Success rates of re-excision after positive margins for invasive lobular carcinoma of the breast.

Rates of positive margins after surgical resection of invasive lobular carcinoma (ILC) are high (ranging from 18 to 60%), yet the efficacy of re-excision lumpReceptor subtypeectomy for clearing positive margins is unknown. Concerns about the diffuse nature of ILC may drive increased rates of completion mastectomy to treat positive margins, thus lowering breast conservation rates. We therefore determined the success rate of re-excision lumpectomy in women with ILC and positive margins after surgical resection. We identified 314 cases of stage I-III ILC treated with breast conserving surgery (BCS) at the University of California, San Francisco. Surgical procedures, pathology reports, and outcomes were analyzed using univariate and multivariate statistics and Cox-proportional hazards models. We evaluated outcomes before and after the year 2014, when new margin management consensus guidelines were published. Positive initial margins occurred in 118 (37.6%) cases. Of these, 62 (52.5%) underwent re-excision lumpectomy, which cleared the margin in 74.2%. On multivariate analysis, node negativity was significantly associated with successful re-excision (odds ratio [OR] 3.99, 95% CI 1.15-13.81, p = 0.029). After 2014, we saw fewer initial positive margins (42.7% versus 25.5%, p = 0.009), second surgeries (54.6% versus 20.2%, p < 0.001), and completion mastectomies (27.7% versus 4.5%, p < 0.001). In this large cohort of women with ILC, re-excision lumpectomy was highly successful at clearing positive margins. Additionally, positive margins and completion mastectomy rates significantly decreased over time. These findings highlight improvements in management of ILC, and suggest that completion mastectomy may not be required for those with positive margins after initial BCS

Machine Learning on Syngeneic Mouse Tumor Profiles To Model Clinical Immunotherapy Response

Most patients with cancer are refractory to immune checkpoint blockade (ICB) therapy, and proper patient stratification remains an open question. Primary patient data suffer from high heterogeneity, low accessibility, and lack of proper controls. In contrast, syngeneic mouse tumor models enable controlled experiments with ICB treatments. Using transcriptomic and experimental variables from \u3e700 ICB-treated/control syngeneic mouse tumors, we developed a machine learning framework to model tumor immunity and identify factors influencing ICB response. Projected on human immunotherapy trial data, we found that the model can predict clinical ICB response. We further applied the model to predicting ICB-responsive/resistant cancer types in The Cancer Genome Atlas, which agreed well with existing clinical reports. Last, feature analysis implicated factors associated with ICB response. In summary, our computational framework based on mouse tumor data reliably stratified patients regarding ICB response, informed resistance mechanisms, and has the potential for wide applications in disease treatment studies

Use and awareness of and willingness to self-test for HIV: an analysis of cross-sectional population-based surveys in Malawi and Zimbabwe.

BACKGROUND: Many southern African countries are nearing the global goal of diagnosing 90% of people with HIV by 2020. In 2016, 84 and 86% of people with HIV knew their status in Malawi and Zimbabwe, respectively. However, gaps remain, particularly among men. We investigated awareness and use of, and willingness to self-test for HIV and explored sociodemographic associations before large-scale implementation. METHODS: We pooled responses from two of the first cross-sectional Demographic and Health Surveys to include HIV self-testing (HIVST) questions in Malawi and Zimbabwe in 2015-16. We investigated sociodemographic factors and sexual risk behaviours associated with previously testing for HIV, and past use, awareness of, and future willingness to self-test using univariable and multivariable logistic regression, adjusting for the sample design and limiting analysis to participants with a completed questionnaire and valid HIV test result. We restricted analysis of willingness to self-test to Zimbabwean men, as women and Malawians were not systematically asked this question. RESULTS: Of 31,385 individuals, 31.2% of men had never tested compared with 16.5% of women (p < 0.001). For men, the likelihood of having ever tested increased with age. Past use and awareness of HIVST was very low, 1.2 and 12.6%, respectively. Awareness was lower among women than men (9.1% vs 15.3%, adjusted odds ratio [aOR] = 1.55; 95% confidence interval [CI]: 1.37-1.75), and at younger ages, and lower education and literacy levels. Willingness to self-test among Zimbabwean men was high (84.5%), with greater willingness associated with having previously tested for HIV, being at high sexual risk (highest willingness [aOR = 3.74; 95%CI: 1.39-10.03, p < 0.009]), and being ≥25 years old. Wealthier men had greater awareness of HIVST than poorer men (p < 0.001). The highest willingness to self-test (aOR = 3.74; 95%CI: 1.39-10.03, p < 0.009) was among men at high HIV-related sexual risk. CONCLUSIONS: In 2015-16, many Malawian and Zimbabwean men had never tested for HIV. Despite low awareness and minimal HIVST experience, willingness to self-test was high among Zimbabwean men, especially older men with moderate-to-high HIV-related sexual risk. These data provide a valuable baseline against which to investigate population-level uptake of HIVST as programmes scale up. Programmes introducing, or planning to introduce, HIVST should consider including relevant questions in population-based surveys

