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The density of wood is a key indicator of the carbon investment strategies of trees, impacting productivity and carbon storage. Despite its importance, the global variation in wood density and its environmental controls remain poorly understood, preventing accurate predictions of global forest carbon stocks. Here we analyse information from 1.1 million forest inventory plots alongside wood density data from 10,703 tree species to create a spatially explicit understanding of the global wood density distribution and its drivers. Our findings reveal a pronounced latitudinal gradient, with wood in tropical forests being up to 30% denser than that in boreal forests. In both angiosperms and gymnosperms, hydrothermal conditions represented by annual mean temperature and soil moisture emerged as the primary factors influencing the variation in wood density globally. This indicates similar environmental filters and evolutionary adaptations among distinct plant groups, underscoring the essential role of abiotic factors in determining wood density in forest ecosystems. Additionally, our study highlights the prominent role of disturbance, such as human modification and fire risk, in influencing wood density at more local scales. Factoring in the spatial variation of wood density notably changes the estimates of forest carbon stocks, leading to differences of up to 21% within biomes. Therefore, our research contributes to a deeper understanding of terrestrial biomass distribution and how environmental changes and disturbances impact forest ecosystems.

Forests are a substantial terrestrial carbon sink, but anthropogenic changes in land use and climate have considerably reduced the scale of this system1. Remote-sensing estimates to quantify carbon losses from global forests2-5 are characterized by considerable uncertainty and we lack a comprehensive ground-sourced evaluation to benchmark these estimates. Here we combine several ground-sourced6 and satellite-derived approaches2,7,8 to evaluate the scale of the global forest carbon potential outside agricultural and urban lands. Despite regional variation, the predictions demonstrated remarkable consistency at a global scale, with only a 12% difference between the ground-sourced and satellite-derived estimates. At present, global forest carbon storage is markedly under the natural potential, with a total deficit of 226 Gt (model range = 151-363 Gt) in areas with low human footprint. Most (61%, 139 Gt C) of this potential is in areas with existing forests, in which ecosystem protection can allow forests to recover to maturity. The remaining 39% (87 Gt C) of potential lies in regions in which forests have been removed or fragmented. Although forests cannot be a substitute for emissions reductions, our results support the idea2,3,9 that the conservation, restoration and sustainable management of diverse forests offer valuable contributions to meeting global climate and biodiversity targets.

Abstract The organosulfur compound dimethylsulfoniopropionate (DMSP) has key roles in stress protection, global carbon and sulfur cycling, chemotaxis, and is a major source of climate-active gases. Saltmarshes are global hotspots for DMSP cycling due to Spartina cordgrasses that produce exceptionally high concentrations of DMSP. Here, in Spartina anglica, we identify the plant genes that underpin high-level DMSP synthesis: methionine S-methyltransferase (MMT), S-methylmethionine decarboxylase (SDC) and DMSP-amine oxidase (DOX). Homologs of these enzymes are common in plants, but differences in expression and catalytic efficiency explain why S. anglica accumulates such high DMSP concentrations and other plants only accumulate low concentrations. Furthermore, DMSP accumulation in S. anglica is consistent with DMSP having a role in oxidative and osmotic stress protection. Importantly, administration of DMSP by root uptake or over-expression of Spartina DMSP synthesis genes confers plant tolerance to salinity and drought offering a route for future bioengineering for sustainable crop production.

Understanding what controls global leaf type variation in trees is crucial for comprehending their role in terrestrial ecosystems, including carbon, water and nutrient dynamics. Yet our understanding of the factors influencing forest leaf types remains incomplete, leaving us uncertain about the global proportions of needle-leaved, broadleaved, evergreen and deciduous trees. To address these gaps, we conducted a global, ground-sourced assessment of forest leaf-type variation by integrating forest inventory data with comprehensive leaf form (broadleaf vs needle-leaf) and habit (evergreen vs deciduous) records. We found that global variation in leaf habit is primarily driven by isothermality and soil characteristics, while leaf form is predominantly driven by temperature. Given these relationships, we estimate that 38% of global tree individuals are needle-leaved evergreen, 29% are broadleaved evergreen, 27% are broadleaved deciduous and 5% are needle-leaved deciduous. The aboveground biomass distribution among these tree types is approximately 21% (126.4 Gt), 54% (335.7 Gt), 22% (136.2 Gt) and 3% (18.7 Gt), respectively. We further project that, depending on future emissions pathways, 17-34% of forested areas will experience climate conditions by the end of the century that currently support a different forest type, highlighting the intensification of climatic stress on existing forests. By quantifying the distribution of tree leaf types and their corresponding biomass, and identifying regions where climate change will exert greatest pressure on current leaf types, our results can help improve predictions of future terrestrial ecosystem functioning and carbon cycling.

