John Colter- The Man Who Turned Back

"Colter makes his first appearance when he enlisted as a private in the Lewis and Clark Expedition, on October 15, 1803.

Nonadherence to primary prophylaxis against Pneumocystis jirovecii pneumonia.

BackgroundDespite the effectiveness of prophylaxis, Pneumocystis jirovecii pneumonia (PCP) continues to be the most common serious opportunistic infection among HIV-infected persons. We describe factors associated with nonadherence to primary PCP prophylaxis.Methodology/principal findingsWe used 2000-2004 data from the Supplement to HIV/AIDS Surveillance (SHAS) project, a cross-sectional interview project of HIV-infected persons >or=18 years conducted in 18 states. We limited the analysis to persons who denied having prior PCP, reported having a current prescription to prevent PCP, and answered the question "In the past 30 days, how often were you able to take the PCP medication(s) exactly the way your doctor told you to take them?" We used multivariable logistic regression to describe factors associated with nonadherence. Of 1,666 subjects prescribed PCP prophylaxis, 305 (18.3%) were nonadherent. Persons were more likely to be nonadherent if they reported using marijuana (adjusted odds ratio [aOR] = 1.6, 95% confidence interval [CI] = 1.1-2.4), non-injection drugs other than marijuana (aOR = 1.5, 95% CI = 1.0-2.1), or injection drugs (aOR = 2.3, 95% CI = 1.3-4.1) in the past year; their mental health was "not good" for >or=1 day during the past month (aOR = 1.6, 95% CI = 1.2-2.2); their most recent CD4 count was <200 cells/microL (aOR = 1.6, 95% CI = 1.1-2.2); or taking ART usually (aOR = 9.6, 95% CI = 6.7-13.7) or sometimes/rarely/never (aOR = 18.4, 95% CI = 11.1-30.4), compared with always, as prescribed.Conclusion/significanceProviders should inquire about and promote strategies to improve adherence to PCP prophylaxis, particularly among persons who use illicit drugs, have mental health issues, and who are not compliant with ART to reduce the occurrence of PCP

Impact of 13-Valent Pneumococcal Conjugate Vaccine on Colonization and Invasive Disease in Cambodian Children

Background Cambodia introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in January 2015 using a 3 + 0 dosing schedule and no catch-up campaign. We investigated the effects of this introduction on pneumococcal colonization and invasive disease in children aged <5 years. Methods There were 6 colonization surveys done between January 2014 and January 2018 in children attending the outpatient department of a nongovernmental pediatric hospital in Siem Reap. Nasopharyngeal swabs were analyzed by phenotypic and genotypic methods to detect pneumococcal serotypes and antimicrobial resistance. Invasive pneumococcal disease (IPD) data for January 2012–December 2018 were retrieved from hospital databases. Pre-PCV IPD data and pre-/post-PCV colonization data were modelled to estimate vaccine effectiveness (VE). Results Comparing 2014 with 2016–2018, and using adjusted prevalence ratios, VE estimates for colonization were 16.6% (95% confidence interval [CI] 10.6–21.8) for all pneumococci and 39.2% (95% CI 26.7–46.1) for vaccine serotype (VT) pneumococci. There was a 26.0% (95% CI 17.7–33.0) decrease in multidrug-resistant pneumococcal colonization. The IPD incidence was estimated to have declined by 26.4% (95% CI 14.4–35.8) by 2018, with a decrease of 36.3% (95% CI 23.8–46.9) for VT IPD and an increase of 101.4% (95% CI 62.0–145.4) for non-VT IPD. Conclusions Following PCV13 introduction into the Cambodian immunization schedule, there have been declines in VT pneumococcal colonization and disease in children aged <5 years. Modelling of dominant serotype colonization data produced plausible VE estimates

Identifying the favored mutation in a positive selective sweep.

Most approaches that capture signatures of selective sweeps in population genomics data do not identify the specific mutation favored by selection. We present iSAFE (for "integrated selection of allele favored by evolution"), a method that enables researchers to accurately pinpoint the favored mutation in a large region (∼5 Mbp) by using a statistic derived solely from population genetics signals. iSAFE does not require knowledge of demography, the phenotype under selection, or functional annotations of mutations

Hunting and mountain sheep: Do current harvest practices affect horn growth?

