LArPix: Demonstration of low-power 3D pixelated charge readout for liquid argon time projection chambers

We report the demonstration of a low-power pixelated readout system designed for three-dimensional ionization charge detection and digital readout of liquid argon time projection chambers (LArTPCs). Unambiguous 3D charge readout was achieved using a custom-designed system-on-a-chip ASIC (LArPix) to uniquely instrument each pad in a pixelated array of charge-collection pads. The LArPix ASIC, manufactured in 180 nm bulk CMOS, provides 32 channels of charge-sensitive amplification with self-triggered digitization and multiplexed readout at temperatures from 80 K to 300 K. Using an 832-channel LArPix-based readout system with 3 mm spacing between pads, we demonstrated low-noise ($<$500 e$^-$ RMS equivalent noise charge) and very low-power ($<$100 $\mu$W/channel) ionization signal detection and readout. The readout was used to successfully measure the three-dimensional ionization distributions of cosmic rays passing through a LArTPC, free from the ambiguities of existing projective techniques. The system design relies on standard printed circuit board manufacturing techniques, enabling scalable and low-cost production of large-area readout systems using common commercial facilities. This demonstration overcomes a critical technical obstacle for operation of LArTPCs in high-occupancy environments, such as the near detector site of the Deep Underground Neutrino Experiment (DUNE).Comment: 19 pages, 10 figures, 1 ancillary animation. V3 includes minor revisions based on referee comment

Fecal-Based Colorectal Cancer Screening Among the Uninsured in Northern Manhattan

Background Colorectal cancer (CRC) screening reduces CRC mortality; however, for many reasons, uninsured individuals are less likely to utilize CRC screening tests. Purpose To compare CRC screening behaviors and outcomes with guaiac fecal occult blood testing (gFOBT) from 1998 to 2006 and fecal immunochemical testing (FIT) from 2006 to 2010 in a community-based program serving uninsured patients in northern Manhattan. Methods In 2013, we conducted a retrospective record review of individuals aged ≥50 years who received fecal-based CRC screening at the Northern Manhattan Cancer Screening Partnership between 1998 and 2010. Included were those with household income ≤250% of the federal poverty level, no medical insurance coverage, and who were not up to date with CRC screening. We assessed screening positivity rate, positive predictive value, differences in the use of diagnostic colonoscopy, colonoscopic findings, and adenoma detection rates for gFOBT versus FIT. Results In total, 7,710 patients completed CRC screenings (4,951 gFOBT and 2,759 FIT). The majority were female, Hispanic, foreign born, and young at age of first screening. Compared to gFOBT, FIT detected twice as many positive tests (3.2% vs 1.5%, p≤0.001) and had a higher adenoma detection rate (18.2 vs 11.8, p=0.002). Conclusions The improved positivity and adenoma detection rates with greater number of screening tests over time favor the use of FIT over gFOBT for colorectal screening among uninsured populations in northern Manhattan

Familial association of abstinent remission from alcohol use disorder in first-degree relatives of alcohol-dependent treatment-seeking probands

Background and Aims Studies that have included family history of alcohol use disorder (AUD) as a predictor of remission from AUD have yielded few significant results. The goals of this study were to estimate the association of persistent AUD, non-abstinent remission and abstinent remission (‘AUD/remission status’) in a proband with AUD/remission status in a relative and to test whether this association differed in related and unrelated proband-relative pairs. Design High-risk family study of alcohol dependence. Probands were recruited from treatment settings and relatives were invited to participate. Baseline assessments occurred between 1991 and 1998 with follow-up between 1996 and 2005. Half of probands were matched with a biological 1st-degree relative with life-time AUD (related group) and half of probands were paired with an unrelated individual with life-time AUD (unrelated group). Setting Brooklyn, New York; Indianapolis, Indiana; Iowa City, Iowa; San Diego, California; Farmington, Connecticut; and St Louis, Missouri, USA. Participants A total of 606 probands (25.7% female, mean age 37.7) with baseline and follow-up data and 606 of their 1st-degree relatives who had life-ime AUDs (45.8% female, mean age 36.2 years). Measurements Persistent AUD, non-abstinent remission and abstinent remission were based on self-report interview data on most recent AUD symptoms and alcohol consumption. Dependent variable was relatives’ AUD/remission status. Independent variable was probands’ AUD/remission status. Findings A total of 34.6% of probands and 20.6% of relatives were abstinent and 11.1% of probands and 22.8% of relatives were in non-abstinent remission. AUD/remission status was correlated significantly in related (r = 0.23, P = 0.0037) but not in unrelated pairs. A significant interaction of probands’ abstinent remission with a variable representing related (versus unrelated, P = 0.003) pairs suggested a familial association for abstinent remission. In related pairs, individuals with an abstinent proband were more likely to be abstinent themselves than were individuals whose proband had persistent AUD [relative risk ratio = 3.27, 95% confidence interval (CI) = 1.56–6.85, P = 0.002]; this association was not significant in unrelated pairs. Conclusions The likelihood of abstinent remission among people with alcohol use disorder appears to be more than three times greater for individuals who are related to an abstinent proband versus those related to a proband with persistent alcohol use disorder

