants received simulation-based training (group of interest) and which received theory-based training (control group). Secondary outcomes are the effect of SIMUL-CHD on empathy and anxiety levels in young pediatric cardiologists. Baseline scores pre and post-intervention will be compared, and skill improvement resulting from the intervention measured. Discussion Simulation-based training has proven efficacy in teaching technical skills in various scenarios however its application to communication skills in pediatric cardiology remains unexplored. The involvement of experienced parents provides a unique perspective, incorporating their profound understanding of the emotional challenges and specific hurdles faced by families dealing with congenital heart disease. Trial registration This trial is registered with the OSF registry (registered https://osf.io/ed78q ).

Abstract Objective In our study, we aim to explore the structural differences between the aortic root and the pulmonary artery to better understand the process of pulmonary autograft dilatation during the Ross procedure. Materials and methods We studied twenty human fetuses (aged 14–36 weeks of gestation) and four adults (one female and three males, aged 30–45 years, mean age = 37 ± 16 years). Samples of aortic root and pulmonary artery were obtained through dissection. Histological examinations, including hematoxylin–eosin, Masson’s trichrome, and orcein staining, as well as immunohistochemical technique with caldesmon staining, were performed. Microscopic counting was conducted to assess the number of elastic laminae and smooth muscle cells in each arterial wall. Statistical analyses were performed using R software. Means and standard deviations were used to present central tendencies and data dispersion for elastic laminae and smooth muscle. Results Significant histological differences were observed between the aortic root and pulmonary artery in both adults and fetuses. In fetuses, no difference was found between the two vessels in terms of elastic laminae (p = 0.26) and smooth muscle cells (p = 0.69). However, in adults, significant differences were found for elastic laminae (p

Abstract Background Few studies have quantified multimorbidity and frailty trends within hospital settings, with even fewer reporting how much is attributable to the ageing population and individual patient factors. Studies to date have tended to focus on people over 65, rarely capturing older people or stratifying findings by planned and unplanned activity. As the UK’s national health service (NHS) backlog worsens, and debates about productivity dominate, it is essential to understand these hospital trends so health services can meet them. Methods Hospital Episode Statistics inpatient admission records were extracted for adults between 2006 and 2021. Multimorbidity and frailty was measured using Elixhauser Comorbidity Index and Soong Frailty Scores. Yearly proportions of people with Elixhauser conditions (0, 1, 2, 3 +) or frailty syndromes (0, 1, 2 +) were reported, and the prevalence between 2006 and 2021 compared. Logistic regression models measured how much patient factors impacted the likelihood of having three or more Elixhauser conditions or two or more frailty syndromes. Results were stratified by age groups (18–44, 45–64 and 65 +) and admission type (emergency or elective). Results The study included 107 million adult inpatient hospital episodes. Overall, the proportion of admissions with one or more Elixhauser conditions rose for acute and elective admissions, with the trend becoming more prominent as age increased. This was most striking among acute admissions for people aged 65 and over, who saw a 35.2% absolute increase in the proportion of admissions who had three or more Elixhauser conditions. This means there were 915,221 extra hospital episodes in the last 12 months of the study, by people who had at least three Elixhauser conditions compared with 15 years ago. The findings were similar for people who had one or more frailty syndromes. Overall, year, age and socioeconomic deprivation were found to be strongly and positively associated with having three or more Elixhauser conditions or two or more frailty syndromes, with socioeconomic deprivation showing a strong dose–response relationship. Conclusions Overall, the proportion of hospital admissions with multiple conditions or frailty syndromes has risen over the last 15 years. This matches smaller-scale and anecdotal reports from hospitals and can inform how hospitals are reimbursed.

Abstract With the ever-growing reliance on polymeric materials for numerous applications, new avenues to induce, design and control degradation are clearly important. Here, we describe a previously unreported approach to controlling enzymatic hydrolysis of high molecular weight branched polymers formed from the new free-radical polymer synthesis strategy transfer-dominated branching radical telomerisation (TBRT). Modifying the chemical nature of TBRT polymers may be accomplished through telogen selection and multi-vinyl taxogen (MVT) design, and we show telogen-driven control of enzyme-catalysed hydrolysis and the impact of careful placement of hydrolytically susceptible groups within readily synthesised MVTs. Our results indicate that utilising conventional free-radical chemistries and unsaturated monomers as feedstocks for highly branched polymer architectures has considerable potential for the design of future materials that degrade into very low molecular weight byproducts at variable and controllable rates.

Abstract Introduction Recurrent Clostridioides difficile infection (rCDI) often occurs after standard-of-care antibiotics. VOWST oral spores (VOS, previously SER-109), an FDA-approved orally administered microbiome therapeutic, is indicated to prevent rCDI following antibiotics for rCDI. Objective, Design, and Patients To evaluate safety and efficacy of VOS from two phase 3 trials, (randomized, placebo-controlled [ECOSPOR III: NCT03183128] and open-label, single arm [ECOSPOR IV: NCT03183141]) of 349 adults with rCDI and prevalent comorbidities. Methods VOS or placebo [ECOSPOR III only] (4 capsules once daily for 3 days). Integrated analysis of treatment-emergent adverse events (TEAEs) collected through week 8; serious TEAEs and TEAEs of special interest collected through week 24; and rates of rCDI (toxin-positive diarrhea requiring treatment) evaluated through weeks 8 and 24. Results TEAEs were mostly mild or moderate and gastrointestinal. Most common treatment-related TEAEs were flatulence, abdominal pain and distension, fatigue, and diarrhea. There were 11 deaths (3.2%) and 48 patients (13.8%) with serious TEAEs, none treatment-related. The rCDI rate through week 8 was 9.5% (95% CI 6.6–13.0) and remained low through 24 weeks (15.2%; 95% CI 11.6–19.4). Safety and rCDI rates were consistent across subgroups including age, renal impairment/failure, diabetes, and immunocompromise/immunosuppression. Conclusions VOS was well tolerated and rates of rCDI remained low through week 24 including in those with comorbidities. These data support the potential benefit of VOS following antibiotics to prevent recurrence in high-risk patients. Trial Registration ClinicalTrials.gov identifier, NCT03183128 and NCT03183141.

Abstract Within the Industry 4.0 landscape, humans collaborate with cyber and physical elements to form human‐cyber‐physical systems (HCPS). These environments are increasingly complex and challenging workspaces due to increasing levels of automation and data availability. An effective system design requires suitable frameworks that consider human activities and needs whilst supporting overall system efficacy. Although several reviews of frameworks for technology were identified, none of these focused on the human in the system (moving towards Industry 5). The critical literature review presented provides a summary of HCPS frameworks, maps the considerations for a human in HCPS, and provides insight for future framework and system development. The challenges, recommendations, and areas for further research are discussed.

