Search

Abstract Objective Memory is one of the most sensitive markers of cognitive compromise in people with new‐onset epilepsy. Nonetheless, around half of these cases score within the normal range on standard memory testing. Here we explore whether memory retention at a 1‐week delay reveals otherwise undetected memory compromise in such individuals, and how it relates to subjective memory complaints and mood. Methods Using a prospective design, 38 adults with new‐onset epilepsy underwent baseline memory screening via telephone using an abbreviated Rey Auditory Verbal Learning Test (RAVLT). Psychological screening occurred via online questionnaires. One week later, without forewarning, participants completed three follow‐up memory tasks. Of particular focus, we explored longer‐term memory performances and forgetting trajectories in those individuals (n = 23) who demonstrated normal memory performances (scores >10th percentile) at baseline (30‐min delay). Outcomes were compared to 32 healthy controls, matched for age, sex, and education. Results As a group, people with epilepsy performed worse than controls on all memory measures, with 44 percent impaired at baseline testing. Of those unimpaired at baseline, the rate and volume of information loss over 1 week was significantly greater than for controls. Contextual memory performance at 1 week was also significantly poorer for people with epilepsy. At the individual level, the prevalence of impaired forgetting was not significantly different between patients and controls. Subjective memory complaints were not related to any objective tests but were strongly related to self‐reported mood and anxiety symptoms. Significance People with new‐onset epilepsy show reduced memory at short and extended intervals. For those showing normal memory at baseline, information does appear to be forgotten more quickly than in healthy controls, though the effect is not large. The findings indicate that while extended delay memory testing is not essential in all new epilepsy cases, it could provide useful information for particular individuals. Plain Language Statement Memory problems are common in people with epilepsy shortly after seizure onset, however, many individuals still show normal memory performances on standard neuropsychological testing. Through testing memory at an extended timepoint (1 week), our study found that on average, these individuals showed a slightly quicker rate of forgetting over a 1‐week period than people without a brain condition. Self‐reported memory complaints in people with new epilepsy were unrelated to their actual memory skills on testing at short and long timepoints but were rather linked to lower mood and quality of life.

Abstract Purpose Depression is prevalent in patients undergoing bariatric surgery (BSx). Long-term use of antidepressant is associated with weight gain, particularly the use of selective serotonin reuptake inhibitors (SSRIs). Little is known about whether different types of antidepressants affect the response to BSx. The purpose of this study was to determine the relationship between SSRI use and nutritional and biochemical measurements in those with obesity pre-/post-BSx. Methods This is a cross-sectional and prospective cohort study. Patients were enrolled pre-BSx and divided into 3 groups: SSRI, non-SSRI and no antidepressant. Nutritional, biochemical and pharmacological data were collected pre- and 6 months post-BSx. Results Pre-BSx, 77 patients were enrolled: 89.6% female, median age 45 years and body mass index (BMI) of 45.3 kg/m2. 14.3% were taking SSRIs and had a significantly higher BMI (52.1 kg/m2) compared to 62.3% in no antidepressant (46.0 kg/m2) and 23.4% in non-SSRI antidepressants (43.1 kg/m2). At 6 months post-BSx (n = 58), the SSRI group still had significantly higher BMI in comparison to the other two groups. No other significant differences found between groups. Conclusion Despite higher BMI, patients taking SSRI and undergoing BSx had similar responses, based on nutritional and biochemical parameters, to those on non-SSRI or no antidepressants. Level of evidence Level III: Evidence obtained from well-designed cohort or case–control analytic studies.

Abstract To mitigate climate change, some seek to store carbon from the atmosphere in agricultural soils. However, our understanding about how agriculture affects soil organic carbon is muddied by studies (1) lacking longitudinal data, (2) ignoring bulk density changes, or (3) sampling only surface soils. To better understand soil organic carbon trends, here we measured changes over 30 years in density-corrected, full-soil-depth (90 cm) soil organic carbon stocks under 6 cropping systems and a restored prairie in a Mollisol of southern Wisconsin, USA. Cash-grain systems and alfalfa-based systems lost soil organic carbon. Prairie and rotationally-grazed pasture maintained soil organic carbon. Average soil organic carbon losses for cash-grain and alfalfa-based systems were −0.80 (±0.12) and −0.54 (±0.13) Mg C ha−1 yr−1, respectively. Sensitivity analysis showed that incomplete methodologies overestimated soil organic carbon improvements. Our findings using more comprehensive methods demonstrate the inadequacy of row-crop systems and the need for well-managed grasslands to protect soil organic carbon in productive agricultural soils of the Upper Midwest USA.

Purpose Prospective, multicentric observational cohort study in Switzerland investigating measures to prevent mother-to-child transmission in pregnant women with HIV (WWH) and assessing health and development of their exposed children as well as of children with HIV (CWH) in general.Participants Between January 1986 and December 2022, a total of 1446 mother–child pairs were enrolled. During the same period, the study also registered 187 CWH and 521 HIV-exposed but uninfected children (HEU), for whom detailed maternal information was not available. Consequently, the cohort comprises a total of 2154 children.Findings to date During these 37 years, research by the Swiss Mother and Child HIV Cohort Study (MoCHiV) and its international collaborators has strongly influenced the prevention of vertical transmission of HIV (eg, introduction and discontinuation of elective caesarean section, neonatal postexposure prophylaxis and breastfeeding). Contributions have also been made to the management of diagnostics (eg, p24 antigen assay) and the effects of antiretroviral treatment (eg, prematurity, growth) in HEU and CWH.Future plans Most children present within the cohort are now HEU, highlighting the need to investigate other vertically transmitted pathogens such as hepatitis B and C viruses, cytomegalovirus or Treponema pallidum. In addition, analyses are planned on the longitudinal health status of CWH (eg, resistance and prolonged exposure to antiretroviral therapy), on social aspects including stigma in CWH and HEU, and on interventions to further optimise antenatal and postpartum care in WWH.

