Human trafficking and violence: Findings from the largest global dataset of trafficking survivors

Background: Human trafficking is a recognized human rights violation, and a public health and global development issue. Violence is often a hallmark of human trafficking. This study aims to describe documented cases of violence amongst persons identified as victims of trafficking, examine associated factors throughout the trafficking cycle and explore prevalence of abuse in different labour sectors. Methods and findings: The IOM Victim of Trafficking Database (VoTD) is the largest database on human trafficking worldwide. This database is actively used across all IOM regional and country missions as a standardized anti-trafficking case-management tool. This analysis utilized the cases of 10,369 trafficked victims in the VoTD who had information on violence. Results: The prevalence of reported violence during human trafficking included: 54% physical and/or sexual violence; 50% physical violence; and 15% sexual violence, with 25% of women reporting sexual violence. Experiences of physical and sexual violence amongst trafficked victims were significantly higher amongst women and girls (AOR 2.48 (CI: 2.01,3.06)), individuals in sexual exploitation (AOR 2.08 (CI: 1.22,3.54)) and those experiencing other forms of abuse and deprivation, such as threats (AOR 2.89 (CI: 2.10,3.98)) and forced use of alcohol and drugs (AOR 2.37 (CI: 1.08,5.21)). Abuse was significantly lower amongst individuals trafficked internationally (AOR 0.36 (CI: 0.19,0.68)) and those using forged documents (AOR 0.64 (CI: 0.44,0.93)). Violence was frequently associated with trafficking into manufacturing, agriculture and begging (> 55%). Conclusions: An analysis of the world's largest data set on trafficking victims indicates that violence is indeed prevalent and gendered. While these results show that trafficking-related violence is common, findings suggest there are patterns of violence, which highlights that post-trafficking services must address the specific support needs of different survivors

Inhibitory NKG2A⁺ and absent activating NKG2C⁺ NK cell responses are associated with the development of EBV⁺ lymphomas

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus, which infects over 90% of the adult human population worldwide. After primary infections, EBV is recurrently reactivating in most adult individuals. It is, however, unclear, why these EBV reactivations progress to EBV+ Hodgkin (EBV+HL) or non-Hodgkin lymphomas (EBV+nHL) only in a minority of EBV-infected individuals. The EBV LMP-1 protein encodes for a highly polymorphic peptide, which upregulates the immunomodulatory HLA-E in EBV-infected cells, thereby stimulating the inhibitory NKG2A-, but also the activating NKG2C-receptor on natural killer (NK) cells. Using a genetic-association approach and functional NK cell analyses, we now investigated, whether these HLA-E-restricted immune responses impact the development of EBV+HL and EBV+nHL. Therefore, we recruited a study cohort of 63 EBV+HL and EBV+nHL patients and 192 controls with confirmed EBV reactivations, but without lymphomas. Here, we demonstrate that in EBV+ lymphoma patients exclusively the high-affine LMP-1 GGDPHLPTL peptide variant-encoding EBV-strains reactivate. In EBV+HL and EBV+nHL patients, the high-expressing HLA-E*0103/0103 genetic variant was significantly overrepresented. Combined, the LMP-1 GGDPHLPTL and HLA-E*0103/0103 variants efficiently inhibited NKG2A+ NK cells, thereby facilitating the in vitro spread of EBV-infected tumor cells. In addition, EBV+HL and EBV+nHL patients, showed impaired pro-inflammatory NKG2C+ NK cell responses, which accelerated the in vitro EBV-infected tumor cells spread. In contrast, the blocking of NKG2A by monoclonal antibodies (Monalizumab) resulted in efficient control of EBV-infected tumor cell growth, especially by NKG2A+NKG2C+ NK cells. Thus, the HLA-E/LMP-1/NKG2A pathway and individual NKG2C+ NK cell responses are associated with the progression toward EBV+ lymphomas.</p

Intervention with Microfinance for AIDS and Gender Equity (IMAGE): Women's Engagement with the Scaled-up IMAGE Programme and Experience of Intimate Partner Violence in Rural South Africa.

The Intervention with Microfinance for AIDS and Gender Equity (IMAGE) programme has been scaled up to three provinces in South Africa. This paper explores associations between women's engagement in the intervention, intimate partner violence (IPV) and factors associated with IPV and partner abuse. We enrolled women receiving group-based microfinance loans plus gender training into the scaled-up IMAGE cohort study (n = 860). We present cross-sectional analysis on participants' characteristics and intervention engagement and use multivariate logistic regression to explore associations. 17% of women reported lifetime (95% CI 15 to 20%) and 7% past year (95% CI 5 to 9%) IPV, 9% past-year economic (95% CI 7 to 11%) and 11% past-year emotional (95% CI 9 to 14%) abuse. Women under 35 years had higher levels of IPV and emotional abuse. 53% of women attended all the trainings, 83% continuously borrowed and 98% agreed the training had a major impact on their life. Attendance was associated with improved partner relationships (χ2p < 0.001), but not lower IPV risk. Odds of past-year IPV decreased the more types of support (e.g. advice) women received from group members (aOR 0.27, p < 0.001 among those reporting all support versus none or some). A similar pattern was seen for economic, but not emotional, abuse. The scaled-up IMAGE intervention is widely acceptable and may support improvements in partner relationships, but younger women need to be targeted. Group support appears to be a potentially important component of the intervention

