Quantile regressions as a tool to evaluate how an exposure shifts and reshapes the outcome distribution: A primer for epidemiologists.

Quantifying how an exposure affects the entire outcome distribution is often important, e.g., for outcomes such as blood pressure which have non-linear effects on long-term morbidity and mortality. Quantile regressions offer a powerful way of estimating an exposure's relationship with the outcome distribution but remain underused in epidemiology. We introduce quantile regressions with a focus on distinguishing estimators for quantiles of the conditional and unconditional outcome distributions. We also present an empirical example in which we fit mean and quantile regressions to investigate educational attainment's association with later-life systolic blood pressure (SBP). We use data on 8,875 US-born respondents aged 50+ years from the US Health and Retirement Study. More education was negatively associated with mean SBP. Conditional and unconditional quantile regressions both suggested a negative association between education and SBP at all levels of SBP, but the absolute magnitudes of these associations were higher at higher SBP quantiles relative to lower quantiles. In addition to showing that educational attainment shifted the SBP distribution left-wards, quantile regression results revealed that education may have reshaped the SBP distribution through larger protective associations in the right tail, thus benefiting those at highest risk of cardiovascular diseases.

Osteoporotic Fractures: Diagnosis, Evaluation, and Significance From the International Working Group on DXA Best Practices.

Osteoporotic fractures, also known as fragility fractures, are reflective of compromised bone strength and are associated with significant morbidity and mortality. Such fractures may be clinically silent, and others may present clinically with pain and deformity at the time of the injury. Unfortunately, and even at the time of detection, most individuals sustaining fragility fractures are not identified as having underlying metabolic bone disease and are not evaluated or treated to reduce the incidence of future fractures. A multidisciplinary international working group with representation from international societies dedicated to advancing the care of patients with metabolic bone disease has developed best practice recommendations for the diagnosis and evaluation of individuals with fragility fractures. A comprehensive narrative review was conducted to identify key articles on fragility fractures and their impact on the incidence of further fractures, morbidity, and mortality. This document represents consensus among the supporting societies and harmonizes best practice recommendations consistent with advances in research. A fragility fracture in an adult is an important predictor of future fractures and requires further evaluation and treatment of the underlying osteoporosis. It is important to recognize that most fragility fractures occur in patients with bone mineral density T scores higher than -2.5, and these fractures confirm the presence of skeletal fragility even in the presence of a well-maintained bone mineral density. Fragility fractures require further evaluation with exclusion of contributing factors for osteoporosis and assessment of clinical risk factors for fracture followed by appropriate pharmacological intervention designed to reduce the risk of future fracture. Because most low-trauma vertebral fractures do not present with pain, dedicated vertebral imaging and review of past imaging is useful in identifying fractures in patients at high risk for vertebral fractures. Given the importance of fractures in confirming skeletal fragility and predicting future events, it is recommended that an established classification system be used for fracture identification and reporting.

Race-specific FRAX models are evidence-based and support equitable care: a response to the ASBMR Task Force report on Clinical Algorithms for Fracture Risk.

Task Force on 'Clinical Algorithms for Fracture Risk' commissioned by the American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee has recommended that FRAX® models in the US do not include adjustment for race and ethnicity. This position paper finds that an agnostic model would unfairly discriminate against the Black, Asian and Hispanic communities and recommends the retention of ethnic and race-specific FRAX models for the US, preferably with updated data on fracture and death hazards. In contrast, the use of intervention thresholds based on a fixed bone mineral density unfairly discriminates against the Black, Asian and Hispanic communities in the US. This position of the Working Group on Epidemiology and Quality of Life of the International Osteoporosis Foundation (IOF) is endorsed both by the IOF and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

The embodiment of the neighborhood socioeconomic environment in the architecture of the immune system.