Abstract BackgroundYoung men who have sex with men and young transgender women (YMSM-YTW) use online spaces to meet sexual partners with increasing regularity, and research shows that experiences of racism online mimics the real world. ObjectiveWe analyzed differences by race and ethnicity in web-based and mobile apps used to meet sexual partners as reported by Chicago-based YMSM-YTW in 2016‐2017. MethodsA racially and ethnically diverse sample of 643 YMSM-YTW aged 16‐29 years were asked to name websites or mobile apps used to seek a sexual partner in the prior 6 months, as well as provide information about sexual partnerships from the same period. We used logistic regression to assess the adjusted association of race and ethnicity with (1) use of any website or mobile apps to find a sexual partner, (2) use of a “social network” to find a sexual partner compared to websites or mobile apps predominantly used for dating or hookups, (3) use of specific websites or mobile apps, and (4) reporting successfully meeting a sexual partner online among website or mobile app users. ResultsWhile most YMSM-YTW (454/643, 70.6%) used websites or mobile apps to find sexual partners, we found that Black non-Hispanic YMSM-YTW were significantly less likely to report doing so (comparing White non-Hispanic to Black non-Hispanic: adjusted odds ratio [aOR] 1.74, 95% CI 1.10‐2.76). Black non-Hispanic YMSM-YTW were more likely to have used a social network site to find a sexual partner (comparing White non-Hispanic to Black non-Hispanic: aOR 0.20, 95% CI 0.11‐0.37), though this was only reported by one-third (149/454, 32.8%) of all app-using participants. Individual apps used varied by race and ethnicity, with Grindr, Tinder, and Scruff being more common among White non-Hispanic YMSM-YTW (93/123, 75.6%; 72/123, 58.5%; and 30/123, 24.4%, respectively) than among Black non-Hispanic YMSM-YTW (65/178, 36.5%; 25/178, 14%; and 4/178, 2.2%, respectively) and Jack’d and Facebook being more common among Black non-Hispanic YMSM-YTW (105/178, 59% and 64/178, 36%, respectively) than among White non-Hispanic YMSM-YTW (6/123, 4.9% and 8/123, 6.5%, respectively). Finally, we found that while half (230/454, 50.7%) of YMSM-YTW app users reported successfully meeting a new sexual partner on an app, Black non-Hispanic YMSM-YTW app users were less likely to have done so than White non-Hispanic app users (comparing White non-Hispanic to Black non-Hispanic: aOR 2.46, 95% CI 1.50‐4.05). ConclusionsWe found that Black non-Hispanic YMSM-YTW engaged with websites or mobile apps and found sexual partners systematically differently than White non-Hispanic YMSM-YTW. Our findings give a deeper understanding of how racial and ethnic sexual mixing patterns arise and have implications for the spread of sexually transmitted infections among Chicago’s YMSM-YTW.

Abstract By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC+ mucus secretory cells, and that ITLN-1 protein is a secreted component of IL-13-induced mucus. Additionally, we find ITLN-1 protein binds the C-terminus of the MUC5AC mucin and that its deletion in airway epithelial cells partially reverses IL-13-induced mucostasis. Through analysis of nasal airway epithelial brushings, we find that ITLN1 is highly expressed in T2-high asthmatics, when compared to T2-low children. Furthermore, we demonstrate that both ITLN-1 gene expression and protein levels are significantly reduced by a common genetic variant that is associated with protection from the formation of mucus plugs in T2-high asthma. This work identifies an important biomarker and targetable pathways for the treatment of mucus obstruction in asthma.

Abstract Objective Epilepsy is a common and serious neurological disorder. This cross‐sectional analysis addresses the burden of epilepsy at different stages of the disease. Methods This pilot study is embedded within the Australian Epilepsy Project (AEP), aiming to provide epilepsy support through a national network of dedicated sites. For this analysis, adults aged 18–65 years with first unprovoked seizure (FUS), newly diagnosed epilepsy (NDE), or drug‐resistant epilepsy (DRE) were recruited between February–August 2022. Baseline clinicodemographic data were collected from the participants who completed questionnaires to assess their quality of life (QOLIE‐31, EQ‐5D‐5L), work productivity (Work Productivity and Activity Impairment [WPAI]), and care needs. Univariate analysis and multivariate regression was performed. Results 172 participants formed the study cohort (median age 34, interquartile range [IQR]: 26–45), comprising FUS (n = 44), NDE (n = 53), and DRE (n = 75). Mean QOLIE‐31 score was 56 (standard deviation [SD] ± 18) and median EQ‐5D‐5L score was 0.77 (IQR: 0.56–0.92). QOLIE‐31 but not EQ‐5D‐5L scores were significantly lower in the DRE group compared to FUS and NDE groups (p

Abstract Objective Neuropsychological comorbidities found in chronic epilepsy have also been reported earlier in the disease course. However, recurrent seizures, antiseizure medication (ASM), and adjustment to a chronic diagnosis remain potential confounds of this literature. It thus remains unclear whether these comorbidities are primary or secondary attributes of epilepsy. To capture individuals as close to disease onset as possible, we studied the cognitive and psychological functioning in adults after their first seizure, yet prior to epilepsy diagnosis and treatment. Methods Using a telehealth‐based prospective design, we screened cognition, mood, and anxiety symptoms in adult patients referred to a First Seizure Clinic (FSC), who were over 18 years, English‐speaking and not taking ASM. We screened cognition via telephone, and psychological symptoms via online questionnaires, all prior to the patients' diagnostic evaluation. Data were collected on 32 individuals subsequently diagnosed with epilepsy at the FSC, and 30 healthy controls from the community, who were matched to the epilepsy group for age, gender, and education. Results A multivariate analysis of variance revealed that the groups differed significantly on combined cognitive measures with a large effect size (F[1,56] = 5.75, p

Abstract Caspase-2, one of the most evolutionarily conserved members of the caspase family, is an important regulator of the cellular response to oxidative stress. Given that ferroptosis is suppressed by antioxidant defense pathways, such as that involving selenoenzyme glutathione peroxidase 4 (GPX4), we hypothesized that caspase-2 may play a role in regulating ferroptosis. This study provides the first demonstration of an important and unprecedented function of caspase-2 in protecting cancer cells from undergoing ferroptotic cell death. Specifically, we show that depletion of caspase-2 leads to the downregulation of stress response genes including SESN2, HMOX1, SLC7A11, and sensitizes mutant-p53 cancer cells to cell death induced by various ferroptosis-inducing compounds. Importantly, the canonical catalytic activity of caspase-2 is not required for its role and suggests that caspase-2 regulates ferroptosis via non-proteolytic interaction with other proteins. Using an unbiased BioID proteomics screen, we identified novel caspase-2 interacting proteins (including heat shock proteins and co-chaperones) that regulate cellular responses to stress. Finally, we demonstrate that caspase-2 limits chaperone-mediated autophagic degradation of GPX4 to promote the survival of mutant-p53 cancer cells. In conclusion, we document a novel role for caspase-2 as a negative regulator of ferroptosis in cells with mutant p53. Our results provide evidence for a novel function of caspase-2 in cell death regulation and open potential new avenues to exploit ferroptosis in cancer therapy.

