Early childhood lower respiratory tract infection and premature adult death from respiratory disease in Great Britain: a national birth cohort study.

BACKGROUND: Lower respiratory tract infections (LRTIs) in early childhood are known to influence lung development and lifelong lung health, but their link to premature adult death from respiratory disease is unclear. We aimed to estimate the association between early childhood LRTI and the risk and burden of premature adult mortality from respiratory disease. METHODS: This longitudinal observational cohort study used data collected prospectively by the Medical Research Council National Survey of Health and Development in a nationally representative cohort recruited at birth in March, 1946, in England, Scotland, and Wales. We evaluated the association between LRTI during early childhood (age <2 years) and death from respiratory disease from age 26 through 73 years. Early childhood LRTI occurrence was reported by parents or guardians. Cause and date of death were obtained from the National Health Service Central Register. Hazard ratios (HRs) and population attributable risk associated with early childhood LRTI were estimated using competing risks Cox proportional hazards models, adjusted for childhood socioeconomic position, childhood home overcrowding, birthweight, sex, and smoking at age 20-25 years. We compared mortality within the cohort studied with national mortality patterns and estimated corresponding excess deaths occurring nationally during the study period. FINDINGS: 5362 participants were enrolled in March, 1946, and 4032 (75%) continued participating in the study at age 20-25 years. 443 participants with incomplete data on early childhood (368 [9%] of 4032), smoking (57 [1%]), or mortality (18 [<1%]) were excluded. 3589 participants aged 26 years (1840 [51%] male and 1749 [49%] female) were included in the survival analyses from 1972 onwards. The maximum follow-up time was 47·9 years. Among 3589 participants, 913 (25%) who had an LRTI during early childhood were at greater risk of dying from respiratory disease by age 73 years than those with no LRTI during early childhood (HR 1·93, 95% CI 1·10-3·37; p=0·021), after adjustment for childhood socioeconomic position, childhood home overcrowding, birthweight, sex, and adult smoking. This finding corresponded to a population attributable risk of 20·4% (95% CI 3·8-29·8) and 179 188 (95% CI 33 806-261 519) excess deaths across England and Wales between 1972 and 2019. INTERPRETATION: In this prospective, life-spanning, nationally representative cohort study, LRTI during early childhood was associated with almost a two times increased risk of premature adult death from respiratory disease, and accounted for one-fifth of these deaths. FUNDING: National Institute for Health and Care Research Imperial Biomedical Research Centre, Royal Brompton and Harefield National Health Service (NHS) Foundation Trust, Royal Brompton and Harefield Hospitals Charity and Imperial College Healthcare NHS Trust, UK Medical Research Council.

PhosPiR: an automated phosphoproteomic pipeline in R.

Large-scale phosphoproteome profiling using mass spectrometry (MS) provides functional insight that is crucial for disease biology and drug discovery. However, extracting biological understanding from these data is an arduous task requiring multiple analysis platforms that are not adapted for automated high-dimensional data analysis. Here, we introduce an integrated pipeline that combines several R packages to extract high-level biological understanding from large-scale phosphoproteomic data by seamless integration with existing databases and knowledge resources. In a single run, PhosPiR provides data clean-up, fast data overview, multiple statistical testing, differential expression analysis, phosphosite annotation and translation across species, multilevel enrichment analyses, proteome-wide kinase activity and substrate mapping and network hub analysis. Data output includes graphical formats such as heatmap, box-, volcano- and circos-plots. This resource is designed to assist proteome-wide data mining of pathophysiological mechanism without a need for programming knowledge.

Increased mortality in acromegaly is due to vascular and respiratory disease and is normalised by control of GH levels-A retrospective analysis from the UK Acromegaly Register 1970-2016.