Awareness, use and willingness to self-test for HIV: An analysis of cross-sectional population-based surveys in Malawi and Zimbabwe

Abstract Background Many southern African countries are nearing the global goal to diagnose 90% of people with HIV by 2020. In 2016, 84% and 86% of people with HIV knew their status in Malawi and Zimbabwe respectively. Despite this progress, gaps remain, particularly among men (≥25 years). We investigated awareness, use and willingness to HIV self-test (HIVST) prior to large scale implementation and explored sociodemographic associations.Methods We pooled responses from two of the first cross-sectional Demographic Health Surveys to include HIVST questions: Malawi and Zimbabwe in 2015-16. Sociodemographic factors and sexual risk behaviours associated with never testing for HIV, and awareness, past use and future willingness to self-test were investigated using univariable and multivariable logistic regression, adjusting for the sample design and limiting analysis to participants with completed questionnaire and a valid HIV result. Analysis of willingness to self-test was restricted to Zimbabwean men as Malawians and women were not asked this question.Results Of 31 385 individuals, the proportion never-tested was higher for men (31.2%) than women (16.5%), p&lt;0.001. For men, having ever tested increased with age. Past use and awareness of HIVST was very low, 1.2% and 12.6% respectively. Awareness was lower among women than men (9.1% vs 15.3%, adjusted odds ratio (aOR)=1.55; 95% confidence interval [CI]: 1.37-1.75), and at younger age, and lower education and literacy levels. Willingness to self-test among Zimbabwean men was high (84.5%), with having previously tested for HIV, high sexual risk, and being older (≥25 years) associated with greater willingness. Wealthy men had greater awareness of HIVST than poorer men (p&lt;0.001). Men at higher sexual risk, compared to men at lower risk, had the greatest willingness to self-test (aOR=3.74; 95%CI: 1.39-10.03, p&lt;0.009).Conclusions In 2015-16 many Malawian and Zimbabwean men had never tested for HIV. Despite low awareness and minimal HIVST experience at that time, willingness to self-test was high, especially in older men with moderate to high sexual risk. These data provide a valuable baseline against which to investigate population-level uptake of HIVST as programmes scale-up. Programmes introducing, or planning to introduce HIVST, should consider including questions in population-based surveys.</jats:p

Use, awareness and willingness to self-test for HIV: An analysis of cross-sectional population-based surveys in Malawi and Zimbabwe

Abstract Background Many southern African countries are nearing the global goal to diagnose 90% of people with HIV by 2020. In 2016, 84% and 86% of people with HIV knew their status in Malawi and Zimbabwe respectively. Despite this progress, gaps remain, particularly among men (≥25 years). We investigated awareness, use and willingness to HIV self-test (HIVST) prior to large scale implementation and explored sociodemographic associations. Methods We pooled responses from two of the first cross-sectional Demographic Health Surveys to include HIVST questions: Malawi and Zimbabwe in 2015-16. Sociodemographic factors and sexual risk behaviours associated with previously testing for HIV, and awareness, past use and future willingness to self-test were investigated using univariable and multivariable logistic regression, adjusting for the sample design and limiting analysis to participants with completed questionnaire and a valid HIV result. Analysis of willingness to self-test was restricted to Zimbabwean men, as Malawians and women were not asked this question. Results Of 31 385 individuals, the proportion never-tested was higher for men (31.2%) than women (16.5%), p&lt;0.001. For men, having ever tested increased with age. Past use and awareness of HIVST was very low, 1.2% and 12.6% respectively. Awareness was lower among women than men (9.1% vs 15.3%, adjusted odds ratio (aOR)=1.55; 95% confidence interval [CI]: 1.37-1.75), and at younger ages, and lower education and literacy levels. Willingness to self-test among Zimbabwean men was high (84.5%), with having previously tested for HIV, high sexual risk, and being ≥25 years associated with greater willingness. Wealthier men had greater awareness of HIVST than poorer men (p&lt;0.001). Men at higher HIV-related sexual risk, compared to men at lower HIV-related sexual risk, had the greatest willingness to self-test (aOR=3.74; 95%CI: 1.39-10.03, p&lt;0.009).Conclusions In 2015-16 many Malawian and Zimbabwean men had never tested for HIV. Despite low awareness and minimal HIVST experience at that time, willingness to self-test was high among Zimbabwean men, especially in older men with moderate to high HIV-related sexual risk. These data provide a valuable baseline against which to investigate population-level uptake of HIVST as programmes scale-up. Programmes introducing, or planning to introduce HIVST, should consider including questions in population-based surveys.</jats:p