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (

In the rapidly evolving field of plasmonic metasurfaces, achieving homogeneous, reliable, and reproducible fabrication of sub-5 nm dielectric nanogaps is a significant challenge. This article presents an advanced fabrication technology that addresses this issue, capable of realizing uniform and reliable vertical nanogap metasurfaces on a whole wafer of 100 mm diameter. By leveraging fast patterning techniques, such as variable-shaped and character projection electron beam lithography (EBL), along with atomic layer deposition (ALD) for defining a few nanometer gaps with sub-nanometer precision, we have developed a flexible nanofabrication technology to achieve gaps as narrow as 2 nm in plasmonic nanoantennas. The quality of our structures is experimentally demonstrated by the observation of resonant localized and collective modes corresponding to the lattice, with Q-factors reaching up to 165. Our technological process opens up new and exciting opportunities to fabricate macroscopic devices harnessing the strong enhancement of light–matter interaction at the single nanometer scale.

Abstract Background Comprehensive care is important for ensuring patients receive coordinated delivery of healthcare that aligns with their needs and preferences. While comprehensive care programs are recognised as beneficial, optimal implementation strategies in the real world remain unclear. This study utilises existing implementation theory to investigate barriers and enablers to implementing the Australian National Safety and Quality Health Service Standard 5 - Comprehensive Care Standard in acute care hospitals. The aim is to develop implementation enhancement strategies for work with comprehensive care standards in acute care. Methods Free text data from 256 survey participants, who were care professionals working in acute care hospitals across Australia, were coded using the Consolidated Framework for Implementation Research (CFIR) using deductive content analysis. Codes were then converted to barrier and enabler statements and themes using inductive theme analysis approach. Subsequently, CFIR barriers and enablers were mapped to the Expert Recommendations for Implementing Change (ERIC) using the CFIR-ERIC Matching Tool, facilitating the development of implementation enhancement strategies. Results Twelve (n = 12) CFIR barriers and 10 enablers were identified, with 14 barrier statements condensed into 12 themes and 11 enabler statements streamlined into 10 themes. Common themes of barriers include impact of COVID-19 pandemic; heavy workload; staff shortage, lack of skilled staff and high staff turnover; poorly integrated documentation system; staff lacking availability, capability, and motivation; lack of resources; lack of education and training; culture of nursing dependency; competing priorities; absence of tailored straties; insufficient planning and adjustment; and lack of multidisciplinary collaboration. Common themes of enablers include leadership from CCS committees and working groups; integrated documentation systems; established communication channels; access to education, training and information; available resources; culture of patient-centeredness; consumer representation on committees and working groups; engaging consumers in implementation and in care planning and delivery; implementing changes incrementally with a well-defined plan; and regularly collecting and discussing feedback. Following the mapping of CFIR enablers and barriers to the ERIC tool, 15 enhancement strategies were identified. Conclusion This study identified barriers, enablers, and recommended strategies associated with implementing a national standard for comprehensive care in Australian acute care hospitals. Understanding and addressing these challenges and strategies is not only crucial for the Australian healthcare landscape but also holds significance for the broader international community that is striving to advance comprehensive care.

Abstract Background Malaria community case management (CCM) can improve timely access to healthcare, and CCM programmes in sub-Saharan Africa are expanding from serving children under 5 years (CU5) only to all ages. This report characterizes malaria case management in the setting of an age-expanded CCM programme in Chadiza District, Zambia. Methods Thirty-three households in each of 73 eligible communities were randomly selected to participate in a household survey preceding a trial of proactive CCM (NCT04839900). All household members were asked about fever in the prior two weeks and received a malaria rapid diagnostic test (RDT); those reporting fever were asked about healthcare received. Weighted population estimates were calculated and mixed effects regression was used to assess factors associated with malaria care seeking. Results Among 11,030 (98.6%) participants with RDT results (2,357 households), parasite prevalence was 19.1% by RDT; school-aged children (SAC, 5–14 years) had the highest prevalence (28.8%). Prior fever was reported by 12.4% of CU5, 7.5% of SAC, and 7.2% of individuals ≥ 15 years. Among those with prior fever, 34.0% of CU5, 56.0% of SAC, and 22.6% of individuals ≥ 15 years had a positive survey RDT and 73.7% of CU5, 66.5% of SAC, and 56.3% of individuals ≥ 15 years reported seeking treatment; 76.7% across all ages visited a CHW as part of care. Nearly 90% (87.8%) of people who visited a CHW reported a blood test compared with 73.5% seen only at a health facility and/or pharmacy (p

Background In patients with coronavirus disease 2019 (COVID-19) requiring supplemental oxygen, dexamethasone reduces acute severity and improves survival, but longer-term effects are unknown. We hypothesised that systemic corticosteroid administration during acute COVID-19 would be associated with improved health-related quality of life (HRQoL) 1 year after discharge. Methods Adults admitted to hospital between February 2020 and March 2021 for COVID-19 and meeting current guideline recommendations for dexamethasone treatment were included using two prospective UK cohort studies (Post-hospitalisation COVID-19 and the International Severe Acute Respiratory and emerging Infection Consortium). HRQoL, assessed by the EuroQol-Five Dimensions–Five Levels utility index (EQ-5D-5L UI), pre-hospital and 1 year after discharge were compared between those receiving corticosteroids or not after propensity weighting for treatment. Secondary outcomes included patient-reported recovery, physical and mental health status, and measures of organ impairment. Sensitivity analyses were undertaken to account for survival and selection bias. Findings Of the 1888 participants included in the primary analysis, 1149 received corticosteroids. There was no between-group difference in EQ-5D-5L UI at 1 year (mean difference 0.004, 95% CI −0.026–0.034). A similar reduction in EQ-5D-5L UI was seen at 1 year between corticosteroid exposed and nonexposed groups (mean±sd change −0.12±0.22 versus −0.11±0.22). Overall, there were no differences in secondary outcome measures. After sensitivity analyses modelled using a cohort of 109 318 patients admitted to hospital with COVID-19, EQ-5D-5L UI at 1 year remained similar between the two groups. Interpretation Systemic corticosteroids for acute COVID-19 have no impact on the large reduction in HRQoL 1 year after hospital discharge. Treatments to address the persistent reduction in HRQoL are urgently needed.

Vertical farming is considered to be a key enabler for transforming agrifood systems, especially in or nearby urbanized areas. Vertical farming systems (VFS) are advanced indoor cropping systems that allow for highly intensified and standardized plant production. The close control of environmental parameters makes crop production stable and repeatable, ensuring year-round uniform product quality and quantity irrespective of location. However, due to continuous changes in plant physiology and development, as well as frequent changes in electricity prices, the optimum conditions for crop production and its associated costs can change within days or even minutes. This makes it beneficial to dynamically adjust setpoints for light (intensity, spectrum, pattern, and daylength), CO2, temperature, humidity, air flow, and water and nutrient availability. In this review, we highlight the beneficial effects that dynamic growth conditions can have on key plant processes, including improvements in photosynthetic gas exchange, transpiration, organ growth, development, light interception, flowering, and product quality. Our novel findings based on modeling and experimentation demonstrate that a dynamic daily light intensity pattern that responds to frequent changes in electricity prices can save costs without reducing biomass. Further, we argue that a smart, dynamic VFS climate management requires feedback mechanisms: several mobile and immobile sensors could work in combination to continuously monitor the crop, generating data that feeds into crop growth models, which, in turn, generate climate setpoints. In addition, we posit that breeding for the VFS environment is at a very early stage and highlight traits for breeding for this specialized environment. We envision a continuous feedback loop between dynamic crop management, crop monitoring, and trait selection for genotypes that are specialized for these conditions.

