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Groundwater is the most ubiquitous source of liquid freshwater globally, yet its role in supporting diverse ecosystems is rarely acknowledged1,2. However, the location and extent of groundwater-dependent ecosystems (GDEs) are unknown in many geographies, and protection measures are lacking1,3. Here, we map GDEs at high-resolution (roughly 30 m) and find them present on more than one-third of global drylands analysed, including important global biodiversity hotspots4. GDEs are more extensive and contiguous in landscapes dominated by pastoralism with lower rates of groundwater depletion, suggesting that many GDEs are likely to have already been lost due to water and land use practices. Nevertheless, 53% of GDEs exist within regions showing declining groundwater trends, which highlights the urgent need to protect GDEs from the threat of groundwater depletion. However, we found that only 21% of GDEs exist on protected lands or in jurisdictions with sustainable groundwater management policies, invoking a call to action to protect these vital ecosystems. Furthermore, we examine the linkage of GDEs with cultural and socio-economic factors in the Greater Sahel region, where GDEs play an essential role in supporting biodiversity and rural livelihoods, to explore other means for protection of GDEs in politically unstable regions. Our GDE map provides critical information for prioritizing and developing policies and protection mechanisms across various local, regional or international scales to safeguard these important ecosystems and the societies dependent on them.

Science is humanity's best insurance against threats from nature, but it is a fragile enterprise that must be nourished and protected. The preponderance of scientific evidence indicates a natural origin for SARS-CoV-2. Yet, the theory that SARS-CoV-2 was engineered in and escaped from a lab dominates media attention, even in the absence of strong evidence. We discuss how the resulting anti-science movement puts the research community, scientific research, and pandemic preparedness at risk.

BackgroundColectomies and proctectomies are commonly performed by both general surgeons (GS) and colorectal surgeons (CRS). The aim of our study was to examine the outcomes of elective colectomy, urgent colectomy, and elective proctectomy according to surgeon training.Study designData were obtained from the Vizient database for adults who underwent elective colectomy, urgent colectomy, and elective proctectomy from 2020-2022. Operations performed in the setting of trauma and patients within the database's highest relative expected mortality risk group were excluded. Outcomes were compared according to surgeon's specialty: GS vs. CRS. The primary outcome was in-hospital mortality. The secondary outcome was in-hospital complication rate. Data were analyzed using multivariate logistic regression.ResultsOf 149,516 elective colectomies, 75,711(50.6%) were performed by GS and 73,805(49.4%) by CRS. Compared to elective colectomies performed by CRS, elective colectomies performed by GS had higher rates of complications(4.9% vs. 3.9%, OR1.23, 95%CI 1.17-1.29,p

In the United States (US), biosafety and biosecurity oversight of research on viruses is being reappraised. Safety in virology research is paramount and oversight frameworks should be reviewed periodically. Changes should be made with care, however, to avoid impeding science that is essential for rapidly reducing and responding to pandemic threats as well as addressing more common challenges caused by infectious diseases. Decades of research uniquely positioned the US to be able to respond to the COVID-19 crisis with astounding speed, delivering life-saving vaccines within a year of identifying the virus. We should embolden and empower this strength, which is a vital part of protecting the health, economy, and security of US citizens. Herein, we offer our perspectives on priorities for revised rules governing virology research in the US.

Abstract Cell survival under nutrient-deprived conditions relies on cells’ ability to adapt their organelles and rewire their metabolic pathways. In yeast, glucose depletion induces a stress response mediated by mitochondrial fragmentation and sequestration of cytosolic ribosomes on mitochondria. This cellular adaptation promotes survival under harsh environmental conditions; however, the underlying mechanism of this response remains unknown. Here, we demonstrate that upon glucose depletion protein synthesis is halted. Cryo-electron microscopy structure of the ribosomes show that they are devoid of both tRNA and mRNA, and a subset of the particles depicted a conformational change in rRNA H69 that could prevent tRNA binding. Our in situ structural analyses reveal that the hibernating ribosomes tether to fragmented mitochondria and establish eukaryotic-specific, higher-order storage structures by assembling into oligomeric arrays on the mitochondrial surface. Notably, we show that hibernating ribosomes exclusively bind to the outer mitochondrial membrane via the small ribosomal subunit during cellular stress. We identify the ribosomal protein Cpc2/RACK1 as the molecule mediating ribosomal tethering to mitochondria. This study unveils the molecular mechanism connecting mitochondrial stress with the shutdown of protein synthesis and broadens our understanding of cellular responses to nutrient scarcity and cell quiescence.

