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Background\ud \ud Brazil has the second highest annual number of new leprosy cases. The aim of this study is to formally compare predictions of future new case detection rate (NCDR) trends and the annual probability of NCDR falling below 10/100,000 of four different modelling approaches in four states of Brazil: Rio Grande do Norte, Amazonas, Ceará, Tocantins.\ud \ud Methods\ud \ud A linear mixed model, a back-calculation approach, a deterministic compartmental model and an individual-based model were used. All models were fitted to leprosy data obtained from the Brazilian national database (SINAN). First, models were fitted to the data up to 2011, and predictions were made for NCDR for 2012–2014. Second, data up to 2014 were considered and forecasts of NCDR were generated for each year from 2015 to 2040. The resulting distributions of NCDR and the probability of NCDR being below 10/100,000 of the population for each year were then compared between approaches.\ud \ud Results\ud \ud Each model performed well in model fitting and the short-term forecasting of future NCDR. Long-term forecasting of NCDR and the probability of NCDR falling below 10/100,000 differed between models. All agree that the trend of NCDR will continue to decrease in all states until 2040. Reaching a NCDR of less than 10/100,000 by 2020 was only likely in Rio Grande do Norte. Prediction until 2040 showed that the target was also achieved in Amazonas, while in Ceará and Tocantins the NCDR most likely remain (far) above 10/100,000.\ud \ud Conclusions\ud \ud All models agree that, while incidence is likely to decline, achieving a NCDR below 10/100,000 by 2020 is unlikely in some states. Long-term prediction showed a downward trend with more variation between models, but highlights the need for further control measures to reduce the incidence of new infections if leprosy is to be eliminated.

Key Points Question Is the incarceration of a family member associated with well-being and projected life expectancy? Findings In this cross-sectional study including 2815 individuals, any family member incarceration was associated with lower well-being and a projected 2.6-year reduction in life expectancy compared with no family member incarceration experience. Among those with any family incarceration, Black respondents had an estimated 0.5 fewer years of projected life expectancy compared with White respondents. Meaning These findings suggest that efforts to decarcerate may improve population-level health and well-being by reducing racial disparities and detrimental outcomes associated with incarceration for nonincarcerated family members., This cross-sectional study assesses the associations of incarceration of a family member with perceived well-being and projected life expectancy among adults in the US., Importance More than half of the adult population in the United States has ever had a family member incarcerated, an experience more common among Black individuals. The impacts of family incarceration on well-being are not fully understood. Objective To assess the associations of incarceration of a family member with perceived well-being and differences in projected life expectancy. Design, Setting, and Participants This nationally representative cross-sectional study used data from the 2018 Family History of Incarceration Survey to examine how experiences of family member incarceration were associated with a holistic measure of well-being, including physical, mental, social, financial, and spiritual domains. Well-being was used to estimate change in life expectancy and was compared across varying levels of exposure to immediate and extended family member incarceration using logistic regression models to adjust for individual and household characteristics. Data were analyzed from October 2019 to April 2020. Exposures Respondents’ history of family member incarceration, including immediate and extended family members. Main Outcomes and Measures The main outcome was self-reported life-evaluation, a measure of overall well-being from the 100 Million Healthier Lives Adult Well-being Assessment. Respondents were considered thriving with a current life satisfaction score of 7 or greater and a future life optimism score of 8 or greater, each on a scale of 0 to 10. Other outcomes included physical health, mental health, social support, financial well-being, and spiritual well-being, each measured with separate scales. Additionally, life expectancy projections were estimated using population-level correlations with the Life Evaluation Index. All percentages were weighted to more closely represent the US population. Results Of 2815 individuals included in analysis, 1472 (51.7%) were women, 1765 (62.8%) were non-Hispanic White, and 868 (31.5%) were aged 35 to 54 years. A total of 1806 respondents (45.0%) reported having an immediate family member who was incarcerated. Compared with respondents with no family incarceration, any family member incarceration was associated with lower well-being overall (thriving: 69.5% [95% CI, 65.0%-75.0%] vs 56.9% [95% CI, 53.9%-59.9%]) and in every individual domain (eg, physical thriving: 51.1% [95% CI, 46.2-56.0] vs 35.5% [95% CI, 32.6%-38.3%]) and with a mean (SE) estimated 2.6 (0.03) years shorter life expectancy. Among those with any family incarceration, Black respondents had a mean (SE) estimated 0.46 (0.04) fewer years of life expectancy compared with White respondents. Conclusions and Relevance These findings suggest that family member health and well-being may be an important avenue through which incarceration is associated with racial disparities in health and mortality. Decarceration efforts may improve population-level well-being and life expectancy by minimizing detrimental outcomes associated with incarceration among nonincarcerated family members.

We propose a 3D convolutional neural network to simultaneously segment and detect cell nuclei in confocal microscopy images. Mirroring the co-dependency of these tasks, our proposed model consists of two serial components: the first part computes a segmentation of cell bodies, while the second module identifies the centers of these cells. Our model is trained end-to-end from scratch on a mouse parotid salivary gland stem cell nuclei dataset comprising 107 image stacks from three independent cell preparations, each containing several hundred individual cell nuclei in 3D. In our experiments, we conduct a thorough evaluation of both detection accuracy and segmentation quality, on two different datasets. The results show that the proposed method provides significantly improved detection and segmentation accuracy compared to state-of-the-art and benchmark algorithms. Finally, we use a previously described test-time drop-out strategy to obtain uncertainty estimates on our predictions and validate these estimates by demonstrating that they are strongly correlated with accuracy., Comment: We were not able to reproduce the results

Recent studies suggest that adult pituitary stem cells may play a role in pituitary tumorigenesis. We sought to explore whether the Glial cell-line derived neurotrophic factor receptor alpha 2 (GFRα2), a recently described pituitary stem/progenitor marker, might be differentially expressed in pituitary adenomas versus normal pituitary.The expression of GFRα2 and other members of the GFR receptor family (GFRα1, α3, α4) were analyzed using RT-PCR, western blot, and immunohistochemistry in 39 pituitary adenomas, 14 normal pituitary glands obtained at autopsy, and cDNA from 3 normal pituitaries obtained commercially.GFRα2 mRNA was ~2.6 fold under-expressed in functioning adenomas (p0.01) and ~3.5 fold over-expressed in non-functioning adenomas (NFAs) (p0.05) compared to normal pituitary. Among NFAs, GFRα2 was significantly over-expressed (~5-fold) in the gonadotropinoma subtype only (p0.05). GFRα2 protein expression appeared to be higher in most NFAs, although there was heterogeneity in protein expression in this group. GFRα2 protein expression appeared consistently lower in functioning adenomas by IHC and western blot. In normal pituitary, GFRα2 was localized in Rathke's remnant, the putative pituitary stem cell niche, and in corticotropes.Our results suggest that the pituitary stem cell marker GFRα2 is under-expressed in functioning adenomas and over-expressed in NFAs, specifically gonadotropinomas. Further studies are required to elucidate whether over-expression of GFRα2 in gonadotropinomas might play a role in pituitary tumorigenesis.