Burn care quality indicators are used to monitor and improve quality of care and for benchmark purposes. The perspectives of burn survivors, however, are not included in current sets of quality indicators while patient-centred care gains importance. The aim of this study was to explore burn survivors’ perspectives on quality aspects of burn care, which was used to translate their perspectives into patient-centred quality of care indicators. Qualitative descriptive research was conducted in a patient panel group. First, thematic analysis was applied to the focus groups to identify overarching themes. Second, patient-centred quality indicators, informed by burn survivors’ valued aspects of care, were defined. Ten burn survivors with an average age of 54 years (SD = 11; range 38–72 years) and mean TBSA burned of 14% (SD = 11%; range 5–35%) participated in two focus groups. Four overarching themes were identified, pointing to the importance of (1) information tailored to the different phases of recovery, (2) significant others’ wellbeing and involvement, (3) a therapeutic relationship and low-threshold access to healthcare professionals and (4) to participate in decision-making. Eighteen patient-centred process quality of care indicators within nine aspects of care were formulated. The overarching themes are reflected in patient-centred quality indicators, which present a broadened and complementary view of existing clinical quality indicators for burn care. Evaluating these patient-centred quality indicators may increase quality of care and refine patient-centred care.

In this study, we consider the introduction of new mobility services and technologies into the megacity of Beijing, China, as per developed strategy and action plans, in order to investigate their potential contribution to sustainable mobility. This includes population relocation (decentralization), the construction of new rail lines, the introduction of shared bike services as a feeder to subway stations, the electrification of passenger vehicles and the adoption of automated and shared vehicles. The well-established, system dynamics-based MARS model is adapted to Beijing and further improved via the inclusion of these new services, technologies and policies. We find that decentralization can have a profound effect on overall sustainability if not considered in conjunction with other policies and that new rail lines and shared bikes may only have benefits in specific zones. Shared and automated vehicles could increase VKT by 60% and reduce active and public transport trips by a quarter. As such, nuanced integrated policy approaches will be required that are similar to those currently in place, such as imposed car shedding and taxi fleet control.

Abstract Background People with serious mental health problems (SMHP) are more likely to be admitted to psychiatric hospital following contact with crisis services. Admissions can have significant personal costs, be traumatic and are the most expensive form of mental health care. There is an urgent need for treatments to reduce suicidal thoughts and behaviours and reduce avoidable psychiatric admissions. Methods A multi-stage, multi-arm (MAMS) randomised controlled trial (RCT) with four arms conducted over two stages to determine the clinical and cost effectiveness of three psychosocial treatments, compared to treatment as usual (TAU), for people with SMHP who have had recent suicidal crisis. Primary outcome is any psychiatric hospital admissions over a 6-month period. We will assess the impact on suicidal thoughts and behaviour, hope, recovery, anxiety and depression. The remote treatments delivered over 3 months are structured peer support (PREVAIL); a safety planning approach (SAFETEL) delivered by assistant psychologists; and a CBT-based suicide prevention app accessed via a smartphone (BrighterSide). Recruitment is at five UK sites. Stage 1 includes an internal pilot with a priori progression criteria. In stage 1, the randomisation ratio was 1:1:1:2 in favour of TAU. This has been amended to 2:2:3 in favour of TAU following an unplanned change to remove the BrighterSide arm following the release of efficacy data from an independent RCT. Randomisation is via an independent remote web-based randomisation system using randomly permuted blocks, stratified by site. An interim analysis will be performed using data from the first 385 participants from PREVAIL, SAFETEL and TAU with outcome data at 6 months. If one arm is dropped for lack of benefit in stage 2, the allocation ratio of future participants will be 1:1. The expected total sample size is 1064 participants (1118 inclusive of BrighterSide participants). Discussion There is a need for evidence-based interventions to reduce psychiatric admissions, via reduction of suicidality. Our focus on remote delivery of established brief psychosocial interventions, utilisation of different modalities of delivery that can provide sustainable and scalable solutions, which are also suitable for a pandemic or national crisis context, will significantly advance treatment options. Trial registration ISRCTN33079589. Registered on June 20, 2022.

Erectile dysfunction (ED) poses a significant challenge in clinical practice, necessitating accurate diagnostic strategies to distinguish between organic and psychogenic causes. Current guidelines advocate a comprehensive approach involving medical history, physical examination and blood tests, with second-level analyses like the intracavernous injection of vasoactive drugs (ICI test) and penile duplex ultrasound (PDU) reserved for specific cases. A survey involving 24 urologists experienced in ED was conducted to assess their opinions on the appropriateness of the ICI test and PDU in six clinical scenarios. Results were analyzed using pie charts, revealing varied preferences among experts. The responses indicated diverse viewpoints, with preferences for the ICI test or PDU depending on the patient’s age, comorbidities, response to phosphodiesterase type 5 inhibitors (PDE5i) and concomitant Peyronie’s disease. In some cases, a significant proportion of experts opted for neither test. The study highlights the lack of consensus among experts regarding the routine use of PDU in ED management. Despite its diagnostic capabilities, the clinical utility of PDU remains unclear, and its role may be more justified in certain populations with anatomical abnormalities or specific conditions. The need for rigorous research to determine the impact of PDU on ED management decision-making is emphasized.

Abstract Background The presence of nucleated red blood cells (NRBCs) in the peripheral blood of critically ill patients is associated with poor outcome. Evidence regarding the predictive value of NRBCs in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) remains elusive. The aim of this study was to evaluate the predictive validity of NRBCs in these patients. Methods Daily NRBC values of adult patients with SARS-CoV-2-induced ARDS were assessed and their predictive validity for mortality was statistically evaluated. A cut-off level based on the patient’s maximum NRBC value during ICU stay was calculated and further specified according to Youden’s method. Based on this cut-off value, further analyses such as logistic regression models and survival were performed. Results 413 critically ill patients with SARS-CoV-2-induced ARDS were analyzed. Patients who did not survive had significantly higher NRBC values during their ICU stay compared to patients who survived (1090/µl [310; 3883] vs. 140/µl [20; 500]; p

The first registered Paeonia Itoh hybrid cv. Hexie in China is a naturally occurring intersectional hybrid of Sect. Paeonia and Sect. Moutan. In this study, we sequenced, assembled, and analyzed the complete chloroplast genome of Paeonia Itoh hybrid cv. Hexie. The result showed that the chloroplast genome of Hexie, with a typical circular tetrad structure, is 152,958 bp in length, comprising a large single copy (LSC) region of 84,613 bp, a small single copy (SSC) region of 17,051 bp, and two reverse complementary sequences (IRs) of 25,647 bp. The chloroplast genome encoded 116 genes, including 80 protein-coding genes, 32 tRNA genes, and 4 rRNA genes. Phylogenetic analysis inferred from the shared protein-coding genes showed that the Paeonia Itoh hybrid cv. Hexie had the closest phylogenetic relationship with P. suffruticosa, followed by P. ostii, indicating that P. suffruticosa was its maternal parent. This study provides a molecular resource for phylogenetic and maternal parent studies of Paeonia Itoh hybrid, contributing to a basis for Paeonia Itoh hybrid breeding strategies in the future.