AAV-mediated expression of anti-tau scFvs decreases tau accumulation in a mouse model of tauopathy

Tauopathies are characterized by the progressive accumulation of hyperphosphorylated, aggregated forms of tau. Our laboratory has previously demonstrated that passive immunization with an anti-tau antibody, HJ8.5, decreased accumulation of pathological tau in a human P301S tau-expressing transgenic (P301S-tg) mouse model of frontotemporal dementia/tauopathy. To investigate whether the

Renal and Cardiovascular Morbidities Associated with APOL1 Status among African-American and Non-African-American Children with Focal Segmental Glomerulosclerosis

Background and objectives: African American (AA) children with focal segmental glomerulosclerosis (FSGS) have later onset disease that progresses more rapidly than in non-AA children. It is unclear how APOL1 genotypes contribute to kidney disease risk, progression and cardiovascular morbidity in children. Design, setting, participants, & measurements: We examined the prevalence of APOL1 genotypes and associated cardiovascular phenotypes among children with FSGS in the Chronic Kidney Disease in Children (CKiD) study; an ongoing multicenter prospective cohort study of children aged 1-16 years with mild to moderate kidney disease.Results: A total of 140 AA children in the CKiD study were genotyped. HR APOL1 genotypes were present in 24% of AA children (33/140) and were associated with FSGS, p 3 mg/L (33% vs. 15%, p=0.12) and obesity (48% vs. 19%, p=0.01). There were no differences in glomerular filtration rate, hemoglobin, iPTH, or calcium-phosphate product. Conclusions: AA children with HR APOL1 genotype and FSGS have increase prevalence of obesity and LVH despite a later age of FSGS onset, while adjusting for socioeconomic status. Treatment of obesity may be an important component of CKD and LVH management in this population

Detectors for the James Webb Space Telescope Near-Infrared Spectrograph I: Readout Mode, Noise Model, and Calibration Considerations

We describe how the James Webb Space Telescope (JWST) Near-Infrared Spectrograph's (NIRSpec's) detectors will be read out, and present a model of how noise scales with the number of multiple non-destructive reads sampling-up-the-ramp. We believe that this noise model, which is validated using real and simulated test data, is applicable to most astronomical near-infrared instruments. We describe some non-ideal behaviors that have been observed in engineering grade NIRSpec detectors, and demonstrate that they are unlikely to affect NIRSpec sensitivity, operations, or calibration. These include a HAWAII-2RG reset anomaly and random telegraph noise (RTN). Using real test data, we show that the reset anomaly is: (1) very nearly noiseless and (2) can be easily calibrated out. Likewise, we show that large-amplitude RTN affects only a small and fixed population of pixels. It can therefore be tracked using standard pixel operability maps.Comment: 55 pages, 10 figure

Sundaic elephants prefer habitats on the periphery of protected areas

Protected areas (PAs) are a cornerstone of global conservation strategies. PAs, however, are not equally effective for all threatened taxa, and it is important to understand taxa-specific effectiveness of PAs networks. In this study, we evaluate the role of the PAs network on the protection of Asian elephants Elephas maximus and their habitats in Southeast Asia's Sundaic region. Since Asian elephants tend to prefer secondary forests or forest gaps, we predicted that PAs would not represent the species preferred habitats. We conducted the most comprehensive analysis of Asian elephant space and habitat use to date through home range estimations and step selection function analyses using over 600,000 Global Positioning System locations from 102 different elephants from Peninsular Malaysia and Borneo. Our results revealed important similarities in the habitat use of elephants in both regions, with both females and males in Peninsular Malaysia and Sabah preferring secondary forest, forest gaps and areas of regrowth and new plantations. Our results supported our prediction that PAs do not represent Asian elephants' preferred habitats, since for most of the elephants, more than half of their ranges were outside PAs and the probability of selection values for both sexes in both geographical areas were lower inside than outside the PAs. Synthesis and applications. Our analysis suggests that conservation strategies need to acknowledge that the long-term survival of Asian elephants in the Sundaic region relies on our capacity to promote human–elephant coexistence at the boundaries of PAs. We advocate that Asian elephant conservation strategies should be based on the following three key points: (1) large PAs with core areas where elephants can find safety and potentially survive in the long term; (2) promoting connectivity among PAs using a system of wildlife corridors; and (3) effective human–elephant conflict management outside PAs