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Recovery capital is a framework in addiction research aiming to understand substance use disorder recovery holistically by considering individuals' access to resources across the four domains of human, physical, social, and community capital. Each domain is opposed by negative capital. The underrepresentation of women's experiences in substance use research and the limited understanding of substance use treatment's effect on recovery capital limits our understanding of how treatment programs can support women in developing and maintaining recovery capital. This secondary qualitative analysis of data collected from the RENEW study explores the experiences of n = 19 women enrolled in substance use disorder treatment in Connecticut at baseline. Interviews occurred at two time points three months apart between February 2020 and April 2021 and discussed participants' experiences with treatment and the resources they have access to early in recovery. Thematic analysis identified four main themes related to recovery capital development. First, the direct effects of treatment, defined as clinical pathways to recovery capital, promoted resource growth primarily in the domains of human and physical capital. Second, non-clinical pathways, including indirect effects of treatment, facilitated maintenance of treatment-related improvements in human, social, and community capital. Third, interactions between domains promoted recovery capital resource growth across domains. Finally, goals and expectations for treatment motivated resource development across study time points. This study's findings have important implications for operationalization of the recovery capital framework and highlight the importance of more robust integration of non-clinical interventions to improve the experiences of women in treatment for substance use disorders.

Objectives: To investigate the potential value and feasibility of creating a listing system-wide registry of patients with at-risk and established Atherosclerotic Cardiovascular Disease (ASCVD) within a large healthcare system using automated data extraction methods to systematically identify burden, determinants, and the spectrum of at-risk patients to inform population health management. Additionally, the Houston Methodist Cardiovascular Disease Learning Health System (HM CVD-LHS) registry intends to create high-quality data-driven analytical insights to assess, track, and promote cardiovascular research and care. Methods: We conducted a retrospective multi-center, cohort analysis of adult patients who were seen in the outpatient settings of a large healthcare system between June 2016 - December 2022 to create an EMR-based registry. A common framework was developed to automatically extract clinical data from the EMR and then integrate it with the social determinants of health information retrieved from external sources. Microsoft's SQL Server Management Studio was used for creating multiple Extract-Transform-Load scripts and stored procedures for collecting, cleaning, storing, monitoring, reviewing, auto-updating, validating, and reporting the data based on the registry goals. Results: A real-time, programmatically deidentified, auto-updated EMR-based HM CVD-LHS registry was developed with ∼450 variables stored in multiple tables each containing information related to patient's demographics, encounters, diagnoses, vitals, labs, medication use, and comorbidities. Out of 1,171,768 adult individuals in the registry, 113,022 (9.6%) ASCVD patients were identified between June 2016 and December 2022 (mean age was 69.2 ± 12.2 years, with 55% Men and 15% Black individuals). Further, multi-level groupings of patients with laboratory test results and medication use have been analyzed for evaluating the outcomes of interest. Conclusions: HM CVD-LHS registry database was developed successfully providing the listing registry of patients with established ASCVD and those at risk. This approach empowers knowledge inference and provides support for efforts to move away from manual patient chart abstraction by suggesting that a common registry framework with a concurrent design of data collection tools and reporting rapidly extracting useful structured clinical data from EMRs for creating patient or specialty population registries.

Introduction: Historical maps of racialized evaluation of mortgage lending risk (i.e., redlined neighborhoods) have been linked to adverse health outcomes. Little research has examined whether living in historically redlined neighborhoods is associated with obesity, differentially by race or gender. Methods: This is a cross-sectional study to examine whether living in historically redlined neighborhoods is associated with BMI and waist circumference among Black and White adults in 1985–1986. Participants’ addresses were linked to the 1930s Home Owners’ Loan Corporation maps that evaluated mortgage lending risk across neighborhoods. The authors used multilevel linear regression models clustered on Census tract, adjusted for confounders to estimate main effects, and stratified, and interaction models by (1) race, (2) gender, and (3) race by gender with redlining differentially for Black versus White adults and men versus women. To better understand strata differences, they compared Census tract–level median household income across race and gender groups within Home Owners’ Loan Corporation grade. Results: Black adults (n=2,103) were more likely than White adults (n=1,767) to live in historically rated hazardous areas and to have higher BMI and waist circumference. Redlining and race and redlining and gender interactions for BMI and waist circumference were statistically significant (p

Objective: Cannabis use is increasingly pervasive throughout the U.S. People in treatment for substance use disorders (SUD) may be especially at-risk of harm due to this changing context of cannabis in the U.S. This study’s objective was to qualitatively describe experiences and beliefs around cannabis among people who had entered treatment for any SUD in the past 12-months. Methods: From May to November of 2022, we conducted 27 semi-structured interviews (n=16 in Georgia, n=11 in Connecticut) with individuals in treatment for SUD in Georgia and Connecticut. Interviews were recorded, transcribed, and thematically analyzed using an emergent approach. Results: All participants had used cannabis in the past. Four themes emerged from the interviews. Participants: (1) perceived cannabis as an important contributor to non-cannabis substance use initiation in adolescence; (2) viewed cannabis as a substance with the potential to improve health with fewer side effects than prescription medications; (3) expressed conflicting opinions regarding cannabis as a trigger or tool to manage cravings for other non-cannabis substances currently; and 4) described concerns related to negative legal, social service, and treatment-related consequences as well as negative peer perception relating to the use of cannabis. Conclusion: Although participants described cannabis’s important role as an initiatory drug in adolescence and young adulthood, many felt that cannabis was a medicinal substance for a range of health challenges. These findings suggest SUD treatment clinicians should address medicinal beliefs related to cannabis among their clients and emphasizes the need for research on cannabis use and SUD treatment outcomes.

Objective: Psychosocial stress is associated with increased cardiovascular disease (CVD) risk. The relationship between financial strain, a toxic form of psychosocial stress, and ideal cardiovascular health (CVH) is not well established. We examined whether financial strain was associated with poorer CVH in a multi-ethnic cohort free of CVD at baseline. Methods: This was a cross-sectional analysis of 6,453 adults aged 45–84 years from the Multi-Ethnic Study of Atherosclerosis. Financial strain was assessed by questionnaire and responses were categorized as yes or no. CVH was measured from 7 metrics (smoking, body mass index, physical activity, diet, total cholesterol, blood glucose and blood pressure). A CVH score of 14 was calculated by assigning points to the categories of each metric (poor = 0 points, intermediate = 1 point, ideal = 2 points). Multinomial logistic regression was used to examine the association of financial strain with the CVH score (inadequate 0–8, average 9–10, and optimal 11–14 points) adjusting for sociodemographic factors, depression and anxiety. Results: The mean age (SD) was 62 (10) and 53 % were women. Financial strain was reported by 25 % of participants. Participants who reported financial strain had lower odds of average (OR, 0.82 [95 % CI, 0.71, 0.94]) and optimal (0.73 [0.62, 0.87]) CVH scores. However, in the fully adjusted model, the association was only significant for optimal CVH scores (0.81, [0.68, 0.97]). Conclusion: Financial strain was associated with poorer CVH. More research is needed to understand this relationship so the burden of CVD can be decreased, particularly among people experiencing financial hardship.

