Description and Cross-Sectional Analyses of 25,880 Adults and Children in the UK National Registry of Rare Kidney Diseases Cohort.

Introduction: The National Registry of Rare Kidney Diseases (RaDaR) collects data from people living with rare kidney diseases across the UK, and is the world's largest, rare kidney disease registry. We present the clinical demographics and renal function of 25,880 prevalent patients and sought evidence of bias in recruitment to RaDaR. Methods: RaDaR is linked with the UK Renal Registry (UKRR, with which all UK patients receiving kidney replacement therapy [KRT] are registered). We assessed ethnicity and socioeconomic status in the following: (i) prevalent RaDaR patients receiving KRT compared with patients with eligible rare disease diagnoses receiving KRT in the UKRR, (ii) patients recruited to RaDaR compared with all eligible unrecruited patients at 2 renal centers, and (iii) the age-stratified ethnicity distribution of RaDaR patients with autosomal dominant polycystic kidney disease (ADPKD) was compared to that of the English census. Results: We found evidence of disparities in ethnicity and social deprivation in recruitment to RaDaR; however, these were not consistent across comparisons. Compared with either adults recruited to RaDaR or the English population, children recruited to RaDaR were more likely to be of Asian ethnicity (17.3% vs. 7.5%, P-value < 0.0001) and live in more socially deprived areas (30.3% vs. 17.3% in the most deprived Index of Multiple Deprivation (IMD) quintile, P-value < 0.0001). Conclusion: We observed no evidence of systematic biases in recruitment of patients into RaDaR; however, the data provide empirical evidence of negative economic and social consequences (across all ethnicities) experienced by families with children affected by rare kidney diseases.

Cost-effectiveness of intervention combinations towards the elimination of vertical transmission of HIV in limited-resource settings: a mathematical modelling study.

BACKGROUND: Since 2000, there has been a substantial global reduction in the vertical transmission of HIV. Despite effective interventions, gaps still remain in progress towards elimination in many low-income and middle-income countries. We developed a mathematical model to determine the most cost-effective combinations of interventions to prevent vertical transmission. METHODS: We developed a 12-month Markov model to follow a cohort of women of childbearing age (aged 15-49 years) in Zambia (n=1 107 255) who were either pregnant, in delivery, or breastfeeding; the population included in the model reflects the estimated number of pregnant women in Zambia from the 2018 Zambia Demographic and Health Survey. The model incorporated nine interventions: infant prophylaxis; three different HIV retesting schedule options; oral pre-exposure prophylaxis; maternal peer-support groups; regimen shift; tracing of loss to follow-up; and point-of-care viral load testing. We analysed incident HIV infections among mothers and infants, intervention costs, and evaluated 190 scenarios of different combinations of inventions to calculate the incremental cost-effectiveness ratios (ICERs) over 1 year. FINDINGS: Three interventions with the greatest reduction in vertical transmission, individually, were support groups for 80% of those in need (35% reduction in infant infections), HIV retesting schedules (6·5% reduction), and infant prophylaxis (4·5% reduction). Of all 190 scenarios evaluated, eight were on the cost-effectiveness frontier (ie, were considered to be cost-effective); all eight included increasing infant prophylaxis, regimen shift, and use of support groups. Excluding the highest-cost scenarios, for a 1-22% increase in total budget, 23-43% of infant infections could be prevented, producing ICERs between US$244 and $16 242. INTERPRETATION: Using the interventions modelled, it is possible to reduce vertical transmission and to cost-effectively prevent up to 1734 infant HIV infections (43% reduction) in Zambia over a period of 1 year. To optimise their effect, these interventions must be scaled with fidelity. Future work is needed to incorporate evidence on additional innovative interventions and HIV risk factors, and to apply the model to other country contexts to support targeted implementation and resource use. FUNDING: The ELMA Foundation.

Anidulafungin Levels in Breast Milk After Cessation of Treatment: A Case Report.