BACKGROUND: Uranium exposure remains an important environmental legacy and physiological health concern, with hundreds of abandoned uranium mines located in the Southwestern United States largely impacting underserved indigenous communities. The negative effects of heavy metals on barrier permeability and inhibition of intestinal epithelial healing have been described; however, transcriptomic changes within the intestinal epithelial cells and impacts on lineage differentiation are largely unknown. OBJECTIVES: Herein, we sought to determine the molecular and cellular changes that occur in the colon in response to uranium bearing dust (UBD) exposure. METHODS: Human colonoids from three biologically distinct donors were acutely exposed to UBD then digested for single cell RNA sequencing to define the molecular changes that occur to specific identities of colonic epithelial cells. Validation in colonoids was assessed using morphological and imaging techniques. RESULTS: Human colonoids acutely exposed to UBD exhibited disrupted proliferation and hyperplastic differentiation of the secretory lineage cell, enteroendocrine cells (EEC). Single-cell RNA sequencing also showed more EEC subtypes present in UBD-exposed colonoids. DISCUSSION: These findings highlight the significance of crypt-based proliferative cells and secretory cell differentiation using human colonoids to model major colonic responses to uranium-bearing particulate dust exposure. https://doi.org/10.1289/EHP13855, Introduction Uranium mining in the United States arose in the 1940s, peaked in the 1970s, and subsided in the late 1980s, with extensive activity concentrated in Navajo, Puebloan, and other [...]