Focus Group Study of Diverse Local Populations and Their Health Care Experiences in Northeastern Pennsylvania: Cross-Cultural Issues

This investigation was conducted through the support of the College Misericordia Diversity Institute and a grant from the Blue Ribbon Foundation of Blue Cross of Northeastern Pennsylvania. Focus group participants were 49 adults from seven minority populations residing in northeastern Pennsylvania’s Luzerne and Lackawanna counties. Data was collected by 11 focus group leaders who were members of a Blue Ribbon Grant Core Committee at College Misericordia in 2004. The seven populations studied were African Americans, Arabic Muslims, Asian-Chinese and Korean, Gay and Lesbian, Hispanic, Jewish, and Asian Indian. A 30-question survey was used to collect data during one to two hour focus group interviews. Through content analysis, six problematic issues faced by many of the participants were identified. All of the findings were validated by a review process. The six issues faced by the 7 groups were: 1) Economics, Education, and Employment Influence Life for Newcomers, 2) Customs and Traditions Sometimes Sacrificed- The Influence of American Culture, 3) Socialization Often Limited to Same Population Group, 4) Mixed Acceptance Level from Area Natives, 5) Bilingual Challenges Impede Optimal Inclusion, 6) Health Care Access Problems. The aforementioned cross-groups study is explored in this report. The study also yielded seven other reports (one for each diverse population) which provide a description of that particular focus group’s perspective on topics such as religion, food, family, customs, and health care (see Appendices A, B, C, D, E, F, and G). Findings of this study are being disseminated in a local effort to educate health care professionals. Future research will be needed to determine if progress is being made in fulfilling the health care needs of all diverse populations living in Luzerne and Lackawanna County, as well as other parts of northeastern Pennsylvania

Risk Factors for Small-for-Gestational-age and Preterm Births among 19,269 Tanzanian Newborns.

Few studies have differentiated risk factors for term-small for gestational age (SGA), preterm-appropriate for gestational age (AGA), and preterm-SGA, despite evidence of varying risk of child mortality and poor developmental outcomes. We analyzed birth outcome data from singleton infants, who were enrolled in a large randomized, double-blind, placebo-controlled trial of neonatal vitamin A supplementation conducted in Tanzania. SGA was defined as birth weight <10th percentile for gestation age and sex using INTERGROWTH standards and preterm birth as delivery at <37 complete weeks of gestation. Risk factors for term-SGA, preterm-AGA, and preterm-SGA were examined independently using log-binomial regression. Among 19,269 singleton Tanzanian newborns included in this analysis, 68.3 % were term-AGA, 15.8 % term-SGA, 15.5 % preterm-AGA, and 0.3 % preterm-SGA. In multivariate analyses, significant risk factors for term-SGA included maternal age <20 years, starting antenatal care (ANC) in the 3(rd) trimester, short maternal stature, being firstborn, and male sex (all p < 0.05). Independent risk factors for preterm-AGA were maternal age <25 years, short maternal stature, firstborns, and decreased wealth (all p < 0.05). In addition, receiving ANC services in the 1(st) trimester significantly reduced the risk of preterm-AGA (p = 0.01). Significant risk factors for preterm-SGA included maternal age >30 years, being firstborn, and short maternal stature which appeared to carry a particularly strong risk (all p < 0.05). Over 30 % of newborns in this large urban and rural cohort of Tanzanian newborns were born preterm and/or SGA. Interventions to promote early attendance to ANC services, reduce unintended young pregnancies, increased maternal height, and reduce poverty may significantly decrease the burden of SGA and preterm birth in sub-Saharan Africa