Background: Anidulafungin has poor oral bioavailability, with hardly any available information on how it affects breast milk, oral absorption, or gastrointestinal side effects in the infant. Case Presentation: A 40-year-old woman who recently gave birth to a healthy infant was treated for a period of 14 days for a Candida glabrata with 100 mg anidulafungin once a day. The department of clinical pharmacy was consulted to provide advice on how long the patient had to wait after ceasing anidulafungin before it was safe to start breastfeeding, with regard to preventing possible side effects of the drug to the infant, such as diarrhea or cholestasis and increase in liver enzyme values. The advice of the hospital pharmacist was pragmatic: to start breastfeeding within 2 days after the medication was discontinued based on half-time. Results: Owing to this lack of information, we measured anidulafungin concentrations in breast milk and found low levels. Conclusion: We concluded that anidulafungin is detectable in breast milk until 32 hours after anidulafungin treatment was stopped, and that no side effects were observed by the infant.

Computed tomography analysis of the anterior epitympanic recess and sinus tympani depths Among Filipino adults at the De La Salle University Medical Center

Objective@#To assess the depths of the anterior epitympanic recess (AER) and the sinus tympani (ST) among Filipino adults and to classify the AER and ST according to grade and type, respectively.@*Methods@#Design:Retrospective Review of CT ScansSetting:Tertiary Private Teaching Hospital Participants: Scans of 182 non-pathologic ears from patients aged 18 and above with non-pathologic temporal bones (paranasal sinus, screening sinus, temporal bone, facial and cranial) with 0.62mm cuts seen from CT scans from January 01, 2010 to September 31, 2022 were analyzed. The depths of the AER and ST were measured separately and classified according to AER grade and ST type.@*Results@#The mean depth of the AER (AER-D) was 3.64 mm (SD 1.17). No significant difference was seen between right and left ears. The AER grading of the anterior-posterior depth was found to be Grade 1 (<3mm) in 54 ears (29.7%), Grade 2 (3-5mm) in 106 ears (58.2%), and Grade 3 (>5mm) in 22 ears (12.1%). The mean depth of the sinus tympani (ST-D) was 3.30 mm (SD 0.80). Out of the 182 ears, 121 (66.5%) had Type A, 50 (27.5%) had Type B while 11 (6%) had Type C.@*Conclusion@#Majority of the AER depths measured 3-5mm while most of the sinus tympani were Type A. These hidden recesses should be separately analyzed in preoperative planning for cholesteatoma surgery in order to prepare the adequate equipment to be used and approach towards these areas thereby reducing the risk for residual cholesteatomas and recurrence.

Implementing an APRN-Led Integrated Behavioral Health Clinic in a Rural Community.

OBJECTIVE: A rural primary care clinic implemented an advance practice providers, including nurse practitioner (APRN)-led integrated behavioral health program to facilitate holistic health care delivery. METHODS: Implementation was facilitated by Health Resources and Services Administration Grant funding to a state University College of Nursing. The College formed an academic-practice partnership with a Federally Qualified Health Center (FQHC) to implement integrated care in a rural satellite clinic administered by the FQHC. An interdisciplinary team (two family APRNs, a psychiatric APRN, a licensed behavioral health provider, and the Grant Project Director who is a Psychiatric APRN and a licensed Psychologist) provided the integrated care based on the University of Washington's Collaborative Care Model. RESULTS: This brief report describes the implementation of integrated care during the clinic's first year, services provided, lessons learned, community response, and improvement in anxiety and depressive symptoms for patients who were treated for behavioral health problems. An exemplar illustrates how collaborative care addressed one patient's behavioral health and primary care needs. CONCLUSIONS: APRN-led collaborative care can expand access to holistic, affordable care in rural areas to improve mental health. Adaptation and flexibility in traditional roles may be necessary and determining post-grant access to funding for services will be necessary for sustainability.

Improving Integrated Mental Health Care Through an Advanced Practice Registered Nurse-Led Program: Challenges and Successes.

