Adipose Tissue Distribution and Survival Among Women with Nonmetastatic Breast Cancer.

ObjectivePrevious studies of breast cancer survival have not considered specific depots of adipose tissue such as subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT).MethodsThis study assessed these relationships among 3,235 women with stage II and III breast cancer diagnosed between 2005 and 2013 at Kaiser Permanente Northern California and between 2000 and 2012 at Dana Farber Cancer Institute. SAT and VAT areas (in centimeters squared) were calculated from routine computed tomography scans within 6 (median: 1.2) months of diagnosis, covariates were collected from electronic health records, and vital status was assessed by death records. Hazard ratios (HRs) and 95% CIs were estimated using Cox regression.ResultsSAT and VAT ranged from 19.0 to 891 cm2 and from 0.484 to 454 cm2 , respectively. SAT was related to increased risk of death (127-cm2 increase; HR [95% CI]: 1.13 [1.02-1.26]), but no relationship was found with VAT (78.18-cm2 increase; HR [95% CI]: 1.02 [0.91-1.14]). An association with VAT was noted among women with stage II cancer (stage II: HR: 1.17 [95% CI: 0.99-1.39]; stage III: HR: 0.90 [95% CI: 0.76-1.07]; P interaction < 0.01). Joint increases in SAT and VAT were associated with mortality above either alone (simultaneous 1-SD increase: HR 1.19 [95% CI: 1.05-1.34]).ConclusionsSAT may be an underappreciated risk factor for breast cancer-related death

Menstrual disturbances in perimenopausal women: What's best?

It's best to start with nonsteroidal anti- inflammatory drugs (NSAIDs), which effectively reduce heavy menstrual bleeding (strength of recommendation [SOR]: B, systematic review of randomized clinical trials [RCTs]). Perimenopausal women with heavy bleeding not controlled by NSAIDs, or other forms of dysfunctional uterine bleeding, can benefit from continuous, combined hormonal therapy with estrogen and progestin; hormonal therapy with estrogen and a cyclical progestin; or a cyclical progestin alone (SOR: B, RCTs and a systematic review of RCTs). Intrauterine devices (IUDs) containing levonorgestrel also effectively reduce bleeding and may avoid surgical intervention (SOR: B, systematic review of RCTs)

Effect of ovariectomy on the progression of chronic kidney disease-mineral bone disorder (CKD-MBD) in female Cy/+ rats

Male Cy/+ rats have shown a relatively consistent pattern of progressive kidney disease development that displays multiple key features of late stage chronic kidney disease-mineral bone disorder (CKD-MBD), specifically the development of cortical bone porosity. However, progression of disease in female Cy/+ rats, assessed in limited studies, is more heterogeneous and to date has failed to show development of the CKD-MBD phenotype, thus limiting their use as a practical model of progressive CKD-MBD. Animal and human studies suggest that estrogen may be protective against kidney disease in addition to its established protective effect on bone. Therefore, in this study, we aimed to determine the effect of ovariectomy (OVX) on the biochemical and skeletal manifestations of CKD-MBD in Cy/+ female rats. We hypothesized that OVX would accelerate development of the biochemical and skeletal features of CKD-MBD in female Cy/+ rats, similar to those seen in male Cy/+ rats. Female Cy/+ rats underwent OVX (n = 8) or Sham (n = 8) surgery at 15 weeks of age. Blood was collected every 5 weeks post-surgery until 35 weeks of age, when the rats underwent a 4-day metabolic balance, and the tibia and final blood were collected at the time of sacrifice. OVX produced the expected changes in trabecular and cortical parameters consistent with post-menopausal disease, and negative phosphorus balance compared with Sham. However, indicators of CKD-MBD were similar between OVX and Sham (similar kidney weight, plasma blood urea nitrogen, creatinine, creatinine clearance, phosphorus, calcium, parathyroid hormone, and no cortical porosity). Contrary to our hypothesis, OVX did not produce evidence of development of the CKD-MBD phenotype in female Cy/+ rats

Prostate-specific antigen, sexual behavior, and sexually transmitted infections in US men 40–59 years old, 2001–2004: a cross – sectional study

<p>Abstract</p> <p>Background</p> <p>Sexually transmitted infections (STIs) are hypothesized to play a role in the development of prostate cancer, perhaps due to inflammation-induced oncogenesis. We assessed in a nationally representative population of middle-aged men whether sexual behavior indicators for an increased risk of genital infection were associated with serum prostate-specific antigen (PSA) concentration, a marker of prostatic disease and inflammation.</p> <p>Results</p> <p>The percentage of men between the ages of 40 and 59 with a PSA ≥ 4.0 ng/ml was 2.6% (95% confidence interval [CI], 1.8% – 3.8%). The percentage of men between the ages of 40 and 59 self-reporting a past diagnosis of genital warts or genital herpes, or a recent diagnosis of gonorrhea or chlamydia is estimated to be 7.3% (95% CI, 6.2% – 8.6%). Men self-reporting that they had had sex without using a condom in the past month had a lower PSA concentration and higher %fPSA than those who did not. There were no associations between any of the other sexual activity or laboratory measures and PSA or %fPSA.</p> <p>Conclusion</p> <p>In this nationally representative sample of middle-aged American men, we did not find consistent evidence for an association between sexual behavior or a history of STIs and PSA levels. Therefore, sexual factors are unlikely to lead to falsely elevated PSA tests in this population. We cannot rule out the role of these factors in causing false positive PSA tests in subgroups of the population that have a higher prevalence of high-risk sexual behavior, and more protracted or recent exposures to these agents.</p