CONTEXT: Epidemiological studies involving patients with acromegaly have yielded conflicting results regarding cancer incidence and causes of mortality in relation to control of growth hormone (GH) excess. OBJECTIVE: The objective of this retrospective cohort study is to clarify these questions and identify goals for treatment and monitoring patients. METHODS: We studied 1845 subjects from the UK Acromegaly Register (1970-2016), obtaining cancer standardised incidence rates (SIR) and all causes standardised mortality rates (SMR) from UK Office for National Statistics, to determine the relationship between causes of mortality-age at diagnosis, duration of disease, post-treatment and mean GH levels. RESULTS: We found an increased incidence of all cancers (SIR, 1.38; 95% CI: 1.06-1.33, p < .001), but no increase in incidence of female breast, thyroid, colon cancer or any measure of cancer mortality. All-cause mortality rates were increased (SMR, 1.35; 95% CI: 1.24-1.46, p < .001), as were those due to vascular and respiratory diseases. All-cause, all cancer and cardiovascular deaths were highest in the first 5 years following diagnosis. We found a positive association between post-treatment and mean treatment GH levels and all-cause mortality (p < .001 and p < .001), which normalised with posttreatment GH levels of <1.0 µg/L or meantreatment GH levels of <2.5 µg/L. CONCLUSION: Acromegaly is associated with increased incidence of all cancers but not thyroid or colon cancer and no increase in cancer mortality. Excess mortality is due to vascular and respiratory disease. The risk is highest in the first 5 years following diagnosis and is mitigated by normalising GH levels.

Long-term noise exposures and cardiovascular diseases mortality: A study in 5 U.S. states.

BACKGROUND: Previous studies have linked noise exposure with adverse cardiovascular events. However, evidence remains inconsistent, and most previous studies only focused on traffic noise, excluding other anthropogenic sources like constructions, industrial process and commercial activities. Additionally, few studies have been conducted in the U.S. or evaluated the non-linear exposure-response relationships. METHODS: We conducted a relative incidence analysis study using all cardiovascular diseases mortality as cases (n = 936,019) and external causes mortality (n = 232,491) as contrast outcomes. Mortality records geocoded at residential addresses were obtained from five U.S. states (Indiana, 2007; Kansas, 2007-2009, Missouri, 2010-2019, Ohio, 2007-2013, Texas, 2007-2016). Time-invariant long-term noise exposure was obtained from a validated model developed based on acoustical measurements across 2000-2014. Noises from both natural sources (natural activities, including animals, insects, winds, water flows, thunder, etc.) and anthropogenic sources (human activities, including transportation, industrial activities, community facilities & infrastructures, commercial activities, entertainments, etc.) were included. We used daytime and nighttime total anthropogenic noise & day-night average sound pressure level combining natural and anthropogenic sources as exposures. Logistic regression models were fit controlling for Census tract-level & individual-level characteristics. We examined potential modification by sex by interaction terms and potential non-linear associations by thin plate spline terms. RESULTS: We observed positive associations for daytime anthropogenic L50 (sound level exceeded 50% of time) noise (10-dBA OR = 1.047, 95%CI 1.025-1.069), nighttime anthropogenic L50 noise (10-dBA OR = 1.061, 95%CI 1.033-1.091) in a two-exposure-term model, and overall Ldn (day-night average) sound pressure level (10-dBA OR = 1.064, 95%CI 1.040-1.089) in single-exposure-term model. Females were more susceptible to all three exposures. All exposures showed monotonic positive associations with cardiovascular mortality up to certain thresholds around 45-55 dBA, with a generally flattened or decreasing trend beyond those thresholds. CONCLUSIONS: Both daytime anthropogenic and nighttime anthropogenic noises were associated with cardiovascular disease mortality, and associations were stronger in females.

The paradox of high greenness and poor health in rural Central Appalachia.

While many studies have found positive correlations between greenness and human health, rural Central Appalachia is an exception. The region has high greenness levels but poor health. The purpose of this commentary is to provide a possible explanation for this paradox: three sets of factors overwhelming or attenuating the health benefits of greenness. These include environmental (e.g., steep typography and limited access to green space used for outdoor recreation), social (e.g., chronic poverty, declining coal industry, and limited access to healthcare), and psychological and behavioral factors (e.g., perceptions about health behaviors, healthcare, and greenness). The influence of these factors on the expected health benefits of greenness should be considered as working hypotheses for future research. Policymakers and public health officials need to ensure that greenness-based interventions account for contextual factors and other determinants of health to ensure these interventions have the expected health benefits.