Relapsing fever (RF), a vector-borne disease caused by Borrelia spp., is characterized by recurring febrile episodes due to repeated bouts of bacteremia. RF spirochetes can be geographically and phylogenetically divided into two distinct groups; Old World RF Borrelia (found in Africa, Asia, and Europe) and New World RF Borrelia (found in the Americas). While RF is a rarely reported disease in the Americas, RF is prevalent in endemic parts of Africa. Despite phylogenetic differences between Old World and New World RF Borrelia and higher incidence of disease associated with Old World RF spirochete infection, genetic manipulation has only been described in New World RF bacteria. Herein, we report the generation of genetic tools for use in the Old World RF spirochete, Borrelia duttonii. We describe methods for transformation and establish shuttle vector- and integration-based approaches for genetic complementation, creating green fluorescent protein (gfp)-expressing B. duttonii strains as a proof of principle. Allelic exchange mutagenesis was also used to inactivate a homolog of the Borrelia burgdorferi p66 gene, which encodes an important virulence factor, in B. duttonii and demonstrate that this mutant was attenuated in a murine model of RF. Finally, the B. duttonii p66 mutant was complemented using shuttle vector- and cis integration-based approaches. As expected, complemented p66 mutant strains were fully infectious, confirming that P66 is required for optimal mammalian infection. The genetic tools and techniques reported herein represent an important advancement in the study of RF Borrelia that allows for future characterization of virulence determinants and colonization factors important for the enzootic cycle of Old World RF spirochetes.

After decades of research, there are almost half a dozen efficiently pumped rare earth laser transitions in a fiber laser format capable of Watt-level output. These systems use near-IR laser diodes for excitation and have developed into reliable sources of high beam quality light with some commercially available. This maturation of the mid-IR fiber laser is entirely based on a high quality fluoride glass fiber, which has emerged as the primary fiber gain material for emission up to 4 µm. The other major mid-IR transparent glass families, the heavy metal oxides, and chalcogenides have always been challenged by consistent hydrogen diffusion into the glass that creates strong absorption features in the high-frequency portions of the mid-IR. This problem along with challenges to sufficiently concentrate the rare earth doping level has historically stifled progress preventing fiber laser emission in the mid-IR. In recent years, great efforts in precursor purification and reducing contamination during fabrication have resulted in pioneering demonstrations of mid-IR lasing using these glasses with emission now extending beyond 5 µm. As a result, mid-IR fiber laser research has entered a new era with more breakthroughs and applications to benefit from the efficiency potential, reliability, and relatively simple architecture of the optical fiber.

A subgroup of patients with atopic dermatitis (AD) suffers from recurrent, disseminated herpes simplex virus skin infection, termed eczema herpeticum. To determine the transcriptional mechanisms of the skin and immune system pathobiology that underlie development of AD with eczema herpeticum (ADEH), we performed RNA-sequencing analysis of nonlesional skin (epidermis, dermis) from AD patients with and without a history of ADEH (ADEH+, n = 15; ADEH−, n = 13) along with healthy controls (n = 15). We also performed RNA sequencing on participants’ plasmacytoid dendritic cells infected in vitro with herpes simplex virus 1. ADEH+ patients exhibited dysregulated gene expression, limited in the dermis (14 differentially expressed genes) and more widespread in the epidermis (129 differentially expressed genes). ADEH+-upregulated epidermal differentially expressed genes were enriched in type 2 cytokine (IL4R, CCL22, CRLF2, IL7R), interferon (CXCL10, ICAM1, IFI44, IRF7), and IL-36γ (IL36G) inflammatory gene pathways. All ADEH+ participants exhibited type 2 cytokine and inteferon endotypes, and 87% were IL36G-high. In contrast, these endotypes were more variably expressed among ADEH− participants. ADEH+ skin also had dysregulated epidermal differentiation complex gene expression of the late-cornified envelope, S100A, and small proline-rich gene families, which are involved in skin barrier function and antimicrobial activities. Plasmacytoid dendritic cell transcriptional responses to herpes simplex virus 1 infection were unaltered by ADEH status. The study concluded that the pathobiology underlying ADEH+ risk is associated with a unique, multifaceted epidermal inflammation that accompanies dysregulation of epidermal differentiation complex genes. These findings will help direct future studies that define how these inflammatory patterns may drive risk of eczema herpeticum in AD.

Abstract Background As interest in the voluntary soil carbon market surges, carbon registries have been developing new soil carbon measurement, reporting, and verification (MRV) protocols. These protocols are inconsistent in their approaches to measuring soil organic carbon (SOC). Two areas of concern include the type of SOC stock accounting method (fixed-depth (FD) vs. equivalent soil mass (ESM)) and sampling depth requirement. Despite evidence that fixed-depth measurements can result in error because of changes in soil bulk density and that sampling to 30 cm neglects a significant portion of the soil profile’s SOC stock, most MRV protocols do not specify which sampling method to use and only require sampling to 30 cm. Using data from UC Davis’s Century Experiment (“Century”) and UW Madison’s Wisconsin Integrated Cropping Systems Trial (WICST), we quantify differences in SOC stock changes estimated by FD and ESM over 20 years, investigate how sampling at-depth (> 30 cm) affects SOC stock change estimates, and estimate how crediting outcomes taking an empirical sampling-only crediting approach differ when stocks are calculated using ESM or FD at different depths. Results We find that FD and ESM estimates of stock change can differ by over 100 percent and that, as expected, much of this difference is associated with changes in bulk density in surface soils (e.g., r = 0.90 for Century maize treatments). This led to substantial differences in crediting outcomes between ESM and FD-based stocks, although many treatments did not receive credits due to declines in SOC stocks over time. While increased variability of soils at depth makes it challenging to accurately quantify stocks across the profile, sampling to 60 cm can capture changes in bulk density, potential SOC redistribution, and a larger proportion of the overall SOC stock. Conclusions ESM accounting and sampling to 60 cm (using multiple depth increments) should be considered best practice when quantifying change in SOC stocks in annual, row crop agroecosystems. For carbon markets, the cost of achieving an accurate estimate of SOC stocks that reflect management impacts on soils at-depth should be reflected in the price of carbon credits.