This original paper, based on data from the Erasmus+Blurred Lives Project, presents a new multi-dimensional categorisation model to describe negative online experiences, including forms of cyberbullying, based on a study of internet usage among over N = 2,500 adolescents with lower socio-economic status (SES) backgrounds across five European countries. The paper first sets out the rationale for the development of a new coding system, before describing the current study and nature of the survey data collected. There follows a description of the development of the new system and the series of reliability checks undertaken by the research team (N= 11, from 5 countries) and of the refinements made to the categories and codes. The resulting coding system is presented with consideration of the strengths and limitations, and description of two early pilot studies which have successfully adopted the new system.

Abstract Background Alzheimer's disease (AD) is a progressive neurodegenerative disorder that severely affects cognitive functions and social behaviors, leading to a significant decline in an individual’s quality of life. Auditory processing deficits often precede the clinical symptoms of AD, prompting interest in auditory-based interventions as potential treatments. This scoping review aimed to compile the existing evidence on active and passive auditory-based interventions for individuals with AD and its prodromal stages. Method and results This scoping review followed Arksey and O’Malley's five-step framework to identify the existing evidence on auditory-based interventions for AD. Four databases (PubMed, Web of Science, CINAHL, and Embase) were used to search for studies on auditory stimulation techniques to treat cognitive decline in AD patients. In total, 14 studies were included in the analysis. Seven studies explored active auditory stimulation techniques, such as the Brain Fitness Program (BrainHQ), aiming to improve cognitive function in individuals with Mild Cognitive Impairment (MCI). The other seven studies focused on passive auditory stimulation, often combined with other sensory stimuli such as light or tactile inputs. Passive stimulation studies have focused mainly on Gamma Entrainment Using Sensory Stimulation (GENUS). The intervention frequency and duration varied across studies, ranging from one session lasting 8 h to a year. Both active and passive auditory stimulation showed potential for enhancing cognitive function in individuals with AD. Conclusion The literature suggests that auditory stimulation may positively influence cortical wiring and enhance cognitive abilities. Multimodal interventions that combine auditory stimulation with other sensory or behavioural approaches could yield more substantial effects on global cognition. However, the study design, intervention characteristics and outcome measures varied across studies, underscoring the necessity for standardised reporting. Well-designed studies using standard cognitive assessment protocols are recommended.

OBJECTIVE: To assess the effect of age on overall survival (OS) in women with ovarian cancer receiving chemotherapy. Secondary objectives were to describe the effect of age on treatment compliance, toxicities, progression free survival (PFS), time from surgery to chemotherapy, and rates of optimal cytoreduction. METHODS: Women enrolled in GOG 0182-ICON5 with stage III or IV epithelial ovarian cancer (EOC) who underwent surgery and chemotherapy between 2001 and 2004 were included. Patients were divided into ages

ABSTRACT: Direct introduction of cryopreserved embryonic gonadal germ cells (GGC) into a sterile chicken surrogate host to reconstitute a chicken breed has been demonstrated as a feasible approach for preserving and utilizing chicken genetic resources. This method is highly efficient using male gonads; however, a large number of frozen female embryonic gonads is needed to provide sufficient purified GGC for the generation of fertile surrogate female hosts. Applying this method to indigenous chicken breeds and other bird species is difficult due to small flock numbers and poor egg production in each egg laying cycle. Propagating germ cells from the frozen gonadal tissues may be a solution for the biobanking of these birds. Here, we describe a simplified method for culture of GGC from frozen embryonic 9.5 d gonads. At this developmental stage, the germ cells are autonomously shed into medium, yielding hundreds to thousands of mitosis-competent germ cells. The resulting cultures of GGC have over 90% purity, uniformly express SSEA-1 and DAZL antigens and can re-colonize recipient's gonads. The GGC recovery rate from frozen gonads are 42% to 100%, depending on length of cryopreservation and the breed or line of chickens. Entire chicken embryos can also be directly cryopreserved for later gonadal isolation and culture. This storage method is a supplementary approach to safeguard local indigenous chicken breeds bearing valuable genetic traits and should be applicable to the biobanking of many bird species.

The Mycobacterium tuberculosis (Mtb) pathogen, the causative agent of the airborne infection tuberculosis (TB), harbors a number of mycobacterial membrane protein large (MmpL) transporters. These membrane proteins can be separated into 2 distinct subclasses, where they perform important functional roles, and thus, are considered potential drug targets to combat TB. Previously, we reported both X-ray and cryo-EM structures of the MmpL3 transporter, providing high-resolution structural information for this subclass of the MmpL proteins. Currently, there is no structural information available for the subclass associated with MmpL4 and MmpL5, transporters that play a critical role in iron homeostasis of the bacterium. Here, we report cryo-EM structures of the M. smegmatis MmpL4 and MmpL5 transporters to resolutions of 2.95 Å and 3.00 Å, respectively. These structures allow us to propose a plausible pathway for siderophore translocation via these 2 transporters, an essential step for iron acquisition that enables the survival and replication of the mycobacterium.

