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Background: Transjugular intrahepatic portosystemic shunt (TIPS) is an important therapy for complications of portal hypertension but remains underutilised in regional settings. Aims: The aim of this study is to explore the demographics, indications, outcomes and complications in patients undergoing TIPS in two regional hepatology centres. Methods: Retrospective analysis was undertaken of all patients undergoing TIPS at two regional centres between January 2017 and March 2023. The primary outcome measures were efficacy and complications of TIPS. Patient demographics (such as age, baseline liver severity scores and aetiology of liver disease) and indications for TIPS are detailed. Results: Forty‐eight patients underwent TIPS. Median age was 56 years (interquartile range (IQR): 46–65). The most common indications for TIPS were refractory ascites (n = 17) and failure of secondary prophylaxis of variceal bleeding (n = 13). Cumulative survival at 3 months and 1 year was 93% and 77% respectively. There was no significant difference in outcomes based on TIPS indication. The median number of paracenteses in patients undergoing TIPS for refractory ascites 1 year pre‐ and post‐TIPS were 10 (IQR: 4.5–16) and 2 (IQR: 0–4) respectively (P < 0.001). There were no procedure‐related deaths. Inpatient management of liver disease complications had a mean cost of $32 874.67 (SEM: 7779) in 1 year pre‐TIPS compared with $12 304.70 (SEM: 3531.1) in 1 year post‐TIPS (P < 0.001). Conclusions: TIPS is a safe and effective treatment to reduce complications of portal hypertension and can be performed successfully in the regional setting. [ABSTRACT FROM AUTHOR]

Aims: Fear of hypoglycaemia (FOH) can contribute to impaired sleep for adults with type 1 diabetes (T1D) and parents of children with T1D, although it is unknown how FOH may affect sleep for adolescents with T1D. This study examines the relationship between adolescent FOH and sleep and assessed the influences of continuous glucose monitor (CGM) and insulin pump use. Methods: Adolescents ages 14–18 years with T1D completed questionnaires evaluating FOH (Child Hypoglycemia Fear Survey) and sleep (Pittsburgh Sleep Quality Index, PSQI). Analyses included linear and logistic regression, t‐tests and Fisher's exact tests. Results: Participants included 95 adolescents (52 female) with a median (IQR) age of 16.5 (15.3–17.7) years and a T1D duration of 5.7 (2.5–9.6) years. Analyses showed increased FOH‐Worry subscale scores were associated with reduced sleep duration (β = −0.03, p = 0.042, adjusting for BMI z‐score, race and ethnicity) and increased sleep disturbances (OR = 1.1, p = 0.038, adjusting for race and ethnicity). Frequent CGM users had longer sleep duration (average 7.5 h) compared with infrequent or non‐CGM users (average = 6.8 h; p = 0.029), and pump users had overall improved sleep health as determined by PSQI score (p = 0.019). Technology use did not have significant interactions in the relationships between FOH and sleep duration or sleep disturbances. Conclusions: Worrying about hypoglycaemia was associated with impaired sleep for adolescents with T1D. Diabetes technology users have some sleep improvements, but CGM and pump use do little to alter the relationship between FOH and sleep outcomes. [ABSTRACT FROM AUTHOR]

In this national longitudinal study of incident COVID-19 among unvaccinated adults during the Omicron wave, only 12% of those who entered the wave with anti-RBD antibodies reported a test-confirmed COVID-19 infection, compared to 35% of those without antibodies prior to the Omicron wave. We recently reported that 99% of unvaccinated US adults who had a test-confirmed SARS-CoV-2 infection had detectable anti-receptor-binding domain (anti-RBD) antibodies up to 20 months after their positive COVID-19 test [2]. GLO:0IU/01dec22:joim13555-fig-0001.jpg PHOTO (COLOR): 1 Distribution of self-reported COVID-19 infections after December 1, 2021 among unvaccinated US adults, stratified by pre-Omicron wave anti-receptor-binding domain (anti-RBD) antibody level. gl Having antibodies was 67% effective against reporting test-confirmed COVID-19 (35% vs. 12%, I p i < 0.001). [Extracted from the article]

Fewer than 45% of solid organ transplant recipients (SOTRs) mount a detectable antispike antibody level after two doses of mRNA SARS-CoV-2 vaccination (D2).1 Various vaccination strategies, including mixing platforms, have been proposed, but there is no consensus on the optimal vaccination sequence to improve immunogenicity.2,3 Although using similar technology, the mRNA-1273 vaccine has been associated with higher peak antibody responses than the use of BNT162b2 in immunosuppressed populations, potentially related to a higher vaccine antigen dose.3,4 We therefore studied whether the use of mRNA-1273 versus BNT162b2 as a third primary vaccine dose (D3) might generate a more robust antibody response in SOTR who remained seronegative after two doses of BNT162b2. Improved humoral immunogenicity with mRNA-1273 versus BNT162b2 as third vaccine dose among solid organ transplant recipients seronegative after two BNT162b2 doses METHODS From our national observational study, approved by the Johns Hopkins Institutional Review Board (IRB00248540),4 we included adult SOTRs who tested seronegative after two doses of BNT162b2 and received either a D3-BNT162b2 or D3-mRNA-1273. [Extracted from the article]

