Determinants of intergenerational sexual relationships and HIV risk among South African women outpatients in Gauteng.

Age-discrepant sexual relationships may place women at risk for HIV infection in South Africa. Results are based on medical records and case-control interview data of 889 sexually experienced women outpatients aged 15-29 in a Gauteng township. Women with partners at least ten years older (intergenerational) show an elevated chance of having an early sexual debut, concurrent and transactional partners, and intimate partner violence. Hardship during childhood including parental loss, food insecurity and abuse are related to age asymmetric relationships. HIV is two times more likely (aOR=1.96) with an intergenerational partner. Transactional sex increases the odds of HIV independently (aOR=1.76) as does intimate partner violence (aOR=1.6). To the extent that transactional and intergenerational sex overlap the chance of contracting HIV increases more than two-fold (uOR=4.57). Girls (15-19) with intergenerational partners face the highest chance of HIV (uOR=8.55) compared to other age groups. They are also five times more likely than controls to have lived with a cross-age partner. Our findings indicate there are multiple pathways emanating from childhood leading to women's choice of intergenerational partners, and the link to HIV is strongest among the youngest women.

Pathways From Witnessing Parental Intimate Partner Violence to Involvement in Bullying: Empirically Testing a Proposed Conceptual Framework.

We tested a proposed conceptual framework in which we hypothesized that witnessing parental intimate partner violence (witnessing parental IPV) is linked to children's bullying and peer victimization. We also hypothesized that the relationship between witnessing parental IPV and bullying and peer victimization in childhood would be mediated by increased psychological problem behavior, school absences, and problematic peer interactions. We utilized data from the National Survey of Children's Health. We found that witnessing parental IPV was positively related to children's bullying and peer victimization not only directly, but also indirectly through the mediating role of psychological problem behavior, school absences, and problematic peer interactions. Our findings highlight the importance of exploring the mechanisms by which bullying and peer victimization increase in those who have witnessed parental IPV.

Estimation of hematocrit in filter paper dried bloodspots by potassium measurement: advantage of use of perimeter ring samples over circular center sub-punch samples.

BACKGROUND: Quantitative assays using dried filter paper bloodspots (DBS) may be adversely affected by hematocrit (HCT) as an unknown variable. Studies have demonstrated the utility of the measurement of potassium (K) from DBS punches to estimate HCT. Because there is significant accrual of RBCs at the DBS perimeter, we investigated whether K measurement from ring-shaped specimens inclusive of the perimeter might provide an advantage over conventional interior circular sub-punch samples to estimate HCT. METHODS: Primary samples were Li-heparin whole blood, with HCT as measured on concurrently-drawn K-EDTA specimens. DBS were formed by bolus addition of 40 µL whole blood to filter paper cards. Total bloodspot area was determined by image analysis. Removal of center sub-punch (P) samples of fixed area produced remainder ring (R) samples inclusive of the perimeter. Samples were extracted in K-EDTA (2.5 mmol/L) and measured for diluent-corrected K per area (α, µmol K/cm2). RESULTS: Forty-three patient samples were utilized. α was normally distributed: α(P)=1.23±0.26 µmol K/cm2; α(R)=1.86±0.41 µmol K/cm2; α(R)/α(P)=1.51±0.15. α was correlated with HCT: α(P)=0.030 HCT(%)+0.015 µmol K/cm2 (r2=0.795); α(R)=0.052 HCT(%)+0.010 µmol K/cm2 (r2 = 0.912), but with higher resolution and lesser error for α(R). CONCLUSIONS: K per area (α) was significantly higher in R samples vs. P samples, with higher resolution for α(R) vs. HCT. Use of ring samples inclusive of the perimeter to estimate HCT for DBS via K measurement can provide an advantage over use of center sub-punch samples.

The Effects of Gender-based Violence on Women's Unwanted Pregnancy and Abortion.