Abstract Objectives We evaluated a novel leave‐behind naloxone (LBN) program that allows Emergency Medical Services (EMS) personnel to distribute naloxone after an opioid overdose. Our objective was to explore EMS engagement and experiences with the program, as well as interest in education on addiction and harm reduction. We also assessed the acceptability of LBN programs among people who use drugs (PWUD). Methods We conducted telephone interviews with EMS personnel and residents of substance use recovery housing between February and September 2023. EMS personnel described their direct experiences with the LBN program and perceived facilitating factors and barriers to naloxone distribution. First responder interactions and support for LBN were explored with PWUD. A rapid assessment method was used to analyze the interview data. Results Eighteen of the 23 EMS participants had distributed LBN; most agreed EMS agencies should have an LBN program. Barriers included forgetting, patient acuity, patients declining, and perceived liability. Facilitators included having a clear protocol, accessible kits, and minimal documentation burden. The majority expressed interest in harm reduction education. Eight of the 11 PWUD participants reported recent involvement in an opioid overdose. The majority supported LBN and felt comfortable receiving naloxone training from EMS. Conclusion In this qualitative evaluation, we found broad support for EMS‐based naloxone distribution among EMS personnel and PWUD. We identified several modifiable barriers to the success of such programs, which should be the subject of future investigation. EMS and harm reduction communities should support the expansion of LBN programs across the United States.

Abstract Background Themes of equity, diversity and inclusion (EDI) arise commonly within healthcare simulation. Though faculty development guidance and standards include increasing reference to EDI, information on how faculty might develop in this area is lacking. With increasingly formal expectations being placed on simulation educators to adhere to EDI principles, we require a better understanding of the developmental needs of educators and clear guidance so that teams can work towards these expectations. Our study had two aims: Firstly, to explore the extent to which an existing competency framework for medical teachers to teach ethnic and cultural diversity is relevant for simulation educator competency in EDI, and secondly, informed by the data gathered, to construct a modified competency framework in EDI for simulation educators. Methods We engaged our participants (10 simulation faculty) in a 5-month period of enhanced consideration of EDI, using the SIM-EDI tool to support faculty debriefing conversations focussed on EDI within a pre-existing programme of simulation. We interviewed participants individually at two timepoints and analysed transcript data using template analysis. We employed an existing competency framework for medical teachers as the initial coding framework. Competencies were amended for the simulation context, modified based on the data, and new themes were added inductively, to develop a new developmental framework for simulation educators. Results Interview data supported the relevance of the existing competency framework to simulation. Modifications made to the framework included the incorporation of two inductively coded themes (‘team reflection on EDI’ and ‘collaboration’), as well as more minor amendments to better suit the healthcare simulation context. The resultant Developmental Framework for Simulation Educators in EDI outlines 10 developmental areas we feel are required to incorporate consideration of EDI into simulation programmes during the design, delivery and debriefing phases. We propose that the framework acts as a basis for simulation faculty development in EDI. Conclusions Simulation faculty development in EDI is important and increasingly called for by advisory bodies. We present a Developmental Framework for Simulation Educators in EDI informed by qualitative data. We encourage simulation teams to incorporate this framework into faculty development programmes and report on their experiences.

Abstract We present a study into early modern English production of blue verditer, an early synthetic copper-based blue pigment chemically analogous to azurite. Verditers have been identified in numerous wall and easel paintings. While initial documentation occurs in the mid 1500s and production recipes were documented by the 17th c., the synthesis was known to be unreliable. This study replicates historical and recent scientific work on blue verditer and represents a significant advance in our understanding of verditer production and its challenges. Procedures for verditer synthesis are drawn from both 17th c. documentation and 20th c. replication work. The effects of temperature, copper and carbonate sources, solution stirring, copper ion concentration, and atmospheric composition are studied in order to elucidate the mechanism of synthesis and explain its unreliability in early modern refineries. Products are characterised by polarised light microscopy, scanning electron microscopy, Raman spectroscopy, and powder X-Ray diffraction. Rouaite, a green basic copper nitrate, is for the first time confirmed as a product of the refiners’ synthesis and a precursor to blue verditer in laboratory syntheses. This result problematises the blanket identification of green verditer as basic copper carbonate and provides important clues to the mechanism for blue verditer synthesis. Solution chemistry and ion equilibria allow us to explain the route by which rouaite is first formed and then converted to blue verditer. Conditions favouring blue verditer production are also clarified further. Although it is commonly stated that low temperatures are required for blue verditer production, blue verditer is produced here at a range of ambient temperatures. The reaction is found instead to be controlled by solution equilibria and heavily favoured by high partial pressures of carbon dioxide. Alongside archival materials about refining and verditer production, these results are contextualised and explanations for the unreliability of historical synthesis are proposed.

