Making birth control acceptable : the development of the twentieth century birth control movement.

This thesis is an examination of the tactics used by individuals in the development of the twentieth century birth control movement. It focuses on the creation of a national organization that directed the movement throughout the United States. The twentieth century political and economic environment influenced the birth control movement, but key individuals navigated the environment and developed a program of dissemination and education that furthered the cause of birth control. The intention is to show that Sanger and her cohort expanded upon nineteenth century efforts to provide people reproductive control. The twentieth century political and economic environment influenced the birth control movement, but key individuals navigated the environment and developed a program of dissemination and education that furthered the cause of birth control. The thesis has four chapters including an introduction and conclusion

A Six-Gene Signature Predicts Survival of Patients with Localized Pancreatic Ductal Adenocarcinoma

Jen Jen Yeh and colleagues developed and validated a six-gene signature in patients with pancreatic ductal adenocarcinoma that may be used to better stage the disease in these patients and assist in treatment decisions

Bio-impedance spectroscopy added to a fluid management protocol does not improve preservation of residual kidney function in incident hemodialysis patients in a randomized controlled trial

Avoiding excessive dialysis-associated volume depletion may help preserve residual kidney function (RKF). To establish whether knowledge of the estimated normally hydrated weight from bioimpedance measurements (BI-NHW) when setting the post-hemodialysis target weight (TW) might mitigate rate of loss of RKF, we undertook an open label, randomized controlled trial in incident patients receiving HD, with clinicians and patients blinded to bioimpedance readings in controls. A total of 439 patients with over 500 ml urine/day or residual GFR exceeding 3 ml/min/1.73m2 were recruited from 34 United Kingdom centers and randomized 1:1, stratified by center. Fluid assessments were made for up to 24 months using a standardized proforma in both groups, supplemented by availability of BI-NHW in the intervention group. Primary outcome was time to anuria, analyzed using competing-risk survival models adjusted for baseline characteristics, by intention to treat. Secondary outcomes included rate of RKF decline (mean urea and creatinine clearance), blood pressure and patient-reported outcomes. There were no group differences in cause-specific hazard rates of anuria (0.751; 95% confidence interval (0.459, 1.229)) or sub-distribution hazard rates (0.742 (0.453, 1.215)). RKF decline was markedly slower than anticipated, pooled linear rates in year 1: –0.178 (–0.196, –0.159)), year 2: –0.061 (–0.086, –0.036)) ml/min/1.73m2/month. Blood pressure and patient-reported outcomes did not differ by group. The mean difference agreement between TW and BI-NHW was similar for both groups, Bioimpedance: –0.04 kg; Control: –0.25 kg. Thus, use of a standardized clinical protocol for fluid assessment when setting TW is associated with excellent preservation of RKF. Hence, bioimpedance measurements are not necessary to achieve this

Rationale and design of BISTRO: a randomized controlled trial to determine whether bioimpedance spectroscopy guided fluid management maintains residual kidney function in incident haemodialysis patients

Background: Preserved residual kidney function (RKF) and normal fluid status are associated with better patient outcomes in incident haemodialysis patients. The objective of this trial is to determine whether using bioimpedance technology in prescribing the optimal post-dialysis weight can reduce the rate of decline of RKF and potentially improve patient outcomes. Methods/Design: 516 patients commencing haemodialysis, aged >18 with RKF of > 3 ml/min/1.73 m2 or a urine volume >500 ml per day or per the shorter inter-dialytic period will be consented and enrolled into a pragmatic, open label, randomized controlled trial. The intervention is incorporation of bioimpedance spectroscopy (BI) determination of normally hydrated weight to set a post-dialysis target weight that limits volume depletion, compared to current standard practice. Clinicians and participants will be blinded to BI measures in the control group and a standardized record capturing management of fluid status will be used in all participants. Primary outcome is preservation of residual kidney function assessed as time to anuria (≤100 ml/day or ≤200 ml urine volume in the short inter-dialytic period). A sample size of 516 was based upon a cumulative incidence of 30% anuria in the control group and 20% in the treatment group and 11% competing risks (death, transplantation) over 10 months, with up to 2 years follow-up. Secondary outcomes include rate of decline in small solute clearance, significant adverse events, hospitalization, loss of vascular access, cardiovascular events and interventions, dialysis efficacy and safety, dialysis-related symptoms and quality of life. Economic evaluation will be carried out to determine the cost-effectiveness of the intervention. Analyses will be adjusted for patient characteristics and dialysis unit practice patterns relevant to fluid management. Discussion: This trial will establish the added value of undertaking BI measures to support clinical management of fluid status and establish the relationship between fluid status and preservation of residual kidney function in incident haemodialysis patients. Trial registration: ISCCTN Number: 11342007, completed 26/04/2016; NIHR Portfolio number: CPMS31766; Sponsor: Keele University Keywords: Fluid status, Body composition, Residual kidney function, Haemodialysis, Bioimpedance, Fluid management, Health economic