Using Case Description Information to Reduce Sensitivity to Bias for the Attributable Fraction Among the Exposed

The attributable fraction among the exposed (\textbf{AF}$_e$), also known as the attributable risk or excess fraction among the exposed, is the proportion of disease cases among the exposed that could be avoided by eliminating the exposure. Understanding the \textbf{AF}$_e$ for different exposures helps guide public health interventions. The conventional approach to inference for the \textbf{AF}$_e$ assumes no unmeasured confounding and could be sensitive to hidden bias from unobserved covariates. In this paper, we propose a new approach to reduce sensitivity to hidden bias for conducting statistical inference on the \textbf{AF}$_e$ by leveraging case description information. Case description information is information that describes the case, e.g., the subtype of cancer. The exposure may have more of an effect on some types of cases than other types. We explore how leveraging case description information can reduce sensitivity to bias from unmeasured confounding through an asymptotic tool, design sensitivity, and simulation studies. We allow for the possibility that leveraging case definition information may introduce additional selection bias through an additional sensitivity parameter. The proposed methodology is illustrated by re-examining alcohol consumption and the risk of postmenopausal invasive breast cancer using case description information on the subtype of cancer (hormone-sensitive or insensitive) using data from the Women's Health Initiative (WHI) Observational Study (OS).Comment: 30 pages, 8 tables, 1 figur

A Dense Packing of Regular Tetrahedra

We construct a dense packing of regular tetrahedra, with packing density $D > >.7786157$.Comment: full color versio

Travelers’ diarrhea and other gastrointestinal symptoms among Boston-area international travelers

INTRODUCTION: Travelers' diarrhea (TD) and non-TD gastrointestinal (GI) symptoms are common among international travelers. In a study of short-term travelers from Switzerland to developing countries, the most common symptom experienced was severe diarrhea (8.5%) followed by vomiting or abdominal cramps (4%).1 GI illnesses were the most frequently reported diagnoses (34%) among ill-returned travelers to GeoSentinel clinics.2 Of those returning to U.S. GeoSentinel clinics, acute diarrhea (30%) was the most common diagnosis.3 In one cohort of U.S. travelers, 46% reported diarrhea.4 GI illnesses can last from 2 days to weeks or longer,5 disrupting plans during travel or after returning home. Eighty percent of those who experienced diarrhea during travel treated themselves with medication and 6% sought medical care. METHODS: The Boston Area Travel Medicine Network (BATMN) is a research collaboration of travel clinics in the greater Boston area representing urban-, suburban-, academic-, and university-affiliated facilities. A convenience sample of travelers ≥ 18 years of age attending three BATMN clinics between 2009 and 2011 for pre-travel consultations completed pre-travel surveys, at least one survey weekly during travel, and a post-travel survey 2–4 weeks after return. Travelers were asked to complete a survey at the end of each week of their trip. Institutional review board approvals were obtained at all sites and the Centers for Disease Control and Prevention, and participants provided written informed consent. Information collected included demographic and trip characteristics, vaccines and medications recommended/prescribed before travel, medications taken during travel, dietary practices during travel (consumption of tap water, ice in drinks, unpasteurized dairy products, and salads), symptoms experienced, and impact of illness during and after travel. Vaccinations, prescriptions, and travel health advice given during the pre-travel consultation were recorded by a clinician, and the remainder of the surveys were completed by the traveler. Data were entered into a password-protected database (CS Pro, U.S. Census Bureau, Washington, DC). RESULTS: We enrolled 987 travelers; 628 (64%) completed all three parts (pre-, during, and post-travel) and were included in the study. Comparison of the 628 to the 359 who did not complete all three parts (noncompleters) revealed no differences, except that completion rates were higher for white travelers than all other racial/ethnic groups (P < 0.001) and for older travelers (median age 47 years versus 32 years in noncompleters, P < 0.001).11 Of those 628 travelers, 208 (33%) experienced TD, 45 (7%) experienced non-TD GI symptoms, 147 (23%) experienced non-GI symptoms, and 228 (36%) did not experience any symptoms during or after travel. Of the 208 with TD, 140 (67%) reported diarrhea as their only symptom, whereas 33 (16%) also experienced nausea/vomiting, 23 (11%) abdominal pain, and 27 (13%) fever (Table 1). Of the 45 who reported non-TD GI symptoms, 21 (47%) experienced nausea/vomiting, 19 (42%) experienced constipation, and 10 (22%) experienced abdominal pain during or after travel (Table 2). Almost all travelers (99%) received advice about food and water precautions and diarrhea management during pre-travel consultation

Inhibitors of SARS-CoV entry--identification using an internally-controlled dual envelope pseudovirion assay.

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) emerged as the causal agent of an endemic atypical pneumonia, infecting thousands of people worldwide. Although a number of promising potential vaccines and therapeutic agents for SARS-CoV have been described, no effective antiviral drug against SARS-CoV is currently available. The intricate, sequential nature of the viral entry process provides multiple valid targets for drug development. Here, we describe a rapid and safe cell-based high-throughput screening system, dual envelope pseudovirion (DEP) assay, for specifically screening inhibitors of viral entry. The assay system employs a novel dual envelope strategy, using lentiviral pseudovirions as targets whose entry is driven by the SARS-CoV Spike glycoprotein. A second, unrelated viral envelope is used as an internal control to reduce the number of false positives. As an example of the power of this assay a class of inhibitors is reported with the potential to inhibit SARS-CoV at two steps of the replication cycle, viral entry and particle assembly. This assay system can be easily adapted to screen entry inhibitors against other viruses with the careful selection of matching partner virus envelopes