There is growing recognition of the importance of immune health for understanding the origins of ageing-related disease and decline. Numerous studies have demonstrated consistent associations between the social determinants of health and immunosenescence (i.e. ageing of the immune system). Yet few studies have interrogated the relationship between neighborhood socioeconomic status (nSES) and biologically specific measures of immunosenescence. We used data from the US Health and Retirement Study to measure immunosenescence linked with neighborhood socioeconomic data from the National Neighborhood Data Archive to examine associations between indicators of nSES and immunosenescence. We found associations between both the ratio of terminally differentiated effector memory to naïve (EMRA:Naïve) CD4+ T cells and cytomegalovirus (CMV) immunoglobulin G (IgG) levels and nSES. For the CD4+ EMRA:Naïve ratio, each 1% increase in the neighborhood disadvantage index was associated with a 0.005 standard deviation higher value of the EMRA:Naïve ratio (95% CI: 0.0003, 0.01) indicating that living in a neighborhood that is 10% higher in disadvantage is associated with a 0.05 higher standardized value of the CD4+ EMRA:Naïve ratio. The results were fully attenuated when adjusting for both individual-level SES and race/ethnicity. For CMV IgG antibodies, a 1% increase in neighborhood disadvantage was associated a 0.03 standard deviation higher value of CMV IgG antibodies (ß = 0.03; 95% CI: 0.002, 0.03) indicating that living in a neighborhood that is 10% higher in disadvantage is associated with a 0.3 higher standardized value of CMV. This association was attenuated though still statistically significant when controlling for individual-level SES and race/ethnicity. The findings from this study provide compelling initial evidence that large, nonspecific social exposures, such as neighborhood socioeconomic conditions, can become embodied in cellular processes of immune ageing.

Indicator metrics and temporal aggregations introduce ambiguities in water scarcity estimates.

Water scarcity is a global challenge affecting billions of people worldwide. This study systematically assesses differences in the estimation of the global population exposed to water scarcity based on 7 water scarcity indicators and 11 Environmental Flow Requirements (EFR) evaluated at various spatial and temporal resolutions. All indicators show an increase in water scarcity since 1901. However, considering monthly average water scarcity estimates spatially aggregated at the basin scale found 35% less population exposed than estimates based on a distributed grid over the landscape. Estimates temporally disaggregated to consider water scarcity for at least one month a year found 50% (tenfold) larger population exposed compared to average monthly (annual) estimates. The study illustrates that estimates of the impacts of water scarcity are an artifact of how water scarcity is defined and calculated. This suggests caution is needed when relying on a single method and emphasizes the importance of considering the diversity of factors that can influence estimates of impact when assessing water scarcity.

Institutional Change Affects Perceived and Personal Intergroup Attitudes.

This research tested whether institutional change impacts policy support and attitudes toward the social groups impacted by policy change. Study 1 demonstrated across a variety of topics that, when a hypothetical state legislature banned (vs. affirmed) a practice (e.g., allowing companies to implement mandatory anti-racism training), participants perceived less support for the policy and more negative attitudes toward the group impacted (e.g., Black Americans). Study 2, a longitudinal study, investigated the short- and long-term impact of real-world policy change-the U.S. Supreme Court's Dobbs v. Jackson Women's Health Organization ruling that gave states the right to restrict access to abortion. Although the ruling did not produce lasting change in personal support for abortion restriction, it did lead participants to perceive more support for traditional gender roles and to personally endorse traditional gender attitudes more strongly. These results demonstrate the power of institutional policies to influence individually held intergroup attitudes.

Comparing Transcervical Balloon with Osmotic Dilators for Cervical Preparation Prior to Procedural Abortion: a Non-Inferiority Randomized Trial.

OBJECTIVE: To compare cervical preparation with transcervical balloon to osmotic dilators for second-trimester procedural abortions. STUDY DESIGN: We performed an unblinded, randomized, non-inferiority trial of people undergoing second-trimester procedural abortion at 18+0 to 23+6 weeks gestation. We randomized participants to either overnight osmotic dilators (Dilapan-S) or transcervical balloon (Foley). Both groups received overnight mifepristone and pre-procedural misoprostol. We powered the study on mean difference in procedure duration; non-inferiority limit 5 minutes. We compared pre-procedure cervical dilation; need for additional dilation; and, using 100-point visual analogue scale, measured physician satisfaction and ease of procedure, and participant pain and satisfaction. RESULTS: We recruited 32 participants at a single academic center. Although procedure time (minutes) was similar (balloon: 22.6+8.9 vs Dilapan-S: 22.4+12.8, p=0.96), non-inferiority was not met (mean difference, 0.2 minutes; 95% confidence interval, -7.8 to 8.2). Cervical dilation >2cm was more likely after Dilapan-S (100% vs 62.5%, p=0.02). Placement was well tolerated with similar time (minutes) for insertion (balloon: 4.8+1.0, Dilapan-S: 5.1+2.3, p=0.64) and maximum pain (median) with insertion (balloon 39 (5-78), Dilapan-S: 39 (0-100), p=0.92). Pain immediately post-insertion was higher for Dilapan-S (33 (0-100) vs 18 (0-50), p=0.046), and similar for maximum pain overnight, participant satisfaction, and likelihood to recommend. Complications were minor and similar between groups (p=0.60). CONCLUSION: While significantly more people with transcervical balloon required mechanical dilation, the difference in operative time was clinically negligible. The transcervical balloon was well tolerated and acceptable by participants. IMPLICATIONS: Clinicians experienced in mechanical dilation may consider a transcervical balloon as a lower-cost tool for second-trimester abortion cervical preparation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT05099991.