The aim of this research is to understand how gender-based violence across the life-course affects the likelihood of abortion. Women outpatients (n = 309) revealed their exposure to four different forms of gender-based abuse: child sexual abuse (25.7 percent), teenage physical dating violence (40.8 percent), intimate partner violence (43.1 percent), and sexual assault outside an intimate relationship (22 percent). Logistic regressions revealed that no single form of gender-based abuse predicted abortion. The cumulative effect of multiple forms of abuse did increase the odds of having an abortion (OR = 1.39, CI = 1.13-1.69). Child sexual abuse predicted intimate partner violence (OR = 6.71, CI = 3.36-13.41). The cumulative effect of gender-based violence on women's reproductive health warrants further research. Priority should be given to screening for multiple forms of victimization in reproductive healthcare settings.

Machine learning and metabolic modelling assisted implementation of a novel process analytical technology in cell and gene therapy manufacturing.

Process analytical technology (PAT) has demonstrated huge potential to enable the development of improved biopharmaceutical manufacturing processes by ensuring the reliable provision of quality products. However, the complexities associated with the manufacture of advanced therapy medicinal products have resulted in a slow adoption of PAT tools into industrial bioprocessing operations, particularly in the manufacture of cell and gene therapy products. Here we describe the applicability of a novel refractometry-based PAT system (Ranger system), which was used to monitor the metabolic activity of HEK293T cell cultures during lentiviral vector (LVV) production processes in real time. The PAT system was able to rapidly identify a relationship between bioreactor pH and culture metabolic activity and this was used to devise a pH operating strategy that resulted in a 1.8-fold increase in metabolic activity compared to an unoptimised bioprocess in a minimal number of bioreactor experiments; this was achieved using both pre-programmed and autonomous pH control strategies. The increased metabolic activity of the cultures, achieved via the implementation of the PAT technology, was not associated with increased LVV production. We employed a metabolic modelling strategy to elucidate the relationship between these bioprocess level events and HEK293T cell metabolism. The modelling showed that culturing of HEK293T cells in a low pH (pH 6.40) environment directly impacted the intracellular maintenance of pH and the intracellular availability of oxygen. We provide evidence that the elevated metabolic activity was a response to cope with the stress associated with low pH to maintain the favourable intracellular conditions, rather than being indicative of a superior active state of the HEK293T cell culture resulting in enhanced LVV production. Forecasting strategies were used to construct data models which identified that the novel PAT system not only had a direct relationship with process pH but also with oxygen availability; the interaction and interdependencies between these two parameters had a direct effect on the responses observed at the bioprocess level. We present data which indicate that process control and intervention using this novel refractometry-based PAT system has the potential to facilitate the fine tuning and rapid optimisation of the production environment and enable adaptive process control for enhanced process performance and robustness.

Myth and reality: practical test system for the measurement of anti-DNA antibodies in the diagnosis of systemic lupus erythematosus (SLE).

The myth persists that only the labor intensive Farr radioimmunoassay and Crithidia luciliae immunofluorescence (CL-IFA) are systemic lupus erythematosus (SLE)-specific tests. We compared them to ELISA with bacteriophage lambda DNA (EL-dsDNA) and denatured calf thymus DNA (EL-ssDNA). By percentile ranking, the specificity cut-off level was set both out of clinical context (SOCC) on 100 blood bank donors, and in clinical context (SICC) on 100 patients with either rheumatoid arthritis or scleroderma (50/50). Clinical sensitivity was calculated on 100 random SLE patients. At 95% SICC, the sensitivity of Farr, CL-IFA, EL-dsDNA, and EL-ssDNA was similar (95%CI): 76% (66-84), 76% (66-84), 63% (53-72), and 75% (65-83), respectively; 87% of the patients were positive by at least one method and 55%by all methods. At 99% SICC, the sensitivity was also similar (95% CI): 57% (47-67), 47% (37-57), 58% (47-67), and 43% (33-53), respectively. The areas under ROC curve were similar (95% CI) when patients were used as controls for specificity. At 99% SOCC, EL-ssDNA identified 89% positive, 2 negative but positive by another method at 95% SICC, and 9 negative (i.e. 89/2/9), followed by CL-IFA (80/6/14), Farr (76/12/12), and EL-dsDNA (64/23/13). Thus, at relatively low cost and easy automation, under the same conditions of specificity, the two ELISA tests combined were at least as good, if not superior, to CL-IFA or Farr: they showed similar clinical sensitivity and also identified more patients with anti-DNA antibodies.