Autistic children and adults often have sleep disturbances, which may affect their and their family's quality of life. Yet, the relationship between sleep–wake patterns and autism spectrum traits is understudied. Identifying such relationships could lead to future research elucidating common mechanistic underpinnings. Thus, we aimed to determine whether sleep–wake patterns, specifically related to sleep, physical activity, and the daily sleep–wake rhythm (i.e., circadian rhythm), are associated with autism spectrum‐related traits. Accelerometer‐derived sleep–wake parameters were estimated in individuals with autistic spectrum traits and their family members (N = 267). We evaluated autism spectrum traits using the Social Responsiveness Scale (SRS) to assess the presence and severity of social impairment and the Behavior Rating Inventory of Executive Function (BRIEF) to assess executive function. The linear multivariate regression analysis (using SOLAR‐Eclipse) showed that in adults, increased core autism spectrum traits and executive dysfunction were associated with disruption of several sleep–wake parameters, particularly related to the daily sleep–wake rhythm, and that executive dysfunction was associated with disrupted sleep quality and level of physical activity. We highlight the interplay between daytime function and disrupted sleep–wake patterns, specifically related to the daily sleep–wake rhythm, that could guide future research into common mechanisms. Lay Summary: Autistic children and adults often report sleep disturbances. To dissect the relationship between a range of autism spectrum traits and sleep–wake patterns, we assessed social interaction and executive function in participants who also wore actimetry watches on their wrists to assess their sleep–wake patterns. We found that increased impairments in social and executive function occurred with increased sleep–wake disturbances, particularly those related to the circadian rhythm, suggesting that these perturbations/disruptions in the sleep–wake cycle could be connected to autism spectrum traits. [ABSTRACT FROM AUTHOR]

Solid organ transplant recipients (SOTRs) have reduced immunogenicity to SARS-CoV-2 vaccines and are at increased risk of severe COVID-19 when compared to the general population.[1] Previously, a fourth dose (D4) of SARS-CoV-2 vaccine has shown improved antibody responses in SOTRs, but given the decreasing titers seen by 6 months post-dose 2 and 3, immune responses achieved after D4 could decrease in a similar fashion.[[2]] This study assesses the durability and kinetics of vaccine-induced antibody responses in SOTRs post-D4 and evaluates these responses in the context of the Omicron variant, which requires higher levels of antibody to neutralize. In this study of antibody responses after a fourth dose of SARS-CoV-2 vaccine in SOTRs with 6 months of follow up, 61% demonstrated antibody titers associated in prior studies with potential SARS-CoV-2 Omicron variant neutralization at 3 months. 3 c 5/18 SOTRs with low titers and 8/39 SOTRs with high titers were unable to provide titers at 3-months post-D4. [Extracted from the article]

Heterologous vaccination has been explored in small populations of solid organ transplant recipients (SOTRs),1-4 yet 38% of participants had persistently suboptimal response indicating potential role for further vaccine doses.1 The US CDC currently recommends immunocompromised adults who received an Ad26.COV2.S prime to receive one additional dose of SARS-CoV-2 mRNA vaccine, either BNT162b2 or mRNA-1273, followed by two mRNA vaccine boosters, although the efficacy of this strategy in immunocompromised persons is not known. A third dose of SARS-CoV-2 vaccine increases neutralizing antibodies against variants of concern in solid organ transplant recipients. Immunogenicity of Ad26.COV2.S prime and two subsequent doses of mRNA SARS-CoV-2 vaccines in solid organ transplant recipients: A case series. [Extracted from the article]

Background: Current guidelines suggest using transient elastography (TE) or aspartate aminotransferase to platelet ratio index (APRI) score <1 to exclude cirrhosis prior to commencing treatment for hepatitis C virus (HCV). Recently, fibrosis‐4 (FIB‐4) <0.93 has been shown to have a high negative predictive value (NPV) for the presence of cirrhosis. Aims: To assess FIB‐4 and APRI in a cohort of HCV patients and to validate FIB‐4 <0.93 in populations of HCV‐infected individuals with differing cirrhosis prevalence, including secondary care, primary care and prisons. Methods: From our treatment database, we identified patients with complete data (n = 793). We calculated FIB‐4 and APRI and correlated this with the presence of cirrhosis, determined by TE. We analysed the performance of FIB‐4 and APRI using area under the receiver operating curve analysis. We calculated sensitivity, specificity, positive predictive value, NPV and number of patients misclassified using published cut‐offs in populations with varying cirrhosis prevalence. Results: FIB‐4 was superior to APRI for the diagnosis of cirrhosis (area under the receiver operating curve 0.868 vs 0.802). In secondary care (cirrhosis prevalence 32%), APRI <1 had a NPV of 80% and misclassified 14% of patients. FIB‐4 <0.93 had a NPV of 97% and misclassified 1%. In primary care and prison (cirrhosis prevalence 13% and 8%), the NPV for APRI <1 was 93% and 96%, respectively, but 5% of patients with cirrhosis were misclassified. FIB‐4 <0.93 had excellent NPV in both primary care (97%) and prisoners (100%). Conclusions: FIB‐4 <0.93 is highly efficient at ruling out cirrhosis in HCV patients and allows TE to be appropriately avoided, thereby streamlining treatment algorithms. [ABSTRACT FROM AUTHOR]