The impact of HIV infection on skeletal maturity in peripubertal children in Zimbabwe: a cross-sectional study.

INTRODUCTION: HIV infection and its treatment compromises skeletal development (growth and maturation). Skeletal maturity is assessed as bone age (BA) on hand and wrist radiographs. BA younger than chronological age (CA) indicates delayed development. We conducted a cross-sectional study to determine differences between BA and CA (i.e., skeletal maturity deviation [SMD]), and risk factors associated with SMD in peripubertal children with and without HIV established on antiretroviral therapy (ART) including use of tenofovir disoproxil fumarate (TDF). METHODS: Children with HIV taking ART for at least two years and a comparison group of HIV-negative children, aged 8-16 years and frequency-matched by age and sex, were recruited from HIV clinics and local schools in the same catchment area, in Harare, Zimbabwe. BA was assessed from non-dominant hand-wrist radiographs using the Tanner Whitehouse 3 method. Negative SMD values correspond to delayed development, i.e., BA younger than CA. Multivariable linear regression models determined factors associated with SMD overall, and in children with HIV. RESULTS: In total, 534 participants (54% males) were included; by design CA was similar in males and females, whether living with or without HIV. Mean (SD) SMD was more negative in CWH than in HIV-negative children in both males [-1.4(1.4) vs. -0.4(1.1) years] and females [-1.1(1.3) vs. -0.0(1.2) years]. HIV infection and weight-for-age Z-score<-2 were associated with more negative SMD in both males and females after adjusting for socio-economic status, orphanhood, pubertal stage, and calcium intake. Age at ART initiation was associated with SMD in both males and females with those starting ART later more delayed: starting ART aged 4-8 years 1.14 (-1.84, -0.43), or over 8 years 1.47 (-2.30, -0.65) (p-value for trend < 0.001). Similar non-significant trends were seen in males. TDF exposure TDF exposure whether < 4years or ≥ 4 years was not associated with delayed development. CONCLUSION: Perinatally-acquired HIV infection and being underweight were independently associated with delayed skeletal maturation in both males and females. Starting ART later was independently associated with skeletal maturation delay in CWH. Given the known effects of delayed development on later health, it is important to find interventions to ensure healthy weight gain through early years and in CWH to initiate ART as early as possible.

Changes in male permanent contraception as partner access to long-acting reversible contraception (LARC) increases: an analysis of the National Survey for Family Growth, 2006-2010 versus 2017-2019.

OBJECTIVE: Male permanent contraception (PC), that is, vasectomy, is an effective way of preventing pregnancy. In the United States, male PC use has historically been concentrated among higher-educated/higher-income males of White race. In the last decade, use of long-acting reversible contraception (LARC) has increased dramatically. We sought to understand how sociodemographic patterns of male PC have changed in the context of rising LARC use. STUDY DESIGN: We examined the nationally representative male public use files of the National Survey for Family Growth (NSFG) across five survey waves. Our outcome was primary contraceptive use at last sexual encounter within 12 months. Using four-way multinomial logistic regressions (male PC, female PC, LARC, lower-efficacy methods), we compared sociodemographic factors predictive of male PC use versus reported partner LARC use between 2006-2010 (early) and 2017-2019 (recent) waves. RESULTS: We included 15 964 participants. From 2006 to 2019, there were absolute declines in male PC from 8.0% to 6.8%, while male-reported partner LARC use increased three-fold, from 3.4% to 11.0%. Among the highest economic strata, use of LARC converged with male PC. In adjusted analyses, high income significantly associated with male PC use in the early wave (OR 4.6 (1.4, 14.8)), but no longer in the recent wave (OR 0.9 (0.2, 4.2)). Marital status remained a significant but declining predictor of male PC across survey waves, and instead, by 2019, number of children newly emerged as the strongest predictor of male PC use. CONCLUSION: Sociodemographic variables associated with vasectomy use are evolving, especially among high-income earners.