Adipose tissue is the site of long-term energy storage. During the fasting state, exercise, and cold exposure, the white adipose tissue mobilizes energy for peripheral tissues through lipolysis. The mobilization of lipids from white adipose tissue to the liver can lead to excess triglyceride accumulation and fatty liver disease. Although the white adipose tissue is known to release free fatty acids, a comprehensive analysis of lipids mobilized from white adipocytes in vivo has not been completed. In these studies, we provide a comprehensive quantitative analysis of the adipocyte-secreted lipidome and show that there is interorgan crosstalk with liver. Our analysis identifies multiple lipid classes released by adipocytes in response to activation of lipolysis. Time-dependent analysis of the serum lipidome showed that free fatty acids increase within 30 min of β3-adrenergic receptor activation and subsequently decrease, followed by a rise in serum triglycerides, liver triglycerides, and several ceramide species. The triglyceride composition of liver is enriched for linoleic acid despite higher concentrations of palmitate in the blood. To further validate that these findings were a specific consequence of lipolysis, we generated mice with conditional deletion of adipose tissue triglyceride lipase exclusively in adipocytes. This loss of in vivo adipocyte lipolysis prevented the rise in serum free fatty acids and hepatic triglycerides. Furthermore, conditioned media from adipocytes promotes lipid remodeling in hepatocytes with concomitant changes in genes/pathways mediating lipid utilization. Together, these data highlight critical role of adipocyte lipolysis in interorgan crosstalk between adipocytes and liver.

Background: Dysregulated myocardial calcium handling has been demonstrated in ischemic, non-ischemic and diabetic cardiomyopathy. Manganese-enhanced MRI (MEMRI) provides a unique method to quantify in-vivo myocardial calcium uptake but no studies have so far utilized MEMRI in patients with aortic stenosis (AS). We sought to: 1) determine whether myocardial calcium uptake is perturbed in people with severe AS, and 2) assess change in calcium uptake following aortic valve replacement (AVR). Methods: In this prospective, pilot, case-control study, adults with severe AS underwent MEMRI before and after AVR. A group of healthy controls were also recruited. The primary outcome was the rate of manganese uptake (Ki) as assessed by Patlak modeling to act as a surrogate of myocardial calcium uptake. Comparison of Ki between groups was adjusted for age, body mass index (BMI) and systolic blood pressure. Results: Twenty-eight controls and ten subjects with severe AS (age 72 [61-75] years, 8 male, 7 symptomatic, valve area 0.81 [0.74-1.0] cm2) were recruited, with seven returning for repeat scans post-AVR. AS patients had higher BMI and blood pressure, and a greater incidence of hyperlipidemia compared to controls. Baseline left ventricular (LV) volumes were similar between the groups, but the AS patients had higher indexed left ventricular mass. Global longitudinal strain and peak early diastolic strain rate were lower in the AS group. There was no significant difference in Ki between patients with severe AS and controls (7.09 [6.33-8.99] vs. 8.15 [7.54-8.78] mL/100g of tissue/min, P=0.815). Following AVR, there was regression in indexed LV mass (68 [51-79] to 49 [47-65] g/m2, P=0.018) and mass-volume ratio (0.94 [0.80-1.13] to 0.74 [0.71-0.82] g/mL, P=0.028) but no change in Ki was seen (7.35 [6.81-8.96] to 7.11 [6.16-8.01] mL/100 g of tissue/min, P=0.499). Conclusions: Despite clear features of adverse LV remodeling and systolic dysfunction, patients with severe AS demonstrated no alteration in calcium uptake at baseline compared to controls. Moreover, AVR led to reverse LV remodeling but no notable change in calcium uptake was seen. This may suggest that altered myocardial calcium handling does not play a significant pathophysiological role in AS.

Intimate partner violence (IPV) can constraint Black women’s ability to prioritize and access Human Immunodeficiency Virus (HIV) pre-exposure prophylaxis (PrEP) services. Recent research has called for the development of trauma-informed PrEP implementation programs to improve the delivery of PrEP to Black cisgender women; however, many PrEP-prescribing settings do not reflect this recommendation. The current study sought to identify key components to develop a trauma-informed PrEP implementation program for Black cisgender women and clinical staff. We conducted focus groups with PrEP-eligible Black cisgender women (February-June 2019), and semi-structured interviews with clinical staff offering HIV prevention and treatment services (October-November 2020) in community healthcare clinics in Mississippi. Seven themes were identified as needed to facilitate integration of trauma-informed approaches into existing PrEP programs, including defining intimate partner violence (IPV), appropriate IPV screening and response, HIV prevention in abusive relationships, staff training needs, and creating supportive clinic environments. PrEP-eligible Black women and clinical staff generally agreed on how to best operationalize IPV screening and response, the importance of trauma-informed staff training, and the need for Black women-specific informational campaigns. However, Black women highlighted the need for providers to discuss HIV prevention in controlling relationships, and to respond to IPV disclosure. HIV pre-exposure prophylaxis has yet to achieve the potential impact observed in trials. Ultimately, realizing the HIV prevention potential of PrEP in the US necessitates centering the perspectives of Black cisgender women and staff to better integrate trauma-informed approaches.

Background: This study assessed the potential cost-effectiveness of high (80–100%) vs low (21–35%) fraction of inspired oxygen (FiO2) at preventing surgical site infections (SSIs) after abdominal surgery in Nigeria, India, and South Africa. Methods: Decision-analytic models were constructed using best available evidence sourced from unbundled data of an ongoing pilot trial assessing the effectiveness of high FiO2, published literature, and a cost survey in Nigeria, India, and South Africa. Effectiveness was measured as percentage of SSIs at 30 days after surgery, a healthcare perspective was adopted, and costs were reported in US dollars ($). Results: High FiO2 may be cost-effective (cheaper and effective). In Nigeria, the average cost for high FiO2 was $216 compared with $222 for low FiO2 leading to a −$6 (95% confidence interval [CI]: −$13 to −$1) difference in costs. In India, the average cost for high FiO2 was $184 compared with $195 for low FiO2 leading to a −$11 (95% CI: −$15 to −$6) difference in costs. In South Africa, the average cost for high FiO2 was $1164 compared with $1257 for low FiO2 leading to a −$93 (95% CI: −$132 to −$65) difference in costs. The high FiO2 arm had few SSIs, 7.33% compared with 8.38% for low FiO2, leading to a −1.05 (95% CI: −1.14 to −0.90) percentage point reduction in SSIs. Conclusion: High FiO2 could be cost-effective at preventing SSIs in the three countries but further data from large clinical trials are required to confirm this.

Summary: Current understanding of lipid genetics has come mainly from studies in European-ancestry populations; limited effort has focused on Polynesian populations, whose unique population history and high prevalence of dyslipidemia may provide insight into the biological foundations of variation in lipid levels. Here, we performed an association study to fine map a suggestive association on 5q35 with high-density lipoprotein cholesterol (HDL-C) seen in Micronesian and Polynesian populations. Fine-mapping analyses in a cohort of 2,851 Samoan adults highlighted an association between a stop-gain variant (rs200884524; c.652C>T, p.R218∗; posterior probability = 0.9987) in BTNL9 and both lower HDL-C and greater triglycerides (TGs). Meta-analysis across this and several other cohorts of Polynesian ancestry from Samoa, American Samoa, and Aotearoa New Zealand confirmed the presence of this association (βHDL-C = −1.60 mg/dL, pHDL-C = 7.63 × 10−10; βTG = 12.00 mg/dL, pTG = 3.82 × 10−7). While this variant appears to be Polynesian specific, there is also evidence of association from other multiancestry analyses in this region. This work provides evidence of a previously unexplored contributor to the genetic architecture of lipid levels and underscores the importance of genetic analyses in understudied populations.