Seasonal mixed layer depth shapes phytoplankton physiology, viral production, and accumulation in the North Atlantic

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Diaz, B. P., Knowles, B., Johns, C. T., Laber, C. P., Bondoc, K. G. V., Haramaty, L., Natale, F., Harvey, E. L., Kramer, S. J., Bolaños, L. M., Lowenstein, D. P., Fredricks, H. F., Graff, J., Westberry, T. K., Mojica, K. D. A., Haëntjens, N., Baetge, N., Gaube, P., Boss, E., Carlson, C. A., Behrenfeld, M. J., Van Mooy, B. A. S., Bidle, K. D. Seasonal mixed layer depth shapes phytoplankton physiology, viral production, and accumulation in the North Atlantic. Nature Communications, 12(1), (2021): 6634, https://doi.org/10.1038/s41467-021-26836-1.Seasonal shifts in phytoplankton accumulation and loss largely follow changes in mixed layer depth, but the impact of mixed layer depth on cell physiology remains unexplored. Here, we investigate the physiological state of phytoplankton populations associated with distinct bloom phases and mixing regimes in the North Atlantic. Stratification and deep mixing alter community physiology and viral production, effectively shaping accumulation rates. Communities in relatively deep, early-spring mixed layers are characterized by low levels of stress and high accumulation rates, while those in the recently shallowed mixed layers in late-spring have high levels of oxidative stress. Prolonged stratification into early autumn manifests in negative accumulation rates, along with pronounced signatures of compromised membranes, death-related protease activity, virus production, nutrient drawdown, and lipid markers indicative of nutrient stress. Positive accumulation renews during mixed layer deepening with transition into winter, concomitant with enhanced nutrient supply and lessened viral pressure.This work was made possible by NASA’s Earth Science Program in support of the North Atlantic Aerosol and Marine Ecosystem Study (15-RRNES15-0011 and 0NSSC18K1563 to K.D.B.; NNX15AF30G to M.J.B.), as well as with support from the National Science Foundation (OIA-2021032 to K.D.B., OCE-157943 to C.A.C., and OCE-1756254 to B.A.S.V.M.), the Gordon and Betty Moore Foundation (Award# 3789 to K.G.V.B.), and NASA’s Future Investigators in Space Science and Technology program (FINESST; grant #826380 to K.D.B.; graduate support to BD)

Seasonal Mixed Layer Depth Shapes Phytoplankton Physiology, Viral Production, and Accumulation In the North Atlantic

Seasonal shifts in phytoplankton accumulation and loss largely follow changes in mixed layer depth, but the impact of mixed layer depth on cell physiology remains unexplored. Here, we investigate the physiological state of phytoplankton populations associated with distinct bloom phases and mixing regimes in the North Atlantic. Stratification and deep mixing alter community physiology and viral production, effectively shaping accumulation rates. Communities in relatively deep, early-spring mixed layers are characterized by low levels of stress and high accumulation rates, while those in the recently shallowed mixed layers in late-spring have high levels of oxidative stress. Prolonged stratification into early autumn manifests in negative accumulation rates, along with pronounced signatures of compromised membranes, death-related protease activity, virus production, nutrient drawdown, and lipid markers indicative of nutrient stress. Positive accumulation renews during mixed layer deepening with transition into winter, concomitant with enhanced nutrient supply and lessened viral pressure