Using a global space‐time diagram of column water vapor (CWV) at 30° N latitude from daily reanalysis data, we find two quasi‐stationary parts of atmospheric rivers (QSARs) that feature locally enhanced CWV and evolve from the Eastern Pacific/Atlantic basins in the winter to the Western Pacific/Atlantic in the summer. East Asian Summer Monsoon onset coincides with the time CWV in the Pacific QSAR first exceeds 40 mm, which also typically occurs just before it makes landfall. QSARs exist in 39‐year (1979–2017) daily climatological CWV, demonstrating the seasonal cycles of these features are quasi‐stationary and potentially useful for monsoon onset prediction. East Asian Summer Monsoon onset is particularly predictable following El Niño‐Southern Oscillation, consistently occurring 25–40 days after the QSAR crosses the dateline. Analysis of local wave activity reveals QSARs as fronts of wave breakings, thus opening a new window into dynamics of subtropical monsoon extensions. Key Points: North Atlantic and Pacific atmospheric rivers have quasi‐stationary parts in subtropical latitudes that evolve along predictable pathsThe quasi‐stationary part of the Pacific atmospheric river foretells onset of the East Asian Summer Monsoon a month before it occursOur discovery opens up a new avenue of onset prediction in subtropical monsoon extension regions [ABSTRACT FROM AUTHOR]

Genomic regions of homozygosity (ROH), detectable in outbred populations, have been implicated as determinants of inherited risk. To examine whether ROH is associated with risk of multiple myeloma (MM), we performed whole‐genome homozygosity analysis using single‐nucleotide polymorphism genotype data from 2,282 MM cases and 5,197 controls, with replication in an additional 878 MM cases and 7,083 controls. Globally, the distribution of ROH between cases and controls was not significantly different. However, one ROH at chromosome 9q21, harboring the B‐cell transcription factor gene KLF9, showed evidence of a consistent association and may therefore warrant further investigation as a candidate risk factor for MM. Overall, our analysis provides little support for a homozygosity signature being a significant factor in MM risk. [ABSTRACT FROM AUTHOR]

Typical emotions share important features with paradigmatic intentional states and therefore might admit of distinctions made in theory of intentionality. One such distinction is between attitude and content, where we can specify the content of an intentional state separately from its attitude, and therefore, the same content can be taken up by different intentional attitudes. According to some philosophers, emotions do not admit of this distinction, although there has been no sustained argument for this claim. In this article, I argue that the way values figure in emotional experience qualifies the content of emotional experience such that the attitude‐content distinction cannot be applied. [ABSTRACT FROM AUTHOR]

Summary: Background: Mycophenolate mofetil is a commonly used salvage therapy for patients with autoimmune hepatitis (AIH). Aim: To evaluate the predictors of response to mycophenolate rescue therapy to facilitate clinical decision making. Methods: We performed a retrospective observational cohort study of AIH patients managed in 17 major Australian liver centres who received mycophenolate after an inadequate response or intolerance to corticosteroids with/without thiopurine(s). Baseline demographic, clinical and laboratory variables were compared between responders and nonresponders. A multivariable logistic regression model was developed using forward selection to identify independent predictors of treatment response. Results: A total of 105 patients received mycophenolate rescue therapy of whom 63 (60%) achieved biochemical remission. On univariable analysis, older age (P = 0.003), INR < 1.1 (P = 0.02), and lower immunoglobulin gamma (IgG; P < 0.002) levels were associated with treatment response, while no association was found with cirrhosis status (P = 0.07) or treatment indication (P = 0.63). On multivariable analysis, lower pre‐treatment serum IgG level (P = 0.01), higher age at commencing mycophenolate (P = 0.01) and higher INR (P = 0.03) were the only significant independent predictors. An IgG level <17 g/L had a positive and negative predictive value for response of 71% and 60% respectively, while age ≥54 years when commencing mycophenolate had a positive and negative predictive value for response of 80% and 59% respectively. Conclusion: Mycophenolate remains an excellent treatment option for patients with AIH refractory to or intolerant of standard therapy with those most likely to benefit being older and/or having lower pre‐treatment IgG levels. [ABSTRACT FROM AUTHOR]

This article offers an account of moods as distinctive kinds of personal level affective–evaluative states, which are both intentional and rationally intelligible in specific ways. The account contrasts with those who claim moods are non‐intentional, and so also arational. Section 2 provides a conception of intentionality and distinguishes moods, as occurrent experiential states, from other states in the affective domain. Section 3 argues moods target the subject's total environment presented in a specific evaluative light through felt valenced attitudes (the Mood‐Intentionality thesis). Section 4 argues some moods are experienced as rationally intelligible responses, and so epistemically appropriate, to the way "the world" presents itself (the Mood‐Intelligibility thesis). Finally, Section 5 discusses the epistemology of moods. [ABSTRACT FROM AUTHOR]