Abstract Alteration of basaltic glass and in situ mineral growth are fundamental processes that influence the chemical and material properties of Earth’s oceanic crust. These processes have evolved at the basaltic island of Surtsey (SW Iceland) since eruptions terminated in 1967. Here, subaerial and submarine lapilli tuff samples from a 192 m-deep borehole drilled in 2017 (SE-02b) are characterized through petrographic studies, X-ray powder diffraction analyses, and SEM–EDS imaging and chemical analyses. The integrated results reveal (i) multi-stage palagonitization processes in basaltic glass and precipitation of secondary minerals from matrix pore fluids, (ii) multi-stage crystallization of secondary phillipsite, analcime and Al-tobermorite in the vesicles of basaltic pyroclasts and (iii) variations in palagonitization processes as a function of thermal and hydrological domains. Although temperature appears to be an important factor in controlling rates of secondary mineralization, the chemistry of original basaltic components and interstitial fluids also influences reaction pathways in the young pyroclastic deposits. The integration of systematic mineralogical analyses of the 50-year-old tuff from one of the most carefully monitored volcanic sites on Earth, together with temperature monitoring in boreholes since 1980, provide a reference framework for evaluating mineralogical evolution in other Surtseyan-type volcanoes worldwide.

This paper details the design, development, and evaluation of a 3D-printed rechargeable Ag–AgCl electrode to measure self-potential (SP) in laboratory experiments. The challenge was to make a small, cheap, robust, and stable electrode that could be used in a wide range of applications. The new electrodes are shown to offer comparable performance to custom-machined laboratory standards, and the inclusion of 3D printing (fused filament fabrication or FFF and stereolithography or SLA) makes them more versatile and significantly less expensive – of the order of ×40 to ×75 cost reduction – to construct than laboratory standards. The devices are demonstrated in both low-pressure experiments using bead packs and high-pressure experiments using natural rock samples. Designs are included for both male and female connections to laboratory equipment. We report design drawings, practical advice for electrode printing and assembly, and printable 3D design files to facilitate wide uptake.

Grazing and hay forage crops reduce erosion compared to annual crops, but few studies have compared soil and nutrient loss among grazing systems compared to a control. We evaluated runoff water quality and nutrient loss among three grazing systems and a hay crop production field with manure application (control) using a paired watershed design. Four edge-of-field sites at a research farm in central Wisconsin were managed as hay during calibration (2013–2018) followed by a grazing treatment phase (2018–2020). Grazing treatments of different stocking methods included continuous stocking (CS), primary paddock stocking (PPS), and adaptive multi-paddock stocking (AMPS). Runoff, sediment, nitrogen (N), and phosphorus (P) loads were monitored year-round. Grazing increased average runoff volume by as much as 1.7-fold depending on stocking method and tended to decrease event mean N and P concentrations. CS had larger mean sediment (2.0-fold), total N (1.9-fold), and total P loads (1.2-fold) compared to the control and had the lowest average pasture forage mass. AMPS had lower N and P loss as a percentage of that applied from manure application/livestock excretion (1.3 and 1.6%, respectively) compared to the control (2.5 and 2.1%), PPS (2.5 and 2.6%), and CS (3.2 and 3.0%). Stocking method had a marked impact on nutrient loss in runoff from these systems, suggesting water quality models should account for pasture management, but nutrient losses from all perennial forage systems were small relative to previous data from annual cropping systems.

Abstract Tropical forests are a major component of the global carbon cycle and home to two‐thirds of terrestrial species. Upper‐canopy trees store the majority of forest carbon and can be vulnerable to drought events and storms. Monitoring their growth and mortality is essential to understanding forest resilience to climate change, but in the context of forest carbon storage, large trees are underrepresented in traditional field surveys, so estimates are poorly constrained. Aerial photographs provide spectral and textural information to discriminate between tree crowns in diverse, complex tropical canopies, potentially opening the door to landscape monitoring of large trees. Here we describe a new deep convolutional neural network method, Detectree2, which builds on the Mask R‐CNN computer vision framework to recognize the irregular edges of individual tree crowns from airborne RGB imagery. We trained and evaluated this model with 3797 manually delineated tree crowns at three sites in Malaysian Borneo and one site in French Guiana. As an example application, we combined the delineations with repeat lidar surveys (taken between 3 and 6 years apart) of the four sites to estimate the growth and mortality of upper‐canopy trees. Detectree2 delineated 65 000 upper‐canopy trees across 14 km2 of aerial images. The skill of the automatic method in delineating unseen test trees was good (F1 score = 0.64) and for the tallest category of trees was excellent (F1 score = 0.74). As predicted from previous field studies, we found that growth rate declined with tree height and tall trees had higher mortality rates than intermediate‐size trees. Our approach demonstrates that deep learning methods can automatically segment trees in widely accessible RGB imagery. This tool (provided as an open‐source Python package) has many potential applications in forest ecology and conservation, from estimating carbon stocks to monitoring forest phenology and restoration. Python package available to install at https://github.com/PatBall1/Detectree2.

Abstract Background Albuterol is the first-line asthma medication used in diverse populations. Although DNA methylation (DNAm) is an epigenetic mechanism involved in asthma and bronchodilator drug response (BDR), no study has assessed whether albuterol could induce changes in the airway epithelial methylome. We aimed to characterize albuterol-induced DNAm changes in airway epithelial cells, and assess potential functional consequences and the influence of genetic variation and asthma-related clinical variables. Results We followed a discovery and validation study design to characterize albuterol-induced DNAm changes in paired airway epithelial cultures stimulated in vitro with albuterol. In the discovery phase, an epigenome-wide association study using paired nasal epithelial cultures from Puerto Rican children (n = 97) identified 22 CpGs genome-wide associated with repeated-use albuterol treatment (p

The levels of mercury (Hg) were examined in the leg muscle of the crab Grapsus grapsus from five sites on four islands within the Galápagos archipelago. Mercury values obtained using a Milestone DMA 80 evo direct mercury analyzer varied both within and among sites. Total mercury concentrations (mg kg−1 dry weight) ranged from the lowest at a protected location at Isabela Island (0.06 ± 0.02) to the highest at the San Cristóbal urban location (2.04 ± 0.069). Crabs from South Plaza Island also had surprisingly high levels of mercury with a mean of 1.2 ± 0.6. Values from urban sites at Isabela Island and Academy Bay, Santa Cruz, had intermediate values. When converted to wet weight, crabs from both San Cristóbal and South Plaza were within or above the levels (0.3–0.5 mg kg−1 wet weight set by various government agencies) considered potentially harmful to human health if ingested. A lesser number of both oysters and barnacles were also analyzed for mercury at South Plaza and Academy Bay, and while the values were lower compared to the crabs, they followed the same pattern of elevated levels at South Plaza compared to Academy Bay. It is unclear as to whether the mercury comes from natural sources, such as volcanism, or anthropogenic causes.