Abstract Both unresolved physics in numerical models and limited theoretical understanding of the small-scale diffusion processes occurring near the ocean surface hamper predictability of tropical cyclone (TC) wind changes. An analytical model is here developed to diagnose the short-term evolution of the TC wind profile. An effective frictional parameter is introduced to control the unknown diffusion effects. When this frictional parameter is adjusted to match the TC intensity change, solutions are consistent with observed high-resolution ocean surface wind speeds from satellite synthetic aperture radar (SAR). The initial high-resolution estimate of the near-core wind structure is then found to strongly modulate the wind profile evolution. The frictional parameter can, unfortunately, not efficiently be calibrated using outer-core wind speed changes. Low-resolution observations or standard numerical weather predictions may thus not be directly used to reinterpret and anticipate short-term TC wind changes. The expected accumulation of orbiting SAR sensors as well as improved measurements of the ocean-atmosphere boundary layer characteristics shall then become essential to more precisely monitor TC dynamics.

Objectives To examine trajectories of functional limitations, fatigue, health-related quality of life (HRQL) and societal costs of patients referred to long COVID clinics.Design A population-based longitudinal cohort study using real-time user data.Setting 35 specialised long COVID clinics in the UK.Participants 4087 adults diagnosed with long COVID in primary or secondary care deemed suitable for rehabilitation and registered in the Living With Covid Recovery (LWCR) programme between 4 August 2020 and 5 August 2022.Main outcome measures Generalised linear mixed models were fitted to estimate trajectories of functional limitations, using the Work and Social Adjustment Scale (WSAS); scores of ≥20 indicate moderately severe limitations. Other outcomes included fatigue using the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) reversed score (scores of ≥22 indicate impairment), HRQL using the EQ-5D-5L, and long COVID-related societal costs, encompassing healthcare costs and productivity losses.Results The mean WSAS score at 6 months after registration in the LWCR was 19.1 (95% CI 18.6, 19.6), with 46% of the participants (95% CI 40.3%, 52.4%) reporting a WSAS score above 20 (moderately severe or worse impairment). The mean change in the WSAS score over the 6-month period was −0.86 (95% CI −1.32, –0.41). The mean reversed FACIT-F score at 6 months was 29.1 (95% CI 22.7, 35.5) compared with 32.0 (95% CI 31.7, 32.3) at baseline. The mean EQ-5D-5L score remained relatively constant between baseline (0.63, 95% CI 0.62, 0.64) and 6 months (0.64, 95% CI 0.59, 0.69). The monthly societal cost per patient related to long COVID at 6 months was £931, mostly driven by the costs associated with working days lost.Conclusions Individuals referred to long COVID clinics in the UK reported small improvements in functional limitations, fatigue, HRQL and ability to work within 6 months of registering in the LWCR programme.

Background: Chronic stress has a profound impact on circadian regulation of physiology. In turn, disruption of circadian rhythms increases the risk of developing both psychiatric and metabolic disorders. To explore the role of chronic stress in modulating the links between neural and metabolic rhythms, we characterized the circadian transcriptional regulation across different brain regions and the liver as well as serum metabolomics in mice exposed to chronic social defeat stress, a validated model for studying depressive-like behaviors. Methods: Male C57BL/6J mice underwent chronic social defeat stress, and subsequent social interaction screening identified distinct behavioral phenotypes associated with stress resilience and susceptibility. Stressed mice and their control littermates were sacrificed every 4 hours over the circadian cycle for comprehensive analyses of the circadian transcriptome in the hypothalamus, hippocampus, prefrontal cortex, and liver together with assessments of the circadian circulatory metabolome. Results: Our data demonstrate that stress adaptation was characterized by reprogramming of the brain as well as the hepatic circadian transcriptome. Stress resiliency was associated with an increase in cyclic transcription in the hypothalamus, hippocampus, and liver. Furthermore, cross-tissue analyses revealed that resilient mice had enhanced transcriptional coordination of circadian pathways between the brain and liver. Conversely, susceptibility to social stress resulted in a loss of cross-tissue coordination. Circadian serum metabolomic profiles corroborated the transcriptome data, highlighting that stress-resilient mice gained circadian rhythmicity of circulating metabolites, including bile acids and sphingomyelins. Conclusions: This study reveals that resilience to stress is characterized by enhanced metabolic rhythms and circadian brain-liver transcriptional coordination.

Ultrasonic delamination is a low energy approach for direct recycling of spent lithium-ion batteries. The efficiency of the ultrasonic delamination relies both on the thermophysical properties (such as viscosity, surface tension, and vapour pressure) of the solvent in which the delamination process is carried out, and the properties of the ultrasound source as well as the geometry of the containment vessel. However, the effect of tailoring solutions to optimise cavitation and delamination of battery cathode coatings has not yet been sufficiently investigated. Acoustic detection, high-speed imaging, and sonochemiluminescence (SCL) are employed to study the cavitation processes in water-glycol systems and identify the effect of tailoring solvent composition on cavitation strength. The addition of small volume fractions of organic solvent (ca. 10–30 vol%), including ethylene glycol or glycerol, to the aqueous delamination solution were found to significantly improve the delamination efficiency of lithium-ion battery cathode coatings due to the alteration of these thermophysical properties. However, greater volume fractions of glycol decrease delamination efficiency due to the signal-dampening effect of viscosity on the ultrasonic waves. The findings of this study offer valuable insights for optimising ultrasonic bath solution composition to enhance film delamination processes.