The impact of childhood sexual abuse and intimate partner violence on sexually transmitted infections.

Childhood sexual abuse (CSA) and adult intimate partner violence (IPV) have both been found to be associated with sexually transmitted infections (STIs) independently, but studies of STIs have rarely looked at victimization during both childhood and adulthood. This paper examines the relationship between CSA, IPV and STIs using data from a nested case-control study of 309 women recruited from multiple health care settings. Overall, 37.3% of women experienced no violence, 10.3% experienced CSA only, 27.3% experienced IPV only, and 25.0% experienced both CSA and IPV. Having ever been diagnosed with an STI was associated with violence (CSA only, odds ratios [OR] = 2.8, 95% confidence intervals [CI] = 1.0-7.5; IPV only, OR = 2.2, 95% CI = 1.0-4.9; CSA and IPV: OR = 4.0, 95% CI = 1.7-9.4), controlling for demographic characteristics. Women who experienced CSA were younger when they were first diagnosed. Understanding how both childhood and adult victimization are associated with diagnosis of STIs is important to reducing the incidence and prevalence of STIs, as well as the associated consequences of STIs.

The role of reproductive coercion in women's risk for HIV: A case-control study of outpatients in Gauteng, South Africa.

OBJECTIVES: To investigate how reproductive coercion, or men's attempts to control their partners' use of contraception, may contribute to adverse reproductive health outcomes for women including abortions, sexually transmitted infections, and HIV for young women in South Africa. METHODS: Findings are based on a case-control interview study of 882 South African women outpatients aged 15-29 years, 48.5% (n=427) of whom were HIV seropositive. Covariates include demographics, intimate partner violence, sexually transmitted infections, having an abortion, using long-acting reversible contraception, and unequal sexual relationship power. RESULTS: Most covariates with the exceptions of abortion and unequal relationship power increase the risk of HIV, and all relate to reproductive coercion. Intimate partner violence is strongly associated with reproductive coercion (odds ratio 3.86, 95% confidence interval 2.89-5.15). When intimate partner violence is included in the full model reproductive coercion remains a significant predictor of HIV by 42%, and acts as a partial mediator between IPV and HIV. CONCLUSION: Findings confirm the significance of reproductive coercion as a risk marker for HIV. Reproductive coercion undermines women's reproductive health and warrants clinical intervention. Recommendations are offered for clinical practice within the South African context to increase training and assessment and provide covert long-acting reversible contraception as one pathway towards promoting women's reproductive autonomy.

Intimate partner violence exposure and change in women's physical symptoms over time.

OBJECTIVE: To examine the change in women's self-reported physical symptoms over 2 time points in relation to intimate partner violence (IPV) exposure. DESIGN: Prospective interview study of 267 women recruited from 8 health care settings and surrounding communities in Metropolitan Boston. METHODS: We created sums of somatic symptoms at 2 separate time points (a mean of 9.5 months apart) using items from a modified PHQ-15. A measure of symptom change was computed to measure the net change in symptoms over time. A negative score indicated reduction in total symptoms, or improvement. Exposure to IPV was measured at both time points. RESULTS: Women who reported ongoing IPV across both time points experienced an increase in their overall physical symptoms compared to women with past abuse (p = .0054) and no abuse (p = .0006). In multivariate regression analysis, ongoing IPV at both time points was a statistically significant predictor of symptom change. This relationship persisted even after controlling for age, race, education, depression, self-report of co-morbid illness, and history of child abuse and prior sexual assault (p = .0076). CONCLUSIONS: Women exposed to ongoing IPV report increased physical symptoms over time. Clinicians should consider the possibility of IPV in patients who remain persistently symptomatic over time in addition to employing more traditional means of detecting IPV.

Sexual violence at first intercourse against women in Moshi, northern Tanzania: prevalence, risk factors, and consequences.