PEGylated-l-asparaginase (PEG-ASNase) is a chemotherapeutic agent used to treat pediatric acute lymphoblastic leukemia (ALL). Its use is avoided in adults due to its high risk of liver injury including hepatic steatosis, with obesity and older age considered risk factors of the injury. Our study aims to elucidate the mechanism of PEG-ASNase-induced liver injury. Mice received 1500 U/kg of PEG-ASNase and were sacrificed 1, 3, 5, and 7 days after drug administration. Liver triglycerides were quantified, and plasma bilirubin, ALT, AST, and non-esterified fatty acids (NEFA) were measured. The mRNA and protein levels of genes involved in hepatic fatty acid synthesis, β-oxidation, very low-density lipoprotein (VLDL) secretion, and white adipose tissue (WAT) lipolysis were determined. Mice developed hepatic steatosis after PEG-ASNase, which associated with increases in bilirubin, ALT, and AST. The hepatic genes Ppara, Lcad/Mcad, Hadhb, Apob100, and Mttp were upregulated, and Srebp-1c and Fas were downregulated after PEG-ASNase. Increased plasma NEFA, WAT loss, and adipose tissue lipolysis were also observed after PEG-ASNase. Furthermore, we found that PEG-ASNase-induced liver injury was exacerbated in obese and aged mice, consistent with clinical studies of ASNase-induced liver injury. Our data suggest that PEG-ASNase-induced liver injury is due to drug-induced lipolysis and lipid redistribution to the liver.

Intimate partner violence (IPV) can impact the mental health of survivors; however, little is known about the role of state-level restorative justice policies. Restorative justice policies are survivor-centered justice approaches focused on repairing harm between the survivor and perpetrator, which may buffer mental health outcomes among IPV survivors. Furthermore, the impact of restorative justice policies on mental health may be influenced by the degree of state-level support for policy implementation. This study examined the relationship between (1) IPV exposure and mental health and whether restorative justice policies moderate the relationship; and (2) whether restorative justice policy implementation support moderates the relationship between IPV and mental health among women. Data on state restorative justice policies were drawn from a U.S. restorative justice legislation database. Individual-level data on 5104 adult women were collected from the 2010 National Intimate Partner and Sexual Violence Survey (NISVS), a nationally representative study of noninstitutionalized adult women and men. Generalized estimating equation (GEE) models were conducted to examine associations between IPV, state-level restorative justice policies, restorative justice policy implementation support, and perceived mental health (N ​= ​5104). Women who experienced IPV had worse perceived mental health compared to women without IPV (b [95% CI] ​= ​−0.13 [−0.15, −0.11], p ​

Residential racial segregation in the U.S. has been hypothesized as a fundamental cause driving health disparities across racial groups. Potential mechanisms include economic and social marginalization, subsequent constrained opportunities, and high stress. Yet evidence on residential segregation's association with health among Black and White children—particularly longitudinally—is sparse. This study aims to address this gap. We used data from the Panel Study of Income Dynamics (PSID), a national longitudinal study of U.S. households, analyzing information on 1,251 Black and 1,427 White children who participated in the Child Development Supplement (CDS) at least twice (survey waves 1997, 2002, 2007, 2014). We fit individual fixed-effects models to estimate the within-person association of neighborhood-level residential segregation, measured with local Getis-Ord G* statistics, with three outcomes (general health, weight status, and behavioral problems). We examined heterogeneous effects by age and sex. We also examined associations between health and childhood segregation trajectories, i.e., the pattern of children's residential segregation exposures from birth through when their health outcomes were measured, providing additional insight on dynamic experiences of segregation. In fixed effects models, among Black children, higher segregation was associated with worse self-rated health, especially for Black children who were older (aged 11–17 years). In trajectory models, among White children, moving out of highly segregated neighborhoods was associated with a lower probability of poor self-rated health, while moving into those neighborhoods or back and forth between neighborhood types were both associated with increased behavioral problems. Our findings highlight the importance of early-life residential segregation in shaping persistent racial health disparities, as well as the costs of segregation for all children living in highly segregated neighborhoods.

Racial discrimination is an important predictor of racial inequities in mental and physical health. Scholars have made progress conceptualizing and measuring structural forms of racism, yet, little work has focused on measuring structural racism in social contexts, which are especially relevant for studying the life course consequences of racism for health. Using the National Longitudinal Study of Adolescent to Adult Health, we take a biosocial, life course approach and develop two life stage-specific indices measuring manifestations of structural racism in school contexts in adolescence, a sensitive period of development. The first is a school contextual disadvantage index (CDI), which captures differences in resources and opportunities across schools that have been partly determined by socio-historic structural racism that has sorted Black students into more disadvantaged schools. The second is a school structural racism index (SRI), which measures differences in resources and opportunities between Black and white students within schools. Then, we relate these indices to adolescent depressive symptoms. We find that among both Black and white students of both genders, higher CDI levels are associated with more depressive symptoms. However, Black students are twice as likely to be in schools with a CDI above the median compared to white students. We also find that, controlling for the CDI, the SRI is positively associated with depressive symptoms among Black boys and girls only. Finally, the CDI and the SRI interact to produce a pattern where the likelihood of depressive symptoms increases as the SRI increases, but only among Black boys and girls in low-disadvantage schools. These findings underscore the importance of measuring structural racism in social contexts in multifaceted ways to study life course health inequities.

Abstract Background Low cardiorespiratory fitness (CRF), high body mass index, and excess visceral adiposity are each associated with impairment in left ventricular (LV) peak circumferential strain (Ecc), an intermediate phenotype that precedes the development of clinical heart failure (HF). However, the association of regional fat distribution and CRF with Ecc independent of each other and other potential confounders is not known. Methods Participants from the Dallas Heart Study Phase 2 who underwent dual energy X-ray absorptiometry assessment of regional fat distribution, CRF assessment by submaximal treadmill test, and Ecc quantification by tissue-tagged cardiovascular magnetic resonance were included in the analysis. The cross-sectional associations of measures of regional adiposity, namely visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and lower-body fat (LBF) with Ecc after adjustment for CRF and other potential confounders (independent variables) were assessed using multivariable linear regression analysis. Results The study included 1089 participants (55% female, 39% black). In the unadjusted analysis, higher VAT was associated with greater impairment in Ecc. After adjustment for baseline risk factors, CRF, parameters of LV structure and function, and other fat depots such as SAT and LBF, higher VAT remained associated with greater impairment in Ecc (β: 0.19, P = 0.002). SAT and LBF were not significantly associated with Ecc, however, CRF remained associated with Ecc in the fully adjusted model including all fat depots (β: − 0.15, P

Brain derived neurotrophic factor (BDNF) is critical for the extinction of drug-seeking. Expression of the Bdnf gene is highly epigenetically regulated, including via interactions with non-coding RNA. Here we investigate whether a long non-coding RNA antisense to Bdnf exon IV is involved in extinction of drug-seeking. Strand-specific RNA sequencing confirmed the presence of a novel long non-coding RNA antisense to exon IV of the Bdnf gene in the ventromedial prefrontal cortex of adult male rats (Bdnf-IV-AS). Bdnf-IV-AS expression was validated using strand-specific reverse transcription and quantitative polymerase chain reaction following acquisition, extinction or abstinence from intravenous nicotine self-administration. Expression of Bdnf-IV-AS was elevated following intravenous nicotine self-administration but not experimenter-administered nicotine. Elevated Bdnf-IV-AS persisted across abstinence and to a greater extent following extinction training, suggesting an interaction between Bdnf-IV-AS, nicotine and extinction learning. A functional role of the Bdnf-IV-AS in extinction of nicotine-seeking was established by infusing gapmer oligonucleotides into the infralimbic cortex prior to extinction and testing for the effect of these infusions on reinstatement and reacquisition of nicotine-seeking. Knockdown of the Bdnf-IV-AS across cue-extinction, but not abstinence, significantly attenuated nicotine-primed reinstatement of nicotine-seeking. Bdnf-IV-AS accumulates in the infralimbic cortex across self-administration training, interferes with the inhibitory learning that underpins extinction of drug-seeking, and predisposes animals to drug relapse.