Background Older people living in care homes are at high risk of poor health outcomes and mortality if they contract coronavirus disease 2019. Protective measures include social distancing and isolation, although implementation is challenging. Objectives To explore the real-life experiences of social distancing and isolation in care homes for older people, and to develop a toolkit of guidance and resources. Design A mixed-methods, phased design. Setting Six care homes in England caring for older adults. Participants Care home staff (n = 31), residents (n = 17), family members (n = 17), senior health and care leaders (n = 13). Methods A rapid review to assess the social distancing and isolation measures used by care homes to control the transmission of coronavirus disease 2019 and other infectious diseases (phase 1), in-depth case studies of six care homes, involving remote individual interviews with staff, residents and families, collection of policies, protocols and routinely collected care home data, remote focus groups with senior health and care leaders (phase 2) and stakeholder workshops to co-design the toolkit (phase 3). Interview and focus group data and care home documents were analysed using thematic analysis and care home data using descriptive statistics. Results The rapid review of 103 records demonstrated limited empirical evidence and the limited nature of policy documentation around social distancing and isolation measures in care homes. The case studies found that social distancing and isolation measures presented moral dilemmas for staff and often were difficult, and sometimes impossible to implement. Social distancing and isolation measures made care homes feel like an institution and denied residents, staff and families of physical touch and other forms of non-verbal communication. This was particularly important for residents with cognitive impairment. Care homes developed new visiting modalities to work around social distancing measures. Residents and families valued the work of care homes to keep residents safe and support remote communication. Social distancing, isolation and related restrictions negatively impacted on residents’ physical, psychological, social and cognitive well-being. There were feelings of powerlessness for families whose loved ones had moved into the care home during the pandemic. It was challenging for care homes to capture frequent updates in policy and guidance. Senior health and care leaders shared that the care home sector felt isolated from the National Health Service, communication from government was described as chaotic, and trauma was inflicted on care home staff, residents, families and friends. These multiple data sources have informed the co-design of a toolkit to care for residents, families, friends and care home staff. Limitations The review included papers published in English language only. The six care homes had a Care Quality Commission rating of either ‘good’ or ‘outstanding’. There was a lack of ethnic diversity in resident and family participants. Conclusions Care homes implemented innovative approaches to social distancing and isolation with varying degrees of success. A legacy of learning can help rebuild trust at multiple levels and address trauma-informed care for residents, families, friends and staff. Future work can include evaluation of the toolkit, research to develop a trauma-informed approach to caring for the care home sector and co-designing and evaluating an intervention to enable residents with different needs to transition to living well in a care home. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR132541) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 45. See the NIHR Funding and Awards website for further award information. Plain language summary Older people living in care homes are at risk of poor health and death if they get coronavirus disease 2019 (COVID-19). To protect older people from COVID-19, care homes use different measures, including social distancing and isolation. These measures can be challenging. Our research aimed to explore the challenges and solutions to using social distancing and isolation in care homes. We reviewed existing evidence to examine how care homes have used social distancing and isolation measures to control the spread of COVID-19 and other contagious diseases. We investigated how social distancing and isolation measures have been used in six care homes in England. We spoke with residents, families and staff. We collected care home documents and other data. We held group discussions with senior health and care leaders. The review showed limited research and the limited nature of policy documentation on social distancing and isolation measures. Interviews revealed that social distancing and isolation measures were difficult, and sometimes impossible, for staff to implement. These measures made care homes feel less homely and inhibited touch, for example hugs. Residents and families valued the work of care homes to keep residents safe and the use of technology for keeping connected. Social distancing, isolation and related restrictions negatively affected residents’ physical, psychological, social and cognitive well-being. There were feelings of powerlessness for families whose loved ones had moved into the care home during the pandemic. It was challenging for care homes to capture frequent updates in policy and guidance. Senior health and care leaders shared that the care home sector felt isolated from the National Health Service, communication from government to the care home sector was described as chaotic and trauma was inflicted on care home staff, residents, families and friends. These findings have been used to design guidance to help care homes implement social distancing and isolation measures both now and for any future outbreaks. Scientific summary Background Older people living in care homes (CHs) (i.e. homes that provide residential and/or nursing care) often have complex health and care needs and are at high risk of poor health outcomes and mortality, especially if they contract coronavirus disease 2019 (COVID-19). To protect older people from COVID-19, CHs use interventions such as social distancing and isolation, but these measures have been reported as challenging. Research is needed to explore and understand the challenges experienced by CHs endeavouring to implement these interventions while mitigating any negative consequences. Objectives The overall aim of the study was to explore and understand the real-life experiences of social distancing and isolation measures for older people living in CHs in England from the perspective of multiple stakeholders, and to develop a toolkit of evidence-informed guidance and resources for CHs now and for future outbreaks. The study objectives were as follows: (1) to investigate the mechanisms and measures used by CHs currently and previously to socially distance and isolate older people to prevent and control the spread of COVID-19 and other infectious and contagious diseases (2) to examine the experiences of residents and families/friends of social distancing and isolation measures during the COVID-19 pandemic, including how these measures impacted upon their well-being and how they adapted to change (3) to explore how registered nurses and care staff adapted to and managed the delivery of personal, social and psychological care for residents with different needs while maintaining social distancing and isolation measures (4) to identify how CH managers, owners and external stakeholders developed, managed and adapted policies, procedures and protocols to implement social distancing and isolation measures including workforce organisation, training and support, use of communal spaces, visiting, and working with external health and social care professionals (5) to use the findings to develop a toolkit of evidence-informed guidance and resources, including a mosaic film, detailing which interventions and strategies for social distancing and isolation work well and which do not work in specific situations and contexts to support decision-making about health and care delivery in CHs and to facilitate resilience-building for future planning. Methods A mixed-methods, phased design was undertaken to identify the challenges, consequences and solutions to implementing social distancing and isolation measures in CHs for older adults to prevent and control the spread of COVID-19. The study was conducted in three phases: (1) a rapid evidence review of measures used to prevent or control the transmission of COVID-19 and other infectious diseases in CHs for older people, following the guidance for conducting rapid reviews1 (2) in-depth case studies of six purposively sampled CHs in England involving individual interviews with care staff, managers, residents and family/friends, the collection of social distancing and isolation policies/protocols and routinely collected CH data, and focus groups with purposively sampled CH owners and external stakeholders. Reporting guidance for qualitative research was used2 (3) development of a toolkit of evidence-informed guidance and resources, and a mosaic film for CHs. The findings from earlier phases were used in two co-design workshops with external stakeholders to develop the toolkit. Findings from the 103 papers included in the rapid review were synthesised using tables and a narrative summary organised around the review questions. Interview audio-recordings were transcribed verbatim and data analysed using thematic analysis. Descriptive summary statistics described the quantitative data collected. For the CH documents, information was collated around the key themes of social distancing, isolation, cohorting, zoning and other restrictions. Concurrent data collection and analysis informed decision-making about the need for further data and from which source. Patient and public involvement (PPI) was an integral part of this study, informing its design, method, analysis and dissemination. PPI group members also participated in online workshops to contribute to the co-design of the toolkit. Results The rapid review highlighted the following: There is a lack of empirical evidence around how measures to prevent or control COVID-19 and other infectious diseases are implemented in CHs. Most papers were grey literature or policy documents, which were mainly descriptive, or opinion based. Furthermore, these interventions were generally mentioned as part of a wider discussion of COVID-19 strategies and were not the primary focus of the papers. Key interventions for preventing and controlling the transmission of