BackgroundCurrently, patients with cystic fibrosis do not routinely monitor their respiratory function at home. ObjectiveThis study aims to assess the clinical validity of using different connected health devices at home to measure 5 physiological parameters to help prevent exacerbations on a personalized basis from the perspective of patient empowerment. MethodsA multicenter interventional pilot study including 36 patients was conducted. Statistical process control—the cumulative sum control chart (CUSUM)—was used with connected health device measures with the objective of sending patients alerts at a relevant time in order to identify their individual risk of exacerbations. Associated patient education was delivered. Quantitative and qualitative data were collected. ResultsOne-half (18/36) of the patients completed the protocol through the end of the study. During the 12-month intervention, 6162 measures were collected with connected health devices, 387 alerts were sent, and 33 exacerbations were reported. The precision of alerts to detect exacerbations was weak for all parameters, which may be partly related to the low compliance of patients with the measurements. However, a decrease in the median number of exacerbations from 12 months before the study to after the 12-month intervention was observed for patients. ConclusionsThe use of connected health devices associated with statistical process control showed that it was not acceptable for all patients, especially because of the burden related to measurements. However, the results suggest that it may be promising, after adaptations, for early identification and better management of exacerbations. Trial RegistrationClinicalTrials.gov NCT03304028; https://clinicaltrials.gov/study/NCT03304028

Objectives Early treatment of individuals at risk of developing rheumatoid arthritis (RA-risk) in the preclinical phase has the potential to positively impact both patients and society by preventing disease onset and improving patients’ quality of life. The PRAIRI study was a randomised, double-blind, placebo-controlled trial with the B-cell depleting agent rituximab (RTX), which resulted in a significant delay of arthritis development of up to 12 months in seropositive RA-risk individuals. Here, we report our findings on patient-reported outcomes (PROs) in this study population.Methods Seventy-eight RA-risk individuals were treated with one single dose of either placebo (PBO) or 1000 mg RTX plus 100 mg methylprednisolone (MP) and anti-histamines, regardless of treatment allocation, as co-medication. Data on quality of life were collected at baseline and 1, 4, 6, 12 and 24 months using established PRO questionnaires (visual analogue scale (VAS) pain, health assessment questionnaire disability index (HAQ-DI) score, EuroQol five dimension (EQ-5D) and both physical and mental component score of the 36-item short-form heath survey (SF-36)).Results No significant changes in quality of life over a 2 year follow-up were observed in at-risk individuals treated with RTX compared to PBO given the PRO scores at 24 months (mean difference±SEM: HAQ score=0.07±0.16; EQ-5D=−0.02±0.05; VAS pain=11.11±7.40). Furthermore, no significant effect of treatment on perceived arthritis severity at the time of clinically manifest disease (arthritis) was found.Conclusion One single dose of RTX plus MP administered to RA-risk individuals does not have a meaningful and measurable positive effect on PROs after 2 years of follow-up and/or perceived disease severity at the time of arthritis development.Trial registration number Trial registered at EU Clinical Trial Register, EudraCT Number: 2009-010955-29 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=Prevention+of+RA+by+B+cell+directed+therapy).

ABSTRACT The Enterobacteriaceae are a scientifically and medically important clade of bacteria, containing the model organism Escherichia coli, as well as major human pathogens including Salmonella enterica and Klebsiella pneumoniae. Essential gene sets have been determined for several members of the Enterobacteriaceae, with the Keio E. coli single-gene deletion library often regarded as a gold standard. However, it remains unclear how gene essentiality varies between related strains and species. To investigate this, we have assembled a collection of 13 sequenced high-density transposon mutant libraries from five genera within the Enterobacteriaceae. We first assess several gene essentiality prediction approaches, investigate the effects of transposon density on essentiality prediction, and identify biases in transposon insertion sequencing data. Based on these investigations, we develop a new classifier for gene essentiality. Using this new classifier, we define a core essential genome in the Enterobacteriaceae of 201 universally essential genes. Despite the presence of a large cohort of variably essential genes, we find an absence of evidence for genus-specific essential genes. A clear example of this sporadic essentiality is given by the set of genes regulating the σE extracytoplasmic stress response, which appears to have independently acquired essentiality multiple times in the Enterobacteriaceae. Finally, we compare our essential gene sets to the natural experiment of gene loss in obligate insect endosymbionts that have emerged from within the Enterobacteriaceae. This isolates a remarkably small set of genes absolutely required for survival and identifies several instances of essential stress responses masked by redundancy in free-living bacteria.IMPORTANCEThe essential genome, that is the set of genes absolutely required to sustain life, is a core concept in genetics. Essential genes in bacteria serve as drug targets, put constraints on the engineering of biological chassis for technological or industrial purposes, and are key to constructing synthetic life. Despite decades of study, relatively little is known about how gene essentiality varies across related bacteria. In this study, we have collected gene essentiality data for 13 bacteria related to the model organism Escherichia coli, including several human pathogens, and investigated the conservation of essentiality. We find that approximately a third of the genes essential in any particular strain are non-essential in another related strain. Surprisingly, we do not find evidence for essential genes unique to specific genera; rather it appears a substantial fraction of the essential genome rapidly gains or loses essentiality during evolution. This suggests that essentiality is not an immutable characteristic but depends crucially on the genomic context. We illustrate this through a comparison of our essential genes in free-living bacteria to genes conserved in 34 insect endosymbionts with naturally reduced genomes, finding several cases where genes generally regarded as being important for specific stress responses appear to have become essential in endosymbionts due to a loss of functional redundancy in the genome.

La estenosis del canal anal es una forma infrecuente de malformación anorrectal, representando el 1%. Existen pocos casos registrados sobre esta patología. Se trata de una entidad donde el ano presenta una estenosis de longitud variable, se encuentra normo-implantado, de apariencia normal,rodeado de complejo esfinteriano adecuado. Se debe descartar la presencia de malformaciones asociadas, cardiovasculares, renales, osteoarticulares, y especialmente se debe evaluar la presencia demasa pre-sacra, pudiendo presentarse teratomas, mielomeningocele anterior, entre otras. El tratamiento quirúrgico consiste en resecar el sector estenótico, realizar anoplastia respetando el complejo esfinteriano mediante un abordaje posterior, sin disección de la cara anterior del recto Debido a la presencia de un complejo esfinteriano circundante normal, el pronóstico funcional intestinal de estos pacientes es excelente. Presentamos el primer caso clínico en nuestro paísde un paciente con estenosis del canal anal, su forma de presentación, tratamiento quirúrgico y evolución.

ABSTRACT Swinhoe's (or Yangtze) giant softshell turtle (Rafetus swinhoei) is a large, critically endangered freshwater turtle and considered among the rarest species in the world. As of 2024, only two individuals have been confirmed to remain alive, one at the Suzhou Zoo in China and one in Xuan Khanh Lake, Viet Nam. The only hope for the long‐term survival of R. swinhoei is finding additional, as yet undiscovered, animals that have thus far eluded detection by traditional survey methods. In recent years, numerous studies have been published on the use of environmental DNA (eDNA) for species detection and monitoring. This method takes advantage of the persistence of DNA in the environment, such as in water, soil, and air. An organism's DNA is shed into the environment through urine, feces, and the sloughing of skin. Species‐specific quantitative polymerase chain reaction (qPCR) testing can be used to detect eDNA in samples collected from the environment. eDNA trials to detect R. swinhoei were initiated by the Asian Turtle Program and Washington State University in 2013. To expand the use of eDNA for species detection by conservationists, we developed and validated a first‐of‐its‐kind innovative point‐of‐detection (POD) qPCR platform for the rapid, onsite detection of R. swinhoei from water samples. Here we show that the portable eDNA test kit can be used for the successful detection of R. swinhoei in a large body of water and that pooling filters may be a useful strategy to reduce test costs and improve detection efficiency. Use of this test can expand the search for R. swinhoei in unexplored and understudied lakes, reservoirs, and other bodies of water where this species may be present and could inform field surveys utilizing eDNA for other threatened species that are rare in nature.