Abstract This study provides an overview and discussion of controls on the distribution of organic reefs during the Early Ordovican Period, in the Yangtze Platform, a region of epicontinental sedimentary rocks in South China. The Yangtze Platform was located in low latitudes during the Early Ordovician and recorded rich and diverse reefs through that time. During the late Tremadocian Epoch, dolomitic and stratiform stromatolites were common in supratidal to intertidal zones of the western Yangtze Platform, while columnar stromatolites formed in deeper waters of the eastern Yangtze Platform. Skeletal-dominated reefs occurred in upper subtidal settings of the central Yangtze Platform. A transition from microbial-dominated to metazoan-dominated reefs with shallowing-upward cycles was evident, indicating that the composition of the main reef-builders was driven mainly by water depth. Increasing metazoan competition during the Great Ordovician Biodiversification Event reduced the abundance of microbial reefs. Sufficient nutrient supply is interpreted to have promoted development of skeletal-dominated reefs locally in shallow settings in the central Yangtze Platform, especially represented by the expansion of abundant solitary fossils of lithistid sponges and Calathium. High salinity environmental settings facilitated the bloom of stromatolites in near-shore locations. Low oxygen content in deep subtidal settings may have led to the absence of skeletal reefs in these habitats, so the mass occurrences of stromatolites was located in the shallower-water central and eastern platform. No keratose sponge-bearing stromatolite can be confirmed across the platform during this interval.

Abstract Stromatoporoid sponges were very abundant during the middle Palaeozoic Era and are thought to disappear at the end of the Devonian Period in the Hangenberg Crisis. However, there are records of organisms with stromatoporoid-type structure in Carboniferous strata, the subject of this study. The Viséan fossil Labechia carbonaria Smith 1932 has been discussed previously in literature and its affinity has not been confirmed. In this study, the type material of L. carbonaria collected from the middle part of the Frizington Limestone Formation (previously called Seventh Limestone), Holkerian Substage, stored in the Natural History Museum (London, UK) and British Geological Survey (Keyworth, UK) was re-examined. The Holkerian Substage, in which L. carbonaria was found, lies between ca 335–339 Ma, and the Frizington Limestone Formation ranges from topmost Arundian to upper Holkerian, so middle Frizington Limestone Formation is likely approximately 337 Ma. L. carbonaria comprises thick long pillars connected by thin curved cyst plates consistent with the structure of the stromatoporoid genus Labechia. However, a common opinion is that L. carbonaria fossils may be mistaken for fragments of rugose corals, but there are problems with assigning it to the Rugosa. In vertical section (VS) L. carbonaria could be mistaken for a transverse section (TS) of a Carboniferous rugose coral. However, in TS L. carbonaria shows the rounded cross sections of stromatoporoid pillars. If it was a coral, septal sheets of the VS of a coral should be seen. For a rugose affinity to still apply, a coral structure would have to be composed of free trabeculae, but these are not known after the middle of the Devonian Period; there are no corals of Early Carboniferous age with the structure of L. carbonaria. Another interpretation, that L. carbonaria is a chaetetid, is discounted because it lacks calicles and is very different in structure from chaetetids. We conclude that L. carbonaria is a stromatoporoid. Because the beginning of the Carboniferous Period was ca 359 Ma, stromatoporoids thus occur approximately 22 million years after their purported disappearance at the end-Devonian Hangenberg Crisis. L. carbonaria, together with other rare occurrences in Carboniferous strata of stromatoporoid-form sponges Newellia mira (Newell) in USA, and uncertain taxa Komia Korde and Palaeoaplysina Krottow that have been attributed to stromatoporoids by some authors, supports some published views that end-Devonian stromatoporoid extinction may not have been as final as is traditionally interpreted. Thus Mesozoic stromatoporoids may represent resurgence of sponge lineages that survived the late Palaeozoic, perhaps in uncalcified form. Palaeogeographically, during the Early Carboniferous, the UK was positioned in low latitudes and in a central location of global distribution of reefal buildups during the late Palaeozoic continental assembly towards Pangaea. Thus it is curious that L. carbonaria is found in only one place; future search may determine its true palaeographic distribution, with potential reconsideration of the extinction of stromatoporoids at the end of the Devonian Period.

At the European Laboratory for Particle Physics (CERN), commercial greases and oils are extensively used to lubricate moving devices operating in high-radiation areas, absorbing doses up to the MGy range. Due to their sensitivity to radiation, lubricants can become fluid or solid in operation, potentially causing component failures and compromising the operation of the accelerator complex. CERN is therefore developing methodologies to select radiation tolerant commercial lubricants for critical Beam Intercepting Devices (BIDs) such as high-power targets, dumps and collimators. A careful selection of greases is fundamental to reduce the risk of failure, to optimize equipment lifetime and to minimize maintenance and unwanted radiation exposure of personnel in high radiation areas.Three different parameters are considered to select commercial lubricants: the expected total dose absorbed in operation, the maintenance feasibility and the failure impact in terms of accelerator downtime and of personnel involvement in replacement procedures. Based on these criteria, an example of relevant application is presented: the lubrication of the new internal beam dump of the Super Proton Synchrotron (SPS). Experimental radiation damage data allowed the identification of two radiation tolerant commercial greases to lubricate the dump support jack assembly.

Summary: eIF2B is the guanine nucleotide exchange factor (GEF) required for cytoplasmic protein synthesis initiation in eukaryotes and its regulation within the integrated stress response (ISR). It activates its partner factor eIF2, thereby promoting translation initiation. Here we provide evidence through biochemical and genetic approaches that eIF2B can bind directly to GTP and this can enhance its rate of GEF activity toward eIF2–GDP in vitro. GTP binds to a subcomplex of the eIF2Bγ and ε subunits. The eIF2Bγ amino-terminal domain shares structural homology with hexose sugar phosphate pyrophosphorylase enzymes that bind specific nucleotides. A K66R mutation in eIF2Bγ is especially sensitive to guanine or GTP in a range of functional assays. Taken together, our data suggest eIF2Bγ may act as a sensor of purine nucleotide availability and thus modulate eIF2B activity and protein synthesis in response to fluctuations in cellular nucleotide levels.

Objective: The Pooled Cohort Equations (PCE) serve as the platform for quantitative risk assessment for atherosclerotic cardiovascular disease (ASCVD). Data are sparse regarding the benefit of adding health-related quality of life (HRQoL) measures to the PCE. We sought to estimate the association of HRQoL with ASCVD events and evaluate the potential utility of adding HRQoL to the PCE in refining quantitative risk assessment for primary prevention decisions. Methods: Three multi-ethnic longitudinal cohorts were included in the study. HRQoL was measured using the SF-12 physical component summary (PCS) and mental component summary (MCS); higher PCS or MCS scores indicate better HRQoL. We constructed a four-level HRQoL status variable: MCS

The aim of this study was to determine if oxygen supplementation improved the PaO2 of pregnant ewes during short anaesthesia, when compared to a previous study where oxygen was not provided (Musk and Kemp, 2018). Twenty-six pregnant Merino cross ewes at 121–123 days of gestation were anaesthetised with intravenous midazolam and ketamine for subarachnoid administration of 60 mg of lignocaine and caesarean delivery of the preterm lamb. 100% oxygen was administered to the ewe by a face mask. Arterial blood samples were collected from the ewe immediately after delivery of the foetus. The ewes weighed 60.7 ± 5.5 kg and received 0.51 (0.47–0.58) mg/kg of midazolam and 10.3 (9.4–11.6) mg/kg of ketamine intravenously. The PaO2 of ewes receiving oxygen by face mask was higher than previously reported [92.6 ± 44.0 mmHg compared to 45.2 ± 11.8 mmHg (Musk and Kemp, 2018) (p = 0.0007)]. Oxygen delivery by mask improved the PaO2 of pregnant ewes during short term anaesthesia.