Integrated and collaborative care delivery models have demonstrated efficacy for the management of psychiatric conditions in the primary care environment, yet organizations struggle with implementation of integrated efforts in clinical practice. Delivering care with a population focus versus face-to-face encounters with individual patients requires financial investment and adjustment in care delivery. We discuss the early implementation process of an advanced practice registered nurse (APRN)-led integrated behavioral health care program, including the challenges, barriers, and successes in the first 9 months of the program (January-September 2021), for an academic institution in the Midwest. A total of 161 Patient Health Questionnaire 9 (PHQ-9) and 162 Generalized Anxiety Disorder (GAD-7) rating scales were completed on 86 patients. The mean PHQ-9 score at the initial visit was 11.3 (moderate depression); after 5 visits, it decreased significantly to 8.6 (mild depression) (P < .001). The mean GAD-7 score at the initial visit was 10.9 (moderate anxiety); after 5 visits, it decreased significantly to 7.6 (mild anxiety) (P < .001). A survey completed by 14 primary care physicians 9 months after program launch revealed improvements in satisfaction with collaboration but, most notably, in perception of access to and overall satisfaction with behavioral health consultation/patient care services. Program challenges included adapting the environment to enhance leadership roles for the program and adjusting to virtual availability of psychiatric support. A case example highlights the value of integrated care along with improved depression and anxiety-related outcomes. Next steps should include efforts that capitalize on nursing leadership strengths while also promoting equity among integrated populations.

Reduced C9orf72 expression exacerbates polyGR toxicity in patient iPSC-derived motor neurons and a Type I protein arginine methyltransferase inhibitor reduces that toxicity.

Introduction: Intronic repeat expansions in the C9orf72 gene are the most frequent known single genetic causes of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). These repeat expansions are believed to result in both loss-of-function and toxic gain-of-function. Gain-of-function results in the production of toxic arginine-rich dipeptide repeat proteins (DPRs), namely polyGR and polyPR. Small-molecule inhibition of Type I protein arginine methyltransferases (PRMTs) has been shown to protect against toxicity resulting from polyGR and polyPR challenge in NSC-34 cells and primary mouse-derived spinal neurons, but the effect in human motor neurons (MNs) has not yet been explored. Methods: To study this, we generated a panel of C9orf72 homozygous and hemizygous knockout iPSCs to examine the contribution of C9orf72 loss-of-function toward disease pathogenesis. We differentiated these iPSCs into spinal motor neurons (sMNs). Results: We found that reduced levels of C9orf72 exacerbate polyGR15 toxicity in a dose-dependent manner. Type I PRMT inhibition was able to partially rescue polyGR15 toxicity in both wild-type and C9orf72-expanded sMNs. Discussion: This study explores the interplay of loss-of-function and gain-of-function toxicity in C9orf72 ALS. It also implicates type I PRMT inhibitors as a possible modulator of polyGR toxicity.

Burden of Chronic Obstructive Pulmonary Disease Attributable to Tuberculosis: A Microsimulation Study.

Tuberculosis (TB) is a risk factor for chronic obstructive pulmonary disease (COPD), but COPD is also a predictor of TB. The excess life-years lost to COPD caused by TB can potentially be saved by screening for and treating TB infection. We examined the number of life-years that could be saved by preventing TB and TB-attributable COPD. We compared the observed (no intervention) and counterfactual microsimulation models constructed from observed rates in the Danish National Patient Registry (covering all Danish hospitals between 1995 and 2014). In the Danish population of TB and COPD-naive individuals (n = 5,206,922), 27,783 persons (0.5%) developed TB. Among those who developed TB, 14,438 (52.0%) developed TB with COPD. Preventing TB saved 186,469 life-years overall. The excess number of life-years lost to TB alone was 7.07 years per person, and the additional number of life-years lost among persons who developed COPD after TB was 4.86 years per person. The life-years lost to TB-associated COPD are substantial, even in regions where TB can be expected to be identified and treated promptly. Prevention of TB could prevent a substantial amount of COPD-related morbidity; the benefit of screening and treatment for TB infection is underestimated by considering morbidity from TB alone.

Screening for pediatric behavioral health in primary care in rural and urban clinics.