Cannabis use and its psychosocial correlates among school-going adolescents in Sierra Leone.

BACKGROUND: In Sierra Leone, adolescents are increasingly engaging in risky activities, including cannabis use, which can lead to substance abuse, poor academic performance, and psychotic symptoms. This study aims to investigate the prevalence and associated factors of cannabis use among school-going adolescents in the country. METHOD: Data for the study was sourced from the 2017 Sierra Leone Global School-based Student Health Survey (GSHS), a nationally representative survey conducted among adolescents aged 10-19 years using a multistage sampling methodology. A weighted sample of 1,467 adolescents in Sierra Leone was included in the study. The study utilised bivariate and multivariable logistic regression analysis to identify factors linked to cannabis use, presenting results using adjusted odds ratios and 95% confidence intervals. RESULTS: The prevalence of cannabis use was 5.1% [3.0,8.6] among school-going adolescents in Sierra Leone. School-going adolescents who attempted suicide [aOR = 6.34, 95% CI = 1.71-23.45], used amphetamine [aOR = 15.84, 95% CI = 7.94-31.62] and were involved in sexual risk behaviour [aOR = 5.56, 95% CI = 2.18-14.20] were more likely to be associated with cannabis use. CONCLUSION: In Sierra Leone, a small but non-trivial minority of students use cannabis. Ever-used amphetamines or methamphetamines, suicidal attempts, and sexual risk behaviour were the factors associated with cannabis use in Sierra Leone. The development of school-based health intervention programmes is crucial to address the risk factors associated with cannabis use among school-going adolescents.

A globally fragmented and mobile lithosphere on Venus.

Venus has been thought to possess a globally continuous lithosphere, in contrast to the mosaic of mobile tectonic plates that characterizes Earth. However, the Venus surface has been extensively deformed, and convection of the underlying mantle, possibly acting in concert with a low-strength lower crust, has been suggested as a source of some surface horizontal strains. The extent of surface mobility on Venus driven by mantle convection, however, and the style and scale of its tectonic expression have been unclear. We report a globally distributed set of crustal blocks in the Venus lowlands that show evidence for having rotated and/or moved laterally relative to one another, akin to jostling pack ice. At least some of this deformation on Venus postdates the emplacement of the locally youngest plains materials. Lithospheric stresses calculated from interior viscous flow models consistent with long-wavelength gravity and topography are sufficient to drive brittle failure in the upper Venus crust in all areas where these blocks are present, confirming that interior convective motion can provide a mechanism for driving deformation at the surface. The limited but widespread lithospheric mobility of Venus, in marked contrast to the tectonic styles indicative of a static lithosphere on Mercury, the Moon, and Mars, may offer parallels to interior-surface coupling on the early Earth, when global heat flux was substantially higher, and the lithosphere generally thinner, than today.

An ecosystem service perspective on urban nature, physical activity, and health.

Nature underpins human well-being in critical ways, especially in health. Nature provides pollination of nutritious crops, purification of drinking water, protection from floods, and climate security, among other well-studied health benefits. A crucial, yet challenging, research frontier is clarifying how nature promotes physical activity for its many mental and physical health benefits, particularly in densely populated cities with scarce and dwindling access to nature. Here we frame this frontier by conceptually developing a spatial decision-support tool that shows where, how, and for whom urban nature promotes physical activity, to inform urban greening efforts and broader health assessments. We synthesize what is known, present a model framework, and detail the model steps and data needs that can yield generalizable spatial models and an effective tool for assessing the urban nature-physical activity relationship. Current knowledge supports an initial model that can distinguish broad trends and enrich urban planning, spatial policy, and public health decisions. New, iterative research and application will reveal the importance of different types of urban nature, the different subpopulations who will benefit from it, and nature's potential contribution to creating more equitable, green, livable cities with active inhabitants.