Reducing indium consumption in transparent conductive oxide (TCO) layers is crucial for mass production of silicon heterojunction (SHJ) solar cells. In this contribution, optical simulation‐assisted design and optimization of SHJ solar cells featuring MoOx hole collectors with ultra‐thin TCO layers is performed. Firstly, bifacial SHJ solar cells with MoOx as the hole transport layer (HTL) and three types of n‐contact as electron transport layer (ETL) are fabricated with 50 nm thick ITO on both sides. It is found that bilayer (nc‐Si:H/a‐Si:H) and trilayer (nc‐SiOx:H/nc‐Si:H/a‐Si:H) as n‐contacts performed electronically and optically better than monolayer (a‐Si:H) in bifacial SHJ cells, respectively. Then, as suggested by optical simulations, the same stack of tungsten‐doped indium oxide (IWO) and optimized MgF2 layers are applied on both sides of front/back‐contacted SHJ solar cells. Devices endowed with 10 nm thick IWO and bilayer n‐contact exhibit a certified efficiency of 21.66% and 20.66% when measured from MoOx and n‐contact side, respectively. Specifically, when illuminating from the MoOx side, the short‐circuit current density and the fill factor remain well above 40 mA cm−2 and 77%, respectively. Compared to standard front/rear TCO thicknesses (75 nm/150 nm) deployed in monofacial SHJ solar cells, this represents over 90% TCO reduction. As for bifacial cells featuring 50 nm thick IWO layers, a champion device with a bilayer n‐contact as ETL is obtained, which exhibits certified conversion efficiency of 23.25% and 22.75% when characterized from the MoOx side and the n‐layer side, respectively, with a bifaciality factor of 0.98. In general, by utilizing a n‐type bilayer stack, bifaciality factor is above 0.96 and it can be further enhanced up to 0.99 by switching to a n‐type trilayer stack. Again, compared to the aforementioned standard front/rear TCO thicknesses, this translates to a TCO reduction of more than 67%.

Abstract Due to the unique microstructure of hydrogenated nanocrystalline silicon oxide (nc‐SiOx:H), the optoelectronic properties of this material can be tuned over a wide range, which makes it adaptable to different solar cell applications. In this work, the authors review the material properties of nc‐SiOx:H and the versatility of its applications in different types of solar cells. The review starts by introducing the growth principle of doped nc‐SiOx:H layers, the effect of oxygen content on the material properties, and the relationship between optoelectronic properties and its microstructure. A theoretical analysis of charge carrier transport mechanisms in silicon heterojunction (SHJ) solar cells with wide band gap layers is then presented. Afterwards, the authors focus on the recent developments in the implementation of nc‐SiOx:H and hydrogenated amorphous silicon oxide (a‐SiOx:H) films for SHJ, passivating contacts, and perovskite/silicon tandem devices.

Abstract Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) may be useful in treating exsanguinating trauma patients. This study seeks to compare rates of success, complications and time required for vascular access between ultrasound-guidance and surgical cut-down for femoral sheath insertion as a prospective observational case control study. Participating clinicians from either trauma surgery or anesthesiology were allocated to surgical cut-down or percutaneous ultrasound-guided puncture on a 1:1 ratio. Time spans to vessel identification, successful puncture, and balloon inflation were recorded. 80 study participants were recruited and allocated to 40 open cut-down approaches and 40 percutaneous ultrasound-guided approaches. REBOA catheter placement was successful in 18/40 cases (45%) using a percutaneous ultrasound guided technique and 33/40 times (83%) using the open cut-down approach (p

Data on the safety and efficiency of perventricular device closure of complex ventricular septal defects (VSDs) are scarce. We report successful one-stage combined hybrid perventricular and percutaneous closure of the muscular VSDs in a critically ill 4-kg infant, using the new multifunctional occluder.

Our study aimed to provide a description of the early childhood development of pediatric burn patients relative to Dutch reference values, using both pre- and post-burn data from the Dutch Development Instrument and the D-score. Data from the Dutch Development Instrument were used to calculate the D-score and age-standardized D-score. Similar to a growth chart, the D-score was used to plot pediatric burn patients’ development relative to Dutch reference values for their age. Pediatric burn patients’ (n = 38) median age at the time of injury was 1.0 (1.0–2.0) years old. Burn size ranged from 1.0% to 36.0% of the total body surface area. Ninety-five percent (± 6.0%) of pediatric burn patients passed each of the age-appropriate developmental milestones at the target age. The mean age-standardized D-score was just above the Dutch average (+0.49 SD [0.18, 0.80]) and did not vary depending on sex (p = 0.06) or burn size (p = 0.41). In conclusion, among pediatric patients aged up to two-and-a-half years old, with non-full thickness burns, development was on track relative to the Dutch reference values. Our findings offer valuable first insights into the early childhood development of pediatric burn patients and may alleviate some parental concerns.

Abstract Well-differentiated liposarcoma (WDLS) displays amplification of genes on chromosome 12 (Chr12) in supernumerary ring or giant marker chromosomes. These structures have been suggested to develop through chromothripsis, followed by circularization and breakage-fusion-bridge (BFB) cycles. To test this hypothesis, we compared WDLSs with Chr12 amplification in rod-shaped chromosomes with WDLSs with rings. Both types of amplicons share the same spectrum of structural variants (SVs), show higher SV frequencies in Chr12 than in co-amplified segments, have SVs that fuse the telomeric ends of co-amplified chromosomes, and lack interspersed deletions. Combined with the finding of cells with transient rod-shaped structures in tumors with ring chromosomes, this suggests a stepwise process starting with the gain of Chr12 material that, after remodeling which does not fit with classical chromothripsis, forms a dicentric structure with other chromosomes. Depending on if and when telomeres from other chromosomes are captured, circularized or linear gain of 12q sequences will predominate.

Abstract For many years Norway has been in the forefront of promoting electromobility. Today, Norway has the world’s highest per capita fleet of plug-in electric cars. In 2021, 1.6% of the cars in the EU fleet were plug-in electric vehicles, whereas their share was 21% in Norway. Part of the successful market take-up rate is due to wide-ranging tax exemptions. Increasing plug-in electric vehicles numbers causes tax revenue losses, making exemptions unsustainable. Norway has the ambitious goal that from 2025, all newly registered cars shall be zero-emission vehicles. Keeping tax exemptions in place might be crucial for this goal. The objective of this paper is to provide information to solve this dilemma. Tax exemption reduction and abolition paths which offer a compromise between minimal effects on the development of zero-emission vehicles and tax revenues have been identified. An updated and re-calibrated version of the stock-flow-model SERAPIS was used to simulate and assess different scenarios. Results show that a controlled tax phase-in allows Norway to reach its environmental targets of 100% zero emission vehicles by 2025 and a 55% decrease of CO2-emissions in 2030 relative to 2005 while simultaneously increasing public revenues significantly.