ABSTRACT: Osteoporosis is a complex disease with developmental origins. It is therefore important to understand the genetic contribution to pediatric areal bone mineral density (aBMD). Individual skeletal site phenotyping has been primarily used to identify pediatric aBMD loci. However, this approach is limited because there is a degree of aBMD discordance across skeletal sites. We therefore applied a novel multidimensional phenotyping approach to further understand the genetic regulation of pediatric aBMD. Our sample comprised a prospective, longitudinal cohort of 1293 children of European ancestry (52% female; up to seven annual measurements). Principal components analysis was applied to dual‐energy X‐ray absorptiometry–derived aBMD Z‐scores for total hip, femoral neck, spine, and distal radius to generate multidimensional aBMD phenotypes (ie, principal component scores). We tested the association between a genetic score (percentage of bone lowering alleles at 63 loci) and each principal component. We also performed a genomewide association study (GWAS) using the multiethnic baseline data (n = 1885) to identify novel loci associated with these principal components. The first component (PC1) reflected a concordant phenotypic model of the skeleton (eg, higher loading score = higher BMD across all sites). In contrast, PC2 was discordant for distal radius versus spine and hip aBMD, and PC3 was discordant for spine versus distal radius and hip aBMD. The genetic score was associated with PC1 (beta = –0.05, p = 3.9 × 10–10), but was not associated with discordant PC2 or PC3. Our GWAS discovered variation near CPED1 that associated with PC2 (rs67991850, p = 2.5 × 10–11) and near RAB11FIP5 (rs58649746, p = 4.8 × 10–9) that associated with PC3. In conclusion, an established bone fragility genetic summary score was associated with a concordant skeletal phenotype, but not discordant skeletal phenotypes. Novel associations were observed for the discordant multidimensional skeletal phenotypes that provide new biological insights into the developing skeleton. © 2017 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT: Later puberty associates with lower areal bone mineral density (aBMD), and both are risk factors for osteoporosis. However, the association between puberty timing–associated genetic variants and aBMD during development, and the causal relationship between puberty timing and aBMD, remain uncharacterized. We constructed sex‐specific polygenic risk scores (GRS) consisting of 333 genetic variants associated with later puberty in European‐descent children in the Bone Mineral Density in Childhood Study (BMDCS), consisting of a longitudinal cohort with up to seven assessments (n = 933) and a cross‐sectional cohort (n = 486). These GRS were tested for associations with age‐ and sex‐specific aBMD Z‐scores at the lumbar spine (LS), femoral neck (FN), total hip, and distal radius, accounting for clinical covariates using sex‐stratified linear mixed models. The causal relationship between puberty timing and aBMD was tested in the BMDCS and in publicly available adult data (GEFOS consortium) using two‐sample Mendelian randomization (MR). The puberty‐delaying GRS was associated with later puberty and lower LS‐aBMD in the BMDCS in both sexes (combined beta ± SE = –0.078 ± 0.024; p = 0.0010). In the MR framework, the puberty‐delaying genetic instrument also supported a causal association with lower LS‐aBMD and FN‐aBMD in adults of both sexes. Our results suggest that pubertal timing is causal for diminished aBMD in a skeletal site‐ and sex‐specific manner that tracks throughout life, potentially impacting later risk for osteoporosis, which should be tested in future studies. © 2017 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT Failure to achieve optimal bone mineral accretion during childhood and adolescence results in subsequent suboptimal peak bone mass, contributing to osteoporosis risk later in life. To identify novel genetic factors that influence pediatric bone mass at discrete skeletal sites, we performed a sex-stratified genomewide association study of areal bone mineral density (BMD) measured by dual-energy X-ray absorptiometry at the 1/3 distal radius, spine, total hip, and femoral neck in a cohort of 933 healthy European American children. We took forward signals with p < 5 × 10−5 and minor allele frequency (MAF) >5% into an independent cohort of 486 European American children in search of replication. In doing so, we identified five loci that achieved genome wide significance in the combined cohorts (nearest genes: CPED1, IZUMO3, RBFOX1, SPBT, and TBPL2), of which the last four were novel and two were sex-specific ( SPTB in females and IZUMO3 in males), with all of them yielding associations that were particularly strong at a specific skeletal site. Annotation of potential regulatory function, expression quantitative trait loci (eQTL) effects and pathway analyses identified several potential target genes at these associated loci. This study highlights the importance of sex-stratified analyses at discrete skeletal sites during the critical period of bone accrual, and identifies novel loci for further functional follow-up to pinpoint key genes and better understand the regulation of bone development in children. © 2017 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Behavioral shifts can initiate morphological evolution by pushing lineages into new adaptive zones. This has primarily been examined in ecological behaviors, such as foraging, but social behaviors may also alter morphology. Swallows and martins (Hirundinidae) are aerial insectivores that exhibit a range of social behaviors, from solitary to colonial breeding and foraging. Using a well-resolved phylogenetic tree, a database of social behaviors, and morphological measurements, we ask how shifts from solitary to social breeding and foraging have affected morphological evolution in the Hirundinidae. Using a threshold model of discrete state evolution, we find that shifts in both breeding and foraging social behavior are common across the phylogeny of swallows. Solitary swallows have highly variable morphology, while social swallows show much less absolute variance in all morphological traits. Metrics of convergence based on both the trajectory of social lineages through morphospace and the overall morphological distance between social species scaled by their phylogenetic distance indicate strong convergence in social swallows, especially socially foraging swallows. Smaller physical traits generally observed in social species suggest that social species benefit from a distinctive flight style, likely increasing maneuverability and foraging success and reducing in-flight collisions within large flocks. These results highlight the importance of sociality in species evolution, a link that had previously been examined only in eusocial insects and primates. [ABSTRACT FROM AUTHOR]