Lower Risk of Revision With 32- and 36-Millimeter Femoral Heads Compared With 28-mm Heads in Primary Total Hip Arthroplasty: A Comparative Single-Center Study (10,104 Hips).

BACKGROUND: We aimed to compare the clinical outcomes of different head sizes (28-, 32-, and 36- millimeter) in primary total hip arthroplasty (THA) at mean 6 years follow-up (range, 1 to 17.5 years). METHODS: This was a retrospective consecutive study of primary THA at our institution (2003 to 2019). Demographic and surgical data were collected. The primary outcome measures were all-cause revision, revision for dislocation, and all-cause revision excluding dislocation. Continuous descriptive statistics used means, median values, ranges, and 95% confidence intervals, where appropriate. Kaplan-Meier survival curves were used to estimate time to revision. Cox proportional hazard regression analyses were used to compare revision rates between the femoral head size groups. Adjustments were made for age at surgery, sex, primary diagnosis, American Society of Anesthesiologists score, articulation type, and fixation methods. There were 10,104 primary THAs included; median age was 69 years (range, 13 to 101) with 61.5% women. A posterior approach was performed in 71.6%. There were 3,295 hips with 28-mm heads (32.6%), 4,858 (48.1%) with 32-mm heads, and 1,951 (19.3%) with 36-mm heads. RESULTS: Overall rate of revision was 1.7% with the lowest rate recorded for the 36-mm group (2.7 versus 1.3 versus 1.1%). Cox regression analyses showed a decreased risk of all-cause revision for 32 and 36-mm head sizes as compared to 28-mm; this was statistically significant for the 32-mm group (P = .01). Risk of revision for dislocation was significantly reduced in both 32-mm (P = .03) and 36-mm (P = .03) head sizes. Analysis of all cause revision excluding dislocation showed no significant differences between head sizes. CONCLUSIONS: We found a significantly reduced risk of revision for all causes, but particularly revision for dislocation with larger head sizes. Concerns regarding increased risk of early revision for aseptic loosening, polyethylene wear, or taper corrosion with larger heads appear to be unfounded in this cohort of 10,104 patients with up to 17 years follow-up.

Modeling Development of a Diamagnetically Stabilized Magnetically Levitated Gravimeter.

The aim of this work is to create a new type of gravimeter that can function effectively in the challenging conditions of space, specifically on the surfaces of planets and moons. The proposed device, called a diamagnetically stabilized magnetically levitated gravimeter (DSMLG), uses magnetic forces to balance a test mass against the force of gravity, allowing for accurate measurements. A diamagnetically stabilized levitation structure comprises a floating magnet, diamagnetic material, and a lifting magnet. The floating magnet levitates between two diamagnetic plates without the need for external energy input due to the interaction between the magnetic forces of the floating magnet and the stabilizing force of the diamagnetic material. This structure allows for stable levitation of the floating magnet without requiring additional energy. The goal is to design a gravimeter that is lightweight, requires minimal power, can withstand extreme temperatures and shocks, and has a low data rate. The authors envision this gravimeter being used on various robotic spacecraft, such as landers and rovers, to study the interiors of rocky and icy celestial bodies. This paper reports on the results of a finite element model analysis of the DSMLG and the strength of the resulting diamagnetic spring. The findings contribute to the understanding of the levitation characteristics of diamagnetically stabilized structures and provide valuable insights for their practical applications, including in the development of the proposed DSMLG.

Near-infrared spectroscopy (NIRS) for monitoring the nutritional composition of black soldier fly larvae (BSFL) and frass.