Abstract Background Vascular pathologies of the head and neck are rare but can present as musculoskeletal problems. The International Federation of Orthopedic Manipulative Physical Therapists (IFOMPT) Cervical Framework (Framework) aims to assist evidence-based clinical reasoning for safe assessment and management of the cervical spine considering potential for vascular pathology. Clinical reasoning is critical to physiotherapy, and developing high-level clinical reasoning is a priority for postgraduate (post-licensure) educational programs. Objective To explore the influence of the Framework on clinical reasoning processes in postgraduate physiotherapy students. Methods Qualitative case study design using think aloud methodology and interpretive description, informed by COnsolidated criteria for REporting Qualitative research. Participants were postgraduate musculoskeletal physiotherapy students who learned about the Framework through standardized delivery. Two cervical spine cases explored clinical reasoning processes. Coding and analysis of transcripts were guided by Elstein’s diagnostic reasoning components and the Postgraduate Musculoskeletal Physiotherapy Practice model. Data were analyzed using thematic analysis (inductive and deductive) for individuals and then across participants, enabling analysis of key steps in clinical reasoning processes and use of the Framework. Trustworthiness was enhanced with multiple strategies (e.g., second researcher challenged codes). Results For all participants (n = 8), the Framework supported clinical reasoning using primarily hypothetico-deductive processes. It informed vascular hypothesis generation in the patient history and testing the vascular hypothesis through patient history questions and selection of physical examination tests, to inform clarity and support for diagnosis and management. Most participant’s clinical reasoning processes were characterized by high-level features (e.g., prioritization), however there was a continuum of proficiency. Clinical reasoning processes were informed by deep knowledge of the Framework integrated with a breadth of wider knowledge and supported by a range of personal characteristics (e.g., reflection). Conclusions Findings support use of the Framework as an educational resource in postgraduate physiotherapy programs to inform clinical reasoning processes for safe and effective assessment and management of cervical spine presentations considering potential for vascular pathology. Individualized approaches may be required to support students, owing to a continuum of clinical reasoning proficiency. Future research is required to explore use of the Framework to inform clinical reasoning processes in learners at different levels.

Abstract The objective of this study was to obtain fuel through pyrolysis using barley husk and recycled compact polystyrene as raw materials, which were obtained from urban solid waste from the city of Riobamba, Ecuador. The barley hulls were sampled from different warehouses and mills in the city where grain peeling processes are carried out, while the plastic sampled was completely random. The pyrolysis process was carried out at a temperature of 400 ∘ C in a batch reactor to analyze the effect of temperature on the yield of the liquid product. The product was characterized using Fourier transform infrared spectroscopy (FTIR), density, viscosity, flash point, fragmentary distillation, gas chromatography coupled to mass spectrometry, and calorific value. The pyrolysis result had a high calorific value of 44546.81 kJ/kg. The highest liquid yield was 67.133%, with this, it was determined that the optimum pyrolysis temperature is at 400 ∘ C with a higher amount of light hydrocarbons of about 49% comprised between C4 and C12.

Abstract This comprehensive study examines fossil remains from Niedźwiedzia Cave in the Eastern Sudetes, offering detailed insights into the palaeobiology and adversities encountered by the Pleistocene cave bear Ursus spelaeus ingressus. Emphasising habitual cave use for hibernation and a primarily herbivorous diet, the findings attribute mortality to resource scarcity during hibernation and habitat fragmentation amid climate shifts. Taphonomic analysis indicates that the cave was extensively used by successive generations of bears, virtually unexposed to the impact of predators. The study also reveals that alkaline conditions developed in the cave during the post-depositional taphonomic processes. Mortality patterns, notably among juveniles, imply dwindling resources, indicative of environmental instability. Skeletal examination reveals a high incidence of forelimb fractures, indicating risks during activities like digging or confrontations. Palaeopathological evidence unveils vulnerabilities to tuberculosis, abscesses, rickets, and injuries, elucidating mobility challenges. The cave’s silts exhibit a high zinc concentration, potentially derived from successive bear generations consuming zinc-rich plants. This study illuminates the lives of late cave bears, elucidating unique environmental hurdles faced near their species’ end.

Aims: Patients with proximal femoral fractures (PFFs) are often multimorbid, thus unplanned readmissions following surgery are common. We therefore aimed to analyze 30-day and one-year readmission rates, reasons for, and factors associated with, readmission risk in a cohort of patients with surgically treated PFFs across Austria. Methods: Data from 11,270 patients with PFFs, treated surgically (osteosyntheses, n = 6,435; endoprostheses, n = 4,835) at Austrian hospitals within a one-year period (January to December 2021) was retrieved from the Leistungsorientierte Krankenanstaltenfinanzierung (Achievement-Oriented Hospital Financing). The 30-day and one-year readmission rates were reported. Readmission risk for any complication, as well as general medicine-, internal medicine-, and surgery/injury-associated complications, and factors associated with readmissions, were investigated. Results: The 30-day and one-year readmission rates due to any complication were 15% and 47%, respectively. The 30-day readmission rate (p = 0.001) was higher in endoprosthesis than osteosynthesis patients; this was not the case for the one-year readmission rate (p = 0.138). Internal medicine- (n = 2,273 (20%)) and surgery/injury-associated complications (n = 1,612 (14%)) were the most common reason for one-year readmission. Regardless of the surgical procedure, male sex was significantly associated with higher readmission risk due to any, as well as internal medicine-associated, complication. Advanced age was significantly associated with higher readmission risk after osteosynthesis. In both cohorts, treatment at mid-sized hospitals was significantly associated with lower readmission risk due to any complication, while prolonged length of stay was associated with higher one-year readmission risks due to any complication, as well as internal-medicine associated complications. Conclusion: Future health policy decisions in Austria should focus on optimization of perioperative and post-discharge management of this vulnerable patient population. Cite this article: Bone Jt Open 2024;5(4):294–303.

Abstract Background Capnography is a quantitative and reliable method of determining the ventilatory status of patients. We describe the test characteristics of capnography obtained during Emergency Department triage for screening acidemia. Results We performed an observational, pilot study of adult patients presenting to Emergency Department (ED) triage. The primary outcome was acidemia, as determined by the basic metabolic panel and/or blood gas during the ED visit. Secondary outcomes include comparison of estimated and measured respiratory rates (RR), relationships between end-tidal CO2 (EtCO 2 ) and venous partial pressure of CO 2 , admission disposition, in-hospital mortality during admission, and capnogram waveform analysis. A total of 100 adult ED encounters were included in the study and acidemia ( $$ \left[HC{O}_{3}^{-}\right]\le 22 \text{mEq/L}$$ or $$ pH< 7.35$$ ) was identified in 28 patients. The measured respiratory rate (20.3 ± 6.4 breaths/min) was significantly different from the estimated rate (18.4 ± 1.6 breaths/min), and its area under the receiver operating curve (c-statistic) to predict acidemia was only 0.60 (95% CI 0.51–0.75, p = 0.03). A low end-tidal CO2 (EtCO 2