Activated iNKT Cells Promote Memory CD8+ T Cell Differentiation during Viral Infection

α-galactosylceramide (α-GalCer) is the prototypical lipid ligand for invariant NKT cells. Recent studies have proposed that α-GalCer is an effective adjuvant in vaccination against a range of immune challenges, however its mechanism of action has not been completely elucidated. A variety of delivery methods have been examined including pulsing dendritic cells with α-GalCer to optimize the potential of α-GalCer. These methods are currently being used in a variety of clinical trials in patients with advanced cancer but cannot be used in the context of vaccine development against pathogens due to their complexity. Using a simple delivery method, we evaluated α-GalCer adjuvant properties, using the mouse model for cytomegalovirus (MCMV). We measured several key parameters of the immune response to MCMV, including inflammation, effector, and central memory CD8+ T cell responses. We found that α-GalCer injection at the time of the infection decreases viral titers, alters the kinetics of the inflammatory response, and promotes both increased frequencies and numbers of virus-specific memory CD8+ T cells. Overall, our data suggest that iNKT cell activation by α-GalCer promotes the development of long-term protective immunity through increased fitness of central memory CD8+ T cells, as a consequence of reduced inflammation

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups

Letter from Elizabeth G. Caskey to Emmett L. Bennett Jr., March 03, 1953

Caskey thanks Bennett for his donation of the Complete Greek Drama.Classic

Clostridium subterminale

Clostridium subterminale is a rare member of the Clostridiaceae family that is rarely cultured. This report examines a case of Clostridium subterminale cultured from the blood of a 72-year-old man who was ultimately diagnosed with metastatic gastrointestinal (GI) adenocarcinoma. The patient was receiving treatment for nosocomial pneumonia prior to culture of the C. subterminale, which led to suspicion for malignancy. Extensive GI and oncologic workup demonstrated multiple comorbidities and a primary GI cancer, which likely caused a breach in the GI mucosa and C. subterminale entrance into the bloodstream. After a prolonged intensive care unit (ICU) stay, the patient died on hospital day 23. Though rarely reported, C. subterminale septicemia has been demonstrated in patients with malignancy, specifically of the GI tract. Therefore, this case represents a typical C. subterminale septicemia patient. Given the prevalence of Clostridia and the contemporary emergence of multidrug resistant (MDR) microorganisms, both typical and atypical cases regarding rare members of the species have a significant role in the clinical management and public health planning

Clostridium subterminale Septicemia in a Patient with Metastatic Gastrointestinal Adenocarcinoma

Clostridium subterminale is a rare member of the Clostridiaceae family that is rarely cultured. This report examines a case of Clostridium subterminale cultured from the blood of a 72-year-old man who was ultimately diagnosed with metastatic gastrointestinal (GI) adenocarcinoma. The patient was receiving treatment for nosocomial pneumonia prior to culture of the C. subterminale, which led to suspicion for malignancy. Extensive GI and oncologic workup demonstrated multiple comorbidities and a primary GI cancer, which likely caused a breach in the GI mucosa and C. subterminale entrance into the bloodstream. After a prolonged intensive care unit (ICU) stay, the patient died on hospital day 23. Though rarely reported, C. subterminale septicemia has been demonstrated in patients with malignancy, specifically of the GI tract. Therefore, this case represents a typical C. subterminale septicemia patient. Given the prevalence of Clostridia and the contemporary emergence of multidrug resistant (MDR) microorganisms, both typical and atypical cases regarding rare members of the species have a significant role in the clinical management and public health planning