BACKGROUND: The demand for protein obtained from animal sources is growing rapidly, as is the necessity for sustainable animal feeds. The use of black soldier fly larvae (BSFL) reared on organic side streams as sustainable animal feed has been receiving attention lately. This study assessed the ability of near-infrared spectroscopy (NIRS) combined with chemometrics to evaluate the nutritional profile of BSFL instars (fifth and sixth) and frass obtained from two different diets, namely soy waste and customised bread-vegetable diet. Partial least squares (PLS) regression with leave one out cross-validation was used to develop models between the NIR spectral data and the reference analytical methods. RESULTS: Calibration models with good [coefficient of determination in calibration (Rcal 2 ): 0.90; ratio of performance to deviation (RPD) value: 3.6] and moderate (Rcal 2 : 0.76; RPD value: 2.1) prediction accuracy was observed for acid detergent fibre (ADF) and total carbon (TC), respectively. However, calibration models with moderate accuracy were observed for the prediction of crude protein (CP) (Rcal 2 : 0.63; RPD value: 1.4), crude fat (CF) (Rcal 2 : 0.70; RPD value: 1.6), neutral detergent fibre (NDF) (Rcal 2 : 0.60; RPD value: 1.6), starch (Rcal 2 : 0.52; RPD value: 1.4), and sugars (Rcal 2 : 0.52; RPD value: 1.4) owing to the narrow or uneven distribution of data over the range evaluated. CONCLUSION: The near-infrared (NIR) calibration models showed a good to moderate prediction accuracy for the prediction of ADF and TC content for two different BSFL instars and frass reared on two different diets. However, calibration models developed for predicting CP, CF, starch, sugars and NDF resulted in models with limited prediction accuracy. © 2023 Society of Chemical Industry.

Influence of Neighborhood Social and Natural Environment on Prostate Tumor Histology in a Cohort of Male Health Professionals.

Adverse neighborhood social and natural (green space) environments may contribute to the etiology of prostate cancer (CaP), but mechanisms are unclear. We examined associations between neighborhood environment and prostate intratumoral inflammation in 967 men diagnosed with CaP with available tissue samples from 1986-2009 in the Health Professionals Follow-up Study. Exposures were linked to work or residential addresses in 1988. We estimated indices of neighborhood socioeconomic status (nSES) and segregation (Index of Concentration at the Extremes (ICE)) using US Census tract-level data. Surrounding greenness was estimated using seasonal averaged Normalized Difference Vegetation Index (NDVI) data. Surgical tissue underwent pathological review for acute and chronic inflammation, corpora amylacea, and focal atrophic lesions. Adjusted odds ratios (aORs) for inflammation (ordinal) and focal atrophy (binary) were estimated using logistic regression. No associations were observed for acute or chronic inflammation. Each interquartile-range increase in NDVI within 1,230 m of the participant's work or home address (aOR = 0.74, 95% confidence interval (CI): 0.59, 0.93), in ICE-income (aOR = 0.79, 95% CI: 0.61, 1.04), and in ICE-race/income (aOR = 0.79, 95% CI: 0.63, 0.99) was associated with lower odds of postatrophic hyperplasia. Interquartile-range increases in nSES (aOR = 0.76, 95% CI: 0.57, 1.02) and ICE-race/income (aOR = 0.73, 95% CI: 0.54, 0.99) were associated with lower odds of tumor corpora amylacea. Histopathological inflammatory features of prostate tumors may be influenced by neighborhood.

Outdoor light at night and risk of endometrial cancer in the NIH-AARP diet and health study.

PURPOSE: Outdoor light at night (LAN) can result in circadian disruption and hormone dysregulation and is a suspected risk factor for some cancers. Our study is the first to evaluate the association between LAN and risk of endometrial cancer, a malignancy with known relationship to circulating estrogen levels. METHODS: We linked enrollment addresses (1996) for 97,677 postmenopausal women in the prospective NIH-AARP cohort to satellite imagery of nighttime radiance to estimate LAN exposure. Multivariable Cox models estimated hazard ratios (HR) and 95% confidence intervals (95% CI) for LAN quintiles and incident endometrial cancer overall (1,669 cases) and endometrioid adenocarcinomas (991 cases) through follow-up (2011). We tested for interaction with established endometrial cancer risk factors. RESULTS: We observed no association for endometrial cancer overall (HRQ1vsQ5 0.92; 95% CI 0.78-1.08; p trend = 0.67) or endometrioid adenocarcinoma (HRQ1vsQ5 1.01; 95% CI 0.82-1.24; p trend = 0.36). Although body mass index and menopause hormone therapy were both associated with risk, there was no evidence of interaction with LAN (p interactions = 0.52 and 0.50, respectively). CONCLUSION: Our study did not find an association between outdoor LAN and endometrial cancer risk, but was limited by the inability to account for individual-level exposure determinants. Future studies should consider approaches to improve characterization of personal exposures to light.