To explore the relationship between sexual violence at first intercourse and later sexually transmitted infections (STIs) in Moshi, Tanzania, we analysed data from a representative household survey that comprised face-to-face interviews with 1,835 women and tests for six STIs on biological samples from 1,235 of these women. Overall, 10.9 per cent report forced first intercourse and 15.3 per cent report unwanted first intercourse. Unadjusted analysis shows a relationship between forced first intercourse and STIs (OR: 1.72, 95 per cent CI: 1.19-2.51). Life-course variables mediate this relationship. Significant predictors of having an STI include older age, more sexual partners, and a partner who has children with other women. Coerced first intercourse appears to be associated with changes in the life course of women and with a heightened risk of contracting an STI.

Intimate partner violence and women's contraceptive use.

Intimate partner violence has been hypothesized as a factor associated with women's risk for problems in contraception use or access. This article explores differences in contraceptive use between abused and nonabused women, using a case-control study of 225 women. Women experiencing physical and emotional abuse were more likely to report not using their preferred method of contraception in the past 12 months compared with nonabused women (OR = 1.9; 95% CI = 1.0 to 3.7). Health care providers need to consider how intimate partner violence may influence their patients' use of contraceptives, which has implications for the high risk of unintended pregnancies among abused women.

Intersections of harm and health: a qualitative study of intimate partner violence in women's lives.

Eight focus groups of women with recent exposure to intimate partner violence (IPV) were conducted to elicit women's descriptions of how IPV affects their health. Their shared narratives reveal a complex relationship with three main points of intersection between IPV and health: IPV leading to adverse health effects; IPV worsening already compromised health; and women's illness or disability increasing dependency on abusive partners, thereby lengthening the duration of IPV exposure. Women describe bidirectional and cyclical ways through which IPV and health intersect over time. Service providers, including physicians, need to better understand the myriad ways that abuse affects women's health.

Safety and Efficacy of OXB-202, a Genetically Engineered Tissue Therapy for the Prevention of Rejection in High-Risk Corneal Transplant Patients.

Due to both the avascularity of the cornea and the relatively immune-privileged status of the eye, corneal transplantation is one of the most successful clinical transplant procedures. However, in high-risk patients, which account for >20% of the 180,000 transplants carried out worldwide each year, the rejection rate is high due to vascularization of the recipient cornea. The main reason for graft failure is irreversible immunological rejection, and it is therefore unsurprising that neovascularization (NV; both pre and post grafting) is a significant risk factor for subsequent graft failure. NV is thus an attractive target to prevent corneal graft rejection. OXB-202 (previously known as EncorStat®) is a donor cornea modified prior to transplant by ex vivo genetic modification with genes encoding secretable forms of the angiostatic human proteins, endostatin and angiostatin. This is achieved using a lentiviral vector derived from the equine infectious anemia virus called pONYK1EiA, which subsequently prevents rejection by suppressing NV. Previously, it has been shown that rabbit donor corneas treated with pONYK1EiA substantially suppress corneal NV, opacity, and subsequent rejection in an aggressive rabbit model of cornea graft rejection. Here, efficacy data are presented in a second rabbit model, which more closely mirrors the clinical setting for high-risk corneal transplant patients, and safety data from a 3-month good laboratory practice toxicology and biodistribution study of pONYK1EiA-modified rabbit corneas in a rabbit corneal transplant model. It is shown that pONYK1EiA-modified rabbit corneas (OXB-202) significantly reduce corneal NV and the rate of corneal rejection in a dose-dependent fashion, and are tolerated with no adverse toxicological findings or significant biodistribution up to 13 weeks post surgery in these rabbit studies. In conclusion, angiogenesis is a valid target to prevent corneal graft rejection in a high-risk setting, and transplanted genetically modified corneas are safe and well-tolerated in an animal model. These data support the evaluation of OXB-202 in a first-in-human trial.

Abused women disclose partner interference with health care: an unrecognized form of battering.

