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The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed to answer circuit questions, and provide procedures linking the neurons defined by our analysis with genetic reagents. Biologically, we examine distributions of connection strengths, neural motifs on different scales, electrical consequences of compartmentalization, and evidence that maximizing packing density is an important criterion in the evolution of the fly’s brain.

Abstract Background Physician reporting is commonly used to ascertain adverse events or outcomes measured in epidemiologic studies. However, little is known on the accuracy of physician reported malignancies compared to pertinent medical record review in large cohort studies. Methods The Consortium of Rheumatology Researchers of North America (CORRONA) registry gathers physician-completed questionnaires for rheumatoid arthritis (RA) patients, including request for information on incident malignancies, approximately every three months. For incident malignancies reported from October 1st, 2001, through December 31st, 2007, we retrospectively requested completion of a Targeted Adverse Event (TAE) form for additional information as well as primary source documents to adjudicate the malignancy reports. CORRONA has employed a prospective request for source documentation for these events since 2008. We classified each malignancy as definite, probable, possible, or not a malignancy. Results From 20,837 RA patients enrolled in CORRONA, 461 incident malignancies were initially reported on physician questionnaires. After review of returned source documents with adjudication, 234 were deemed definite, 69 probable, 101 possible, and 57 not an incident malignancy. The positive predictive value (PPV) of initial physician report of a malignancy versus “definite or probable” malignancy based on adjudication was 0.66 (95% CI 0.61 - 0.70). The PPV was 0.68 (95% CI 0.63 – 0.72) when the subsequent TAE form also confirmed the presence of malignancy. When possible malignancies were included, the PPV of physician-reported malignancies without a subsequent TAE form increased to 0.86 (0.83 – 0.89), and with a subsequent TAE form, 0.89 (0.85-0.91). Conclusion Twelve percent of initial physician reports of incident malignancy could not be confirmed with review of source documents. The most common reason for lack of confirmation was inability to obtain documents or insufficient data in source materials. These results suggest that timely collection of relevant medical records and an adjudication process are required to improve the accuracy of cancer reporting in epidemiologic studies.

Abstract Background Despite the demonstrated need to increase screening mammography utilization and strong evidence that mail and telephone outreach to women can increase screening, most managed care organizations have not adopted comprehensive outreach programs. The uncertainty about optimum strategies and cost effectiveness have retarded widespread acceptance. While 70% of women report getting a mammogram within the prior 2 years, repeat mammography rates are less than 50%. This 5-year study is conducted though a Central Massachusetts healthcare plan and affiliated clinic. All womenhave adequate health insurance to cover the test. Methods/Design This randomized study compares 3 arms: reminder letter alone; reminder letter plus reminder call; reminder letter plus a second reminder and booklet plus a counselor call. All calls provide women with the opportunity to schedule a mammogram in a reasonable time. The invention period will span 4 years and include repeat attempts. The counselor arm is designed to educate, motivate and counsel women in an effort to alleviate PCP burden. All women who have been in the healthcare plan for 24 months and who have a current primary care provider (PCP) and who are aged 51-84 are randomized to 1 of 3 arms. Interventions are limited to women who become ≥18 months from a prior mammogram. Women and their physicians may opt out of the intervention study. Measurement of completed mammograms will use plan billing records and clinic electronic records. The primary outcome is the proportion of women continuously enrolled for ≥24 months who have had ≥1 mammogram in the last 24 months. Secondary outcomes include the number of women who need repeat interventions. The cost effectiveness analysis will measure all costs from the provider perspective. Discussion So far, 18,509 women aged 51-84 have been enrolled into our tracking database and were randomized into one of three arms. At baseline, 5,223 women were eligible for an intervention. We anticipate that the outcome will provide firm data about the maximal effectiveness as well as the cost effectiveness of the interventions both for increasing the mammography rate and the repeat mammography rate. Trial registration http://clinicaltrials.gov/NCT01332032

Abstract Background US Latinos have greater prevalence of type 2 diabetes (diabetes), uncontrolled diabetes and diabetes co-morbidities compared to non-Latino Whites. They also have lower literacy levels and are more likely to live in poverty. Interventions are needed to improve diabetes control among low-income Latinos. Methods and design This randomized clinical trial tested the efficacy of a culturally- and literacy-tailored diabetes self-management intervention (Latinos en Control) on glycemic control among low-income Latinos with diabetes, compared to usual care (control). Participants were recruited from five community health centers (CHCs) in Massachusetts. The theory-based intervention included an intensive phase of 12 weekly sessions and a follow-up maintenance phase of 8 monthly sessions. Assessments occurred at baseline, and at 4 and 12 months. The primary outcome was glycosylated hemoglobin (HbA1c). Secondary outcomes were self-management behaviors, weight, lipids and blood pressure. Additional outcomes included diabetes knowledge, self-efficacy, depression and quality of life. The study was designed for recruitment of 250 participants (estimated 20% dropout rate) to provide 90% power for detecting a 7% or greater change in HbA1c between the intervention and control groups. This is a difference in change of HbA1c of 0.5 to 0.6%. Discussion Low-income Latinos bear a great burden of uncontrolled diabetes and are an understudied population. Theory-based interventions that are tailored to the needs of this high-risk population have potential for improving diabetes self-management and reduce health disparities. This article describes the design and methods of a theory driven intervention aimed at addressing this need. Trial registration http://www.clinicaltrials.gov # NCT00848315