Abstract The reefs in the Xiannüdong Formation (Cambrian Series 2) are the oldest archaeocyathan–microbial bioconstructions in China, but the details of their microbial structures have not been previously described. However, a new section at Tangjiahe site, northern Sichuan Province, contains very well-preserved microbial fabrics that provide these details, and is described in this study. The Tangjiahe section contains three levels of reefal buildups that were constructed by a consortium of archaeocyaths and calcimicrobes in varying proportions. The lowest (oldest) reefal buildup is a calcimicrobial biostrome, possibly in the form of a wide mound with a low relief (unconfirmed due to outcrop limitation), which was formed by Epiphyton with rare small archaeocyaths, and is sandwiched by flat-pebble conglomerates. The middle reefal buildup is a high-relief calcimicrobial mound, enclosed by oolites, that was built by intergrown Renalcis and Tarthinia. Archaeocyath fossils are uncommon, and were bound into the framework by microbial carbonates. The uppermost (youngest) reefal buildup is a low-relief archaeocyathan mound lacking calcimicrobes but partly having microbially-clotted textures attached on archaeocyaths. Calcimicrobes built or aided archaeocyaths to form the framework of Tangjiahe reefs. The three buildups formed in low-energy lagoons behind ooid shoals, and the environment was nutrient-rich due to terrigenous influx from adjacent lands. Tangjiahe reefs thus resemble most Early Cambrian reefs, in settings consistent with eutrophic, calm environments, and are characterized by the domination or aid of calcimicrobial components in framework construction.

Longitudinal analysis of supermarkets over time is essential to understanding the dynamics of foodscape environments for healthy living. Supermarkets for 2007, 2011, and 2014 for the City of Chicago were curated and further validated. The average distance to all supermarkets along the street network was constructed for each resident-populated census tract. These analytic results were generated with GIS software and stored as spatially enabled data files, facilitating further research and analysis. The data presented in this article are related to the research article entitled “Urban foodscape trends: Disparities in healthy food access in Chicago, 2007–2014” (Kolak et al., 2018).

Mangafodipir was approved for use as an MRI contrast agent in the late 1990s for liver and pancreas imaging but it was removed from the European market for commercial reasons in 2012. Previously, preliminary work in mice and in diabetic patients showed that Mn2+ ions could be used as a contrast agent to monitor the function of insulin-producing β-cells by acting as a calcium analogue. Clinical translation of this work was hampered by a lack of available Mn contrast agents, but both mangafodipir and Mn gluconate are currently being used in clinical trials.As a first step towards using Mn in diabetic patients to monitor treatment or disease progression, we imaged the pancreas of healthy rats using mangafodipir, Mn gluconate and Mn chloride (as a control). The hypothesis was that Mn gluconate produces pancreatic enhancement similar to that seen previously with mangafodipir and Mn chloride, with greater enhancement following glucose challenge vs saline challenge. 18 Wistar rats were imaged at 7 T and normalised plateau pancreatic enhancement over baseline was compared for saline vs glucose challenge, calculated from a sigmoid fit to the enhancement curve. For saline vs glucose challenge, mean increases in plateau height ± sd were: 22 ± 18% for Mn chloride, 31 ± 29% for mangafodipir and 41 ± 17% for Mn gluconate. A paired t-test indicated that enhancement was greater for glucose vs saline (p=0.01) and that there was no significant difference in the percentage enhancement between any of the compounds (p>0.2). In conclusion, all three contrast agents produced similar enhancement, with greater plateau height under glucose challenge vs saline challenge. Mangafodipir and Mn gluconate show potential for translation into a clinical study investigating beta cell imaging of the pancreas in type 1 diabetes mellitus and type 2 diabetes.

In mammals, white adipose tissue (WAT) stores and releases lipids, whereas brown adipose tissue (BAT) oxidizes lipids to fuel thermogenesis. In obese individuals, WAT undergoes profound changes; it expands, becomes dysfunctional, and develops a low-grade inflammatory state. Importantly, BAT content and activity decline in obese subjects, mainly as a result of the conversion of brown adipocytes to white-like unilocular cells. Here, we show that BAT “whitening” is induced by multiple factors, including high ambient temperature, leptin receptor deficiency, β-adrenergic signaling impairment, and lipase deficiency, each of which is capable of inducing macrophage infiltration, brown adipocyte death, and crown-like structure (CLS) formation. Brown-to-white conversion and increased CLS formation were most marked in BAT from adipose triglyceride lipase (Atgl)-deficient mice, where, according to transmission electron microscopy, whitened brown adipocytes contained enlarged endoplasmic reticulum, cholesterol crystals, and some degenerating mitochondria, and were surrounded by an increased number of collagen fibrils. Gene expression analysis showed that BAT whitening in Atgl-deficient mice was associated to a strong inflammatory response and NLRP3 inflammasome activation. Altogether, the present findings suggest that converted enlarged brown adipocytes are highly prone to death, which, by promoting inflammation in whitened BAT, may contribute to the typical inflammatory state seen in obesity.

Carbonate sediments deposited in normally-oxygenated shallow ocean waters of the latest Permian period, immediately prior to the end-Permian mass extinction, contain well-developed diverse shelly faunas. After the extinction of these skeletal metazoans, the sediments commonly comprise microbialites (regarded by most authors as benthic) and associated facies bearing evidence interpreted by many authors to indicate reduced oxygenation of the shallow ocean waters. However, the evidence of oxygenation state is inconsistent and the sequences have gaps, indicated in the following 5 points: 1) Shelly fossils occur commonly in post-extinction shallow marine limestones, and likely to have been aerated in contact with the atmosphere. Nevertheless, although the largest mass extinction in Earth history may have caused reduced body size in shelly organisms, such reduction is arguably due to environmental stress of lowered oxygenation. Discriminating between these controls remains a challenge. 2) Abundant pyrite framboids in many post-extinction limestones are interpreted by several authors as indicating dysoxic contemporaneous waters, so the organisms that lived there, now shelly fossils, were dysaerobic. However, verification is problematic because pyrite framboids scattered amongst shelly fossils cannot have formed amongst living organisms, which need at least some oxygen; synsedimentary framboid formation requires anoxic conditions in the redox boundary where sulphate-reducing processes work. Thus, framboids and shelly fossils found together means taphonomic mixing of sediments, destroying original depositional relationships so that it is not possible to determine whether the shells were aerobic or dysaerobic prior to sediment mixing. Furthermore, diagenetic growth of framboids is possible, as is import of previously-formed framboids from deeper water during upwelling. Thus, there is no proof of an environmental link between framboid size and occurrence, and contemporaneous oxygenation in these post-extinction shallow water facies, so we question the validity of this model in those facies, but consider that the model is valid for deeper water facies. 3) Some publications provide evidence of oxygenation, from redox-sensitive elements in post-extinction limestones, while others indicate low oxygen conditions. Redox-sensitive geochemistry requires further work to explore this issue at higher resolution of sampling than has been so far applied. 4) Biomarkers recorded in some post-extinction facies contain evidence of anoxic conditions (including green sulphur bacteria) but other examples lack these, which may be indicate fluctuations of water oxygenation. However, a key issue that has not yet been resolved is determination of whether biomarkers were imported into the sites of deposition, for example by upwelling currents, or formed where they are found. Thus, there is currently no verification that biomarkers of low oxygen organisms in shallow water settings actually formed in the places where they are sampled. 5) The common occurrence of small erosion surfaces and stylolites represents loss of evidence, and must be accounted for in future studies. The oxygenation state of post-end-Permian extinction shallow marine facies continues to present a challenge of interpretation, and requires high-resolution sampling and careful attention to small-scale changes, as well as loss of rock through pressure solution, as the next step to resolve the issue.

