"After my husband's circumcision, I know that I am safe from diseases": Women's Attitudes and Risk Perceptions Towards Male Circumcision in Iringa, Tanzania.

While male circumcision reduces the risk of female-to-male HIV transmission and certain sexually transmitted infections (STIs), there is little evidence that circumcision provides women with direct protection against HIV. This study used qualitative methods to assess women's perceptions of male circumcision in Iringa, Tanzania. Women in this study had strong preferences for circumcised men because of the low risk perception of HIV with circumcised men, social norms favoring circumcised men, and perceived increased sexual desirability of circumcised men. The health benefits of male circumcision were generally overstated; many respondents falsely believed that women are also directly protected against HIV and that the risk of all STIs is greatly reduced or eliminated in circumcised men. Efforts to engage women about the risks and limitations of male circumcision, in addition to the benefits, should be expanded so that women can accurately assess their risk of HIV or STIs during sexual intercourse with circumcised men

Eef1a2 Promotes Cell Growth, Inhibits Apoptosis and Activates JAK/STAT and AKT Signaling in Mouse Plasmacytomas

The canonical function of EEF1A2, normally expressed only in muscle, brain, and heart, is in translational elongation, but recent studies suggest a non-canonical function as a proto-oncogene that is overexpressed in a variety of solid tumors including breast and ovary. Transcriptional profiling of a spectrum of primary mouse B cell lineage neoplasms showed that transcripts encoding EEF1A2 were uniquely overexpressed in plasmacytomas (PCT), tumors of mature plasma cells. Cases of human multiple myeloma expressed significantly higher levels of EEF1A2 transcripts than normal bone marrow plasma cells. High-level expression was also a feature of a subset of cell lines developed from mouse PCT and from the human MM.Heightened expression of EEF1A2 was not associated with increased copy number or coding sequence mutations. shRNA-mediated knockdown of Eef1a2 transcripts and protein was associated with growth inhibition due to delayed G1-S progression, and effects on apoptosis that were seen only under serum-starved conditions. Transcriptional profiles and western blot analyses of knockdown cells revealed impaired JAK/STAT and PI3K/AKT signaling suggesting their contributions to EEF1A2-mediated effects on PCT induction or progression.EEF1A2 may play contribute to the induction or progression of some PCT and a small percentage of MM. Eef1a2 could also prove to be a useful new marker for a subset of MM and, ultimately, a possible target for therapy

Risk assessment and decision making about in-labour transfer from rural maternity care: a social judgment and signal detection analysis

Background: The importance of respecting women's wishes to give birth close to their local community is supported by policy in many developed countries. However, persistent concerns about the quality and safety of maternity care in rural communities have been expressed. Safe childbirth in rural communities depends on good risk assessment and decision making as to whether and when the transfer of a woman in labour to an obstetric led unit is required. This is a difficult decision. Wide variation in transfer rates between rural maternity units have been reported suggesting different decision making criteria may be involved; furthermore, rural midwives and family doctors report feeling isolated in making these decisions and that staff in urban centres do not understand the difficulties they face. In order to develop more evidence based decision making strategies greater understanding of the way in which maternity care providers currently make decisions is required. This study aimed to examine how midwives working in urban and rural settings and obstetricians make intrapartum transfer decisions, and describe sources of variation in decision making. Methods: The study was conducted in three stages. 1. 20 midwives and four obstetricians described factors influencing transfer decisions. 2. Vignettes depicting an intrapartum scenario were developed based on stage one data. 3. Vignettes were presented to 122 midwives and 12 obstetricians who were asked to assess the level of risk in each case and decide whether to transfer or not. Social judgment analysis was used to identify the factors and factor weights used in assessment. Signal detection analysis was used to identify participants' ability to distinguish high and low risk cases and personal decision thresholds. Results: When reviewing the same case information in vignettes midwives in different settings and obstetricians made very similar risk assessments. Despite this, a wide range of transfer decisions were still made, suggesting that the main source of variation in decision making and transfer rates is not in the assessment but the personal decision thresholds of clinicians. Conclusions: Currently health care practice focuses on supporting or improving decision making through skills training and clinical guidelines. However, these methods alone are unlikely to be effective in improving consistency of decision making