Abstract Background To examine the associations between vision-targeted health-related quality of life (VT-HRQ) and ocular surface parameters in patients with Sjögren's syndrome, a systemic autoimmune disease characterized by dry eye and dry mouth. Methods Forty-two patients fulfilling European / American diagnostic criteria for Sjögren's syndrome underwent Schirmer testing without anesthesia, ocular surface vital dye staining; and measurement of tear film breakup time (TBUT). Subjects were administered the Ocular Surface Disease Index (OSDI) and the 25-item National Eye Institute Vision Functioning Questionnaire (NEI-VFQ). Main outcome measures included ocular surface parameters, OSDI subscales describing ocular discomfort (OSDI-symptoms), vision-related function (OSDI-function), and environmental triggers, and NEI-VFQ subscales. Results Participants (aged 31–81 y; 95% female) all had moderate to severe dry eye. Associations of OSDI subscales with the ocular parameters were modest (Spearman r (ρ) < 0.22) and not statistically significant. Associations of NEI-VFQ subscales with the ocular parameters reached borderline significance for the near vision subscale with TBUT (ρ = 0.32, p = .05) and for the distance vision subscale with van Bijsterveld score (ρ = 0.33, p = .04). The strongest associations of the two questionnaires were for: ocular pain and mental function with OSDI-symptoms (ρ = 0.60 and 0.45, respectively); and general vision, ocular pain, mental function, role function, and driving with OSDI-function (ρ = 0.60, 0.50, 0.61, 0.64, 0.57, and 0.67, respectively). Conclusions Associations between conventional objective measures of dry eye and VT-HRQ were modest. The generic NEI-VFQ was similar to the disease-specific OSDI in its ability to measure the impact of Sjögren's syndrome-related dry eye on VT-HRQ.

Objective: The classic conception of pain etiology in rheumatologic disease is nociceptive pain—tissue injury and inflammation signaling through peripheral and central nerve fibers. But this can be mixed with other pain etiologies, including nociplastic, which is augmented pain experience due to central sensitization. The pain of fibromyalgia (FM) is nociplastic, occurs in 10% to 30% of patients with rheumatologic disease, and its presence can influence disease severity assessment. The objective of our study was to (1) ascertain the prevalence of FM and widespread pain (WP) in the CorEvitas psoriatic arthritis (PsA) registry as assessed by the Widespread Pain Index (WPI) and Symptom Severity Scale (SSS) questionnaires; (2) characterize the demographic and clinical factors associated with FM and WP; and (3) ascertain the association of FM and WP on the Clinical Disease Activity in Psoriatic Arthritis (cDAPSA) score and other disease activity measures. Methods: PsA registry patients completing the WPI/SSS questionnaires since May 2020, at their most recent visit recorded in the registry, were analyzed. Results: The analysis included 1,823 patients with PsA; 11.1% fulfilled the FM definition and 20.6% fulfilled the WP definition. Several factors were associated with the FM definition, including female sex, depression and/or anxiety, impaired function, increased body mass index, and increased number of comorbidities. cDAPSA, patient pain and global assessment, and tender joint count were twice as severe in patients with FM compared to those without. Conclusion: FM prevalence is elevated in PsA and is associated with elevated disease measures, confounding reliable disease assessment for treat‐to‐target goals. Identification of FM as an influential contextual factor in disease assessment is recommended. [ABSTRACT FROM AUTHOR]

The escalating rates of gonorrhea globally are associated with higher numbers of disseminated gonococcal infection (DGI). Expression of the PorB1A allele of the major outer membrane porin protein, PorB, is associated with DGI. This meta-analysis shows that the odds of PorB1A strains to disseminate is 20.53 compared to PorB1B isolates. [ABSTRACT FROM AUTHOR]