BACKGROUND: Some providers observe that partners interfere with health care visits or treatment. There are no systematic investigations of the prevalence of or circumstances surrounding partner interference with health care and intimate partner violence (IPV). OBJECTIVE: To determine whether abused women report partner interference with their health care and to describe the co-occurring risk factors and health impact of such interference. DESIGN: A written survey of women attending health care clinics across 5 different medical departments (e.g., emergency, primary care, obstetrics-gynecology, pediatrics, addiction recovery) housed in 8 hospital and clinic sites in Metropolitan Boston. PARTICIPANTS: Women outpatients (N = 2,027) ranging in age, 59% White, 38% married, 22.6% born outside the U.S. MEASUREMENT: Questions from the Severity of Violence and Abuse Assessment Scale, the SF-36, and questions about demographics. RESULTS: One in 20 women outpatients (4.6%) reported that their partners prevented them from seeking or interfered with health care. Among women with past-year physical abuse (n = 276), 17% reported that a partner interfered with their health care in contrast to 2% of women without abuse (adjusted odds ratios [OR] = 7.5). Further adjusted risk markers for partner interference included having less than a high school education (OR = 3.2), being born outside the U.S. (OR = 2.0), and visiting the clinic with a man attending (OR = 1.9). Partner interference raised the odds of women having poor health (OR = 1.8). CONCLUSIONS: Partner interference with health care is a significant problem for women who are in abusive relationships and poses an obstacle to health care. Health care providers should be alert to signs of patient noncompliance or missed appointments as stemming from abusive partner control tactics.

Measuring the effect of intimate partner violence on health-related quality of life: a qualitative focus group study.

BACKGROUND: Health related quality of life (HRQOL) can be measured by a wide range of instruments, many of which have been designed for specific conditions or uses. "Preference-based" measures assess the value individuals place on health, and are included in economic evaluations of treatments and interventions (such as cost effectiveness analysis). As economic evaluation becomes more common, it is important to assess the applicability of preference-based health related quality of life (HRQOL) measures to public health issues. This study investigated the usefulness of such instruments in the context of intimate partner violence (IPV), a public health concern that that can seriously affect quality of life. METHODS: The study consisted of focus groups with abused women to determine the aspects of life affected by IPV, and an analysis of existing HRQOL measures. Eight focus groups (n = 40) were conducted in which participants discussed the domains of health affected by IPV. Results were content analyzed and compared with the domains of health included in four commonly-used, preference-based HRQOL measures. RESULTS: The average focus group participant was 43 years old, unemployed, African American, with 3 children. Domains of health reported to be affected by IPV included physical functioning, emotional and psychological functioning, social functioning and children's functioning. Psychological health was the most severely affected domain. The Short Form 36, the Health Utilities Index, the EuroQol 5D, and the Quality of Well-being Scale were found to vary in the degree to which they include domains of health important in IPV. Psychological health is included to a limited extent, and the spill-over effect of a condition on other family members, including children, is not included at all. CONCLUSION: Emotional and psychological health plays an important role in the overall HRQOL of abused women but is relatively underemphasized in preference-based HRQOL measures. This may lead to an underestimation of the impact of partner violence on HRQOL when using these measures and in economic evaluations that rely thereon. Holistic measurement approaches or expanded measures that capture the far-reaching effects of IPV on HRQOL may be needed to accurately measure the effect of this condition on women's health.

Predicting the timing of women's departure from abusive relationships.

The aim of this study was to investigate forces that affect the timing of women's exit from violent relationships with men. Abused women were recruited from posters in the community and battered women's shelters, interviewed, and followed up for 10 years. Data for this study are based on 100 women and were analyzed using event history analysis. Age, ethnicity, and alcohol consumption levels of both partners predicted the timing of women's termination of abusive relationships. An interaction effect showed that women who scored above the mean on an index of physical aggression and who never used shelter services had the longest trajectories of violence exposure; severely abused women without shelter use were more likely to stay. Our findings indicate that women who receive shelter services endure shorter periods of violence than women who do not access such services. Further outreach, especially to women experiencing high rates of physical aggression, is recommended.

Intimate Partner Violence is Associated with Voluntary Sterilization in Women.