CYP2A6 metabolism in the development of smoking behaviors in young adults

Cytochrome P450 2A6 (CYP2A6) encodes the enzyme responsible for the majority of nicotine metabolism. Previous studies support that slow metabolizers smoke fewer cigarettes once nicotine dependent but provide conflicting results on the role of CYP2A6 in the development of dependence. By focusing on the critical period of young adulthood, this study examines the relationship of CYP2A6 variation and smoking milestones. A total of 1209 European American young adults enrolled in the Collaborative Study on the Genetics of Alcoholism were genotyped for CYP2A6 variants to calculate a previously well-validated metric that estimates nicotine metabolism. This metric was not associated with the transition from never smoking to smoking initiation nor with the transition from initiation to daily smoking (P > 0.4). But among young adults who had become daily smokers (n = 506), decreased metabolism was associated with increased risk of nicotine dependence (P = 0.03) (defined as Fagerström Test for Nicotine Dependence score ≥4). This finding was replicated in the Collaborative Genetic Study of Nicotine Dependence with 335 young adult daily smokers (P = 0.02). Secondary meta-analysis indicated that slow metabolizers had a 53 percent increased odds (OR = 1.53, 95 percent CI 1.11-2.11, P = 0.009) of developing nicotine dependence compared with normal metabolizers. Furthermore, secondary analyses examining four-level response of time to first cigarette after waking (>60, 31-60, 6-30, ≤5 minutes) demonstrated a robust effect of the metabolism metric in Collaborative Study on the Genetics of Alcoholism (P = 0.03) and Collaborative Genetic Study of Nicotine Dependence (P = 0.004), illustrating the important role of this measure of dependence. These findings highlight the complex role of CYP2A6 variation across different developmental stages of smoking behaviors

Clinical, environmental, and genetic risk factors for substance use disorders : characterizing combined effects across multiple cohorts

Substance use disorders (SUDs) incur serious social and personal costs. The risk for SUDs is complex, with risk factors ranging from social conditions to individual genetic variation. We examined whether models that include a clinical/environmental risk index (CERI) and polygenic scores (PGS) are able to identify individuals at increased risk of SUD in young adulthood across four longitudinal cohorts for a combined sample of N = 15,134. Our analyses included participants of European (N-EUR = 12,659) and African (N-AFR = 2475) ancestries. SUD outcomes included: (1) alcohol dependence, (2) nicotine dependence; (3) drug dependence, and (4) any substance dependence. In the models containing the PGS and CERI, the CERI was associated with all three outcomes (ORs = 01.37-1.67). PGS for problematic alcohol use, externalizing, and smoking quantity were associated with alcohol dependence, drug dependence, and nicotine dependence, respectively (OR = 1.11-1.33). PGS for problematic alcohol use and externalizing were also associated with any substance dependence (ORs = 1.09-1.18). The full model explained 6-13% of the variance in SUDs. Those in the top 10% of CERI and PGS had relative risk ratios of 3.86-8.04 for each SUD relative to the bottom 90%. Overall, the combined measures of clinical, environmental, and genetic risk demonstrated modest ability to distinguish between affected and unaffected individuals in young adulthood. PGS were significant but added little in addition to the clinical/environmental risk index. Results from our analysis demonstrate there is still considerable work to be done before tools such as these are ready for clinical applications.Peer reviewe

Whether weather matters: Evidence of association between in utero meteorological exposures and foetal growth among Indigenous and non-Indigenous mothers in rural Uganda

Pregnancy and birth outcomes have been found to be sensitive to meteorological variation, yet few studies explore this relationship in sub-Saharan Africa where infant mortality rates are the highest in the world. We address this research gap by examining the association between meteorological factors and birth weight in a rural population in southwestern Uganda. Our study included hospital birth records (n = 3197) from 2012 to 2015, for which we extracted meteorological exposure data for the three trimesters preceding each birth. We used linear regression, controlling for key covariates, to estimate the timing, strength, and direction of meteorological effects on birth weight. Our results indicated that precipitation during the third trimester had a positive association with birth weight, with more frequent days of precipitation associated with higher birth weight: we observed a 3.1g (95% CI: 1.0–5.3g) increase in birth weight per additional day of exposure to rainfall over 5mm. Increases in average daily temperature during the third trimester were also associated with birth weight, with an increase of 41.8g (95% CI: 0.6–82.9g) per additional degree Celsius. When the sample was stratified by season of birth, only infants born between June and November experienced a significant associated between meteorological exposures and birth weight. The association of meteorological variation with foetal growth seemed to differ by ethnicity; effect sizes of meteorological were greater among an Indigenous subset of the population, in particular for variation in temperature. Effects in all populations in this study are higher than estimates of the African continental average, highlighting the heterogeneity in the vulnerability of infant health to meteorological variation in different contexts. Our results indicate that while there is an association between meteorological variation and birth weight, the magnitude of these associations may vary across ethnic groups with differential socioeconomic resources, with implications for interventions to reduce these gradients and offset the health impacts predicted under climate change