INTRODUCTION: The prevalence of behavioral health disorders in children is approximately 15%-20%, yet less than half of the children ever receive treatment for these conditions. The lack of access to behavioral health care is common in urban areas but even more difficult to access in rural areas. Screening for behavioral health in a primary care setting is one of the first strategies to reduce this problem and improve access to care. The primary goal of this study was to examine behavioral health screening practices of pediatric primary care providers in a rural midwestern state. METHOD: A survey that queried family practice/internal medicine and pediatric providers who provide care to pediatric patients was delivered to over 300 primary care providers across the state. The number of surveys returned was 112. RESULTS: The Modified Checklist for Autism tool was administered by 80% of pediatric providers and 30% of family practice primary care providers. The Patient Health Questionnaire for depression was administered by 72% of pediatric and 80% of family practice providers. Most of the primary care providers had a behavioral health provider present in the clinic, which likely resulted in higher screening rates compared to the national average. DISCUSSION: The screening practices of the family practice and pediatric subspecialities reflect their respective current professional organization recommendations. Although most providers believe it is important to screen for developmental and behavioral disorders, further system changes are needed to support screening for development and broader behavioral problems along with depression among family practice providers. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Addressing the Need for Training More School Psychologists to Serve Toddlers and Preschoolers with Autism Spectrum Disorders.

The prevalence of autism spectrum disorder (ASD) has risen significantly in the past two decades. Unfortunately, there is a shortage of mental health providers who have specialized training in delivering evidenced-based services to this population. Early intensive behavioral intervention (EIBI) is an evidenced-based treatment recommended for toddlers with ASD, and school psychologists are uniquely positioned to help children with ASD receive it. However, many school psychologists do not receive adequate training in this subspecialty. This paper makes recommendations to school psychology training programs about how to add or improve training in this subspecialty based on the results of an Office of Special Education Programs grant-funded ASD training program which involved collaboration between a NASP-approved and APA-accredited school psychology training program and a community-based early intensive behavioral intervention (EIBI) clinic. The grant supported development of an interdisciplinary didactic and clinical training program to increase the ASD knowledge, skills, and competencies of school psychology graduate students, with the broader goals of developing a replicable training model and increasing the workforce of trained providers for this underserved population. Fifteen graduate students completed the training program. Outcomes related to trainee knowledge, skills, and competencies, trainee satisfaction, and lessons learned over time analyzed within a logic model that guided the project's development and execution can be informative for other school psychology programs undertaking training in this subspecialty.

Spatial heterogeneity of extensively drug resistant-tuberculosis in Western Cape Province, South Africa.

Tuberculosis (TB) remains a leading infectious disease killer globally. Treatment outcomes are especially poor among people with extensively drug-resistant (XDR) TB, until recently defined as rifampicin-resistant (RR) TB with resistance to an aminoglycoside (amikacin) and a fluoroquinolone (ofloxacin). We used laboratory TB test results from Western Cape province, South Africa between 2012 and 2015 to identify XDR-TB and pre-XDR-TB (RR-TB with resistance to one second-line drug) spatial hotspots. We mapped the percentage and count of individuals with RR-TB that had XDR-TB and pre-XDR-TB across the province and in Cape Town, as well as amikacin-resistant and ofloxacin-resistant TB. We found the percentage of pre-XDR-TB and the count of XDR-TB/pre-XDR-TB highly heterogeneous with geographic hotspots within RR-TB high burden areas, and found hotspots in both percentage and count of amikacin-resistant and ofloxacin-resistant TB. The spatial distribution of percentage ofloxacin-resistant TB hotspots was similar to XDR-TB hotspots, suggesting that fluoroquinolone-resistace is often the first step to additional resistance. Our work shows that interventions used to reduce XDR-TB incidence may need to be targeted within spatial locations of RR-TB, and further research is required to understand underlying drivers of XDR-TB transmission in these locations.

Psychosis-like experiences and resilience: A systematic and critical review of the literature.