COVID-19 and other infectious diseases in CHs for older people include social distancing; isolation of residents and staff; restrictions for residents, family members and staff; zoning and cohorting; and surveillance. Evaluative research on the use of these interventions in CHs is needed urgently. The six case study sites were geographically spread and all had a Care Quality Commission rating of good (n = 4) or outstanding (n = 2). All were part of organisations (ranging in size from 7 to 114 CHs per organisation, and between 767 and 5875 beds per organisation). Four of the CHs were part of privately run organisations, and two were part of voluntary/not-for-profit organisations. One CH had a ‘dual’ registration, three had a ‘nursing’ registration and two were registered as ‘without nursing’. Most provided some specialist care such as for dementia, learning disabilities, physical and mental health problems. The number of beds offered ranged between 37 and 73. One CH comprised a household of 12 residents within a village complex. Care homes varied on the number of positive COVID-19 cases, for example one reported only one case between March 2020 and February 2021, while another reported 27 cases within the month November 2020 alone – this home had opened a specially allocated ‘COVID-ward’. In one CH no residents had died within 28 days of a positive COVID-19 test, while 10 residents had died from another home. Policies and protocols about social distancing and isolation measures were collected from each CH and compared. Key findings were as follows: There was significant variation between CHs in the content, length and level of detail presented in policy and guidance documents. Capturing the frequent updates in guidance was challenging with documents sometimes being repetitive and unclear. Many documents had further, embedded documents or links to government guidance that provided a great deal of information, which might be unrealistic for CH staff to read. Shorter documents were less comprehensive and may not provide the necessary detail to guide CH staff. None of the documents included guidance on staff training and development. Research at the case study sites included individual interviews with 31 CH staff. Key findings were as follows: The impact that the COVID-19 pandemic had upon CH staff must not be underestimated. Staff reported trauma and emotional distress. For many staff, the difficulties experienced during the pandemic were compounded by the government’s response to CHs. Some staff felt they had been abandoned by the government, while others criticised the ‘blanket approach’ to government guidance and the rapidly changing rules for CHs. Care home managers valued the support of their senior leadership to help them interpret and implement government guidance. Staff talked of the difficulties of ‘policing’ social distancing measures while simultaneously trying to maintain a sense of ‘normality’ for their residents. Although staff and residents were supposed to maintain a social distance from each other, this was often impossible to uphold when providing personal care. Care homes were perceived as a resident’s home rather than an institution, which made some staff question whether social distancing was appropriate. Many staff felt that social distancing measures denied residents (and themselves) of the important need for touch, as hugs were felt to have a vital role in CH life. Understanding fully the impact on residents living with dementia was recognised as a challenge and not always possible to achieve. The design and layout of CHs meant that there was not always the physical space for social distancing to be implemented. Staff felt that new admissions to CHs had the most difficult experience with isolation regulations. For some managers, isolation measures went against the ethos of the CH environment and ruined the family feel of the CH. The requirement for residents to isolate when returning from hospital could lead to a reluctance in residents to attend hospital appointments and a disinclination of staff to refer residents for hospital care. Several different resident restrictions were implemented in CHs, but restrictions around residents leaving the home, changes to food preparation/delivery and visitor restrictions were perceived to have the greatest negative impact. On occasions, staff became a target of anger and frustration from residents and their families, who could not comprehend that they were being prevented from seeing each other. Good support from CH management was considered by staff to make the process of implementing these measures easier. Individual interviews were conducted with 17 residents and 17 family members. Key findings were as follows: The experiences of residents and families were varied, and their impact was influenced by the existing pattern of relationships residents and families maintained within and beyond the CH. Residents and families valued the work of the CHs in keeping residents safe. They accepted the need for restrictions. Residents and families appreciated the support they received in communicating with one another virtually and the importance of this communication for residents’ health and well-being. Measures relating to isolation were particularly difficult for residents, particularly for those unable to communicate with the outside world through technology. Measures to make isolation less difficult for residents included ensuring that they were entertained purposefully with regular socially distanced visits from staff and various resources to occupy their time. Creative approaches to activities for residents not isolating were also evidenced, for example indoor gardening, yoga and quizzes. Social distancing made aspects of CH life and social visiting difficult and sometimes unsatisfactory; residents and families missed physical touch and other non-verbal forms of communication. This was particularly important for residents with cognitive impairment. Residents and families were involved with staff in complex judgements of risk, choice and control, which were complicated by two factors. First, families (and some residents) were aware that those in CHs were in the twilight of their lives and that time was ebbing away. Second, many families and residents were also learning how to manage their relationships in the new living context of a CH. Two focus groups were conducted with a purposive sample of 13 external senior health and care leaders. Key findings were as follows: Isolation of the sector: the sector felt cut off from the National Health Service (NHS) and pre-pandemic sources of service and support. Government guidance for CHs and communication processes: ‘chaos’ described the approach to cascading information to CHs, especially in the first wave of the pandemic. Visiting: regulations evolved throughout the different waves of the pandemic and led to variations in interpreting and implementing visiting guidance. Trauma: as the pandemic wore on and the different waves and variants emerged, there was a need to take account of the broader health and well-being of residents, families, visitors and the workforce. Trauma impacted at several different levels – for staff, residents and family members. Implications for practice and policy For practice Implications of the study findings for practice are captured in our toolkit for supporting CHs with social distancing and isolation measures. These are framed around six areas: caring for residents when they are social distancing; caring for residents when they are isolating; supporting residents, families and friends to communicate when visiting is not permitted; supporting visits from families and friends when visiting is allowed but with restrictions; caring for care staff; and caring for managers. For policy The study findings can inform discussions involving CH providers, managers and external stakeholders to enhance understanding of social distancing and isolation measures for residents – consequences, challenges, solutions and learning. Our findings also have implications about how guidelines are developed and disseminated. They reinforce the need for CHs and social care to be considered as an integral part of integrated care systems, to ensure that actions taken during national emergencies fully account for the impact on all parts of health and social care. Our findings can inform discussions about developing digital technologies to help residents with different needs stay connected with families and friends, and for CHs to communicate effectively with residents’ families and friends. Our findings can contribute to the content of the digital hub for the social care workforce. Recommendations for further research This study has identified that research is needed in several areas including the following: Evaluations of the toolkit. Evaluation of social distancing and isolation measures used in CHs to prepare for future pandemics. Research to develop and evaluate remote social interaction for residents living with dementia and their families. Research to understand what a trauma-informed approach looks like for the CH sector – to care for residents, families, friends and staff in CHs caring for older people. Research to co-design and evaluate an intervention to enable residents with different needs to transition to living well in a CH. The study of an intervention that cares for families and friends. Conclusions The CH sector was ill-prepared and under-resourced for the COVID-19 pandemic. During the pandemic and for any further surges, it is paramount that CH services are safe, effective, caring, responsive to individual needs and well-led. The loss of older people living in CHs due to COVID-19 has been substantial; it is essential to learn from this devastation, to understand the consequences, challenges, solutions and to evaluate these solutions. Evidence to support learning and recovery of the CH sector from the pandemic and to inform policy-making is paramount. Care homes need evidence-informed guidance that sets out what and how social distancing and isolation measures should be operationalised, while meeting residents’ individual needs. Our toolkit is designed to capture such innovative approaches. Our study makes an important contribution to this learning and recovery, as one of the first to study the challenges and solutions to implementing social distancing and isolation measures for older people living in CHs in England. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR132541) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 45. See the NIHR Funding and Awards website for further award information.