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study

Purpose: To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate. Methods: In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. Results: Significantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low ( 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. Conclusions: 177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov: NCT01578239, EudraCT: 2011-005049-11

User's perspectives of barriers and facilitators to implementing quality colonoscopy services in Canada: a study protocol

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) represents a serious and growing health problem in Canada. Colonoscopy is used for screening and diagnosis of symptomatic or high CRC risk individuals. Although a number of countries are now implementing quality colonoscopy services, knowledge synthesis of barriers and facilitators perceived by healthcare professionals and patients during implementation has not been carried out. In addition, the perspectives of various stakeholders towards the implementation of quality colonoscopy services and the need of an efficient organisation of such services have been reported in the literature but have not been synthesised yet. The present study aims to produce a comprehensive synthesis of actual knowledge on the barriers and facilitators perceived by all stakeholders to the implementation of quality colonoscopy services in Canada.</p> <p>Methods</p> <p>First, we will conduct a comprehensive review of the scientific literature and other published documentation on the barriers and facilitators to implementing quality colonoscopy services. Standardised literature searches and data extraction methods will be used. The quality of the studies and their relevance to informing decisions on colonoscopy services implementation will be assessed. For each group of users identified, barriers and facilitators will be categorised and compiled using narrative synthesis and meta-analytical techniques. The principle factors identified for each group of users will then be validated for its applicability to various Canadian contexts using the Delphi study method. Following this study, a set of strategies will be identified to inform decision makers involved in the implementation of quality colonoscopy services across Canadian jurisdictions.</p> <p>Discussion</p> <p>This study will be the first to systematically summarise the barriers and facilitators to implementation of quality colonoscopy services perceived by different groups and to consider the local contexts in order to ensure the applicability of this knowledge to the particular realities of various Canadian jurisdictions. Linkages with strategic partners and decision makers in the realisation of this project will favour the utilisation of its results to support strategies for implementing quality colonoscopy services and CRC screening programs in the Canadian health system.</p

Genome-Wide Association Study Identifies Genetic Loci Associated with Iron Deficiency

The existence of multiple inherited disorders of iron metabolism in man, rodents and other vertebrates suggests genetic contributions to iron deficiency. To identify new genomic locations associated with iron deficiency, a genome-wide association study (GWAS) was performed using DNA collected from white men aged ≥25 y and women ≥50 y in the Hemochromatosis and Iron Overload Screening (HEIRS) Study with serum ferritin (SF) ≤ 12 µg/L (cases) and iron replete controls (SF>100 µg/L in men, SF>50 µg/L in women). Regression analysis was used to examine the association between case-control status (336 cases, 343 controls) and quantitative serum iron measures and 331,060 single nucleotide polymorphism (SNP) genotypes, with replication analyses performed in a sample of 71 cases and 161 controls from a population of white male and female veterans screened at a US Veterans Affairs (VA) medical center. Five SNPs identified in the GWAS met genome-wide statistical significance for association with at least one iron measure, rs2698530 on chr. 2p14; rs3811647 on chr. 3q22, a known SNP in the transferrin (TF) gene region; rs1800562 on chr. 6p22, the C282Y mutation in the HFE gene; rs7787204 on chr. 7p21; and rs987710 on chr. 22q11 (GWAS observed P<1.51×10−7 for all). An association between total iron binding capacity and SNP rs3811647 in the TF gene (GWAS observed P = 7.0×10−9, corrected P = 0.012) was replicated within the VA samples (observed P = 0.012). Associations with the C282Y mutation in the HFE gene also were replicated. The joint analysis of the HEIRS and VA samples revealed strong associations between rs2698530 on chr. 2p14 and iron status outcomes. These results confirm a previously-described TF polymorphism and implicate one potential new locus as a target for gene identification