Gender Differences in Smoking Among an Urban Emergency Department Sample.

BackgroundUrban emergency department (ED) patients have elevated smoking and substance use compared with the general population. We analyzed gender differences in smoking among an urban ED sample and assessed the contribution of substance use, demographic, and couple factors.MethodsWe conducted a secondary analysis of data obtained from a cross-sectional, observational survey (N = 1037 participants) on drinking, drug use, and intimate partner violence (IPV). Gender-specific logistic regression models for current (past 30-day) smoking and multinomial regression models for smoking intensity (light: ⩽5 cigarettes per day [CPD]; moderate: 6 to 10 CPD; heavier: >10 CPD) were estimated.ResultsSmoking prevalence was higher among men than women (35.5% vs 18.9%; P < .001). Substance use (frequency of intoxication, marijuana, amphetamine, and cocaine use), demographic (food insufficiency, unemployment), and couple-related factors (having a spouse/partner who smoked, IPV involvement, being in a same-gender couple) were differentially associated with current smoking and level of intensity among men and women.ConclusionsEmergency department staff should consider the impact of polysubstance use, food insufficiency, unemployment, and whether both partners in the couple smoke when screening patients for smoking and formulating cessation treatment plans. Women in same-gender relationships and those who have experienced IPV involvement may require additional referral

Divergent Antibody Subclass and Specificity Profiles but Not Protective HLA-B Alleles Are Associated with Variable Antibody Effector Function among HIV-1 Controllers

Understanding the coordination between humoral and cellular immune responses may be the key to developing protective vaccines, and because genetic studies of long-term HIV-1 nonprogressors have associated specific HLA-B alleles with spontaneous control of viral replication, this subject group presents an opportunity to investigate relationships between arms of the adaptive immune system. Given evidence suggesting that cellular immunity may play a role in viral suppression, we sought to determine whether and how the humoral immune response might vary among controllers. Significantly, Fc-mediated antibody effector functions have likewise been associated with durable viral control. In this study, we compared the effector function and biophysical features of HIV-specific antibodies in a cohort of controllers with and without protective HLA-B alleles in order to investigate whether there was evidence for multiple paths to HIV-1 control, or whether cellular and humoral arms of immunity might exhibit coordinated profiles. However, with the exception of IgG2 antibodies to gp41, HLA status was not associated with divergent humoral responses. This finding did not result from uniform antibody responses across subjects, as controllers could be regrouped according to strong differences in their HIV-specific antibody subclass specificity profiles. These divergent antibody profiles were further associated with significant differences in nonneutralizing antibody effector function, with levels of HIV-specific IgG1 acting as the major distinguishing factor. Thus, while HLA background among controllers was associated with minimal differences in humoral function, antibody subclass and specificity profiles were associated with divergent effector function, suggesting that these features could be used to make functional predictions. Because these nonneutralizing antibody activities have been associated with spontaneous viral control, reduced viral load, and nonprogression in infected subjects and protection in vaccinated subjects, understanding the specific features of IgGs with potentiated effector function may be critical to vaccine and therapeutic antibody development

Differences in Disease Severity but Similar Telomere Lengths in Genetic Subgroups of Patients with Telomerase and Shelterin Mutations

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Stable long-term risk of leukaemia in patients with severe congenital neutropenia maintained on G-CSF therapy

In severe congenital neutropenia (SCN), long-term therapy with granulocyte colony-stimulating factor (G-CSF) has reduced mortality from sepsis, revealing an underlying predisposition to myelodysplastic syndrome and acute myeloid leukaemia (MDS/AML). We have reported the early pattern of evolution to MDS/AML, but the long-term risk remains uncertain. We updated a prospective study of 374 SCN patients on long-term G-CSF enrolled in the Severe Chronic Neutropenia International Registry. Long-term, the annual risk of MDS/AML attained a plateau (2·3%/year after 10 years). This risk now appears similar to, rather than higher than, the risk of AML in Fanconi anaemia and dyskeratosis congenita.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79264/1/j.1365-2141.2010.08216.x.pd

Neutrophil elastase mutations and risk of leukaemia in severe congenital neutropenia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73793/1/j.1365-2141.2007.06897.x.pd

Caught in the middle: bottom‑up and top‑down processes impacting recruitment in a small pelagic fsh

