277 research outputs found
Factors deterring and prompting the decision to attempt suicide on the railway networks: findings from 353 online surveys and 34 semi-structured interviews
Background: There is a suicide on the British railways every 36 hours. However, the reasons why people choose to die by train are not well understood.
Aims: To explore factors influencing, and discouraging, the decision to attempt suicide on the railway networks.
Method: We conducted an online survey and qualitative interviews with individuals who had contemplated or attempted suicide by train.
Results: 353 survey responders had considered and 23 attempted suicide at rail locations (including railways and metro/underground), in a third of cases impulsively. The most frequently reported motivations for contemplating or attempting suicide were perceptions of quick and certain lethality (54% and 37%, respectively) and easy access to rail settings (33% and 38%, respectively). The main factor discouraging people from rail suicide was its wider impact, especially on train drivers (19%). In qualitative interviews (N=34) the desire to avoid intervention from others was also a common motivating factor for attempting suicide on the railway networks.
Conclusions: People attempt suicide by train because railway settings are easy to access and because of an inaccurate perception of certain and quick lethality. Tackling exaggerated perceptions of lethality may help reduce suicides by train
Regulation of gene expression is associated with tolerance of the Arctic copepod Calanus glacialis to CO2-acidified sea water
publishedVersio
dynamics of immune cell reconstitution in allogeneic hematopoietic cell transplant patients receiving post transplant cyclophosphamide ptcy
In the setting of haploidentical hematopoietic cell transplantation (haplo-HCT), post-transplant cyclophosphamide (PTCy) selectively eliminates alloreactive T cells in-vivo, resulting in favorable graft versus host disease (GVHD), non-relapse mortality (NRM) and relapse outcomes. However, few studies have examined the impact of PTCy on immune reconstitution (IR). We quantified IR in 63 patients after haplo-HCT with PTCy, mofetil mycophenolate and tacrolimus (TAC) and compared results to 93 patients with 8/8 HLA matched related or unrelated donors (MD) receiving TAC, methotrexate and sirolimus for GVHD prophylaxis. Both groups received reduced intensity conditioning for hematologic malignancies. The median age of the Haplo-PTCy and MD cohorts was 55 and 57 years. Patient samples were analyzed using multi-color flow cytometry panels to characterize distinct lymphocyte populations. All IR values are expressed as median absolute cell count per μL. One month after HCT, recovery of all T cell subsets (CD3, CD4Tcon, Treg, CD8) was significantly reduced in the PTCy cohort compared to MD (Figure A, B, C). Recovery of CD4Tcon was also reduced at 2 and 3 months after PTCy (p NK cells were lower 1 month after PTCy (52.7 vs 91.1, p=0.08), but were significantly higher at 2, 3 and 6 months (153.4 vs 94.8, p=0.001, 153.7 vs 87.5, p=0.008, 180 vs 102, p=0.01, respectively, Figure D) compared to the MD cohort. Delayed NK cell recovery at 1 month after PTCy was due entirely to reduced numbers of CD56dim NK cells (Figure E). Subsequently recovery of CD56dim NK cells was similar in both cohorts. Recovery of CD56bright NK cells was significantly increased in the PTCy cohort (p Consistent with prior reports, 1 year cumulative incidence of extensive cGvHD was lower in the PTCy cohort compared to the MD cohort, 13% (5-26%, 95% CI) and 40% (30-50%, 95% CI) respectively, p=0.003, without increased NRM (p=0.28) or relapse (p=0.17). In summary, the effect of PTCy on IR was most pronounced 1 month after transplant with significantly delayed recovery of CD3, CD4Tcon, Treg, CD8 and CD56dim NK cells. Slow recovery of CD4Tcon persisted for 3 months and delayed recovery of Treg persisted for 1 year. Beginning 2 months after HCT, recovery of both CD56dim and CD56bright NK cells was more rapid in the PTCy cohort. Further studies will examine the effects of these differences in IR on clinical outcomes such as relapse, infections and GVHD
CLUH regulates mitochondrial metabolism by controlling translation and decay of target mRNAs
Mitochondria are essential organelles that host crucial metabolic pathways and produce adenosine triphosphate. The mitochondrial proteome is heterogeneous among tissues and can dynamically change in response to different metabolic conditions. Although the transcriptional programs that govern mitochondrial biogenesis and respiratory function are well known, posttranscriptional regulatory mechanisms remain unclear. In this study, we show that the cytosolic RNA-binding protein clustered mitochondria homologue (CLUH) regulates the expression of a mitochondrial protein network supporting key metabolic programs required under nutrient deprivation. CLUH exerts its function by controlling the stability and translation of target messenger RNAs. In the absence of Cluh, mitochondria are severely depleted of crucial enzymes involved in catabolic energy-converting pathways. CLUH preserves oxidative mitochondrial function and glucose homeostasis, thus preventing death at the fetal–neonatal transition. In the adult liver, CLUH ensures maximal respiration capacity and the metabolic response to starvation. Our results shed new light on the posttranscriptional mechanisms controlling the expression of mitochondrial proteins and suggest novel strategies to tailor mitochondrial function to physiological and pathological conditions.Peer reviewe
Cross-Priming of Naive Cd8 T Cells against Melanoma Antigens Using Dendritic Cells Loaded with Killed Allogeneic Melanoma Cells
The goal of tumor immunotherapy is to elicit immune responses against autologous tumors. It would be highly desirable that such responses include multiple T cell clones against multiple tumor antigens. This could be obtained using the antigen presenting capacity of dendritic cells (DCs) and cross-priming. That is, one could load the DC with tumor lines of any human histocompatibility leukocyte antigen (HLA) type to elicit T cell responses against the autologous tumor. In this study, we show that human DCs derived from monocytes and loaded with killed melanoma cells prime naive CD45RA+CD27+CD8+ T cells against the four shared melanoma antigens: MAGE-3, gp100, tyrosinase, and MART-1. HLA-A201+ naive T cells primed by DCs loaded with HLA-A201− melanoma cells are able to kill several HLA-A201+ melanoma targets. Cytotoxic T lymphocyte priming towards melanoma antigens is also obtained with cells from metastatic melanoma patients. This demonstration of cross-priming against shared tumor antigens builds the basis for using allogeneic tumor cell lines to deliver tumor antigens to DCs for vaccination protocols
Azimuthal Angle Correlations for Rapidity Separated Hadron Pairs in d+Au Collisions at sqrt(s_NN) = 200 GeV
We report on two-particle azimuthal angle correlations between charged
hadrons at forward/backward (deuteron/gold going direction) rapidity and
charged hadrons at mid-rapidity in deuteron-gold (d+Au) and proton-proton (p+p)
collisions at sqrt(s_NN) = 200 GeV. Jet structures are observed in the
correlations which we quantify in terms of the conditional yield and angular
width of away side partners. The kinematic region studied here samples partons
in the gold nucleus carrying nucleon momentum fraction x~0.1 to x~0.01. Within
this range, we find no x dependence of the jet structure in d+Au collisions.Comment: 330 authors, 6 pages text, 4 figures, no tables. Submitted to Phys.
Rev. Lett. Plain text data tables for the points plotted in figures for this
and previous PHENIX publications are (or will be) publicly available at
http://www.phenix.bnl.gov/papers.htm
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