Impact of pre‐analytical sample handling factors on plasma biomarkers of Alzheimer's disease

An unmet need exists for reliable plasma biomarkers of amyloid pathology, in the clinical laboratory setting, to streamline diagnosis of Alzheimer's disease (AD). For routine clinical use, a biomarker must provide robust and reliable results under pre-analytical sample handling conditions. We investigated the impact of different pre-analytical sample handling procedures on the levels of seven plasma biomarkers in development for potential routine use in AD. Using (1) fresh (never frozen) and (2) previously frozen plasma, we evaluated the effects of (A) storage time and temperature, (B) freeze/thaw (F/T) cycles, (C) anticoagulants, (D) tube transfer, and (E) plastic tube types. Blood samples were prospectively collected from patients with cognitive impairment undergoing investigation in a memory clinic. β-amyloid 1-40 (Aβ40), β-amyloid 1-42 (Aβ42), apolipoprotein E4, glial fibrillary acidic protein, neurofilament light chain, phosphorylated-tau (phospho-tau) 181, and phospho-tau-217 were measured using Elecsys® plasma prototype immunoassays. Recovery signals for each plasma biomarker and sample handling parameter were calculated. For all plasma biomarkers measured, pre-analytical effects were comparable between fresh (never frozen) and previously frozen samples. All plasma biomarkers tested were stable for ≤24 h at 4°C when stored as whole blood and ethylenediaminetetraacetic acid (EDTA) plasma. Recovery signals were acceptable for up to five tube transfers, or two F/T cycles, and in both polypropylene and low-density polyethylene tubes. For all plasma biomarkers except Aβ42 and Aβ40, analyte levels were largely comparable between EDTA, lithium heparin, and sodium citrate tubes. Aβ42 and Aβ40 were most sensitive to pre-analytical handling, and the effects could only be partially compensated by the Aβ42/Aβ40 ratio. We provide recommendations for an optimal sample handling protocol for analysis of plasma biomarkers for amyloid pathology AD, to improve the reproducibility of future studies on plasma biomarkers assays and for potential use in routine clinical practice

A genome-wide association meta-analysis on lipoprotein (a) concentrations adjusted for apolipoprotein (a) isoforms.

High lipoprotein (a) [Lp(a)] concentrations are an independent risk factor for cardiovascular outcomes. Concentrations are strongly influenced by apo(a) kringle IV repeat isoforms. We aimed to identify genetic loci associated with Lp(a) concentrations using data from five genome-wide association studies (n = 13,781). We identified 48 independent SNPs in the &lt;i&gt;LPA&lt;/i&gt; and 1 SNP in the &lt;i&gt;APOE&lt;/i&gt; gene region to be significantly associated with Lp(a) concentrations. We also adjusted for apo(a) isoforms to identify loci affecting Lp(a) levels independently from them, which resulted in 31 SNPs (30 in the &lt;i&gt;LPA&lt;/i&gt; , 1 in the &lt;i&gt;APOE&lt;/i&gt; gene region). Seven SNPs showed a genome-wide significant association with coronary artery disease (CAD) risk. A rare SNP (rs186696265; MAF ∼1%) showed the highest effect on Lp(a) and was also associated with increased risk of CAD (odds ratio = 1.73, &lt;i&gt;P&lt;/i&gt; = 3.35 × 10 &lt;sup&gt;-30&lt;/sup&gt; ). Median Lp(a) values increased from 2.1 to 91.1 mg/dl with increasing number of Lp(a)-increasing alleles. We found the &lt;i&gt;APOE2&lt;/i&gt; -determining allele of rs7412 to be significantly associated with Lp(a) concentrations ( &lt;i&gt;P&lt;/i&gt; = 3.47 × 10 &lt;sup&gt;-10&lt;/sup&gt; ). Each &lt;i&gt;APOE2&lt;/i&gt; allele decreased Lp(a) by 3.34 mg/dl corresponding to ∼15% of the population's mean values. Performing a gene-based test of association, including suspected Lp(a) receptors and regulators, resulted in one significant association of the &lt;i&gt;TLR2&lt;/i&gt; gene with Lp(a) ( &lt;i&gt;P&lt;/i&gt; = 3.4 × 10 &lt;sup&gt;-4&lt;/sup&gt; ). In summary, we identified a large number of independent SNPs in the &lt;i&gt;LPA&lt;/i&gt; gene region, as well as the &lt;i&gt;APOE2&lt;/i&gt; allele, to be significantly associated with Lp(a) concentrations

Age at Menarche and Its Association with the Metabolic Syndrome and Its Components: Results from the KORA F4 Study