Understanding the drivers behind fluctuations in fish populations remains a key objective in fishery science. Our predictive capacity to explain these fluctuations is still relatively low, due to the amalgam of interacting bottom-up and top-down factors, which vary across time and space among and within populations. Gaining a mechanistic understanding of these recruitment drivers requires a holistic approach, combining field, experimental and modelling efforts. Here, we use the Western Baltic Spring-Spawning (WBSS) herring (Clupea harengus) to exemplify the power of this holistic approach and the high complexity of the recruitment drivers (and their interactions). Since the early 2000s, low recruitment levels have promoted intense research on this stock. Our literature synthesis suggests that the major drivers are habitat compression of the spawning beds (due to eutrophication and coastal modification mainly) and warming, which indirectly leads to changes in spawning phenology, prey abundance and predation pressure. Other factors include increased intensity of extreme climate events and new predators in the system. Four main knowledge gaps were identified related to life-cycle migration and habitat use, population structure and demographics, life-stage specific impact of multi-stressors, and predator–prey interactions. Specific research topics within these areas are proposed, as well as the priority to support a sustainable management of the stock. Given that the Baltic Sea is severely impacted by warming, eutrophication and altered precipitation, WBSS herring could be a harbinger of potential effects of changing environmental drivers to the recruitment of small pelagic fishes in other coastal areas in the world.publishedVersio

Copy Number Variation of KIR Genes Influences HIV-1 Control

The authors that the number of activating and inhibitory KIR genes varies between individuals and plays a role in the regulation of immune mechanisms that determine HIV-1 control

Antibody to the dendritic cell surface activation antigen CD83 prevents acute graft-versus-host disease

Allogeneic (allo) hematopoietic stem cell transplantation is an effective therapy for hematological malignancies but it is limited by acute graft-versus-host disease (GVHD). Dendritic cells (DC) play a major role in the allo T cell stimulation causing GVHD. Current immunosuppressive measures to control GVHD target T cells but compromise posttransplant immunity in the patient, particularly to cytomegalovirus (CMV) and residual malignant cells. We showed that treatment of allo mixed lymphocyte cultures with activated human DC-depleting CD83 antibody suppressed alloproliferation but preserved T cell numbers, including those specific for CMV. We also tested CD83 antibody in the human T cell–dependent peripheral blood mononuclear cell transplanted SCID (hu-SCID) mouse model of GVHD. We showed that this model requires human DC and that CD83 antibody treatment prevented GVHD but, unlike conventional immunosuppressants, did not prevent engraftment of human T cells, including cytotoxic T lymphocytes (CTL) responsive to viruses and malignant cells. Immunization of CD83 antibody-treated hu-SCID mice with irradiated human leukemic cell lines induced allo antileukemic CTL effectors in vivo that lysed 51Cr-labeled leukemic target cells in vitro without further stimulation. Antibodies that target activated DC are a promising new therapeutic approach to the control of GVHD

Up-regulation of a death receptor renders antiviral T cells susceptible to NK cell-mediated deletion

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).This work was funded by the Medical Research Council (Clinical Research Training Fellowship to DP and grant G0801213 to M.K. Maini)

The inference of gray whale (Eschrichtius robustus) historical population attributes from whole-genome sequences

Commercial whaling caused extensive demographic declines in many great whale species, including gray whales that were extirpated from the Atlantic Ocean and dramatically reduced in the Pacific Ocean. The Eastern Pacific gray whale has recovered since the 1982 ban on commercial whaling, but the Western Pacific gray whale-once considered possibly extinct-consists of only about 200 individuals and is considered critically endangered by some international authorities. Herein, we use whole-genome sequencing to investigate the demographic history of gray whales from the Pacific and use environmental niche modelling to make predictions about future gene flow.Our sequencing efforts and habitat niche modelling indicate that: i) western gray whale effective population sizes have declined since the last glacial maximum; ii) contemporary gray whale genomes, both eastern and western, harbor less autosomal nucleotide diversity than most other marine mammals and megafauna; iii) the extent of inbreeding, as measured by autozygosity, is greater in the Western Pacific than in the Eastern Pacific populations; and iv) future climate change is expected to open new migratory routes for gray whales.Our results indicate that gray whale genomes contain low nucleotide diversity and have been subject to both historical and recent inbreeding. Population sizes over the last million years likely peaked about 25,000 years before present and have declined since then. Our niche modelling suggests that novel migratory routes may develop within the next century and if so this could help retain overall genetic diversity, which is essential for adaption and successful recovery in light of global environmental change and past exploitation