Abstract In the Caribbean there is limited data on orthostatic hypertension (OHT) in elderly hypertensive patients with atherosclerotic disease who are at risk for cardiovascular events. The authors examined the association of antihypertensive classes of drugs with diastolic OHT in patients 60 year and older with hypertension and hyperlipidemia attending public primary care facilities. These relationships were evaluated in a cross‐sectional study of hypertensive hyperlipidemic older patients (n = 400) to determine orthostatic changes in blood pressure based on seated to standing measurements. OHT was defined as an increase in systolic blood pressure of ≥20 mm Hg and/or increase in diastolic blood pressure of ≥10 mm Hg upon orthostasis at 3 min. Patients were categorized based on their orthostatic blood pressure response: orthostatic normotensive (n = 200) and blood pressure dysregulated (n = 200) of which 168 were diastolic OHT. Multivariable logistic regression models were used to examine associations of antihypertensive classes and diastolic OHT. Renin‐angiotensin‐aldosterone‐system (RAAS) blockers were the most commonly prescribed (79.3%), followed by diuretics (DIUs) (61.6%), dihydropyridine calcium channel blockers (dCCBs) (53.8%), and beta‐blockers (BBs) (19.3%). Most normotensive (76.0%) and diastolic OHT (75.0%) patients were prescribed two or more antihypertensive medications. Pharmaceutical prescription of triple combination RAAS blockers + dCCBs + DIUs (OR, 0.55; 95% CI, 0.31–0.99) or RAAS blockers + dCCBs + BBs (OR, 0.23; 95% CI, 0.06–0.92) showed a protective effect of diastolic OHT in analyses adjusted for age, sex, sitting diastolic blood pressure, and comorbidities. Our study suggests prescription of triple combination antihypertensive drugs of RAAS blockers + dCCBs + DIUs or RAAS blockers + dCCBs + BBs may reduce the likelihood of diastolic OHT.

Abstract Tianeptine is an antidepressant drug approved for the treatment of major depressive disorder in countries other than the US. It is classified as an atypical tricyclic antidepressant and has shown potential benefits in addressing anxiety and irritable bowel disease. However, it is important to note that tianeptine is not approved for any use by the United States Federal Drug Administration (FDA). Despite its lack of approval by the FDA, tianeptine has been distributed online and at small retail locations. The term “gas station drugs” refers to a wide range of substances typically available for purchase from gas stations, corner stores, bodegas, mini marts, smoke shops, and the Internet. These substances may be produced commercially by drug manufacturers or in clandestine laboratories to mimic the effects of more well-known illicit/controlled substances such as marijuana, cocaine, opioids, etc. Tianeptine has made its way to convenience stores and gas station shelves, branded as “Zaza” and “Tianna Red.” It can also be obtained online from independent vendors without a prescription. Misuse of tianeptine can lead to euphoric, opioid-like highs with the potential for chronic users to develop dependence and tolerance. Overdose and use in suicide attempts have also been documented. This manuscript is a narrative review, highlighting the dangers of tianeptine and other gas station drugs and underscoring the urgent need to regulate these substances.

Abstract Purpose: Community inclusion in research may increase the quality and relevance of research, but doing so in an equitable way is complex. Novel approaches used to build engagement with historically marginalized communities in other sectors may have relevance in the clinical research sector. Method: To address long-standing gaps and challenges, a stakeholder group was convened to develop a theory of change (ToC), a structured method for obtaining input from stakeholders to enhance the design, conduct, and dissemination of research. The stakeholder group, comprised of Black residents within a metropolitan area, followed a structured monthly meeting schedule for 12 months to produce an outcome map, a model that formally defines aspects of research and engagement for this community. Results: Stakeholders reported significant improvements in trust in and engagement with research over the 12-month period, but not changes in health empowerment (individual, organizational, or community level). Through this convening process, a ToC and outcome map were developed with the focus of building bidirectional relationships between groups identifying as Black, Indigenous, and People of Color (BIPOC) and researchers in Boston, MA. Additionally, the group developed a community ownership model and guidelines for researchers to adhere to when utilizing the ToC and outcome map with BIPOC communities. Conclusion: Co-ownership of models to develop bidirectional relationships between researchers and community members, such as the ToC and outcome map, may advance and further the value and reach of community-based participatory research while increasing levels of trust and engagement in research.

More than half the global population burns biomass fuels for cooking and home heating, especially in low-middle income countries. This practice is a prominent source of indoor air pollution and has been linked to the development of a variety of cardiopulmonary diseases, including Tuberculosis (TB). The purpose of this cross-sectional study was to investigate the association between current biomass smoke exposure and self-reported quality of life scores in a cohort of previous TB patients in Uganda. We reviewed medical records from six TB clinics from 9/2019-9/2020 and conducted phone interviews to obtain information about biomass smoke exposure. A random sample of these patients were asked to complete three validated quality-of-life surveys including the St. Georges Respiratory Questionnaire (SGRQ), the EuroQol 5 Dimension 3 Level system (EQ-5D-3L) which includes the EuroQol Visual Analog Scale (EQ-VAS), and the Patient Health Questionnaire 9 (PHQ-9). The cohort was divided up into 3 levels based on years of smoke exposure-no-reported smoke exposure (0 years), light exposure (1-19 years), and heavy exposure (20+ years), and independent-samples-Kruskal-Wallis testing was performed with post-hoc pairwise comparison and the Bonferroni correction. The results of this testing indicated significant increases in survey scores for patients with current biomass exposure and a heavy smoke exposure history (20+ years) compared to no reported smoke exposure in the SGRQ activity scores (adj. p = 0.018) and EQ-5D-3L usual activity scores (adj. p = 0.002), indicating worse activity related symptoms. There was a decrease in EQ-VAS scores for heavy (adj. p = 0.007) and light (adj. p = 0.017) exposure groups compared to no reported exposure, indicating lower perceptions of overall health. These results may suggest worse outcomes or baseline health for TB patients exposed to biomass smoke at the time of treatment and recovery, however further research is needed to characterize the effect of indoor air pollution on TB treatment outcomes.

Despite federal regulations mandating the inclusion of underrepresented groups in research, recruiting diverse participants remains challenging. Identifying and implementing solutions to recruitment barriers in real time might increase the participation of underrepresented groups. Hence, the present study created a comprehensive dashboard of barriers to research participation. Barriers to participation were recorded in real time for prospective participants. Overall, 230 prospective participants expressed interest in the study but were unable to join due to one or more barriers. Awareness of the most common obstacles to research in real time will give researchers valuable data to meaningfully modify recruitment methods.

The spatial and frontal QRS-T angles are electrocardiographic (ECG) predictors for arrhythmia. This work used genetic analyses to identify associated loci and pathways, and explore their relationships with other ECG traits and cardiovascular disease.