Resilience research has documented the ability to cope with traumatic and stressful situations and/or retain functioning given certain risk factors in the context of psychosis. In this study, we conducted the first systematic review of the literature on psychosis-like experiences (PLEs) and resilience. Fifteen articles (from 11 unique study samples) from 10 countries were included in this systematic review, with a total of 11,937 unique study participants. Inclusion criteria were broad, capturing a wide range of individuals with PLEs who have not yet experienced threshold psychosis, such as individuals in the general population with elevated self-reports of PLEs, as well as clinical groups diagnosed by clinician interviews (i.e., clinical- or ultra-high-risk for psychosis [CHR or UHR]). For this review, studies needed to include research aims and empirical research related to resilience, and use an established or author-defined measure of psychological and/or social resilience. Data reporting quality was assessed with the Strengthening the Reporting of Observational Studies in Epidemiology and place of residence, race/ethnicity/culture/language, occupation, gender/sex, religion, education, socioeconomic status, social capital (PROGRESS) guidelines. Study aims and measurement of key variables varied widely, and all studies were cross-sectional. In 73% of the studies, resilience was inversely associated with PLEs or psychosis risk status (e.g., CHR or UHR). Results related to specific resilience subscales were mixed. Author-defined resilience was typically related to internal/psychological resources. Future research, particularly longitudinal research involving multidimensional measurement of resilience (e.g., internal and external factors), along with well-defined theoretical models, are necessary before drawing firm conclusions on resilience and PLEs. We propose a dynamic, multifaceted, developmentally appropriate, and culturally sensitive model of resilience for future research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Optimal use of COVID-19 Ag-RDT screening at border crossings to prevent community transmission: A modeling analysis.

Countries around the world have implemented restrictions on mobility, especially cross-border travel to reduce or prevent SARS-CoV-2 community transmission. Rapid antigen testing (Ag-RDT), with on-site administration and rapid turnaround time may provide a valuable screening measure to ease cross-border travel while minimizing risk of local transmission. To maximize impact, we developed an optimal Ag-RDT screening algorithm for cross-border entry. Using a previously developed mathematical model, we determined the daily number of imported COVID-19 cases that would generate no more than a relative 1% increase in cases over one month for different effective reproductive numbers (Rt) and COVID-19 prevalence within the recipient country. We then developed an algorithm-for differing levels of Rt, arrivals per day, mode of travel, and SARS-CoV-2 prevalence amongst travelers-to determine the minimum proportion of people that would need Ag-RDT testing at border crossings to ensure no greater than the relative 1% community spread increase. When daily international arrivals and/or COVID-19 prevalence amongst arrivals increases, the proportion of arrivals required to test using Ag-RDT increases. At very high numbers of international arrivals/COVID-19 prevalence, Ag-RDT testing is not sufficient to prevent increased community spread, especially when recipient country prevalence and Rt are low. In these cases, Ag-RDT screening would need to be supplemented with other measures to prevent an increase in community transmission. An efficient Ag-RDT algorithm for SARS-CoV-2 testing depends strongly on the epidemic status within the recipient country, volume of travel, proportion of land and air arrivals, test sensitivity, and COVID-19 prevalence among travelers.

A qualitative study on identity in individuals at clinical high risk for psychosis: " Why does it have to be one thing?".

OBJECTIVE: Qualitative research can shed light on the subjective experiences of individuals at clinical high risk (CHR) for psychosis, complement quantitative research, broaden our understanding of experiencing CHR, and inform intervention development. The aim of this study was to explore life experiences of individuals at CHR through qualitative research. METHOD: Participants were 37 individuals at CHR (20 male, 17 female) aged 16-34 (Mage = 23.32 ± 5.26), and 16 healthy controls (HCs; 7 male, 9 female) aged 18-34 (Mage = 25.37 ± 4.05). Qualitative data were obtained through open-ended interviews (30-45 min). No a priori hypotheses were made, and thematic analyses were used to develop themes. RESULTS: Four major themes and one subtheme related to identity were identified through the iterative thematic analysis: defining a self-concept (with a subtheme of creativity), identity development/formation, feeling different from others, and change from a former self. Over 80% of the CHR cohort spontaneously discussed topics related to their identity, compared to 38% of HCs. HCs only reported content within the defining a self-concept theme, while the CHR group reported content within all themes. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The present study demonstrates that identity formation is a major process for youth in general and that psychosis experiences can make this process more challenging. CHR participants spontaneously brought up multiple themes related to identity in open-ended interviews, suggesting the relevance of this topic in this population. Clinicians should continue to probe identity-related concerns on an individual basis and research should focus on integrating this framework into the conceptualization and treatment of CHR. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Artificial intelligence to diagnose ear disease using otoscopic image analysis: a review.