Lipid accumulation is a pathological feature of every type of kidney injury. Despite this striking histological feature, physiological accumulation of lipids in the kidney is poorly understood. We studied whether the accumulation of lipids in the fasted kidney are derived from lipoproteins or NEFAs. With overnight fasting, kidneys accumulated triglyceride, but had reduced levels of ceramide and glycosphingolipid species. Fasting led to a nearly 5-fold increase in kidney uptake of plasma [14C]oleic acid. Increasing circulating NEFAs using a β adrenergic receptor agonist caused a 15-fold greater accumulation of lipid in the kidney, while mice with reduced NEFAs due to adipose tissue deficiency of adipose triglyceride lipase had reduced triglycerides. Cluster of differentiation (Cd)36 mRNA increased 2-fold, and angiopoietin-like 4 (Angptl4), an LPL inhibitor, increased 10-fold. Fasting-induced kidney lipid accumulation was not affected by inhibition of LPL with poloxamer 407 or by use of mice with induced genetic LPL deletion. Despite the increase in CD36 expression with fasting, genetic loss of CD36 did not alter fatty acid uptake or triglyceride accumulation. Our data demonstrate that fasting-induced triglyceride accumulation in the kidney correlates with the plasma concentrations of NEFAs, but is not due to uptake of lipoprotein lipids and does not involve the fatty acid transporter, CD36.

Shallow marine carbonate sediments that formed after the end-Permian mass extinction are rich in a thin (maximum ca. 15 m) deposit of microbialites. Microbial communities that constructed the microbialites have geographic variability of composition, broadly divisible into two groups: 1) eastern Tethys sites are calcimicrobe-dominated (appearing as thrombolites in the field), with rare occurrence of sediment-constructed microbialites and uncommon cements either within microbial structure or as inorganic precipitates, 2) other Tethys sites are sediment-dominated structures forming stromatolites and thrombolites, composed of micrites and cements, with some inorganic precipitates. These other Tethys locations include western and central Tethys sites but their palaeogeographic positions depend on the accuracy of continental reconstructions, of which there are several opinions. In contrast to geographic variation of microbialites, the conodont Hindeodus parvus, which appeared after the extinction and defines the base of the Triassic, is widespread, indicating easy lateral migration throughout Tethys. Conodont animals were active nekton, although being small animals were presumably at least partly carried by water currents, implying active Tethyan surface water circulation after the extinction event. Post-extinction ammonoid taxa, presumed active swimmers, show poor evidence of a wide distribution in the Griesbachian beds immediately after the extinction, but are more cosmopolitan higher up, in the Dienerian strata in Tethys. Other shelly fossils also have poorly defined distributions after the extinction, but ostracods show some wider distribution suggesting migration was possible after the extinction. Therefore there is a contrast between the geographic differences of microbialites and some shelly fossils. Determining the cause of geographic variation of post-extinction microbialites is problematic and may include one or more of the following possibilities: 1) because calcifying microbial organisms that create calcimicrobes were benthic, they may have lacked planktonic stages that would have allowed migration, 2) eastern Tethyan seas were possibly more saturated with respect to calcium carbonates and microbes, so microbes there were possibly more able to calcify, 3) significant reduction of Tethyan ocean circulation, perhaps by large-scale upwelling disrupting ocean surface circulation, may have limited lateral migration of benthic microbial communities but did not prevent migration of other organisms, and 4) microbes may have been subject to local environmental controls, the mechanisms of which have not yet been recognized in the facies. The difficulty of distinguishing between these possibilities (and maybe others not identified) demonstrates that there is a lot still to learn about the post-extinction microbialites and their controls.

Racial and ethnic disparities in adverse birth outcomes have persistently been wide and may be explained by individual and area-level factors. Our primary objective was to determine if county-level black-white segregation modified the association between maternal race/ethnicity and adverse birth outcomes using birth records from the National Center for Health Statistics (2012). Based on maternal residence at birth, county-level black-white racial residential segregation was calculated along five dimensions of segregation: evenness, exposure, concentration, centralization, and clustering. We conducted a two-stage analysis: (1) county-specific logistic regression to determine whether maternal race and ethnicity were associated with preterm birth and term low birth weight; and (2) Bayesian meta-analyses to determine if segregation moderated these associations. We found greater black-white and Hispanic-white disparities in preterm birth in racially isolated counties (exposure) relative to non-isolated counties. We found reduced Hispanic-white disparities in term low birth weight in racially concentrated and centralized counties relative to non-segregated counties. Area-level poverty explained most of the moderating effect of segregation on disparities in adverse birth outcomes, suggesting that area-level poverty is a mediator of these associations. Segregation appears to modify racial/ethnic disparities in adverse birth outcomes. Therefore, policy interventions that reduce black-white racial isolation, or buffer the poor social and economic correlates of segregation, may help to reduce disparities in preterm birth and term low birth weight. Keywords: Bayesian meta-analysis, Health disparities, Preterm birth, Racial residential segregation, Term low birth weight

Although workplace discrimination and mistreatment (WDM) has recently drawn widespread media attention, our understanding of the prevalence of these phenomena remains limited. In the current study, we generated national prevalence estimates of WDM from a community-based cohort of employed black and white men and women aged ≥48 years. Measures of WDM in the current job were obtained by computer-assisted telephone interview (2011–2013) involving dichotomous responses (yes or no) to five questions and deriving a composite measure of discrimination (yes to at least one). Prevalence estimates and age- and region-adjusted prevalence ratios were derived with use of SUDAAN software to account for the complex sample design. Analyses were stratified by race and sex subgroups. This sample represents over 40 million U.S. workers aged ≥48 years. The prevalence of workplace discrimination ranged from a high of 25% for black women to a low of 11% for white men. Blacks reported a 60% higher rate of discrimination compared to whites; women reported a 53% higher prevalence of discrimination, compared with men. The prevalence of workplace mistreatment ranged from 13% for black women to 8% for white men. Women reported a 52% higher prevalence of mistreatment compared to men, while differences by race were not significant. Mistreatment was 4–8 times more prevalent among those reporting discrimination than among those reporting none. Subgroup differences in mistreatment were confined to the wage-employed. Findings suggest that middle age and older wage-employed blacks and women experience the highest prevalence of WDM; moreover, discrimination is strongly associated with mistreatment. This study contributes to our understanding of at-risk segments of the U.S. labor market and the need for targeted interventions to reduce WDM. Keywords: Workplace discrimination, Racism, Sexism, Ageism, Harassment, Mistreatment

Lead and halide ion compositions of spin coated organo-lead halide perovskite films have been quantified using ion chromatography (IC) and atomic absorption spectroscopy (AAS) using perovskite films manufactured by 5 different researchers (3 replicates per treatment) to monitor variability between researchers and individual researcher reproducibility. Planar and mesoporous TiO2-coated glass substrates have been studied along with tribromide (CH3NH3PbBr3), triiodide (CH3NH3PbI3) and mixed halide (CH3NH3PbI3−xClx) perovskite films. The data show low yields of spin coated perovskite material (ca. 1%) and preferential deposition of I− over Cl− in mixed halide films. Keywords: Solar energy materials, Thin films, Manufacturing, Perovskites, Composition