Abstract Cannabidiol (CBD) is approved for treatment of seizures associated with two forms of epilepsy that become apparent in infancy or early childhood. To consider an adult physiologically‐based pharmacokinetic (PBPK) model for pediatric scaling, we assessed in vitro‐derived cytochrome P450 (CYP) and uridine 5′‐diphospho‐glucuronosyltransferase (UGT) enzyme contributions to CBD clearance in human. An i.v. PBPK model was constructed using CBD physicochemical properties and knowledge of disposition. The i.v. datasets were used for model building and evaluation. Oral PBPK models for CBD administered in fasted and fed states were developed using single dose oral datasets and parameters optimized from the i.v. model and evaluated with multiple dose datasets. Relative contributions of CBD metabolizing enzymes were partitioned according to in vitro studies. Clinical drug–drug interaction (DDI) studies were simulated using CBD fed state, itraconazole, fluconazole, and rifampicin PBPK models. Linear mixed effect modeling was used to estimate area under the concentration‐time curve from zero to infinity (AUC0–∞) perpetrator + CBD versus CBD alone. The i.v. and oral datasets used in model evaluation produced acceptable average fold error (AFE) of 1.28 and absolute AFE of 1.65. Relative contributions of drug‐metabolizing enzymes to CBD clearance were proposed from in vitro data: UGT1A7 4%, UGT1A9 16%, UGT2B7 10%, CYP3A4 38%, CYP2C19 21%, and CYP2C9 11%. The simulated DDI studies using the in vitro‐derived values produced AUC0–∞ treatment ratios comparable to observed: itraconazole 1.24 versus 1.07, fluconazole 1.45 versus 1.22, and rifampicin 0.49 versus 0.69. The constructed CBD PBPK models can predict adult exposures and have potential for use in pediatrics where exposure estimates are limited.

Cannabinoid use has surged in the past decade, with a growing interest in expanding cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) applications into special populations. Consequently, the increased use of CBD and THC raises the risk of drug–drug interactions (DDIs). Nevertheless, DDIs for cannabinoids, especially in special populations, remain inadequately investigated. While some clinical trials have explored DDIs between therapeutic drugs like antiepileptic drugs and CBD/THC, more potential interactions remain to be examined. This review summarizes the published studies on CBD and THC–drug interactions, outlines the mechanisms involved, discusses the physiological considerations in pharmacokinetics (PK) and DDI studies in special populations (including pregnant and lactating women, pediatrics, older adults, patients with hepatic or renal impairments, and others), and presents modeling approaches that can describe the DDIs associated with CBD and THC in special populations. The PK of CBD and THC in special populations remain poorly characterized, with limited studies investigating DDIs involving CBD/THC in these populations. Therefore, it is critical to evaluate potential DDIs between CBD/THC and medications that are commonly used in special populations. Modeling approaches can aid in understanding these interactions.

ABSTRACT Successful pathogens must be able to adapt to a multitude of stressors imposed by their host. Acinetobacter baumannii has emerged as a major global health threat due to its exceptional ability to adapt to hostile environments and skyrocketing rates of multidrug resistance. Recent studies have begun to explore the importance of tRNA methylation in the regulation of bacterial stress responses, including adaptation to antibiotic and oxidative stresses. However, tRNA methyltransferases (trms) have not been investigated in A. baumannii. Bioinformatic analyses revealed nine putative, SAM-dependent trms conserved across clinical A. baumannii isolates and laboratory strains. We generated eight trm mutants in a modern, colistin-resistant clinical isolate, ARC6851, and analyzed the mutants’ stress responses. One mutant, ΔtrmB, was vastly more sensitive to oxidative stress and displayed a growth defect at low pH. Accordingly, ΔtrmB was unable to replicate in J774A.1 macrophages and had decreased virulence in an acute pneumonia murine model. Subsequently, we showed that A. baumannii TrmB makes the m7G tRNA modification. A proteomic analysis revealed that ARC6851 significantly upregulates a siderophore biosynthesis and uptake cluster, acinetobactin, under oxidative stress. In contrast, the upregulation of the acinetobactin proteins in ΔtrmB was only modest, which impacted its ability to withstand iron deprivation under oxidative stress. qRT-PCR data showed that TrmB-dependent regulation of acinetobactin is post-transcriptional. Our results indicate that TrmB-mediated stress responses are important for A. baumannii pathogenesis, highlighting the therapeutic potential of targeting trms to combat the rise of multidrug-resistant A. baumannii. IMPORTANCE As deficiencies in tRNA modifications have been linked to human diseases such as cancer and diabetes, much research has focused on the modifications’ impacts on translational regulation in eukaryotes. However, the significance of tRNA modifications in bacterial physiology remains largely unexplored. In this paper, we demonstrate that the m7G tRNA methyltransferase TrmB is crucial for a top-priority pathogen, Acinetobacter baumannii, to respond to stressors encountered during infection, including oxidative stress, low pH, and iron deprivation. We show that loss of TrmB dramatically attenuates a murine pulmonary infection. Given the current efforts to use another tRNA methyltransferase, TrmD, as an antimicrobial therapeutic target, we propose that TrmB, and other tRNA methyltransferases, may also be viable options for drug development to combat multidrug-resistant A. baumannii.

Background: Sexual minority women (SMW) and transgender and/or nonbinary (TNB) individuals report an elevated prevalence of posttraumatic stress disorder (PTSD) symptoms and negative alcohol-related outcomes compared to heterosexual women and cisgender people. SMW and TNB individuals also face barriers to utilizing treatment, which can result in delayed or missed appointments. Accessible, feasible, and effective treatment approaches, such as web-based expressive writing (EW) treatments, are needed to address PTSD and negative alcohol-related outcomes in these populations. Method: We describe the design of a mixed-method pilot randomized controlled trial which will compare an EW treatment adapted for SMW and TNB people (stigma-adapted EW) and trauma (i.e., non-adapted) EW with an active (neutral-event) control to determine acceptability and feasibility of a future fully powered randomized controlled trial. The sample will include 150 trauma-exposed SMW and TNB individuals from across the United States who will be randomly assigned to stigma-adapted EW (n = 50), trauma EW (n = 50), or control (n = 50). Participants will be assessed before treatment, one-week after the first writing session, and three-months after the first writing session. This paper identifies steps for evaluating the acceptability and feasibility of the proposed study and determining changes in outcomes resulting from adapted and non-adapted EW treatments to inform refinements. This paper also highlights our strategy for testing theory-driven mediators and moderators of treatment outcomes. Conclusions: This mixed-method pilot trial will inform the first fully powered, self-administered, brief web-based treatment to reduce PTSD symptom severity and negative alcohol-related outcomes among trauma-exposed SMW and TNB individuals.