AI relates broadly to the science of developing computer systems to imitate human intelligence, thus allowing for the automation of tasks that would otherwise necessitate human cognition. Such technology has increasingly demonstrated capacity to outperform humans for functions relating to image recognition. Given the current lack of cost-effective confirmatory testing, accurate diagnosis and subsequent management depend on visual detection of characteristic findings during otoscope examination. The aim of this manuscript is to perform a comprehensive literature review and evaluate the potential application of artificial intelligence for the diagnosis of ear disease from otoscopic image analysis.

Reproducible Science Is Vital for a Stronger Evidence Base During the COVID-19 Pandemic.

Reproducible research becomes even more imperative as we build the evidence base on SARS-CoV-2 epidemiology, diagnosis, prevention, and treatment. In his study, Paez assessed the reproducibility of COVID-19 research during the pandemic, using a case study of population density. He found that most articles that assess the relationship of population density and COVID-19 outcomes do not publicly share data and code, except for a few, including our paper, which he stated "illustrates the importance of good reproducibility practices". Paez recreated our analysis using our code and data from the perspective of spatial analysis, and his new model came to a different conclusion. The disparity between our and Paez's findings, as well as other existing literature on the topic, give greater impetus to the need for further research. As there has been near exponential growth of COVID-19 research across a wide range of scientific disciplines, reproducible science is a vital component to produce reliable, rigorous, and robust evidence on COVID-19, which will be essential to inform clinical practice and policy in order to effectively eliminate the pandemic.

Evaluation of Caregiver Training Procedures to Teach Activities of Daily Living Skills.

Caregivers of children with an autism spectrum disorder are often responsible for assisting their children to complete activities of daily living skills. Effective and efficient caregiver training methods are needed to train caregivers. The present study used two concurrent multiple-baseline across-participants designs to evaluate the effects of real-time feedback and behavioral skills training on training eight caregivers to implement teaching procedures for activities of daily living skills with their child. We assessed caregivers' accuracy and correct implementation of the six-component teaching procedure after they received either real-time feedback or behavioral skills training. Caregivers from both groups mastered and maintained correct implementation of the teaching procedures with their child. The overall results suggest that real-time feedback and behavioral skills training are efficacious to train caregivers to implement activities of daily living skills procedures with their children, and that real-time feedback may be an efficient alternative method to train caregivers. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40617-020-00513-z.

Changes in HIV treatment differentiated care uptake during the COVID-19 pandemic in Zambia: interrupted time series analysis.

INTRODUCTION: Differentiated service delivery (DSD) models aim to improve the access of human immunodeficiency virus treatment on clients and reduce requirements for facility visits by extending dispensing intervals. With the advent of the COVID-19 pandemic, minimising client contact with healthcare facilities and other clients, while maintaining treatment continuity and avoiding loss to care, has become more urgent, resulting in efforts to increase DSD uptake. We assessed the extent to which DSD coverage and antiretroviral treatment (ART) dispensing intervals have changed during the COVID-19 pandemic in Zambia. METHODS: We used client data from Zambia's electronic medical record system (SmartCare) for 737 health facilities, representing about three-fourths of all ART clients nationally. We compared the numbers and proportional distributions of clients enrolled in DSD models in the 6 months before and 6 months after the first case of COVID-19 was diagnosed in Zambia in March 2020. Segmented linear regression was used to determine whether the outbreak of COVID-19 in Zambia further accelerated the increase in DSD scale-up. RESULTS AND DISCUSSION: Between September 2019 and August 2020, 181,317 clients aged 15 or older (81,520 and 99,797 from 1 September 2019 to 1 March 2020 and from 1 March to 31 August 2020, respectively) enrolled in DSD models in Zambia. Overall participation in all DSD models increased over the study period, but uptake varied by model. The rate of acceleration increased in the second period for home ART delivery (152%), ≤ 2-month fast-track (143%) and 3-month MMD (139%). There was a significant reduction in the enrolment rates for 4- to 6-month fast-track (-28%) and "other" models (-19%). CONCLUSIONS: Participation in DSD models for stable ART clients in Zambia increased after the advent of COVID-19, but dispensing intervals diminished. Eliminating obstacles to longer dispensing intervals, including those related to supply chain management, should be prioritized to achieve the expected benefits of DSD models and minimize COVID-19 risk.