ABSTRACT More rapid skeletal maturation in African-American (AA) children is recognized and generally attributed to an increased prevalence of obesity. The objective of the present study was to evaluate the effects of population ancestry on relative skeletal maturation in healthy, non-obese children and adolescents, accounting for body composition and sexual maturation. To do this, we leveraged a multiethnic, mixed-longitudinal study with annual assessments for up to 7 years (The Bone Mineral Density in Childhood Study and its ancillary cohort) conducted at five US clinical centers. Participants included 1592 children, skeletally immature (45% females, 19% AA) who were aged 5 to 17 years at study entry. The primary outcome measure was relative skeletal maturation as assessed by hand-wrist radiograph. Additional covariates measured included anthropometrics, body composition by dual-energy X-ray absorptiometry (DXA), and Tanner stage of sexual maturation. Using mixed effects longitudinal models, without covariates, advancement in relative skeletal maturation was noted in self-reported AA girls (∼0.33 years, p < 0.001) and boys (∼0.43 years, p < 0.001). Boys and girls of all ancestry groups showed independent positive associations of height, lean mass, fat mass, and puberty with relative skeletal maturation. The effect of ancestry was attenuated but persistent after accounting for covariates: for girls, 0.19 years (ancestry by self-report, p = 0.02) or 0.29 years (ancestry by admixture, p = 0.004); and for boys, 0.20 years (ancestry by self-report, p = 0.004), or 0.29 years (ancestry by admixture, p = 0.004). In summary, we conclude that advancement in relative skeletal maturation was associated with AA ancestry in healthy, non-obese children, independent of growth, body composition, and puberty. Further research into the mechanisms underlying this observation may provide insights into the regulation of skeletal maturation. © 2016 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Understanding variation in rates of speciation and extinction - both among lineages and through time - is critical to the testing of many hypotheses about macroevolutionary processes. Bayesian Analysis of Macroevolutionary Mixtures ( BAMM) is a flexible Bayesian framework for inferring the number and location of shifts in macroevolutionary rate across phylogenetic trees and has been widely used in empirical studies. BAMM requires that researchers specify a prior probability distribution on the number of diversification rate shifts before conducting an analysis. The consequences of this 'model prior' for inference are poorly known but could potentially influence both the probability of accepting models that are more (high error rate) or less (low power) complex than the generating model., The hierarchical Poisson process prior in BAMM reduces to a simple geometric distribution on number of rate shifts, and we use this property to increase the efficiency of model selection with Bayes factors. Using BAMM v2.5, we analysed phylogenies simulated with and without diversification heterogeneity across a broad range of prior parameterizations. We also assessed the impact of the model prior on MCMC convergence times and on diversification rate estimates., For all simulation scenarios, model evidence (Bayes factor support) for the number of shifts is not sensitive to the choice of model prior over the wide range examined here. The best-supported model found using BAMM rarely includes spurious shifts (<2% of all runs) when diversification models are selected using Bayes factors. BAMM was reliably able to infer the true number of diversification rate shifts across prior expectations that varied by three orders of magnitude. However, we find a strong effect of model prior on MCMC convergence properties: a flatter prior distribution (larger expected number of shifts) can dramatically increase the efficiency of the MCMC simulation., Our results support the use of a liberal model prior in BAMM, as it reduces computation time without distorting the evidence for rate heterogeneity. [ABSTRACT FROM AUTHOR]