Abstract Background Depression is prevalent among Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) Veterans, yet rates of Veteran mental health care utilization remain modest. The current study examined: factors in electronic health records (EHR) associated with lack of treatment initiation and treatment delay; the accuracy of regression and machine learning models to predict initiation of treatment. Methods We obtained data from the VA Corporate Data Warehouse (CDW). EHR data were extracted for 127,423 Veterans who deployed to Iraq/Afghanistan after 9/11 with a positive depression screen and a first depression diagnosis between 2001 and 2021. We also obtained 12-month pre-diagnosis and post-diagnosis patient data. Retrospective cohort analysis was employed to test if predictors can reliably differentiate patients who initiated, delayed, or received no mental health treatment associated with their depression diagnosis. Results 108,457 Veterans with depression, initiated depression-related care (55,492 Veterans delayed treatment beyond one month). Those who were male, without VA disability benefits, with a mild depression diagnosis, and had a history of psychotherapy were less likely to initiate treatment. Among those who initiated care, those with single and mild depression episodes at baseline, with either PTSD or who lacked comorbidities were more likely to delay treatment for depression. A history of mental health treatment, of an anxiety disorder, and a positive depression screen were each related to faster treatment initiation. Classification of patients was modest (ROC AUC = 0.59 95%CI = 0.586–0.602; machine learning F-measure = 0.46). Conclusions Having VA disability benefits was the strongest predictor of treatment initiation after a depression diagnosis and a history of mental health treatment was the strongest predictor of delayed initiation of treatment. The complexity of the relationship between VA benefits and history of mental health care with treatment initiation after a depression diagnosis is further discussed. Modest classification accuracy with currently known predictors suggests the need to identify additional predictors of successful depression management.

Despite the location (Earth or Space), surgical simulation is a vital part of improving technical skills and ensuring patients' safety in the real procedure. The purpose of this study is to describe the Space System for Minimally Invasive Surgery (SY-MIS©) project, which started in 2016 under the supervision of the Center for Space Systems (C-SET). The process connects the best features of the following machines: Biomedik Surgeon, Space Biosurgeon, SP-LAP 1, and SP-LAP 2, which were defined using the VDI 2221 guidelines. This research uses methods based on 3 standards: i) Biomedical design: ISO 9001-13485 / FDA 21 CFR 820.30 / ASTM F1744-96(2016); ii) Aerospace human factors: HF-STD-001; iii) Mechatronics design: VDI 2206. The results depict the conceptual biomedical design of a novel training system named Surgical Engineering and Mechatronic System (SETY©), which integrates the use of 2 laparoscopic tools and 2 anthropomorphic mini-robotic arms (6 DOF). It has been validated by the Evaluation of Technical Criteria, getting a total score of 90% related to clinical assessment, machine adaptability, and robustness. The novelty of the research lies in the introduction of a new procedure that covers the simultaneous use of laparoscopic and robotic systems, named Hybrid Cyber-Physical Surgery (HYS©). In conclusion, the development of SY-MIS© promotes the use of advanced technologies to improve surgical procedures and human-machine medical cooperation for the next frontier of habitability on other planets. Doi: 10.28991/ESJ-2024-08-02-01 Full Text: PDF

ABSTRACTCommitted volunteers are the driving force of successful community-based conservation initiatives. However, many groups struggle with recruitment and retention of volunteers. This research adds to the limited knowledge on what motivates community-based conservation volunteers to become committed to a conservation initiative, by carrying out a case study on community-based conservation volunteers in the Manawatū region of New Zealand. Twenty-one semi-structured interviews with key members of community-conservation groups were carried out along with a survey distributed to all local community-based conservation groups. This research showed that the key long-term motivation factors are ‘to care for the environment’, ‘to help the local community’, ‘to be outside, or amongst nature’ and to have ‘a connection to nature’. There was minimal change between long-term and initial motivation factors, with only three motivation factors increasing in importance; ‘to socialise with others’, ‘for stress relief or escape’ and ‘to help the local community', and one decreasing in importance; ‘to learn new skills and knowledge’. In order to enhance commitment of volunteers there is a need to take motivation factors into account within project design and management, allow time for socialisation, and provide ongoing training, education and recognition.

Abstract Recombinant tissue-type plasminogen activator (r-tPA/Actilyse) stands as the prevailing pharmacological solution for treating ischemic stroke patients, of whom because their endogenous circulating tPA alone is not sufficient to rescue reperfusion and to promote favorable outcome. Beyond the tPA contributed by circulating endothelial cells and hepatocytes, neurons also express tPA, sparking debates regarding its impact on neuronal fate ranging from pro-survival to neurotoxic properties. In order to investigate the role of neuronal tPA during brain injuries, we developed models leading to its conditional deletion in neurons, employing AAV9-pPlat-GFP and AAV9-pPlat-Cre-GFP along with tPA floxed mice. These models were subjected to N-methyl-D-aspartate (NMDA)-induced excitotoxicity or thromboembolic ischemic stroke in mice. Initially, we established that our AAV9 constructs selectively transduce neurons, bypassing other brain cell types. Subsequently, we demonstrated that tPA-expressing neurons exhibit greater resistance against NMDA-induced excitotoxicity compared to tPA negative neurons. The targeted removal of tPA in neurons heightened the susceptibility of these neurons to cell death and prevented a paracrine neurotoxic effect on tPA non-expressing neurons. Under ischemic conditions, the self-neuroprotective influence of tPA encompassed both excitatory (GFP+/Tbr1+) and inhibitory (GFP+/GABA+) neurons. Our data indicate that endogenous neuronal tPA is a protective or deleterious factor against neuronal death in an excitotoxic/ischemic context, depending on whether it acts as an autocrine or a paracrine mediator.

Abstract Wildlife species and populations are being driven toward extinction by a combination of historic and emerging stressors (e.g., overexploitation, habitat loss, contaminants, climate change), suggesting that we are in the midst of the planet’s sixth mass extinction. The invisible loss of biodiversity before species have been identified and described in scientific literature has been termed, memorably, dark extinction. The critically endangered Southern Resident killer whale (Orcinus orca) population illustrates its contrast, which we term bright extinction; namely the noticeable and documented precipitous decline of a data-rich population toward extinction. Here we use a population viability analysis to test the sensitivity of this killer whale population to variability in age structure, survival rates, and prey-demography functional relationships. Preventing extinction is still possible but will require greater sacrifices on regional ocean use, urban development, and land use practices, than would have been the case had threats been mitigated even a decade earlier.

Underprioritization of mental health is a global problem and threatens the decades-long progress of the US President’s Emergency Plan for AIDS Relief (PEPFAR) program. In recent years, mental health has become globally recognized as a part of universal healthcare, making this an opportune moment for the global community to integrate mental health services into routine programming. PEPFAR is well positioned to lead by example. We conceptualized 5 key strategies that might help serve as a framework to support mental health programming as part of PEPFAR’s current 5-year strategic plan. PEPFAR and the global community have an opportunity to identify mental health service gaps and interweave global mental health priorities with actions to end the HIV and TB epidemics by 2030.