Intensified training augments cardiac function, but not blood volume, in male youth elite ice hockey team players.

While it is well-established that a period of interval training performed at near maximal effort, such as speed endurance training (SET), enhances intense exercise performance in well-trained individuals, less is known about its effect on cardiac morphology and function as well as blood volume. To investigate this, we subjected 12 Under-20 Danish national team ice hockey players (age 18 ± 1 years, mean ± SD) to 4 weeks of SET, consisting of 6-10 × 20 s skating bouts at maximal effort interspersed by 2 min of recovery conducted three times weekly. This was followed by 4 weeks of regular training (follow-up). We assessed resting cardiac function and dimensions using transthoracic echocardiography and quantified total blood volume with the carbon monoxide rebreathing technique at three time points: before SET, after SET and after the follow-up period. After SET, stroke volume had increased by 10 (2-18) mL (mean (95% CI)), left atrial end-diastolic volume by 10 (3-17) mL, and circumferential strain improved by 0.9%-points (1.7-0.1) (all P < 0.05). At follow-up, circumferential strain and left atrial end-diastolic volume were reverted to baseline levels, while stroke volume remained elevated. Blood volume and morphological parameters for the left ventricle, including mass and end-diastolic volume, did not change during the study. In conclusion, our findings demonstrate that a brief period of SET elicits beneficial central cardiac adaptations in elite ice hockey players independent of changes in blood volume.

Awareness of Visual Offset Reduces but Does Not Eliminate Joint Repositioning Errors in Virtual Reality.

The present study investigated the effect of visual offset (visuo-proprioceptive mismatch) in joint repositioning task in a three-dimensional virtual reality (VR) environment when participants were instructed to ignore vision. Twenty-five physically healthy young individuals performed shoulder joint position sense test. Repositioning accuracy was tested under two visual conditions, accurate and offset visions, and two instructions, no guidance or ignore vision. In accurate vision trials, the virtual hand of the tested limb seen in VR was congruent with where the participant placed their hand. In the offset vision condition, the virtual hand was seen 8° above or below their actual hand in the vertical plane. Repositioning error (i.e. constant error) in offset vision trials was lower when the participants were instructed to ignore vision compared to when no instruction about the visual offset was given (p < 0.001). However, constant error in offset vision trials was larger than accurate vision trials when the participants tried to ignore vision in both visual conditions (p < 0.001). Our results suggest that humans may be able to down-weight vision to some extent by conscious effort, while the influence of vision is difficult to eliminate when vision is present.

Machine Learning-Based Evaluation of Suicide Risk Assessment in Crisis Counseling Calls.

OBJECTIVE: Counselor assessment of suicide risk is one key component of crisis counseling, and standards require risk assessment in every crisis counseling conversation. Efforts to increase risk assessment frequency are limited by quality improvement tools that rely on human evaluation of conversations, which is labor intensive, slow, and impossible to scale. Advances in machine learning (ML) have made possible the development of tools that can automatically and immediately detect the presence of risk assessment in crisis counseling conversations. METHODS: To train models, a coding team labeled every statement in 476 crisis counseling calls (193,257 statements) for a core element of risk assessment. The authors then fine-tuned a transformer-based ML model with the labeled data, utilizing separate training, validation, and test data sets. RESULTS: Generally, the evaluated ML model was highly consistent with human raters. For detecting any risk assessment, ML model agreement with human ratings was 98% of human interrater agreement. Across specific labels, average F1 (the harmonic mean of precision and recall) was 0.86 at the call level and 0.66 at the statement level and often varied as a result of a low base rate for some risk labels. CONCLUSIONS: ML models can reliably detect the presence of suicide risk assessment in crisis counseling conversations, presenting an opportunity to scale quality improvement efforts.

Activation of autoreactive lymphocytes in the lung by STING gain-of-function mutation expressing radioresistant cells.