This paper reassesses published interpretation that beef and cone-in-cone (B-CIC) fibrous calcite cements were precipitated contemporaneously just below the sea floor in unconsolidated sediment, in limestones associated with the end-Permian (P/T) and end-Triassic (T/J) mass extinctions. That interpretation introduced the concept of a sub-seafloor carbonate factory associated with ocean acidification by raised carbon dioxide driven by volcanic eruption, coinciding with mass extinction. However, our new fieldwork and petrographic analysis, with literature comparison, reveals several problems with this concept. Two key points based on evidence in the T/J transition of the UK are: (1) that B-CIC calcite deposits form thin scattered layers and lenses at several horizons, not a distinct deposit associated with volcanic activity; and (2) B-CIC calcite is more common in Early Jurassic sediments after the extinction and after the end of the Central Atlantic Magmatic Province volcanism proposed to have supplied the carbon dioxide required. Our samples from Late Triassic, Early Jurassic and Early Cretaceous limestones in southern UK show that B-CIC calcite occurs in both marine and non-marine sediments, therefore ocean processes are not mandatory for its formation. There is no proof that fibrous calcite was formed before lithification, but our Early Jurassic samples do prove fibrous calcite formed after compaction, thus interpretation of crystal growth in unconsolidated sediment is problematic. Furthermore, B-CIC crystals mostly grew both upwards and downwards equally, contradicting the interpretation of the novel carbonate factory that they grew preferentially upwards in soft sediment. Finally, Early Jurassic and Early Cretaceous examples are not associated with mass extinction. Three further key points derived from the literature include: (1) B-CIC calcite is widespread geographically and stratigraphically, not clustered around mass extinctions or the Paleocene–Eocene Thermal Maximum (PETM) event; (2) isotope signatures suggest B-CIC calcite formed under high pressure in burial at 70–120 °C, incompatible with interpretation of formation of B-CIC calcite at the redox boundary below the ocean floor; and (3) B-CIC calcite reported in P/T boundary microbialites in one site in Iran is the only occurrence known despite extensive published studies of similar shallow marine settings, demonstrating its formation is localized to the Iran site. Based on the above evidence, our opinion is that B-CIC calcite is best explained as a later diagenetic feature unrelated to rapid Earth-surface environmental change associated with mass extinctions; thus a novel carbonate factory is highly unlikely.

Introduction: Falling when older is a major public health issue. There is compelling evidence to show that specific exercise programs can reduce the risk and rate of falls in community-dwelling older people. Another major health issue for older people living in the community is upper limb dysfunction, including shoulder pain. Home-based exercise programs appeal to some older people, due to their convenience. Research questions: This trial aims to determine the effectiveness and cost-effectiveness of a home-based lower limb exercise program compared with a home-based upper limb exercise program to prevent falls and upper limb dysfunction among community-dwelling people aged 65+ years. Design: Randomised, controlled trial. Participants and setting: A total of 576 community-dwelling people will be recruited from the Illawarra and Shoalhaven regions of New South Wales, Australia. Intervention: Participants will be randomised to either a home-based lower limb exercise intervention or a home-based upper limb exercise intervention. The lower limb program is designed to improve balance and strength in the lower limbs. The upper limb program is designed to improve upper limb strength and mobility. Participants will attend three group-based instruction sessions to learn and progress the exercises, and will be instructed to perform the exercises three times per week at home for 12 months. Outcome measures: The two primary outcomes will be fall rates, recorded with monthly calendars for a 12-month period, and upper limb dysfunction, measured with the Disability of the Arm, Shoulder and Hand questionnaire. Secondary outcomes will include: lower limb strength and balance; shoulder strength and mobility; physical activity; quality of life; attitudes to exercise; proportion of fallers; fear of falling; and health and community service use. The cost-effectiveness of both exercise programs from a health and community service provider perspective will be evaluated. Analysis: Negative binomial regression models will be used to estimate the between-group difference in fall rates. Modified Poisson regression models will be used to compare groups on dichotomous outcome measures. Linear regression models will be used to assess the effect of group allocation on the continuously scored measures, after adjusting for baseline scores. Two economic evaluations will be conducted: the first will assess cost-effectiveness of the lower limb program compared with the upper limb program; and the second will assess cost-effectiveness of the upper limb program compared with the lower limb program. Discussion: If effective, the trial will provide a model for both upper limb and lower limb exercise programs that can be performed at home and implemented at scale to community-dwelling older adults.

Patients with Human Immunodeficiency Virus (HIV) infection and Acquired Immunodeficiency Syndrome (AIDS) are at risk for multiple infectious and oncologic complications. In such cases, Occam’s razor need not apply: multiple infections and malignancies are often present concurrently upon presentation to care. A patient off anti-retroviral therapy (ART) for several years developed advanced HIV infection (CD4 count 19 cells/uL) and presented with five simultaneous opportunistic infections including Pneumocystis jiroveci pneumonia (PJP), cytomegalovirus (CMV) retinitis, Mycobacterium avium complex (MAC) bloodstream infection, chronic hepatitis B virus (HBV), and Epstein-Barr virus (EBV) viremia. Simultaneously, he was found to have primary central nervous system (CNS) B-cell lymphoma.Treatment decisions for such patients are often complex, as ideal therapy for one disease may directly counter or interact with therapy for another. For instance, methotrexate for primary CNS lymphoma and trimethoprim/sulfamethoxazole for PJP is a strictly contraindicated medication combination. It is important to understand not just the management of any single opportunistic disease in patients with advanced HIV, but how to balance management for patients with a variety of concurrent processes. In an era when HIV care is becoming increasingly simplified, patients presenting with advanced infection highlight the lack of data on how best to manage patients with multiple concurrent disease processes. Significant further research is needed to clarify ideal comparative therapy. Keywords: Human Immunodeficiency Virus, Acquired Immunodeficiency Disorder, Opportunistic infection

The modern Black Sea has a mixed upper layer in the top 150–200 m of the water column, below which the water is anoxic, separated from the mixed layer by a redox boundary. There is limited vertical movement of water. Pyrite framboids form in the water column of the anoxic zone, then have been traditionally interpreted to sink immediately and accumulate in the sediments of the Black Sea. Thus the occurrence of framboids in sediments in the rock record is widely interpreted to indicate poorly oxygenated to anoxic conditions in ancient environments. However, in the Permian–Triassic boundary (PTB) microbialites of South China, which formed in shallow marine conditions in contact with the atmosphere, the published occurrence of framboids is inconsistent with abundant gastropod and ostracod shells in the microbialite. Furthermore, in the modern Black Sea, (a) framboids may be suspended, attached to organic matter in the water column, thus not settle to the sea floor immediately after formation; and (b) the redox zone is an unstable complex area subject to rapid vertical water movement including occasional upwelling. The model presented here supposes that upwelling through the redox zone can lead to upward transport of suspended pyrite framboids into the mixed layer. Advective circulation could then draw suspended framboids onto the shelf to be deposited in oxygenated sediments. In the Permian–Triassic transition, if framboids were up-welled from below the redox boundary and mixed with oxygenated waters, sediment deposited in these conditions could provide a mixed signal for potentially misleading interpretations of low oxygen conditions. However, stratigraphic sampling resolution of post-extinction microbialites is currently insufficient to demonstrate possible separation of framboid-bearing layers from those where framboids are absent. Profound differences between microbialite constructors and sequences between the western and eastern Tethys demonstrate barriers to migration of microbial organisms. However, framboid occurrences in both areas indicate upwelling and emphasize vertical movement of water from the lower to upper ocean, yet the mixed layer advective motion may not have been as effective as in modern oceans. In the modern Black Sea, such advection is highly effective in water mixing, and provides an interesting contrast with the PTB times.