AbstractMany types of health science learners, including clinical and translational scientists, students, researchers, and clinicians, seek to increase their knowledge of biostatistics. These learners are heterogeneous in their field, career stage and career focus. Based on the collective experience of an expert panel with over 115 years teaching statistics to health science learners, we propose a framework for considering the needs of health science learners motivated by their career goals. This framework defines four types of health science learners seeking statistical training: (a) consumers, (b) “milestone makers”, (c) biomedical researchers with statistical support, and (d) biomedical researchers without statistical support. Each type of learner has different levels at which they need to understand statistical topics for their careers, such as when to use a particular statistical method or why a given method works; these differing levels of understanding are detailed in our proposed framework. Further, this framework identifies the expectations that each of these types of learners should have for gaining statistical knowledge in a single seminar, multiple seminars, a seminar series, an accredited course, or a certificate/degree program. Advantages and disadvantages of widely used educational formats for these learners are also described. From this work, health science learners seeking biostatistical training or those who are planning a training program for others can gain insight into identifying appropriate statistical training goals for the type of learner with which they identify. Statistical educators may also use these guidelines to help health science learners align expectations for various types of training.

Abstract Organic forms of phosphorus (P) prevail in soils and their quantification is vital to better understand global biogeochemical cycles. P speciation in soil is commonly assessed by 31P NMR spectroscopy of sodium hydroxide‐EDTA (NaOH‐EDTA) extracts. A liquid chromatography‐inductively coupled plasma‐mass spectrometry (LC‐ICP‐MS) method that employs NaOH‐EDTA is described. Comparison with 31P NMR shows that LC‐ICP‐MS is up to three orders of magnitude more sensitive. It allows measurement in samples as small as 1 mg. We reveal variation of inositol phosphate distribution in Swedish boreal forest soil and identify myo‐ and scyllo‐inositol hexakisphosphates and other isomers including scyllo‐inositol pentakisphosphate. Speciation of the major inositol phosphates was not altered by long‐term nitrogen fertilization.

In cell models, changes in the 'accessible' pool of plasma membrane (PM) cholesterol are linked with the regulation of endoplasmic reticulum sterol synthesis and metabolism by the Aster family of nonvesicular transporters; however, the relevance of such nonvesicular transport mechanisms for lipid homeostasis in vivo has not been defined. Here we reveal two physiological contexts that generate accessible PM cholesterol and engage the Aster pathway in the liver: fasting and reverse cholesterol transport. During fasting, adipose-tissue-derived fatty acids activate hepatocyte sphingomyelinase to liberate sequestered PM cholesterol. Aster-dependent cholesterol transport during fasting facilitates cholesteryl ester formation, cholesterol movement into bile and very low-density lipoprotein production. During reverse cholesterol transport, high-density lipoprotein delivers excess cholesterol to the hepatocyte PM through scavenger receptor class B member 1. Loss of hepatic Asters impairs cholesterol movement into feces, raises plasma cholesterol levels and causes cholesterol accumulation in peripheral tissues. These results reveal fundamental mechanisms by which Aster cholesterol flux contributes to hepatic and systemic lipid homeostasis.