ABSTRACT Both genetics and physical activity (PA) contribute to bone mineral density (BMD), but it is unknown if the benefits of physical activity on childhood bone accretion depend on genetic risk. We, therefore, aimed to determine if PA influenced the effect of bone fragility genetic variants on BMD in childhood. Our sample comprised US children of European ancestry enrolled in the Bone Mineral Density in Childhood Study ( N = 918, aged 5 to 19 years, and 52.4% female). We used a questionnaire to estimate hours per day spent in total, high-, and low-impact PA. We calculated a BMD genetic score (% BMD lowering alleles) using adult genome-wide association study (GWAS)-implicated BMD variants. We used dual-energy X-ray absorptiometry to estimate femoral neck, total hip, and spine areal-BMD and total body less head (TBLH) bone mineral content (BMC) Z-scores. The BMD genetic score was negatively associated with each bone Z-score (eg, TBLH-BMC: estimate = -0.03, p = 1.3 × 10−6). Total PA was positively associated with bone Z-scores; these associations were driven by time spent in high-impact PA (eg, TBLH-BMC: estimate = 0.05, p = 4.0 × 10−10) and were observed even for children with lower than average bone Z-scores. We found no evidence of PA-adult genetic score interactions ( p interaction > 0.05) at any skeletal site, and there was no evidence of PA-genetic score-Tanner stage interactions at any skeletal site ( p interaction > 0.05). However, exploratory analyses at the individual variant level revealed that PA statistically interacted with rs2887571 ( ERC1/WNT5B) to influence TBLH-BMC in males ( p interaction = 7.1 × 10−5), where PA was associated with higher TBLH-BMC Z-score among the BMD-lowering allele carriers (rs2887571 AA homozygotes: estimate = 0.08 [95% CI 0.06, 0.11], p = 2.7 × 10−9). In conclusion, the beneficial effect of PA on bone, especially high-impact PA, applies to the average child and those genetically predisposed to lower adult BMD (based on GWAS-implicated BMD variants). Independent replication of our exploratory individual variant findings is warranted. © 2016 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT A recent whole-genome sequencing study in search of variation associated with adult areal bone mineral density (aBMD) identified rare variants near EN1, with markedly large effect sizes, and a common variant near SOX6. To understand the developmental effects of these loci, we sought to determine if they were associated with pediatric dual-energy X-ray absorptiometry-derived aBMD and bone mineral content (BMC) and if the associations were modified by sex. Our sample comprised 733 females and 685 males of European ancestry enrolled in the longitudinal Bone Mineral Density in Childhood Study (up to 7 annual study visits). Sex- and age-specific Z-scores, adjusted for height, were calculated for the total hip, femoral neck, spine, and distal radius. Total body less head (TBLH) BMC Z-scores were also calculated. The previously reported single nucleotide polymorphisms (SNPs) near EN1 and SOX6 were derived from our imputed data set. Linear mixed-effects models were used to test associations between each SNP and bone Z-scores, plus interactions with sex were explored. The rare T allele of lead EN1 SNP rs11692564 was associated with higher aBMD Z-score for total hip (beta = 0.62, p = 9.0 × 10−4) and femoral neck (beta = 0.53, p = 0.010). In sex-stratified analyses, this variant was associated with higher bone Z-scores in females only, with the associations being strongest for total hip (sex interaction p = 1.9 × 10−4; beta females = 0.86, p = 6.6 × 10−6) and femoral neck (sex interaction p = 0.016; beta females = 0.73, p = 0.001). The common G allele of SOX6 SNP rs11024028 was associated with higher aBMD Z-score for total hip (beta = 0.12, p = 0.009), femoral neck (beta = 0.13, p = 0.003), and TBLH-BMC (beta = 0.09, p = 0.007); furthermore, this association strengthened in males in the sex-stratified analyses. Our findings reveal that rare genetic variation near EN1 and common variation near SOX6 operates in childhood and has implications for the lifelong risk of osteoporosis and fracture. The sex differences observed need to be independently replicated. © 2016 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Using adult identified bone mineral density (BMD) loci, we calculated genetic risk scores (GRS) to determine if they were associated with changes in BMD during childhood. Longitudinal data from the Bone Mineral Density in Childhood Study were analyzed (N=798, 54% female, all European ancestry). Participants had up to 6 annual dual energy X-ray scans, from which areal BMD (aBMD) Z-scores for the spine, total hip, and femoral neck were estimated, as well as total body less head bone mineral content (TBLH-BMC) Z-scores. Sixty-three single-nucleotide polymorphisms (SNPs) were genotyped, and the percentage of BMD-lowering alleles carried was calculated (overall adult GRS). Subtype GRS that include SNPs associated with fracture risk, pediatric BMD, WNT signaling, RANKRANKL- OPG, and mesenchymal stem cell differentiation were also calculated. Linear mixed effects models were used to test associations between each GRS and bone Z-scores, and if any association differed by sex and/or chronological age. The overall adult, fracture, and WNT signaling GRS were associated with lower Z-scores (eg, spine aBMD Z-score: βadult=-0.04, p=3.4×10-7; βfracture=-0.02, p=8.9×10-6; βWNT=-0.01, p=3.9×10-4). The overall adult GRS was more strongly associated with lower Z-scores in females (p-interaction≤0.05 for all sites). The fracture GRS was more strongly associated with lower Z-scores with increasing age (p-interaction≤0.05 for all sites). The WNT GRS associations remained consistent for both sexes and all ages (p-interaction>0.05 for all sites). The RANK-RANKL-OPG GRS was more strongly associated in females with increasing age (p-interaction<0.05 for all sites). The mesenchymal stem cell GRS was associated with lower total hip and femoral neck Z-scores, in both boys and girls, across all ages. No associations were observed between the pediatric GRS and bone Z-scores. In conclusion, adult identified BMD loci associated with BMD and BMC in the pediatric setting, especially in females and in loci involved in fracture risk and WNT signaling. [ABSTRACT FROM AUTHOR]

ABSTRACT We aimed to determine if adult bone mineral density (BMD) susceptibility loci were associated with pediatric bone mass and density, and if sex and pubertal stage influenced any association. We analyzed prospective areal BMD (aBMD) and bone mineral content (BMC) data from the Bone Mineral Density in Childhood Study ( n = 603, European ancestry, 54% female). Linear mixed models were used to assess if 77 single-nucleotide polymorphisms (SNPs) near known adult BMD susceptibility loci interacted with sex and pubertal stage to influence the aBMD/BMC; adjusting for age, BMI, physical activity, and dietary calcium. The strongest main association was observed between an SNP near C7orf58 and distal radius aBMD. However, this association had a significant sex•SNP interaction, revealing a significant association only in females (b = -0.32, p = 1.8 × 10-6). Furthermore, the C12orf23 locus had significant interactions with both sex and pubertal stage, revealing associations in females during Tanner stage I for total hip aBMD (b = 0.24, p = 0.001) and femoral neck aBMD (b = 0.27, p = 3.0 × 10-5). In contrast, the sex•SNP interactions for loci near LRP5 and WNT16 uncovered associations that were only in males for total body less head BMC (b = 0.22, p = 4.4 × 10-4) and distal radius aBMD (b = 0.27, p = 0.001), respectively. Furthermore, the LRP5 locus interacted with both sex and pubertal stage, demonstrating associations that were exclusively in males during Tanner V for total hip aBMD (b = 0.29, p = 0.003). In total, significant sex•SNP interactions were found at 15 loci; pubertal stage•SNP interactions at 23 loci and 19 loci interacted with both sex and pubertal stage. In conclusion, variants originally associated with adult BMD influence bone mass in children of European ancestry, highlighting the fact that many of these loci operate early in life. However, the direction and magnitude of associations for a large number of SNPs only became evident when accounting for sex and maturation. © 2015 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Nuclear magnetic resonance (NMR) relaxation times are shown to provide a unique probe of adsorbate-adsorbent interactions in liquid-saturated porous materials. A short theoretical analysis is presented, which shows that the ratio of the longitudinal to transverse relaxation times ( T1/ T2) is related to an adsorbate-adsorbent interaction energy, and we introduce a quantitative metric esurf (based on the relaxation time ratio) characterising the strength of this surface interaction. We then consider the interaction of water with a range of oxide surfaces (TiO2 anatase, TiO2 rutile, γ-Al2O3, SiO2, θ-Al2O3 and ZrO2) and show that esurf correlates with the strongest adsorption sites present, as determined by temperature programmed desorption (TPD). Thus we demonstrate that NMR relaxation measurements have a direct physical interpretation in terms of the characterisation of activation energy of desorption from the surface. Further, for a series of chemically similar solid materials, in this case a range of oxide materials, for which at least two calibration values are obtainable by TPD, the esurf parameter yields a direct estimate of the maximum activation energy of desorption from the surface. The results suggest that T1/ T2 measurements may become a useful addition to the methods available to characterise liquid-phase adsorption in porous materials. The particular motivation for this work is to characterise adsorbate-surface interactions in liquid-phase catalysis. [ABSTRACT FROM AUTHOR]