Gain-of-function mutations in the dsDNA sensing adaptor STING lead to a severe autoinflammatory syndrome known as STING-associated vasculopathy with onset in Infancy (SAVI). SAVI patients develop interstitial lung disease (ILD) and produce autoantibodies that are commonly associated with systemic autoimmune diseases. Mice expressing the most common SAVI mutation STING V154M (VM) similarly develop ILD, but exhibit severe T and B cell lymphopenia, low serum Ig titers, and lack autoantibodies. Importantly, lethally irradiated VM hosts reconstituted with wildtype (WT) stem cells (WT→VM) still develop ILD. In this study, we find that WT→VM chimeras had restored B cell function, produced autoantibodies, and thereby recapitulated the loss of tolerance seen in SAVI patients. Lymphocytes derived from both WT and BCR or TCR transgenic (Tg) donors accumulated in the extravascular lung tissue of WT+Tg→VM mixed chimeras, but lymphocyte activation and germinal center formation required WT cells with a diverse repertoire. Furthermore, when T cells isolated from the WTVM chimeras were adoptively transferred to naïve Rag1-deficient 2º hosts, they trafficked to the lung and recruited neutrophils. Overall, these findings indicated that VM expression by radioresistant cells promoted the activation of autoreactive B cells and T cells that then differentiated into potentially pathogenic effector subsets.

Spatial colocalization and combined survival benefit of natural killer and CD8 T cells despite profound MHC class I loss in non-small cell lung cancer.

Background: MHC class I (MHC-I) loss is frequent in non-small cell lung cancer (NSCLC) rendering tumor cells resistant to T cell lysis. NK cells kill MHC-I-deficient tumor cells, and although previous work indicated their presence at NSCLC margins, they were functionally impaired. Within, we evaluated whether NK cell and CD8 T cell infiltration and activation vary with MHC-I expression. Methods: We used single-stain immunohistochemistry (IHC) and Kaplan-Meier analysis to test the effect of NK cell and CD8 T cell infiltration on overall and disease-free survival. To delineate immune covariates of MHC-I-disparate lung cancers, we used multiplexed immunofluorescence (mIF) imaging followed by multivariate statistical modeling. To identify differences in infiltration and intercellular communication between IFNγ-activated and non-activated lymphocytes, we developed a computational pipeline to enumerate single cell neighborhoods from mIF images followed by multivariate discriminant analysis. Results: Spatial quantitation of tumor cell MHC-I expression revealed intra- and inter-tumoral heterogeneity, which was associated with the local lymphocyte landscape. IHC analysis revealed that high CD56+ cell numbers in patient tumors were positively associated with disease-free survival (DFS) (HR=0.58, p=0.064) and overall survival (OS) (HR=0.496, p=0.041). The OS association strengthened with high counts of both CD56+ and CD8+ cells (HR=0.199, p<1×10-3). mIF imaging and multivariate discriminant analysis revealed enrichment of both CD3+CD8+ T cells and CD3-CD56+ NK cells in MHC-I-bearing tumors (p<0.05). To infer associations of functional cell states and local cell-cell communication, we analyzed spatial single cell neighborhood profiles to delineate the cellular environments of IFNγ+/- NK cells and T cells. We discovered that both IFNγ+ NK and CD8 T cells were more frequently associated with other IFNγ+ lymphocytes in comparison to IFNγ- NK cells and CD8 T cells (p<1×10-30). Moreover, IFNγ+ lymphocytes were most often found clustered near MHC-I+ tumor cells. Conclusions: Tumor-infiltrating NK cells and CD8 T cells jointly affected control of NSCLC tumor progression. Co-association of NK and CD8 T cells was most evident in MHC-I-bearing tumors, especially in the presence of IFNγ. Frequent co-localization of IFNγ+ NK cells with other IFNγ+ lymphocytes in near-neighbor analysis suggests NSCLC lymphocyte activation is coordinately regulated.

Surveyed veterinary students in Australia find ChatGPT practical and relevant while expressing no concern about artificial intelligence replacing veterinarians.