Neighborhood Conditions and Resources in Mid-Childhood and Dampness and Pests at Home in Adolescence.

OBJECTIVE: To examine prospectively associations of neighborhood opportunity with the presence of dampness or pests in the home environment during early adolescence. STUDY DESIGN: We geocoded residential addresses from 831 children (mean age 7.9 years, 2007-2011) in the Project Viva cohort. We linked each address with census tract-level Child Opportunity Index scores, which capture neighborhood conditions and resources influencing child heath including educational, health, environmental, and socioeconomic factors. Our primary outcome was presence of dampness or pests in the home in early adolescence (mean age 13.2 years, 2013-2016). Secondary outcomes included current asthma and lung function testing results. Mixed-effects regression models estimated longitudinal associations of Child Opportunity Index scores with outcomes, adjusting for individual and family sociodemographics. RESULTS: Children residing in neighborhoods with greater overall opportunity were less likely to live in homes with dampness or pests approximately 5 years later (aOR 0.85 per 20-unit increase in Child Opportunity Index percentile rank, 95% CI 0.73-0.998). We observed no significant associations in adjusted models of overall neighborhood opportunity with current asthma or lung function. Lower school poverty or single-parent households and greater access to healthy food or economic resource index were associated with lower odds of a home environment with dampness or pests. CONCLUSIONS: More favorable neighborhood conditions in mid-childhood were associated with lower likelihood of living in a home with dampness or pests in the early adolescence.

Measuring stigma associated with hepatitis B virus infection in Sierra Leone: Validation of an abridged Berger HIV stigma scale.

Stigma associated with hepatitis B virus (HBV) is common in endemic countries; however; instruments are lacking to accurately measure HBV-related stigma. We therefore aimed to develop and validate a concise instrument for measuring perceived HBV-related stigma in Sierra Leone. We enrolled 220 people living with HBV (PWHB) aged ≥18 years from August to November 2022. The initial Likert-scale instrument entailed 12 items adapted from Berger's HIV Stigma Scale. We included four additional items adapted from the USAID indicators for enacted stigma. The proposed scale's psychometric properties were assessed. After item reduction, the final HBV Stigma Scale consisted of 10 items and had good internal consistency (overall Cronbach's α = 0.74), discriminant, and construct validity. Exploratory factor analysis produced a three-dimensional structure accounting for 59.3% of variance: personalized stigma driven by public attitudes (six items), negative self-image (two items), and disclosure concerns (two items). Overall, 72.8% of respondents reported perceived HBV-related stigma (mean score 29.11 ± 4.14) and a similar proportion (73.6%) reported at least one instance of enacted stigma. In assessing criterion-related validity, perceived HBV-related stigma correlated strongly with enacted stigma (r = 0.556) and inversely with having family/friends with HBV (r = -0.059). The 10-item HBV Stigma Scale demonstrated good internal consistency and validity and is suitable for screening for HBV-related stigma in Sierra Leone. The psychometric properties of the scale can be optimized with item additions/modifications and confirmatory factor analysis. The scale may help in combating stigma as a barrier to achieving HBV global elimination goals.

Environmental Exposures and Anti-Müllerian Hormone: A Mixture Analysis in the Nurses' Health Study II.