The potential for tailored synthesis of porous materials using catalytic degradation of block copolymers has been shown, employing an adaptable one-pot method. Carefully selected solvent systems help to control the pore size and molecular weight of the product. In the degradation of PS-PB-PS, 2nd Generation Grubbs' catalyst creates scissions in the PB carbon-carbon double bonds resulting in the formation of a porous structure. Critically, methanol is used to maintain the integrity of the polymeric structure during this etching. Catalyst deactivation effected by methanol can be limited through using an excess of 1-hexene; thereby introducing a competitive metathesis process. Altering the ratio of the co-solvents employed further controls the degradation of PS-PB-PS and hence the resulting pore structures. [ABSTRACT FROM AUTHOR]

In recent work, it was reported that changes in solvent composition, precisely the addition of water, significantly inhibits the catalytic activity of Au/TiO2 catalyst in the aerobic oxidation of 1,4-butanediol in methanol due to changes in diffusion and adsorption properties of the reactant. In order to understand whether the inhibition mechanism of water on diol oxidation in methanol is generally valid, the solvent effect on the aerobic catalytic oxidation of 1,3-propanediol and its two methyl-substituted homologues, 2-methyl-1,3-propanediol and 2,2-dimethyl-1,3-propanediol, over a Au/TiO2 catalyst has been studied here using conventional catalytic reaction monitoring in combination with pulsed-field gradient nuclear magnetic resonance (PFG-NMR) diffusion and NMR relaxation time measurements. Diol conversion is significantly lower when water is present in the initial diol/methanol mixture. A reactivity trend within the group of diols was also observed. Combined NMR diffusion and relaxation time measurements suggest that molecular diffusion and, in particular, the relative strength of diol adsorption, are important factors in determining the conversion. These results highlight NMR diffusion and relaxation techniques as novel, non-invasive characterisation tools for catalytic materials, which complement conventional reaction data. [ABSTRACT FROM AUTHOR]

Objective: To determine whether previously identified adult obesity susceptibility loci were associated uniformly with childhood BMI across the BMI distribution. Design and Methods: Children were recruited through the Children's Hospital of Philadelphia ( n = 7,225). Associations between the following loci and BMI were assessed using quantile regression: FTO (rs3751812), MC4R (rs12970134), TMEM18 (rs2867125), BDNF (rs6265), TNNI3K (rs1514175), NRXN3 (rs10146997), SEC16B (rs10913469), and GNPDA2 (rs13130484). BMI z-score (age and gender adjusted) was modeled as the dependent variable, and genotype risk score (sum of risk alleles carried at the 8 loci) was modeled as the independent variable. Results: Each additional increase in genotype risk score was associated with an increase in BMI z-score at the 5th, 15th, 25th, 50th, 75th, 85th, and 95th BMI z-score percentiles by 0.04 (±0.02, P = 0.08), 0.07 (±0.01, P = 9.58 × 10−7), 0.07 (±0.01, P = 1.10 × 10−8), 0.09 (±0.01, P = 3.13 × 10−22), 0.11 (±0.01, P = 1.35 × 10−25), 0.11 (±0.01, P = 1.98 × 10−20), and 0.06 (±0.01, P = 2.44 × 10−6), respectively. Each additional increase in genotype risk score was associated with an increase in mean BMI z-score by 0.08 (±0.01, P = 4.27 × 10−20). Conclusion: Obesity risk alleles were more strongly associated with increases in BMI z-score at the upper tail compared to the lower tail of the distribution. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine if time spent watching television is associated with changes in cardiovascular disease (CVD) risk factors from age 9 to 19. Design and Methods: Participants were girls enrolled in the NHLBI Growth and Health Study ( n = 1,702), and CVD risk factors were measured at ages 10, 12, 14, 16, and 19. Longitudinal quantile regression was used to determine if television viewing was associated with changes in CVD risk factors over time at the 10th, 25th, 50th, 75th, and 90th percentiles of the CVD risk factors. Results: In black girls, television viewing (h/wk) was positively associated with sum of skinfolds (mm) at the 75th (0.22, 99% CI, 0.06-0.38) and 90th percentiles (0.21, 99% CI, 0.05-0.36), but not at the 10th, 25th, or 50th percentiles. In white girls, television viewing (h/wk) was positively associated with sum of skinfolds (mm) with the strength of the associations progressively stronger toward the upper tail of the skinfold distribution, adjusting for physical activity and other covariates (10th percentile: 0.08, 99% CI, 0.03-0.13; 90th percentile: 0.42, 99% CI, 0.24-0.59). All associations were adjusted for physical activity, dietary factors, sleep, and maturation. No associations were observed between television viewing and changes in systolic blood pressure, triglycerides, or cholesterol levels in black or white girls. Conclusion: Girls who spent more time watching television had greater increases in sum of skinfolds from age 9 to 19, independent of physical activity levels and other covariates. The associations observed were stronger at the upper tail of the skinfold distribution. [ABSTRACT FROM AUTHOR]