Objectives To determine whether an expanded antigen-specific ACPA profile predicts changes in disease activity in patients with RA initiating biologics. Methods The study included participants from a prospective, non-randomized, observational RA cohort. For this sub-study, treatment groups of interest included biologic-naïve initiating anti-TNF, biologic-exposed initiating non-TNF, and biologic-naïve initiating abatacept. ACPAs to 25 citrullinated peptides were measured using banked enrolment serum. Principal component analysis (PCA) was performed and associations of resulting principal component (PC) scores (in quartiles) and anti-CCP3 antibody (≤15, 16–250 or >250 U/ml) with EULAR (good/moderate/none) treatment response at 6 months were examined using adjusted ordinal regression models. Results Participants (n  = 1092) had a mean age of 57 (13) years and 79% were women. At 6 months, 68.5% achieved a moderate/good EULAR response. There were three PCs that cumulatively explained 70% of variation in ACPA values. In models including the three components and anti-CCP3 antibody category, only PC1 and PC2 were associated with treatment response. The highest quartile for PC1 (odds ratio [OR] 1.76; 95% CI: 1.22, 2.53) and for PC2 (OR 1.74; 95% CI: 1.23, 2.46) were associated with treatment response after multivariable adjustment. There was no evidence of interaction between PCs and treatment group in EULAR responses (P -value for interaction >0.1). Conclusion An expanded ACPA profile appears to be more strongly associated with biologic treatment response in RA than commercially available anti-CCP3 antibody levels. However, further enhancements to PCA will be needed to effectively prioritize between different biologics available for the treatment of RA. [ABSTRACT FROM AUTHOR]

Background: Models are needed for implementing weight management interventions for adolescents through readily accessible venues. This study evaluated the feasibility and ef?cacy of a school nurse-delivered intervention in improving diet and activity and reducing body mass index (BMI) among overweight and obese adolescents. Methods: Six high schools were randomized to either a 6-session school nurse-delivered counseling intervention utilizing cognitive-behavioral techniques or nurse contact with provision of information. Eighty-four overweight or obese adolescents in grades 9 through 11 completed behavioral and physiological assessments at baseline and 2- and 6-month follow-ups. Results: At 2 months, intervention participants ate breakfast on more days/week (difference = 1.01 days; 95% CI: 0.11, 1.92), and had a lower intake of total sugar (difference = -45.79 g; 95% CI: -88.34, -3.24) and added sugar (difference= -51.35 g; 95% CI: -92.45, -10.26) compared to control participants. At 6 months, they were more likely to drink soda less than or equal to one time/day (OR 4.10; 95% CI: 1.19, 16.93) and eat at fast food restaurants less than or equal to one time/week (OR 4.62; 95% CI: 1.10, 23.76) compared to control participants. There were no signi?cant differences in BMI, activity, or caloric intake. Conclusion: A brief school nurse-delivered intervention was feasible, acceptable, and improved selected obesogenic behaviors, but not BMI. (Contains 4 tables and 2 figures.)

This study reports the findings of a pilot demonstration project called Together for Kids, which used a mental health consultation model to address the needs of young children with challenging behaviors who are identified in preschool classrooms. The study was conducted in four preschool programs and one Head Start program serving children ages 3-5, including both private-pay families and those using public subsidies. Rates of significant behavior problems as assessed by preschool teachers using a standardized scale were high, with 34% of all children enrolled in preschool classrooms in these sites over a 3-year period identified at-risk of externalizing or internalizing problems. Classroom teachers, as well as individual children and families identified as at-risk, were provided services, including, classroom observation and teacher training, individual child assessment and therapy, family assessment and support, and referrals for other family needs. Analysis of outcomes for 47 children and families with externalizing behavior problems who received individualized consultation, compared to 89 control children, and analysis of outcomes of a matched group of 19 intervention and 19 control children, revealed that the intervention was associated with significant improvements in classroom aggressive and maladaptive behavior, and growth in adaptive behavior. Improvements in child behavior were associated with total hours of individual child services provided, and with improvements in child developmental skills. Significant reductions in the rate of children suspended or terminated from child care programs were also found. Implications for further development of models of early childhood mental health consultation are discussed.

Background: Evaluating the performance of SARS-CoV-2 serological assays and clearly articulating the utility of selected antigen, isotypes and thresholds is crucial to understanding the prevalence of infection within selected communities.Methods: This cross-sectional study, implemented in 2020, screened PCR-confirmed COVID-19 patients (n = 86), banked pre-pandemic and negative donors (n = 96), health care workers and family members (n = 552), and university employees (n = 327) for anti-SARS-CoV-2 receptor-binding domain (RBD), trimeric spike protein (S), and nucleocapsid protein (N) IgG and IgA antibodies with a laboratory developed Enzyme-Linked Immunosorbent Assay (ELISA) and tested how antigen, isotype and threshold choices affected the seroprevalence. The following threshold methods were evaluated: (i) mean + 3 standard deviations of the negative controls; (ii) 100% specificity for each antigen/isotype combination; and (iii) the maximal Youden index.Results: We found vastly different seroprevalence estimates depending on selected antigens, isotypes and the applied threshold method, ranging from 0.0% to 85.4% . Subsequently, we maximized specificity and reported a seroprevalence, based on more than one antigen, ranging from 9.3% to 25.9%.Conclusions: This study revealed the importance of evaluating serosurvey tools for antigen, isotype, and threshold-specific sensitivity and specificity, in order to interpret qualitative serosurvey outcomes reliably and consistently across studies. [ABSTRACT FROM AUTHOR]