BACKGROUND: Previous studies have linked environmental exposures with anti-Müllerian hormone (AMH), a marker of ovarian reserve. However, associations with multiple environment factors has to our knowledge not been addressed. METHODS: We included a total of 2,447 premenopausal women in the Nurses' Health Study II (NHSII) who provided blood samples during 1996-1999. We selected environmental exposures linked previously with reproductive outcomes that had measurement data available in NHSII, including greenness, particulate matter, noise, outdoor light at night, ultraviolet radiation, and six hazardous air pollutants (1,3-butadiene, benzene, diesel particulate matter, formaldehyde, methylene chloride, and tetrachloroethylene). For these, we calculated cumulative averages from enrollment (1989) to blood draw and estimated associations with AMH in adjusted single-exposure models, principal component analysis (PCA), and hierarchical Bayesian kernel machine regression (BKMR). RESULTS: Single-exposure models showed negative associations of AMH with benzene (percentage reduction in AMH per interquartile range [IQR] increase = 5.5%, 95% confidence interval [CI] = 1.0, 9.8) and formaldehyde (6.1%, 95% CI = 1.6, 10). PCA identified four major exposure patterns but only one with high exposure to air pollutants and light at night was associated with lower AMH. Hierarchical BKMR pointed to benzene, formaldehyde, and greenness and suggested an inverse joint association with AMH (percentage reduction comparing all exposures at the 75th percentile to median = 8.2%, 95% CI = 0.7, 15.1). Observed associations were mainly among women above age 40. CONCLUSIONS: We found exposure to benzene and formaldehyde to be consistently associated with lower AMH levels. The associations among older women are consistent with the hypothesis that environmental exposures accelerate reproductive aging.

A novel next-generation sequencing capture-based strategy to report somatic hypermutation status using genomic regions downstream to immunoglobulin rearrangements.

The somatic hypermutation (SHM) status of the clonotypic, rearranged immunoglobulin heavy variable (IGHV) gene is an established prognostic and predictive marker in chronic lymphocytic leukemia (CLL). Analysis of SHM is generally performed by polymerase chain reaction (PCR)-amplification of clonal IGHV-IGHD-IGHJ gene rearrangements followed by sequencing to identify IGHV gene sequences and germline identity. Targeted-hybridization next-generation sequencing (NGS) can simultaneously assess clonality and other genetic aberrations. However, it has limitations for SHM analysis due to sequence similarity between different IGHV genes and mutations introduced by SHM, which can affect alignment efficiency and accuracy. We developed a novel SHM assessment strategy using a targeted-hybridization NGS approach (EuroClonality- NDC assay) and applied it to 331 samples of lymphoproliferative disorder (LPD). Our strategy focuses on analyzing the sequence downstream to the clonotypic, rearranged IGHJ gene up to the IGHM enhancer (IGHJ-E) which provides more accurate alignment. Overall, 84/95 (88.4%) CLL cases with conventional SHM data showed concordant SHM status, increasing to 91.6% when excluding borderline cases. Additionally, IGHJ-E mutation analysis in a wide range of pre- and post-germinal center LPD showed significant correlation with differentiation and lineage status, suggesting that IGHJ-E analysis is a promising surrogate marker enabling SHM to be reported using NGS-capture strategies and whole genome sequencing.

Sabin polio virus protein 1 (VP1) evolution in patients with acute flaccid paralysis from 2010 to 2016 in Uganda.

Acute flaccid paralysis (AFP) is a rare side effect of the oral polio vaccine but can be associated with outbreaks and permanent disability in patients harboring circulating vaccine-derived polioviruses (cVDPVs). With the advancement of polio abolition in a glimpse, cVDPVs are causing outbreaks and slowing the polio eradication process. The polio virus protein 1 (VP1) contains the binding site that is key for virus transmission. Understanding the evolution of VP1 among AFP patients could yield more insight into the early events of cVDPVs. Polioviruses were identified from stool specimens of AFP patients using cell culture; and confirmed by the real time RT PCR intra-typic differentiation and vaccine-derived poliovirus assays. Seventy-nine (79) Sabin-like poliovirus 1 (SL1) and 86 Sabin-like poliovirus 3 (SL3) were sequenced. The VP1 amino acid substitutions T106A in Sabin poliovirus 1 and A54V in Sabin poliovirus 3 were common among the AFP patients as has been found in previous studies. Other substitutions that were associated with AFP were: T290A and A54T in SL1 and SL3 respectively. Nucleotide mutations that were common among the AFP patients included T402C, C670A, and T816C in SL1, and G22A, C375Y, A472R, and A694T in SL3 polioviruses. Characterizing mutations that are associated with AFP could contribute to efforts pursued to mitigate the risk of vaccine-derived polioviruses and promote development of safer vaccines.