The increasing prevalence of stimulant use disorder (StUD) involving methamphetamine and cocaine has been a growing healthcare concern in the United States. Cocaine usage is associated with atherosclerosis, systolic and diastolic dysfunction, and arrhythmias. Furthermore, approximately one of every four MIs is cocaine-induced among patients aged 18 to 45. Methamphetamine use has been associated with nerve terminal damage in the dopaminergic system resulting in impaired motor function, cognitive decline, and co-morbid psychiatric disorders. Current treatment options for StUD are extremely limited, and there are currently no FDA-approved pharmacotherapies. Behavioral interventions are considered first-line treatment; however, in a recent meta-analysis comparing behavioral treatment options for cocaine, contingency management programs provided the only significant reduction in use. Current evidence points to the potential of various neuromodulation techniques as the next best modality in treating StUD. The most promising evidence thus far has been transcranial magnetic stimulation which several studies have shown to reduce risk factors associated with relapse. Another more invasive neuromodulation technique being studied is deep-brain stimulation, which has shown promising results in its ability to modulate reward circuits to treat addiction. Results showing the impact of transcranial magnetic stimulation (TMS) in the treatment of StUD are limited by the lack of studies conducted and the limited understanding of the neurological involvement driving addiction-based diseases such as StUD. Future studies should seek to provide data on consumption-reducing effects rather than craving evaluations.

Abstract Since the early 2010s, synthetic opioids have significantly contributed to overall opioid-related overdose mortalities. For point of reference, of the 68,630 opioid-related deaths recorded in 2020, 56,516 involved synthetic opioids. During much of this period, fentanyl has been the most commonly used synthetic opioid. This time when fentanyl was the most popular opioid has been called the “third wave” of the opioid crisis, partly because it led to a sharp rise in deaths from overdoses. Other synthetic opioids, such as carfentanil, protonitazene, and isotonitazene, have also become more widely diverted for nonmedical used. Carfentanil is an even more potent fentanyl derivative that was initially used in the mid-1980s as a general anesthetic for large animals such as elephants. Related to its strong affinity for mu opioid receptors, carfentanil is still utilized in medicine and science today as a radiotracer for positron emission tomography imaging. Protonitazene and isotonitazene belong to a novel class of synthetic opioids called benzimidazoles that were manufactured in the 1950s as novel analgesics. These agents have come under recent scrutiny as designer synthetic opioids becoming more prevalent. However, to date, there is incomplete data regarding the prevalence of synthetic opioids, as traditional toxicology screenings may not be sensitive to detect these compounds at such low doses post-mortem, particularly when blood is drawn from the periphery instead of central tissues such as the brain, lung, or heart. This narrative review aims to highlight the clinical challenges presented by these new synthetic opioids.

Abstract Ibrutinib is an orally administered Bruton's tyrosine kinase inhibitor approved for the treatment of B‐cell malignancies, including chronic lymphocytic leukemia. Ibrutinib is metabolized primarily via oxidation by cytochrome P450 (CYP) 3A4/5 to M37 (the primary active metabolite), M34, and M25. The objectives of this study were to assess the relationship between formation of the major CYP3A‐specific ibrutinib metabolites in vitro and hepatic CYP3A activity and protein abundance, and to evaluate the utility of the endogenous CYP3A biomarker, plasma 4β‐hydroxycholesterol (4β‐HC) to cholesterol ratio, to predict ibrutinib metabolite formation in individual cadaveric donors with matching hepatocytes. Ibrutinib (5 μM) was incubated with single‐donor human liver microsomes (n = 20) and primary human hepatocytes (n = 15), and metabolites (M37, M34, and M25) were measured by liquid chromatography‐tandem mass spectrometry analysis. CYP3A4/5 protein concentrations were measured by quantitative targeted absolute proteomics, and CYP3A activity was measured by midazolam 1′‐hydroxylation. Ibrutinib metabolite formation positively correlated with midazolam 1′‐hydroxylation in human liver microsomes and hepatocytes. Plasma 4β‐HC and cholesterol concentrations were measured in plasma samples obtained at the time of liver harvest from the same 15 donors with matching hepatocytes. Midazolam 1′‐hydroxylation in hepatocytes correlated with plasma 4β‐HC/cholesterol ratio. When an infant donor (1 year old) was excluded based on previous ontogeny studies, M37 and M25 formation correlated with plasma 4β‐HC/cholesterol ratio in the remaining 14 donors (Spearman correlation coefficients [r] 0.62 and 0.67, respectively). Collectively, these data indicate a positive association among formation of CYP3A‐specific ibrutinib metabolites in human hepatocytes, hepatic CYP3A activity, and plasma 4β‐HC/cholesterol ratio in the same non‐infant donors.

There is an unprecedented need for new treatments for renal failure, as the incidence of this disease is increasing disproportionately to advancements in therapies. Current treatments are limited by the availability of viable organs, for which there is a worldwide lack. These treatment modalities also require a substantial amount of infrastructure, significantly limiting the access to care in most countries. Kidney tissue engineering approaches promise to develop alternative solutions that address many of the inadequacies in current care. Although many advancements have been made—primarily in the past decade—in biofabrication and whole-organ tissue engineering, many challenges remain. One major hindrance to the progress of current tissue engineering approaches is establishing successful vascularization of developed engineered tissue constructs. This review focuses on the recent advancements that address the vascular challenge, including the biofabrication of vasculature, whole-organ engineering through decellularization and recellularization approaches, microscale organogenesis, and vascularization using organoids in the context of kidney tissue engineering. We also highlight the specific challenges that remain in developing successful strategies capable of clinical translation.

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.

ABSTRACT: This study aimed to understand the veterinary-client relationship and perspectives in organic dairy production systems. Twenty-three organic dairy producers and 12 veterinarians were interviewed using semi-structured, one-on-one interviews. Consultation with local veterinarians was typically infrequent, as there was greater reliance on other producers and organic industry professionals for advice on dairy herd health management, perhaps due to a shared focus on organic farming principles. Organic producers generally consulted local veterinarians most frequently to develop vaccine protocols, address animal health emergencies, and gain reproductive services. Common reasons organic producers cited for not regularly consulting a local veterinarian included the cost of veterinary services and a perception that local veterinarians have limited experience with organic systems and products. Some producers also expressed the idea that infrequent veterinarian usage is indicative of a healthy herd. Meanwhile, local veterinarians reported that organic dairy producers often delayed consulting them about individual cases until animal health problems were severe. Local veterinarians also identified challenges in servicing organic herds, such as the lack of standardized regulations between different organic certifiers and limited safety and efficacy data for many herd health products used by organic producers. In addition, their formal training generally did not include organic herd health strategies. Organic dairy clients were typically a small fraction of the overall workload for local veterinarians, which precluded their ability to accumulate experience. In contrast, a handful of specialized veterinarians in the organic milk processing industry work more frequently with organic producers and have published most of the available resource materials on organic dairy herd health. Veterinary-client partnerships could be improved through more open communication and discussion of the challenges identified in this study and through participatory research and outreach engagement that includes local veterinarians, organic certifiers, organic industry veterinarians, and producers.