Background: Chat Generative Pre-trained Transformer (ChatGPT) is a freely available online artificial intelligence (AI) program capable of understanding and generating human-like language. This study assessed veterinary students' perceptions about ChatGPT in education and practice. It compared perceptions about ChatGPT between students who had completed a critical analysis task and those who had not. Methods: This cross-sectional study surveyed 498 Doctor of Veterinary Medicine (DVM) students at The University of Sydney, Australia. Second-year DVM students researched a veterinary pathogen and then completed a critical analysis of ChatGPT (version 3.5) output for the same pathogen. A survey based on the Technology Acceptance Model was then delivered to all DVM students from all years of the programme, collecting data using Likert-style, categorical and free-text items. Results: Over 75% of the 100 respondents reported having used ChatGPT. The students found ChatGPT's output relevant and practical for their use but perceived it as inaccurate. They perceived ChatGPT output to be more useful for veterinary students than for pet owners or veterinarians. Those who had completed the critical analysis assignment had a more positive view of ChatGPT's practicality for veterinary students but noted its authoritative tone even when delivering inaccurate information. Over 50% of the students agreed that information about tools such as ChatGPT should be included in the veterinary curriculum. Students agreed that veterinarians should embrace AI but disagreed that AI would eventually replace the need for veterinarians. Conclusions: A critical appraisal of outputs from AI tools such as ChatGPT may help prepare future veterinarians for the effective use of these tools.

Daily Electronic Media Use and Sleep in Late Life.

OBJECTIVES: Daily electronic media use, including television viewing and computer use, is common in older adulthood. Yet, increased electronic media usage may disrupt nightly sleep, leading to sleeping fewer hours and more sleep disruptions. The current study examined these relationships in older adulthood, as well as the potential buffering effect of having a regular sleep schedule. METHODS: Older adults (N = 273) from the Daily Experiences and Well-Being Study (DEWS) completed 5-6 days of data collection where they answered questions at the beginning of the day about the previous night's sleep as well as questions throughout the day about daily electronic media use. They also wore Actical accelerometers to capture sleep regularity. RESULTS: Older adults reported sleeping fewer hours and having more sleep disturbances on days when they reported more instances of computer use. Sleep regularity moderated the daily association between TV viewing and sleep disturbances such that daily TV viewing was associated with more sleep complaints only for older adults who had less regular sleep patterns. However, sleep regularity no longer moderated this association when accounting for napping behavior. DISCUSSION: These findings provide evidence that older adults sleep worse after days when they engage in more electronic media use. The association with TV viewing with sleep disturbances on any given day is somewhat mitigated by engaging in regular sleep patterns. Researchers discuss the importance of assessing electronic media use and sleep in daily life as the role of sleep regularity may be a modifiable protective factor.

Microbiota dictate T cell clonal selection to augment graft-versus-host disease after stem cell transplantation.

Allogeneic T cell expansion is the primary determinant of graft-versus-host disease (GVHD), and current dogma dictates that this is driven by histocompatibility antigen disparities between donor and recipient. This paradigm represents a closed genetic system within which donor T cells interact with peptide-major histocompatibility complexes (MHCs), though clonal interrogation remains challenging due to the sparseness of the T cell repertoire. We developed a Bayesian model using donor and recipient T cell receptor (TCR) frequencies in murine stem cell transplant systems to define limited common expansion of T cell clones across genetically identical donor-recipient pairs. A subset of donor CD4+ T cell clonotypes differentially expanded in identical recipients and were microbiota dependent. Microbiota-specific T cells augmented GVHD lethality and could target microbial antigens presented by gastrointestinal epithelium during an alloreactive response. The microbiota serves as a source of cognate antigens that contribute to clonotypic T cell expansion and the induction of GVHD independent of donor-recipient genetics.

Effects of maternal calcium supplementation on offspring blood pressure and growth in childhood and adolescence in a population with a low-calcium intake: follow-up study of a randomized controlled trial.

