GateFinder: projection-based gating strategy optimization for flow and mass cytometry

Motivation: High-parameter single-cell technologies can reveal novel cell populations of interest, but studying or validating these populations using lower-parameter methods remains challenging.Results: Here, we present GateFinder, an algorithm that enriches high-dimensional cell types with simple, stepwise polygon gates requiring only two markers at a time. A series of case studies of complex cell types illustrates how simplified enrichment strategies can enable more efficient assays, reveal novel biomarkers and clarify underlying biology

HIV-1 Viral loas assays for resource-limited settings

Tremendous strides have been made in treating HIV-1 infection in industrialized countries. Combination therapy with antiretroviral (ARV) drugs suppresses virus replication, delays disease progression, and reduces mortality. In industrialized settings, plasma viral load assays are used in combination with CD4 cell counts to determine when to initiate therapy and when a regimen is failing. In addition, unlike serologic assays, these assays may be used to diagnose perinatal or acute HIV-1 infection. Unfortunately, the full benefits of antiretroviral drugs and monitoring tests have not yet reached the majority of HIV-1-infected patients who live in countries with limited resources. In this article we discuss existing data on the performance of alternative viral load assays that might be useful in resource-limited settings

Safety and efficacy of diaphragm pacing in patients with respiratory insufficiency due to amyotrophic lateral sclerosis (DiPALS)

Background: Non-invasive ventilation is part of the standard of care for treatment of respiratory failure in patients with amyotrophic lateral sclerosis (ALS). The NeuRx RA/4 Diaphragm Pacing System has received Humanitarian Device Exemption approval from the US Food and Drug Administration for treatment of respiratory failure in patients with ALS. We aimed to establish the safety and efficacy of diaphragm pacing with this system in patients with respiratory muscle weakness due to ALS. Methods: We undertook a multicentre, open-label, randomised controlled trial at seven specialist ALS and respiratory centres in the UK. Eligible participants were aged 18 years or older with laboratory supported probable, clinically probable, or clinically definite ALS; stable riluzole treatment for at least 30 days; and respiratory insufficiency. We randomly assigned participants (1:1), via a centralised web-based randomisation system with minimisation that balanced patients for age, sex, forced vital capacity, and bulbar function, to receive either non-invasive ventilation plus pacing with the NeuRx RA/4 Diaphragm Pacing System or non-invasive ventilation alone. Patients, carers, and outcome assessors were not masked to treatment allocation. The primary outcome was overall survival, defined as the time from randomisation to death from any cause. Analysis was by intention to treat. This trial is registered, ISRCTN number 53817913. Findings: Between Dec 5, 2011, and Dec 18, 2013, we randomly assigned 74 participants to receive either non-invasive ventilation alone (n=37) or non-invasive ventilation plus diaphragm pacing (n=37). On Dec 18, 2013, the Data Monitoring and Ethics Committee (DMEC) recommended suspension of recruitment on the basis of overall survival figures. Randomly assigned participants continued as per the study protocol until June 23, 2014, when the DMEC advised discontinuation of pacing in all patients. Follow-up assessments continued until the planned end of the study in December, 2014. Survival was shorter in the non-invasive ventilation plus pacing group than in the non-invasive ventilation alone group (median 11·0 months [95% CI 8·3-13·6] vs 22·5 months [13·6-not reached]; adjusted hazard ratio 2·27, 95% CI 1·22-4·25; p=0·009). 28 (76%) patients died in the pacing group and 19 (51%) patients died in the non-invasive ventilation alone group. We recorded 162 adverse events (5·9 events per person-year) in the pacing group, of which 46 events were serious, compared with 81 events (2·5 events per person-year) in the non-invasive ventilation alone group, of which 31 events were serious. Interpretation: Addition of diaphragm pacing to standard care with non-invasive ventilation was associated with decreased survival in patients with ALS. Our results suggest that diaphragmatic pacing should not be used as a routine treatment for patients with ALS in respiratory failure. Funding: The National Institute for Health Research Health Technology Assessment Programme; the Motor Neurone Disease Association of England, Wales, and Northern Ireland

Watching the clock: keeping time during pregnancy, birth, and postpartum experiences

In this paper, I analyze how different didactic discourses surrounding pregnancy, birth, and postpartum care portray time in procreative events. I investigate advice regarding procreative experiences offered to women by a variety of "experts", and offered by experts to each other, examining literature which demonstrates the wide range of didactic approaches to procreative events that are accessible in US culture, from masculinist medical orthodoxy--the dominant perspective--to the naturalist/feminist midwifery model, with self-help literature reflecting the influence of both ends of this spectrum as well as of consumer-oriented health activism. I explore how the conceptualization of time in the medical discourse contributes to the overpowering or disempowering of procreating women, and how the self-help and midwifery approaches respond to the medical model--ranging on a continuum from reification to refutation. Obstetrics works on women's bodies to make them stay on time and on course; this quest becomes more obsessively time-focused over time. In contrast, the midwifery discourse centers on women active in time, rather than against it. Self-help book authors line up somewhere in the middle, mostly taking medical management of procreative time for granted and occasionally try to show women ways in which we can buy time or bide our time against medicine.Procreative discourses Childbirth Midwifery Obstetrics Pregnancy Procreation

Emergency contraception and morality: reflections of health care workers and clients

In this study, we explore the retrospective reports of 21 US Planned Parenthood clients about their use of emergency contraception pills (ECPs) and the views of ten Planned Parenthood health care workers at two clinics about providing ECPs. We elucidate the sociological phenomena that frame emergency contraception usage: cultural ideology about contraception, sexuality, unintended pregnancy, and abortion. We focus on the ways in which interactions between health care workers and clients both mediate and reinforce such cultural ideology. Our research indicates that the distinctions between fertilization and pregnancy, between contraception and abortion, between responsible and irresponsible procreative behavior, are not hard and fast boundaries upon which everyone agrees. We illuminate the dividing lines and continuities our participants invoked, affirmed, and questioned when contemplating the continuum from potential fertility to realized (and unwanted) pregnancy.Abortion Contraception Contraceptive counseling Emergency contraception USA

Abortion, revised: participants in the U.S. clinical trials evaluate mifepristone

This paper centers on the questions: How do non-surgical abortion methods affect private experiences of abortion? How might they influence public conceptions of abortion? Drawing on interviews with clients who participated in the 1994-95 U.S. clinical trials of mifepristone at one trial site (conducted during the trials), and focus group interviews conducted with health care workers at all 17 trial sites (after the trials were completed), we examine participants' evaluations of this method of abortion. Surgical abortion functioned as the reference point by which research participants assessed medical abortion. They discussed mifepristone abortion in terms of nature and invasion, privacy and bodily integrity, denial and agency. Clients frequently portrayed mifepristone abortion as a better moral choice than surgical abortion--in some cases even depicting it as not-really-an-abortion but rather as a miscarriage. Clients felt that mifepristone offered them a greater measure of control over their abortion experiences. Health care providers offered critical analysis of their clients' perceptions, yet affirmed the potential of medical abortion to offer women greater variety and latitude in procreative decision-making, and perhaps even to depoliticize the issue of abortion in the U.S. by thwarting the efforts of anti-abortionists to target providers and aborting women.abortion, clinical trials, mifepristone, RU-486