OBJECTIVE: The metabolic syndrome is a major public health challenge and identifies persons at risk for diabetes and cardiovascular disease. The aim of this study was to examine the association between age at menarche and the metabolic syndrome (IDF and NCEP ATP III classification) and its components. DESIGN: 1536 women aged 32 to 81 years of the German population based KORA F4 study were investigated. Data was collected by standardized interviews, physical examinations, and whole blood and serum measurements. RESULTS: Young age at menarche was significantly associated with elevated body mass index (BMI), greater waist circumference, higher fasting glucose levels, and 2 hour glucose (oral glucose tolerance test), even after adjusting for the difference between current BMI and BMI at age 25. The significant effect on elevated triglycerides and systolic blood pressure was attenuated after adjustment for the BMI change. Age at menarche was inversely associated with the metabolic syndrome adjusting for age (p-values: <0.001 IDF, 0.003 NCEP classification) and additional potential confounders including lifestyle and reproductive history factors (p-values: 0.001, 0.005). Associations remain significant when additionally controlling for recollected BMI at age 25 (p-values: 0.008, 0.033) or the BMI change since age 25 (p-values: 0.005, 0.022). CONCLUSION: Young age at menarche might play a role in the development of the metabolic syndrome. This association is only partially mediated by weight gain and increased BMI. A history of early menarche may help to identify women at risk for the metabolic syndrome

A genome-wide association meta-analysis on apolipoprotein A-IV concentrations.

Apolipoprotein A-IV (apoA-IV) is a major component of HDL and chylomicron particles and is involved in reverse cholesterol transport. It is an early marker of impaired renal function. We aimed to identify genetic loci associated with apoA-IV concentrations and to investigate relationships with known susceptibility loci for kidney function and lipids. A genome-wide association meta-analysis on apoA-IV concentrations was conducted in five population-based cohorts (n = 13,813) followed by two additional replication studies (n = 2,267) including approximately 10 M SNPs. Three independent SNPs from two genomic regions were significantly associated with apoA-IV concentrations: rs1729407 near APOA4 (P = 6.77 × 10 (-)  (44)), rs5104 in APOA4 (P = 1.79 × 10(-)(24)) and rs4241819 in KLKB1 (P = 5.6 × 10(-)(14)). Additionally, a look-up of the replicated SNPs in downloadable GWAS meta-analysis results was performed on kidney function (defined by eGFR), HDL-cholesterol and triglycerides. From these three SNPs mentioned above, only rs1729407 showed an association with HDL-cholesterol (P = 7.1 × 10 (-)  (07)). Moreover, weighted SNP-scores were built involving known susceptibility loci for the aforementioned traits (53, 70 and 38 SNPs, respectively) and were associated with apoA-IV concentrations. This analysis revealed a significant and an inverse association for kidney function with apoA-IV concentrations (P = 5.5 × 10(-)(05)). Furthermore, an increase of triglyceride-increasing alleles was found to decrease apoA-IV concentrations (P = 0.0078). In summary, we identified two independent SNPs located in or next the APOA4 gene and one SNP in KLKB1 The association of KLKB1 with apoA-IV suggests an involvement of apoA-IV in renal metabolism and/or an interaction within HDL particles. Analyses of SNP-scores indicate potential causal effects of kidney function and by lesser extent triglycerides on apoA-IV concentrations

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Primary resistance of HIV to antiretrovirals among individuals recently diagnosed at voluntary counselling and testing centres in the metropolitan region of Recife, Pernambuco

Determining the prevalence and type of antiretroviral (ARV) resistance among ARV-naïve individuals is important to assess the potential responses of these individuals to first-line regimens. The prevalence of primary resistance and the occurrence of recent infections among individuals with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) were identified among recently diagnosed patients at five sexually transmitted disease/AIDS testing and counselling centres in the metropolitan region of Recife (RMR), Pernambuco, Brazil, between 2007-2009. One-hundred and eight samples were analysed using the Calypte® BED assay. Males predominated (56%), as did patients aged 31-50 years. Twenty-three percent presented evidence of a recent HIV infection. The median CD4+ T lymphocyte count was 408 cells/mm³ and the median viral load was 3.683 copies/mL. The prevalence of primary resistance was 4.6% (confidence interval 95% = 1-8.2%) based on criteria that excluded common polymorphisms in accordance with the surveillance drug resistance mutation criteria. The prevalence of resistance to non-nucleoside reverse transcriptase, nucleoside/nucleotide reverse transcriptase and protease inhibitors were 3.8%, 1.5% and 0.8%, respectively. Fifty-seven percent of strains were from clade B, 37.7% were clade F and 3.1% were clade C; there were no statistically significant differences with respect to resistance between clades. Recent infection tended to be more common in men (p = 0.06) and in municipalities in the south of the RMR (Jaboatão dos Guararapes and Cabo de Santo Agostinho) (p = 0.046). The high prevalence of recent infection and the high prevalence of non-B strains in this poor Brazilian region merit further attention.Laboratório Central de Saúde Pública de Pernambuco Setor de VirologiaUniversidade Federal de Pernambuco Programa de Pós-Graduação em Medicina TropicalFiocruz Centro de Pesquisa Aggeu MagalhãesCentro de Testagem e Aconselhamento Herbert de SouzaUniversidade Federal de São Paulo (UNIFESP) Laboratório de RetrovirologiaUNIFESP, Laboratório de RetrovirologiaSciEL