Objective: Previous research has examined the association between screen time and average changes in adolescent body mass index (BMI). Until now, no study has evaluated the longitudinal relationship between screen time and changes in the BMI distribution across mid to late adolescence. Design and Methods: Participants ( n = 1,336) were adolescents who were followed from age 14 to age 18 and surveyed every 6 months. Time spent watching television/videos and playing video games was self-reported (<1 h day−1, 1 h day−1, 2 h day−1, 3 h day−1, 4 h day−1, or 5+ h day−1). BMI (kg m−2) was calculated from self-reported height and weight. Longitudinal quantile regression was used to model the 10th, 25th, 50th, 75th, and 90th BMI percentiles as dependent variables. Study wave and screen time were the main predictors, and adjustment was made for gender, race, maternal education, hours of sleep, and physical activity. Results: Increases at all the BMI percentiles over time were observed, with the greatest increase observed at the 90th BMI percentile. Screen time was positively associated with changes in BMI at the 50th (0.17, 95% CI: 0.06, 0.27), 75th (0.31, 95% CI: 0.10, 0.52), and 90th BMI percentiles (0.56, 95% CI: 0.27, 0.82). No associations were observed between screen time and changes at the 10th and 25th BMI percentiles. Conclusions: Positive associations between screen time and changes in the BMI at the upper tail of the BMI distribution were observed. Therefore, lowering screen time, especially among overweight and obese adolescents, could contribute to reducing the prevalence of adolescent obesity. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine the association between sedentary behavior and obesity among 12-year-old children, while adjusting for moderate-to-vigorous physical activity (MVPA) and other potential confounding variables. Cross-sectional analyses were carried out with data from 5,434 children who participated in the Avon Longitudinal Study of Parents and Children (ALSPAC). Fat mass was derived using dual-energy X-ray emission absorptiometry, and height and weight measurements were used to calculate BMI (kg/m2). The children wore an accelerometer for 7 days. The cut points for sedentary behavior and MVPA were ≤199 and ≥3,600 counts per minute (cpm), respectively. Logistic regression analyses were performed to estimate odds ratios (ORs), adjusting for potential confounders of physical activity that included gender, social factors, early life factors, and maturation. The minimally adjusted association between sedentary behavior and obesity was positive, OR = 1.18 (1.08, 1.28). After adjusting for the series of potential confounders of physical activity the positive association remained, OR = 1.32 (1.14, 1.53). The crude association between 15 min of MVPA per day and obesity was negative, OR = 0.54 (0.48, 0.62). When 15 min of MVPA per day was additionally controlled for in the models, the positive associations between sedentary behavior and obesity were negated. Sedentary behavior was positively associated with obesity in the 12-year-old children, but this association was not independent of MVPA; low levels of MVPA among the sedentary children increased the odds of obesity. These findings support the importance of specifically engaging in MVPA during childhood to reduce the prevalence of obesity.Obesity (2009) 17 8, 1596–1602. doi:10.1038/oby.2009.42 [ABSTRACT FROM AUTHOR]

The fat mass and obesity-associated (FTO) gene was genotyped for the participants in the Dose-Response to Exercise in postmenopausal Women (DREW) trial and analyses were performed to determine whether an FTO variant was associated with adiposity and cardiorespiratory fitness (CRF) before and after 6 months of moderate intensity exercise in white women (n = 234). The A/A homozygotes for rs8050136 had a higher BMI (kg/m2) compared to C/C homozygotes at baseline (32.8 (0.6) vs. 31.0 (0.4), respectively; P < 0.05) and at follow-up (31.9 (0.6) vs. 30.4 (0.5), respectively; P < 0.05). Weight loss occurred after exercise, but there was no significant genotype by exercise interaction over time. Exploratory analyses among women exposed to moderate intensity exercise meeting, or exceeding, the physical activity recommendation found that those homozygous A/A lost significantly more weight than the C allele carriers (−3.3 (0.7) kg vs. −1.4 (0.4) kg and −1.5 (0.5) kg, respectively; P < 0.05). CRF, defined as VO2peak (oxygen consumption), increased after exercise and the magnitude of the increase was similar for each genotype. In conclusion, women genetically predisposed to being obese experienced weight loss and CRF benefits with moderate intensity exercise, with additional weight loss observed when the women met or exceeded the physical activity recommendations. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Dunne et al paper. To view this article, visit https://doi.org/10.1111/apt.15797 [ABSTRACT FROM AUTHOR]