Chronic activation of β3-adrenergic receptors (β3-ARs) expands the catabolic activity of both brown and white adipose tissue by engaging uncoupling protein 1 (UCP1)-dependent and UCP1-independent processes. The present work examined de novo lipogenesis (DNL) and TG/glycerol dynamics in classic brown, subcutaneous “beige,” and classic white adipose tissues during sustained β3-AR activation by CL 316,243 (CL) and also addressed the contribution of TG hydrolysis to these dynamics. CL treatment for 7 days dramatically increased DNL and TG turnover similarly in all adipose depots, despite great differences in UCP1 abundance. Increased lipid turnover was accompanied by the simultaneous upregulation of genes involved in FAS, glycerol metabolism, and FA oxidation. Inducible, adipocyte-specific deletion of adipose TG lipase (ATGL), the rate-limiting enzyme for lipolysis, demonstrates that TG hydrolysis is required for CL-induced increases in DNL, TG turnover, and mitochondrial electron transport in all depots. Interestingly, the effect of ATGL deletion on induction of specific genes involved in FA oxidation and synthesis varied among fat depots. Overall, these studies indicate that FAS and FA oxidation are tightly coupled in adipose tissues during chronic adrenergic activation, and this effect critically depends on the activity of adipocyte ATGL.

Palaeozoic stromatoporoids are calcified sponges common between Middle Ordovician and Late Devonian times in reefs and related facies. Taxonomic work is well known, but controversial because of conflict between classification schemes based on the calcareous skeleton versus spicules (which are almost completely lacking in Palaeozoic stromatoporoids); however, lower-level taxonomy (at genus-level) of the calcareous skeleton is considered reliable to be applied in palaeobiological study. Knowledge of stromatoporoid ecology is poorly developed, such that comprehensive information is available for only a few case studies, in some Silurian and Devonian examples. Thus an overall understanding of stromatoporoid responses to environmental conditions has not yet been achieved, although stromatoporoids were likely able to deal with fine-grained sediment where they mostly occur. Many stromatoporoid genera have only certain growth forms, so future focus on the use of low-level taxonomy in ecological studies, by comprehensive sampling in high-resolution studies, may establish the relationships between stromatoporoids and their environments. Intergrown organisms and growth banding in stromatoporoids are aspects that have great potential in such work. Mineralogy of stromatoporoids remains poorly understood. Regardless of their apparent state of preservation (ranging from apparently well-preserved to complete loss of calcareous skeleton features) all stromatoporoids are in fact substantially recrystallized. They underwent a peculiar diagenesis, whereby the calcareous skeleton and gallery cements of all stromatoporoids are overprinted by irregular elongated calcite crystals arranged normal to the growth laminations, most clearly visible in cross-polarized light. Stromatoporoids co-occur with mollusc shells that are always either fully recrystallized or dissolved (present as internal and external moulds); this difference means that while molluscs are likely under-represented in the fossil record, stromatoproids are not, providing confidence for palaeoecological work on their assemblages. Stromatoporoids lack characters which would readily classify them as being originally aragonite or low-Mg calcite; they may have been high-Mg calcite but the evidence is circumstantial. Their peculiar diagenetic fabric also has implications for the debate about the relationship between stromatoporoids and the concept of aragonite/calcite seas, which requires more work.

Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme mediating triglyceride (TG) hydrolysis. The lack of ATGL results in TG accumulation in multiple tissues, underscoring the critical role of ATGL in maintaining lipid homeostasis. Recent evidence suggests that ATGL affects TG metabolism via activation of peroxisome proliferator-activated receptor α (PPARα). To investigate specific effects of intestinal ATGL on lipid metabolism we generated mice lacking ATGL exclusively in the intestine (ATGLiKO). We found decreased TG hydrolase activity and increased intracellular TG content in ATGLiKO small intestines. Intragastric administration of [3H]trioleate resulted in the accumulation of radioactive TG in the intestine, whereas absorption into the systemic circulation was unchanged. Intraperitoneally injected [3H]oleate also accumulated within TG in ATGLiKO intestines, indicating that ATGL mobilizes fatty acids from the systemic circulation absorbed by the basolateral side from the blood. Down-regulation of PPARα target genes suggested modulation of cholesterol absorption by intestinal ATGL. Accordingly, ATGL deficiency in the intestine resulted in delayed cholesterol absorption. Importantly, this study provides evidence that ATGL has no impact on intestinal TG absorption but hydrolyzes TGs taken up from the intestinal lumen and systemic circulation. Our data support the role of ATGL in modulating PPARα-dependent processes also in the small intestine.

PNPLA3 (adiponutrin, calcium-independent phos­pholipase A2 epsilon [iPLA2∊]) is an adipose-enriched, nutritionally regulated protein that belongs to the patatin-like phospholipase domain containing (PNPLA) family of lipid metabolizing proteins. Genetic variations in the human PNPLA3 gene (i.e., the rs738409 I148M allele) has been strongly and repeatedly associated with fatty liver disease. Although human PNPLA3 has triacylglycerol (TAG) hydrolase and transacylase activities in vitro, its in vivo function and physiological relevance remain controversial. The objective of this study was to determine the metabolic consequences of global targeted deletion of the Pnpla3 gene in mice. We found that Pnpla3 mRNA expression is altered in adipose tissue and liver in response to acute and chronic nutritional challenges. However, global targeted deletion of the Pnpla3 gene in mice did not affect TAG hydrolysis, nor did it influence energy/glucose/lipid homoeostasis or hepatic steatosis/injury. Experimental interventions designed to increase Pnpla3 expression (refeeding, high-sucrose diet, diet-induced obesity, and liver X receptor agonism) likewise failed to reveal differences in the above-mentioned metabolic phenotypes. Expression of the Pnpla3 paralog, Pnpla5, was increased in adipose tissue but not in liver of Pnpla3-deficient mice, but compensatory regulation of genes involved in TAG metabolism was not identified. Together these data argue against a role for Pnpla3 loss-of-function in fatty liver disease or metabolic syndrome in mice.

A depth profile of (239)Pu and (240)Pu specific activities and isotope ratios was determined in an inter-tidal sediment core from the Esk Estuary in the northeastern Irish Sea. The study site has been impacted with plutonium through routine radionuclide discharges from the Sellafield nuclear reprocessing plant in Cumbria, NW England. A pronounced sub-surface maximum of ~10 k Bq kg(-1) was observed for (239+240)Pu, corresponding to the peak in Pu discharge from Sellafield in 1973, with a decreasing trend with depth down to ~0.04 k Bq kg(-1) in the deeper layers. The depth profile of (239+240)Pu specific activities together with results from gamma-ray spectrometry for (137)Cs and (241)Am was compared with reported releases from the Sellafield plant in order to estimate a reliable sediment chronology. The upper layers (1992 onwards) showed higher (239+240)Pu specific activities than would be expected from the direct input of annual Sellafield discharges, indicating that the main input of Pu is from the time-integrated contaminated mud patch of the northeastern Irish Sea. The (240)Pu/(239)Pu atom ratios ranged from ~0.03 in the deepest layers to >0.20 in the sub-surface layers with an activity-weighted average of 0.181. The decreasing (240)Pu/(239)Pu atom ratio with depth reflects the changing nature of operations at the Sellafield plant from weapons-grade Pu production to reprocessing spent nuclear fuel with higher burn-up times in the late 1950s. In addition, recent annual (240)Pu/(239)Pu atom ratios in winkles collected during 2003-2008 from three stations along the Cumbrian coastline showed no significant spatial or temporal differences with an overall average of 0.204, which supports the hypothesis of diluted Pu input from the contaminated mud patch., (Copyright © 2011 Elsevier B.V. All rights reserved.)