The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease.

Monocytes are heterogeneous innate effector leukocytes generated in the bone marrow and released into circulation in a CCR2-dependent manner. During infection or inflammation, myelopoiesis is modulated to rapidly meet the demand for more effector cells. Danger signals from peripheral tissues can influence this process. Herein we demonstrate that repetitive TLR7 stimulation via the epithelial barriers drove a potent emergency bone marrow monocyte response in mice. This process was unique to TLR7 activation and occurred independently of the canonical CCR2 and CX3CR1 axes or prototypical cytokines. The monocytes egressing the bone marrow had an immature Ly6C-high profile and differentiated into vascular Ly6C-low monocytes and tissue macrophages in multiple organs. They displayed a blunted cytokine response to further TLR7 stimulation and reduced lung viral load after RSV and influenza virus infection. These data provide insights into the emergency myelopoiesis likely to occur in response to the encounter of single-stranded RNA viruses at barrier sites.

Few guidelines exist for the development of socially responsible health policy, and frameworks that balance considerations of data, strategy, and equity are limited. The Intersectionality-Based Policy Analysis (IBPA) framework utilizes a structured questioning process to consider problems and policies, while applying guiding principles of equity, social justice, power, intersectionality, and diversity of knowledge and input. We apply the IBPA framework’s guiding principles and questions to the pre-vaccine U.S. COVID-19 policy response. Results suggest the IBPA approach is a promising tool for integrating equity considerations in the development of policy solutions to urgent US public health challenges, including the COVID-19 pandemic. We found the IBPA framework particularly useful in differentiating between problems or policies and representations of problems or policies, and in considering the impacts of representations on different groups. The explicit inclusion of short-, medium- and long-term solutions is a reminder of the importance of holding a long-term vision of the equitable public health system we want while working towards immediate change.

# Background Men of African ancestry experience higher burden from prostate cancer compared to men of other ancestral backgrounds. Limitations in the availability of high-quality biospecimens hinder the inclusion of this population in genetic studies of prostate cancer. The use of formalin-fixed paraffin-embedded (FFPE) tissues represent a potential rich source of genetic material particularly in some international settings, where fresh frozen tissue is difficult to obtain. In this study, we investigate the feasibility of using FFPE biospecimens acquired from various international sites for utility in next-generation sequencing. # Methods A total of 976 FFPE blocks were collected between 2002 and 2017 from six international sites in Africa and the Caribbean representing three consortia: Prostate Cancer Transatlantic Consortium; African-Caribbean Cancer Consortium; and Men of African Descent and Carcinoma of the Prostate. Genomic DNA was checked for quality and quantity. Differences in mean quality control (QC) for pre-and-post pathology training were assessed using t-test. Pearson chi-square with trend analysis examined association between time-category and QC success status. Association of continuous DNA quality (Q129/Q41 ratio) and time of specimen collection was estimated with linear regression. Samples with a DNA quantity \>0.2µg and a Q129/Q41 ratio \>0.00225 were submitted for whole exome sequencing (WES). # Results There was a positive relative percentage change in DNA quantity from 2002 to 2017 for Jamaica, Kenya and Senegal. There was a decline in DNA quantity over the same time period for Nigeria. There was a statistically significant improvement in quality of samples from Kenya (*P*=0.032), Nigeria (*P*\

Summary: Background: Low rates of postnatal retention in HIV care and viral suppression have been reported in women living with HIV (WLWH) despite viral suppression at delivery. At the same time, postpartum follow-up is of crucial importance in light of the increasing support offered in many resource-rich countries including Switzerland to WLWH choosing to breastfeed their infant, if optimal scenario criteria are met. Methods: We longitudinally investigated retention in HIV care, viral suppression, and infant follow-up in a prospective multicentre HIV cohort study of WLWH in the optimal scenario who had a live birth between January 2000 and December 2018. Risk factors for adverse outcomes in the first year postpartum were assessed using logistic and proportional hazard models. Findings: Overall, WLWH were retained in HIV care for at least six months after 94.2% of the deliveries (694/737). Late start of combination antiretroviral therapy (cART) during the third trimester was found to be the main risk factor for failure of retention in HIV care (crude odds ratio [OR] 3.91; 95% confidence interval [CI], 1.50–10.22; p = 0.005). Among mothers on cART until at least one year after delivery, 4.4% (26/591) experienced viral failure, with illicit drugs use being the most important risk factor (hazard ratio [HR], 13.2; 95% CI, 2.35–73.6; p = 0.003). The main risk factors for not following the recommendations regarding infant follow-up was maternal depression (OR, 3.52; 95% CI, 1.18–10.52; p = 0.024). Interpretation: Although the results are reassuring, several modifiable risk factors for adverse postpartum outcome, such as late treatment initiation and depression, were identified. These factors should be addressed in HIV care of all WLWH, especially those opting to breastfeed in resource-rich countries. Funding: This study has been financed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (grant #201369), by SHCS project 850 and by the SHCS research foundation.

Alguns observáveis físicos, como o espectro de energia de um sistema quântico, não podem ser calculados de forma exata em problemas não triviais. Nesses casos, estes observáveis geralmente são obtidos por meio de uma série de potências de um parâmetro constante. Esse tipo de série geralmente é divergente, porém, se forem mantidos apenas alguns termos da série, o valor calculado estará razoavelmente de acordo com o valor medido experimentalmente. A questão é: como uma série infinita que não converge pode estar associada ao valor de uma grandeza física? A explicação para esta questão vem da teoria das transéries ressurgentes, que descreve expansões não perturbativas geradas por séries assintoticamente divergentes. Neste trabalho apresentaremos de maneira pedagógica a definição formal de série assintótica, o processo de soma de Borel para séries assintoticamente divergentes e o fenômeno de Stokes (que origina a transérie). Além disso, discutiremos um exemplo de transérie ressurgente que aparece no cálculo do espectro de energia não perturbativa de uma partícula confinada à potencial de poço duplo quântico.