Gadolinium-based contrast agents are increasingly used in clinical practice. While these pharmaceuticals are verified causal agents in nephrogenic systemic fibrosis, there is a growing body of literature supporting their role as causal agents in symptoms associated with gadolinium exposure after intravenous use and encephalopathy following intrathecal administration. Gadolinium-based contrast agents are multidentate organic ligands that strongly bind the metal ion to reduce the toxicity of the metal. The notion that cationic gadolinium dissociates from these chelates and causes the disease is prevalent among patients and providers. We hypothesize that non-ligand-bound (soluble) gadolinium will be exceedingly low in patients. Soluble, ionic gadolinium is not likely to be the initial step in mediating any disease. The Kidney Institute of New Mexico was the first to identify gadolinium-rich nanoparticles in skin and kidney tissues from magnetic resonance imaging contrast agents in rodents. In 2023, they found similar nanoparticles in the kidney cells of humans with normal renal function, likely from contrast agents. We suspect these nanoparticles are the mediators of chronic toxicity from magnetic resonance imaging contrast agents. This article explores associations between gadolinium contrast and adverse health outcomes supported by clinical reports and rodent models.

Abstract d-myo-inositol 1,4,5-trisphosphate (InsP3) is a fundamental second messenger in cellular Ca2+ mobilization. InsP3 3-kinase, a highly specific enzyme binding InsP3 in just one mode, phosphorylates InsP3 specifically at its secondary 3-hydroxyl group to generate a tetrakisphosphate. Using a chemical biology approach with both synthetised and established ligands, combining synthesis, crystallography, computational docking, HPLC and fluorescence polarization binding assays using fluorescently-tagged InsP3, we have surveyed the limits of InsP3 3-kinase ligand specificity and uncovered surprisingly unforeseen biosynthetic capacity. Structurally-modified ligands exploit active site plasticity generating a helix-tilt. These facilitated uncovering of unexpected substrates phosphorylated at a surrogate extended primary hydroxyl at the inositol pseudo 3-position, applicable even to carbohydrate-based substrates. Crystallization experiments designed to allow reactions to proceed in situ facilitated unequivocal characterization of the atypical tetrakisphosphate products. In summary, we define features of InsP3 3-kinase plasticity and substrate tolerance that may be more widely exploitable.

Introduction: More frequent and severe lupus nephritis (LN) has been reported in men compared to women, but data are limited and inconsistent. We conducted a meta-analysis of the literature to compare the histopathologic findings and outcomes between men and women with biopsy-proven LN. Methods: A systematic search of MEDLINE, Embase, Cochrane, and Web of Science databases was conducted through February 2021. Clinical information was extracted and synthesized from 25 studies that met inclusion criteria (1,210 men and 6,635 women). Pooled odds ratios (OR) with corresponding 95% confidence intervals (CIs) were generated via meta-analysis, and meta-regression was performed to assess the impact of several covariates, both using random-effects models. Results: Twenty studies reported kidney histopathology, eleven reported kidney outcomes, and eight reported mortality rates. Men had greater odds of class IV ± V LN (OR 1.26, 95% CI: 1.01–1.56), and the composite of end-stage kidney disease, persistent eGFR