The influence of human harvest on evolution of secondary sexual characteristics has implications for sustainable management of wildlife populations. The phenotypic consequences of selectively removing males with large horns or antlers from ungulate populations have been a topic of heightened concern in recent years. Harvest can affect size of horn-like structures in two ways: (a) shifting age structure toward younger age classes, which can reduce the mean size of horn-like structures, or (b) selecting against genes that produce large, fast-growing males. We evaluated effects of age, climatic and forage conditions, and metrics of harvest on horn size and growth of mountain sheep (Ovis canadensis ssp.) in 72 hunt areas across North America from 1981 to 2016. In 50% of hunt areas, changes in mean horn size during the study period were related to changes in age structure of harvested sheep. Environmental conditions explained directional changes in horn growth in 28% of hunt areas, 7% of which did not exhibit change before accounting for effects of the environment. After accounting for age and environment, horn size of mountain sheep was stable or increasing in the majority (similar to 78%) of hunt areas. Age-specific horn size declined in 44% of hunt areas where harvest was regulated solely by morphological criteria, which supports the notion that harvest practices that are simultaneously selective and intensive might lead to changes in horn growth. Nevertheless, phenotypic consequences are not a foregone conclusion in the face of selective harvest; over half of the hunt areas with highly selective and intensive harvest did not exhibit age-specific declines in horn size. Our results demonstrate that while harvest regimes are an important consideration, horn growth of harvested male mountain sheep has remained largely stable, indicating that changes in horn growth patterns are an unlikely consequence of harvest across most of North America.Utah Division of Wildlife Resources; National Wild Sheep Foundation (WSF); Wyoming Wild Sheep Foundation; Alberta Wild Sheep Foundation; California Wild Sheep Foundation; Arizona Desert Bighorn Sheep Society; Wyoming Governor's Big Game License Coalition; Iowa Foundation for North American Wild Sheep; Utah Foundation for North American Wild Sheep; Pope and Young ClubOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Breast fibroblasts modulate epithelial cell proliferation in three-dimensional in vitro co-culture

BACKGROUND: Stromal fibroblasts associated with in situ and invasive breast carcinoma differ phenotypically from fibroblasts associated with normal breast epithelium, and these alterations in carcinoma-associated fibroblasts (CAF) may promote breast carcinogenesis and cancer progression. A better understanding of the changes that occur in fibroblasts during carcinogenesis and their influence on epithelial cell growth and behavior could lead to novel strategies for the prevention and treatment of breast cancer. To this end, the effect of CAF and normal breast-associated fibroblasts (NAF) on the growth of epithelial cells representative of pre-neoplastic breast disease was assessed. METHODS: NAF and CAF were grown with the nontumorigenic MCF10A epithelial cells and their more transformed, tumorigenic derivative, MCF10AT cells, in direct three-dimensional co-cultures on basement membrane material. The proliferation and apoptosis of MCF10A cells and MCF10AT cells were assessed by 5-bromo-2'-deoxyuridine labeling and TUNEL assay, respectively. Additionally, NAF and CAF were compared for expression of insulin-like growth factor II as a potential mediator of their effects on epithelial cell growth, by ELISA and by quantitative, real-time PCR. RESULTS: In relatively low numbers, both NAF and CAF suppressed proliferation of MCF10A cells. However, only NAF and not CAF significantly inhibited proliferation of the more transformed MCF10AT cells. The degree of growth inhibition varied among NAF or CAF from different individuals. In greater numbers, NAF and CAF have less inhibitory effect on epithelial cell growth. The rate of epithelial cell apoptosis was not affected by NAF or CAF. Mean insulin-like growth factor II levels were not significantly different in NAF versus CAF and did not correlate with the fibroblast effect on epithelial cell proliferation. CONCLUSION: Both NAF and CAF have the ability to inhibit the growth of pre-cancerous breast epithelial cells. NAF have greater inhibitory capacity than CAF, suggesting that the ability of fibroblasts to inhibit epithelial cell proliferation is lost during breast carcinogenesis. Furthermore, as the degree of transformation of the epithelial cells increased they became resistant to the growth-inhibitory effects of CAF. Insulin-like growth factor II could not be implicated as a contributor to this differential effect of NAF and CAF on epithelial cell growth

Willingness of Men Who Have Sex with Men (MSM) in the United States to Be Circumcised as Adults to Reduce the Risk of HIV Infection

BACKGROUND: Circumcision reduces HIV acquisition among heterosexual men in Africa, but it is unclear if circumcision may reduce HIV acquisition among men who have sex with men (MSM) in the United States, or whether MSM would be willing to be circumcised if recommended. METHODS: We interviewed presumed-HIV negative MSM at gay pride events in 2006. We asked uncircumcised respondents about willingness to be circumcised if it were proven to reduce risk of HIV among MSM and perceived barriers to circumcision. Multivariate logistic regression was used to identify covariates associated with willingness to be circumcised. RESULTS: Of 780 MSM, 133 (17%) were uncircumcised. Of these, 71 (53%) were willing to be circumcised. Willingness was associated with black race (exact odds ratio [OR]: 3.4, 95% confidence interval [CI]: 1.3-9.8), non-injection drug use (OR: 6.1, 95% CI: 1.8-23.7) and perceived reduced risk of penile cancer (OR: 4.7, 95% CI: 2.0-11.9). The most commonly endorsed concerns about circumcision were post-surgical pain and wound infection. CONCLUSIONS: Over half of uncircumcised MSM, especially black MSM, expressed willingness to be circumcised. Perceived risks and benefits of circumcision should be a part of educational materials if circumcision is recommended for MSM in the United States