Assessment of association between lower ureteric excision technique and oncological outcomes for upper urinary tract urothelial carcinoma: retrospective analysis from the Scottish Renal Cancer Consortium.

PURPOSE: Nephroureterectomy(NU) remains the gold-standard surgical option for the management of upper urinary tract urothelial carcinoma(UTUC). Controversy exists regarding the optimal excision technique of the lower ureter. We sought to compare post-UTUC bladder tumour recurrence across the Scottish Renal Cancer Consortium(SRCC). METHODS: Patients who underwent NU for UTUC across the SRCC 2012-2019 were identified. The impact of lower-end surgical technique along with T-stage, N-stage, tumour location and focality, positive surgical margin, pre-NU ureteroscopy, upper-end technique and adjuvant mitomycin C administration were assessed by Kaplan-Meier and Cox-regression. The primary outcome was intra-vesical recurrence-free survival (B-RFS). RESULTS: In 402 patients, the median follow-up was 29 months. The lower ureter was managed by open transvesical excision in 90 individuals, transurethral and laparoscopic dissection in 76, laparoscopic or open extra-vesical excision in 31 and 42 respectively, and transurethral dissection and pluck in 163. 114(28.4%) patients had a bladder recurrence during follow-up. There was no difference in B-RFS between lower-end techniques by Kaplan-Meier (p = 0.94). When all factors were taken into account by adjusted Cox-regression, preceding ureteroscopy (HR 2.65, p = 0.001), lower ureteric tumour location (HR 2.16, p = 0.02), previous bladder cancer (HR 1.75, p = 0.01) and male gender (HR 1.61, p = 0.03) were associated with B-RFS. CONCLUSION: These data suggest in appropriately selected patients, lower ureteric management technique does not affect B-RFS. Along with lower ureteric tumour location, male gender and previous bladder cancer, preceding ureteroscopy was associated with a higher recurrence rate following NU, and the indication for this should be carefully considered.

Sleep and Happiness in Urban-Dwelling Older Adults in Ghana: A Serial Multiple Mediation Model of Generalized Anxiety and Depressive Symptoms.

OBJECTIVE: Sleep problems (SP) are highly prevalent and seriously affect health and well-being in old age. The aim of this study was to examine the association between SP and happiness in an urban-dwelling older sample. The authors further explore the effects of generalized anxiety and depressive symptoms in the SP-happiness link using serial mediating modeling. METHODS: Data came from the 2016 to 2018 Aging, Health, Psychological Well-being, and Health-seeking Behavior Study in Ghana (n = 661). The authors measured happiness with the cross-culturally validated item on a five-point scale. The GAD-7 and the CESD-8, respectively, assessed generalized anxiety and depressive symptoms. Participants reported nighttime and daytime SP in the last 30 days. The SPSS-based Hayes' PROCESS macro program (Model 6) was constructed to quantify the hypothesized mediation effect. RESULTS: The analysis included 661 adults aged greater than or equal to 50 years (mean age = 65.53 [SD] = 11.89 years; 65.20% women). After full adjustment, path models showed that SP was negatively associated with happiness (ß = -0.1277, 95%CI = -0.15950 to -0.096). Bootstrapping estimates revealed that the SP-happiness link was serially mediated via generalized anxiety representing 8.77%, depressive symptoms yielding 18.95%, and anxiety symptoms→depressive symptoms accounting for 26.70% of the total effect. CONCLUSION: Generalized anxiety and depressive symptoms may explain the negative association between SP and happiness in urban-dwelling older adults in the sub-Saharan African (SSA) context. Interventions, social and clinical, to improve happiness through sleep quality should include ways to improve mental health. Longitudinal and cross-cultural data are warranted to assess the bi-directionality of this relationship.