Abstract Background In response to concerns about high hospital mortality rates, patient and carer complaints, a Mid Staffordshire NHS Foundation Trust public inquiry was conducted at the request of the UK government. This inquiry found serious failures in the quality of basic care provided and as a consequence, recommended that patients should have more regular visits, organised at predictable times from nursing staff. Intentional rounding, also known as nursing ward rounds, was widely adopted to meet this need. Objective To test, refine or refute eight programme theories to understand what works, for whom, and in what circumstances. Setting Six wards (older people and acute wards) in three NHS trusts in England. Participants Board level and senior nursing managers (N = 17), nursing ward staff (N = 33), allied health and medical professionals (N = 26), patients (N = 34) and relatives (N = 28) participated in an individual, in-depth interview using the realist method. In addition, ward-based nurses (N = 39) were shadowed whilst they conduced intentional rounds (240 rounds in total) and the direct care of patients (188 h of patient care in total) was observed. Methods The mixed methods design included: Phase (1) Theory development - A realist synthesis was undertaken to identify any programme theories which were tested, refined and/or refuted, using data from phases 2 and 3; Phase (2) A survey of all English NHS acute Trusts; Phase (3) Six case studies of wards involving realist interviews, shadowing and non-participant observations, analysis of ward outcome and cost data; and Phase (4) Synthesis of findings from phases 1, 2 and 3. Results The realist synthesis identified eight programme theories of intentional rounding: ‘Consistency and comprehensiveness’, ‘Accountability’, ‘Visibility of nurses’, ‘Anticipation’, ‘Allocated time to care’, ‘Nurse-patient relationships’, ‘Multi-disciplinary teamwork and communication’ and ‘Patient empowerment’. Key findings showed that of the original eight programme theories of intentional rounding, only two partially explained how the intervention worked (‘Consistency and comprehensiveness’ and ‘Accountability’). Of the remaining six programme theories, the evidence for two was inconclusive (‘Visibility of nurses’ and ‘Anticipation’) and there was no evidence for four (‘Allocated time to care’; ‘Nurse-patient relationships’; ‘Multi-disciplinary teamwork and communication’; and ‘Patient empowerment’). Conclusions This first theory-informed evaluation of intentional rounding, demonstrates that the effectiveness of intentional rounding in the English healthcare context is very weak. Furthermore, the evidence collected in this study has challenged and refuted some of the underlying assumptions about how intentional rounding works. This study has demonstrated the crucial role context plays in determining the effectiveness of an intervention and how caution is needed when implementing interventions developed for the health system of one country into another.

We present a unique and innovative course, Biostatistical Literacy, developed at the University of Minnesota. The course is aimed at public health graduate students and health sciences professionals. Its goal is to develop students' ability to read and interpret statistical results in the medical and public health literature. The content spans the typical first-semester introductory material, including data summaries, hypothesis tests and interval estimation, and simple linear regression, as well as material typically presented in a second introductory course, including multiple linear regression, logistic regression, and time-to-event methods. The focus is on when to use a method and how to interpret the results; no statistical software computing is taught. A flipped classroom approach is used, where students are first exposed to the material outside of class, and class time is devoted to actively exploring and applying the concepts in greater depth. The course structure, the class activities, and feedback from students will be shared. Supplementary materials for this article are available online.

An ability to effectively self-manage medications is the result of several factors influencing a person’s decision to take medications. The need for new approaches to medication self-management are evident in the persistent trends of ineffective and unfortunate medication use consequences, referred to as drug-related morbidity and mortality. Fortunately, pioneering initiatives have emerged to reshape our approach for developing a rational organizational paradigm so that patients can confidently self-manage medications. Favorable outcomes of studies pertaining to the delivery of comprehensive medication therapy management services within the practice of pharmaceutical care prompts the question, ‘Can patients and family members apply the 4-step pharmacotherapy workup process to better organize their decision-making and confidence in medication self-management?’ To answer this question an Effective Medication Self-Management Toolkit based on this 4-step process, and a Medication Management Self-efficacy Checklist, were created and evaluated for feasibility, acceptability, and internal consistency reliability. The first evaluation established the preliminary acceptability and feasibility of the toolkit using a convenience sample of 39 residents of independent living facilities in focus group sessions. All participants indicated they perceive that the 4-step process can help individuals successfully self-manage medications. At the conclusion of the focus group sessions, all 39 participants completed the 7-item post-session checklist. This paper presents the second evaluation to establish the internal consistency reliability of the toolkit’s Medication Management Self-efficacy Checklist using Cronbach’s alpha. There was good internal consistency of the self-efficacy checklist with a Cronbach’s alpha value of 0.82. This investigation of a novel approach for applying the 4-step pharmacotherapy assessment process by patients suggests that it is feasible and acceptable to use, and that the medication self-efficacy checklist provides a reliable and useful measure of a patient’s confidence in self-managing medications.

IntroductionInduced modification of plant gene expression is of both fundamental and applied importance. Cis-acting regulatory elements (CREs) are major determinants of the spatiotemporal strength of gene expression. Yet, there are few examples where induced genetic variation in predetermined CREs has been exploited to improve or investigate crop plants. MethodsThe digital PCR based FIND-IT technology was applied to discover barley mutants with CRE variants in the promoter of the nutritional important barley grain phytase (PAPhy_a) gene. Results and discussionMutants with higher or lower gene expression and ultimately higher or lower mature grain phytase activity (MGPA), respectively, were discovered. Field trials and inositol phosphate profiling during germination showed that PAPhy_a does not influence agronomic performance under the trial conditions but it does shorten the lag time of phosphate mobilization during germination. Higher endogenous MGPA is an improvement of grain quality for feed use as it improves the phosphate bioavailability for monogastric animals. Moreover, as the targeted CRE motifs of the PAPhy_a promoter are shared with a range of seed expressed genes like key cereal and legume storage genes, the current results demonstrates a concept for modulating individual gene expression levels of a range of seed genes.