Abstract Background The National Institute of Health and Care Research (NIHR), funds, enables and delivers world-leading health and social care research to improve people’s health and wellbeing. To achieve this aim, effective knowledge sharing (two-way knowledge sharing between researchers and stakeholders to create new knowledge and enable change in policy and practice) is needed. To date, it is not known which knowledge sharing techniques and approaches are used or how effective these are in creating new knowledge that can lead to changes in policy and practice in NIHR funded studies. Methods In this restricted systematic review, electronic databases [MEDLINE, The Health Management Information Consortium (including the Department of Health’s Library and Information Services and King’s Fund Information and Library Services)] were searched for published NIHR funded studies that described knowledge sharing between researchers and other stakeholders. One researcher performed title and abstract, full paper screening and quality assessment (Critical Appraisal Skills Programme qualitative checklist) with a 20% sample independently screened by a second reviewer. A narrative synthesis was adopted. Results In total 9897 records were identified. After screening, 17 studies were included. Five explicit forms of knowledge sharing studies were identified: embedded models, knowledge brokering, stakeholder engagement and involvement of non-researchers in the research or service design process and organisational collaborative partnerships between universities and healthcare organisations. Collectively, the techniques and approaches included five types of stakeholders and worked with them at all stages of the research cycle, except the stage of formation of the research design and preparation of funding application. Seven studies (using four of the approaches) gave examples of new knowledge creation, but only one study (using an embedded model approach) gave an example of a resulting change in practice. The use of a theory, model or framework to explain the knowledge sharing process was identified in six studies. Conclusions Five knowledge sharing techniques and approaches were reported in the included NIHR funded studies, and seven studies identified the creation of new knowledge. However, there was little investigation of the effectiveness of these approaches in influencing change in practice or policy.

PurposeIn patients with high-grade ovarian cancer, predictors of bevacizumab efficacy in first-line setting are needed. In the ICON-7 trial, a poor tumor intrinsic chemosensitivity (defined by unfavorable modeled cancer antigen-125 [CA-125] ELIMination rate constant K [KELIM] score) was a predictive biomarker. Only the patients with high-risk disease (suboptimally resected stage III, or stage IV) exhibiting unfavorable KELIM score < 1.0 had overall survival (OS) benefit from bevacizumab (median: 29.7 v 20.6 months; hazard ratio [HR], 0.78). An external validation study in the GOG-0218 trial was performed.MethodsIn GOG-0218, 1,873 patients were treated with carboplatin-paclitaxel ± concurrent-maintenance bevacizumab/placebo. Patient KELIM values were calculated with CA-125 kinetics during the first 100 chemotherapy days by the Lyon University team. The association between KELIM score (favorable ≥ 1.0, or unfavorable < 1.0) and bevacizumab benefit for progression-free survival (PFS)/OS was independently assessed by NGR-GOG using univariate/multivariate analyses.ResultsKELIM was assessable in 1,662 patients with ≥ 3 CA-125 available values. An unfavorable KELIM score was associated with bevacizumab benefit compared with placebo (PFS: HR, 0.70; 95% CI, 0.59 to 0.82; OS: HR, 0.87; 95% CI, 0.73 to 1.03), whereas a favorable KELIM was not (PFS: HR, 0.96; 95% CI, 0.79 to 1.17; OS: HR, 1.11; 95% CI, 0.89 to 1.39). The highest benefit was observed in patients with a high-risk disease exhibiting unfavorable KELIM, for PFS (median: 9.1 v 5.6 months; HR, 0.64; 95% CI, 0.53 to 0.78), and for OS (median: 35.1 v 29.1 months; HR, 0.79; 95% CI, 0.65 to 0.97).ConclusionThis GOG-0218 trial investigation validates ICON-7 findings about the association between poor tumor chemosensitivity and benefit from concurrent-maintenance bevacizumab, suggesting that bevacizumab may mainly be effective in patients with poorly chemosensitive disease. Bevacizumab may be prioritized in patients with a high-risk and poorly chemosensitive disease to improve their PFS/OS (patient KELIM score calculator available on the Biomarker Kinetics website).