BACKGROUND: The World Health Organization recommends calcium supplementation (1500-2000 mg/d) during pregnancy for women with a low-calcium intake. OBJECTIVES: The purpose of this study was to investigate whether pregnancy calcium supplementation affects offspring blood pressure and growth in The Gambia where calcium intakes are low (300-400 mg/d). METHODS: Follow-up of offspring born during a randomized controlled trial of pregnancy calcium supplementation (ISRCTN96502494, 1996-2000) in which mothers were randomly assigned to 1500 mg Ca/d (Ca) or placebo (P) from 20 wk pregnancy to delivery. Offspring were enrolled at age 3 y in studies where blood pressure and anthropometry were measured under standardized conditions at approximately 2-yearly intervals. Mean blood pressure and growth curves were fitted for females and males separately, using the longitudinal SuperImposition by Translation and Rotation (SITAR) mixed effects model. This generates 3 individual-specific random effects: size, timing, and intensity, reflecting differences in size, age at peak velocity, and peak velocity through puberty relative to the mean curve, respectively. RESULTS: Five hundred twenty-three singleton infants were born during the trial (maternal group assignment: Ca/P = 259/264). Four hundred ninety-one were enrolled as children (females: F-Ca/F-P = 122/129 and males: M-Ca/M-P = 119/121) and measured regularly from 3.0 y to mean age 18.4 y; 90% were measured on ≥8 occasions. SITAR revealed differences in the systolic blood pressure and height curves between pregnancy supplement groups in females, but not in males. F-Ca had lower systolic blood pressure than F-P at all ages (size = -2.1 ± SE 0.8 mmHg; P = 0.005) and lower peak height velocity (intensity = -2.9 ± SE 1.1%, P = 0.009). No significant pregnancy supplement effects were seen for other measures. CONCLUSIONS: This study showed, in female offspring, that pregnancy calcium supplementation may lower systolic blood pressure and slow linear growth in childhood and adolescence, adding to evidence of offspring sexual dimorphism in responses to maternal supplementation. Further research is warranted on the long-term and intergenerational effects of antenatal supplementations. This trial was registered at ISRCTN Registry as ISRCTN96502494.

Enhancement of Low Temperature Superionic Conductivity by Suppression of Li Site Ordering in Li7Si2-xGexS7I.

Ge4+ substitution into the recently discovered superionic conductor Li7Si2S7I is demonstrated by synthesis of Li7Si2-xGexS7I, where x ≤ 1.2. The anion packing and tetrahedral silicon location of Li7Si2S7I are retained upon substitution. Single crystal X-ray diffraction shows that substitution of larger Ge4+ for Si4+ expands the unit cell volume and further increases Li+ site disorder, such that Li7Si0.88Ge1.12S7I has one Li+ site more (sixteen in total) than Li7Si2S7I. The ionic conductivity of Li7Si0.8Ge1.2S7I (x = 1.2) at 303 K is 1.02(3) × 10-2 S cm-1 with low activation energies for Li+ transport demonstrated over a wide temperature range by AC impedance and 7Li NMR spectroscopy. All sixteen Li+ sites remain occupied to temperatures as low as 30 K in Li7Si0.88Ge1.12S7I as a result of the structural expansion. This differs from Li7Si2S7I, where the partial Li+ site ordering observed below room temperature reduces the ionic conductivity. The suppression of Li+ site depopulation by Ge4+ substitution retains the high mobility to temperatures as low as 200 K, yielding low temperature performance comparable with state-of-the-art Li ion conducting materials.

Could self-reported physical performance help predict individuals at the highest risk of mortality and hospital admission events in clinical practice? Findings from the Hertfordshire Cohort Study.

AIM: To consider how self-reported physical function measures relate to adverse clinical outcomes measured over 20 years of follow-up in a community-dwelling cohort (aged 59-73 at baseline) as compared with hand grip strength, a well-validated predictor of adverse events. BACKGROUND: Recent evidence has emphasized the significant association of physical activity, physical performance, and muscle strength with hospital admissions in older people. However, physical performance tests require staff availability, training, specialized equipment, and space to perform them, often not feasible or realistic in the context of a busy clinical setting. METHODS: In total, 2997 men and women were analyzed. Baseline predictors were measured grip strength (Jamar dynamometer) and the following self-reported measures: physical activity (Dallosso questionnaire); physical function score (SF-36 Health Survey); and walking speed. Participants were followed up from baseline (1998-2004) until December 2018 using UK Hospital Episode Statistics and mortality data, which report clinical outcomes using ICD-10 coding. Predictors in relation to the risk of mortality and hospital admission events were examined using Cox regression with and without adjustment for sociodemographic and lifestyle characteristics. FINDINGS: The mean age at baseline was 65.7 and 66.6 years among men and women, respectively. Over follow-up, 36% of men and 26% of women died, while 93% of men and 92% of women were admitted to hospital at least once. Physical activity, grip strength, SF-36 physical function, and walking speed were all strongly associated with adverse health outcomes in both sex- and fully adjusted analyses; poorer values for each of the predictors were related to greater risk of mortality (all-cause, cardiovascular-related) and any, neurological, cardiovascular, respiratory, any fracture, and falls admissions. SF-36 physical function and grip strength were similarly associated with the adverse health outcomes considered.