This article is composed of three independent commentaries about the state of Integrated, Coordinated, Open, Networked (ICON) principles in the American Geophysical Union Biogeosciences section, and discussion on the opportunities and challenges of adopting them. Each commentary focuses on a different topic: (a) Global collaboration, technology transfer, and application (Section 2), (b) Community engagement, community science, education, and stakeholder involvement (Section 3), and (c) Field, experimental, remote sensing, and real-time data research and application (Section 4). We discuss needs and strategies for implementing ICON and outline short- and long-term goals. The inclusion of global data and international community engagement are key to tackling grand challenges in biogeosciences. Although recent technological advances and growing open-access information across the world have enabled global collaborations to some extent, several barriers, ranging from technical to organizational to cultural, have remained in advancing interoperability and tangible scientific progress in biogeosciences. Overcoming these hurdles is necessary to address pressing large-scale research questions and applications in the biogeosciences, where ICON principles are essential. Here, we list several opportunities for ICON, including coordinated experimentation and field observations across global sites, that are ripe for implementation in biogeosciences as a means to scientific advancements and social progress.

Objectives Haiti remains a principal placement country for intercountry adoptees to the United States. This project reports the health status of children adopted from Haiti arriving to the U.S. and compares them to intercountry adoptees from other regions. Methods A retrospective chart review was conducted of adoptees placed in the U.S. from Haiti (n=87), age and sex matched with intercountry adoptees placed in the U.S. from Asia (n=87) and Latin America (n=87) between January 2010 and November 2019. Data on immunization status, contagious diseases, and nutrition and growth were analyzed via linear, logistic, and multinomial regression. Results After adjusting for age, sex, and standardized height, children adopted from Haiti, compared to adoptees from Latin America and Asia, demonstrated a lack of immunity to hepatitis B (OR=5.89;6.87), increased immunity to hepatitis A (OR=0.38;0.30), infection by two or more parasites (OR=8.43;38.48), high lead levels (OR=23.79;7.04), and anemia (OR=15.25;9.18). Unexpectedly, children adopted from Haiti had greater standardized height (-1.28 vs. -1.82 and -2.13) and standardized weight (-0.32 vs. -0.57 and -1.57) than their counterparts from Latin America and Asia. Conclusions Children adopted from Haiti face complex medical challenges undoubtedly related to the country's low socioeconomic status (SES) and the impact of recurrent natural disasters and governmental neglect on public health infrastructure. Appropriate care is critical in preventing and avoiding transmission of infectious diseases in adoptees and family members. The high incidence of anemia and elevated lead levels may further exacerbate the developmental effects of early institutional deprivation., Author(s): Priya E. George [sup.1] , Anna V. Gamble [sup.1] , Elise F. Palzer [sup.2] , Ann M. Brearley [sup.2] , Dana E. Johnson [sup.3] , Judith K. Eckerle [sup.1] [...]

Renewed enthusiasm surrounds the potential for urban industry and its contribution to the socioeconomic diversity of cities, despite concerns about the loss of industrial uses, land, and buildings in high-value, post-industrial cities. Yet, industry is often hidden and undervalued, and methodologies to change the culture around nurturing industry in cities have not been well explored. As a first step in moving this agenda forward, this article proposes effective ways to reveal industrial uses and to advocate for policy protections of the land they occupy. It examines how London Metropolitan University’s School of Art, Architecture and Design (AAD) Cities action researchers applied their Audit, Reveal and Promote methodology to Southwark, a London borough with a high concentration of urban industry. There are key aspects to revealing industrial economies: collecting accurate data on the ground, showcasing local businesses, building stakeholder networks through mutual trust, and creating a space of possibilities between vertical hierarchical and grassroots power networks to enable stakeholders to participate in urban change. This article presents a methodology for cultural change towards valuing a mix of uses, including industry, to transform land development towards retention and densification of industry.

Abstract Social participation, also termed stakeholder voice, is an important component of health system governance. Increased interactions between the community and policy makers could facilitate a more responsive health system that targets the needs of the community better. Recently, the World Health Organization (WHO) published a handbook on social participation that identified five key themes for ministries of health to consider when engaging the input of the community. In this rapid systematic literature review, we aimed to identify quantitative and qualitative measures that have been used to assess aspects of social participation involving people and policy makers. We identified 172 measures from 48 studies from countries in all six WHO regions. These measures were categorized by all five themes from the handbook on social participation and these measures are linked to 27 concepts. This rapid review found that the focus of measures is largely on the existence of participation—be it by the general population or specific vulnerable groups—rather than on the quality of their participation. The measures in this inventory may be useful for ministries of health and other key stakeholders to use when developing methods to assess and encourage social participation in their context.