Brain, behavioral, affective, and sex correlates of recovery from alcohol use disorders.

BACKGROUND: Recovery from alcohol use disorders (AUDs) consists of salutary changes in behavior and affect. While evidence suggests that recovery-related behavioral changes, such as abstinence, emerge in tandem with both neural and affective changes, the precise relationships among these changes are unknown. To understand these relationships, we examined associations between the duration of abstinence (DOA), affective states, and neuroimaging-based structural measures of the brain reward system (BRS) in AUD men (AUDM ) and AUD women (AUDW ). METHODS: Participants were community respondents from the Boston area comprising right-handed abstinent individuals with AUD (n = 60; 30 men) and controls without AUD (NC; n = 60; 29 men). Multivariate linear regressions compared short-/mid-term abstainers (≤5 years), long-term abstainers (>5 years), and the NC group on measures of BRS volume (3T magnetic resonance imaging scans) and measures of affect (Profile of Mood States [POMS]; Multiple Affect Adjective Check List [MAACL]; Hamilton Rating Scale for Depression [HRSD]). Analyses contrasted sex differences and accounted for age, education, drinking severity, and verbal IQ. RESULTS: Compared to the NC group, short-/mid-term abstainers exhibited larger posterior insular volume (total (ß = 0.019, 95% CI: 0.004, 0.034)), higher negative affect (POMS Mood Disturbance (ß = 27.8, 95% CI: 11.56, 44.04), and lower positive affect (POMS Vigor (ß = -4.89, 95% CI: -9.06, -0.72)). Compared to the NC group, Long-term abstainers exhibited significantly smaller volumes of aggregate anterior cingulate cortex (ß = -0.06, 95% CI: -0.113, -0.008) and higher HRSD scores (ß = 1.56, 95% CI: 0.14, 2.98). Relative to AUDM , AUDW exhibited significantly larger right anterior insular volumes (ß = 0.03, 95% CI: 0.01, 0.06) and significantly greater MAACL Positive Affect scores (ß = 7.56, 95% CI: 0.59, 11.55) in association with DOA. CONCLUSIONS: We found that differences in abstinence from alcohol were correlated with differences in both neural recovery and affective dimensions of recovery from AUDs. The observed sex differences extend evidence of dimorphic effects of AUDs and recovery on brain structure and function. Future longitudinal research will test inferences concerning the directionality of these relationships.

Cancer incidence in Thyborøn-Harboøre, Denmark: a cohort study from an industrially contaminated site.

In a fishing community Thyborøn-Harboøre on the Danish West coast, a chemical factory polluted air, sea, and ground with > 100 xenobiotic compounds. We investigated cancer incidence in the community. A historical cohort was identified from the Central Population Register and followed for cancer incidence in the Danish Cancer Register including inhabitants from 1968-1970 at height of pollution, and newcomers in 1990-2006 after pollution control. Two fishing communities without pollution, Holmsland and Hanstholm, were referent cohorts. We calculated rate ratios (RR) and 95% confidence intervals (CI). In 1968-1970, 4914 persons lived in Thyborøn-Harboøre, and 9537 persons in Holmsland-Hanstholm. Thyborøn-Harboøre had a statistically significant excess cancer incidence compared with Holmsland-Hanstholm; RR 1.20 (95% CI 1.11-1.29) deriving from kidney and bladder cancer; stomach and lung cancer in men, and colorectal cancer in women. In 1990-2006, 2933 persons came to live in Thyborøn-Harboøre. Their cancer incidence was the same as for newcomers to Holmsland-Hanstholm; RR 1.07 (95% CI 0.88-1.30). Persons in Thyborøn-Harboøre at height of chemical pollution had a cancer risk 20% above persons living in non-polluted fishing communities with a pattern unlikely to be attributable to life style. The study suggested that chemical pollution may have affected cancer risk.