BACKGROUND: Intimate partner violence (IPV) may interfere with women's use of preferred forms of contraception, resulting in unwanted pregnancies forcing women to seek permanent sterilization. A history of child sexual abuse (CSA) presages the risk for IPV in adulthood setting the stage for adverse reproductive outcomes. OBJECTIVE: To determine whether CSA and IPV are associated with women's voluntary sterilization when adjusting for demographics and reproductive health history. METHODS: This cross-sectional study is based on in-person interviews of women (N = 278) drawn from outpatients surveyed in more than 10 different clinics (N = 2465). Women's history of gender-based violence and bilateral tubal ligation (BTL) were assessed. RESULTS: About half of the women had a past history of IPV and 29% disclosed CSA. CSA predicted later entry into an abusive relationship (odds ratio [OR] = 6.7). Sterilization was reported by 19.6%. Parity (3+ children), having had an abortion, and receipt of welfare were associated with sterilization in univariate tests. Among those women receiving a BTL, 74% had violent partners. Adjusted multivariate logistic regressions, adjusted for demographics and reproductive history, indicated that having had an abusive partner increased the odds of sterilization; parity was also highly associated. CSA exerted only an indirect influence on sterilization via entry into violent relationships. CONCLUSION: IPV raises the likelihood that women will choose sterilization. Despite the importance of women's access to permanent contraception, priority should be given to screening for gender-based violence and promoting interventions.

Assessing intimate partner violence in health care settings leads to women's receipt of interventions and improved health.

OBJECTIVE: This study investigated whether disclosure of violence to health care providers and the receipt of interventions relate to women's exit from an abusive relationship and to their improved health. METHODS: A volunteer sample of 132 women outpatients who described intimate partner violence during the preceding year were recruited from multiple hospital departments and community agencies in suburban and urban metropolitan Boston. Through in-person interviews, women provided information on demographics, past year exposure to violence, past year receipt of interventions, and whether they disclosed partner violence to their health care provider. They also described their past month health status with the 12-Item Short-Form Health Survey and further questions. RESULTS: Of the 132 women, 44% had exited the abusive relationship. Among those who were no longer with their partner, 55% received a domestic violence intervention (e.g. advocacy, shelter, restraining order), compared with 37% of those who remained with their partner. Talking to their health care provider about the abuse increased women's likelihood of using an intervention (odds ratio [OR]=3.9). Those who received interventions were more likely to subsequently exit (OR=2.6) and women no longer with the abuser reported better physical health based on SF-12 summary scores (p=0.05) than women who stayed. CONCLUSIONS: Health care providers may make positive contributions to women's access to intimate partner violence services. Intimate partner violence interventions relate to women's reduced exposure to violence and better health.

Adverse health behaviors and the detection of partner violence by clinicians.

BACKGROUND: Intimate partner violence (IPV) is a major public health problem in the United States, and victims are commonly encountered in medical settings. Many barriers exist to clinician-initiated screening for IPV. However, smoking and problem drinking are conditions that clinicians commonly screen for and both have been strongly associated with IPV in prior studies. By estimating the predicted probability of 12-month and lifetime IPV for a given patient based on whether she presents with these conditions, our study gives clinicians information that can help them identify patients at risk for IPV. METHODS: A cross-sectional written patient survey was administered to 2386 female patients at 8 different health care settings in the Greater Boston (Mass) metropolitan area. The probabilities of 12-month and lifetime IPV were estimated based on the women's self-report of smoking and drinking behaviors. RESULTS: A woman who neither smoked nor engaged in problem drinking had a 10% probability of IPV in the preceding 12 months and a 39% chance of IPV in her lifetime. Smoking increased the probability to 14% and 49%, respectively. Problem drinking resulted in a doubling of the predicted probability of 12-month IPV to 21%, with a lifetime probability of 43%. When both conditions were present, the effects were additive, with a woman having a 27% probability of experiencing IPV in the preceding 12 months and 54% chance of IPV in her lifetime. CONCLUSIONS: The presence of smoking or problem drinking should raise clinicians' suspicion for IPV. This paradigm should not replace direct questioning about IPV but may aid in the detection of abuse in patient populations.