Is the sexual behaviour of young people in sub-Saharan Africa influenced by their peers? A systematic review.

Adolescents in sub-Saharan Africa are highly vulnerable to HIV, other sexually transmitted infections (STIs) and unintended pregnancies. Evidence for the effectiveness of individual behaviour change interventions in reducing incidence of HIV and other biological outcomes is limited, and the need to address the social conditions in which young people become sexually active is clear. Adolescents' peers are a key aspect of this social environment and could have important influences on sexual behaviour. There has not yet been a systematic review on the topic in sub-Saharan Africa. We searched 4 databases to find studies set in sub-Saharan Africa that included an adjusted analysis of the association between at least one peer exposure and a sexual behaviour outcome among a sample where at least 50% of the study participants were aged between 13 and 20 years. We classified peer exposures using a framework to distinguish different mechanisms by which influence might occur. We found 30 studies and retained 11 that met quality criteria. There were 3 cohort studies, 1 time to event and 7 cross-sectional. The 11 studies investigated 37 different peer exposure-outcome associations. No studies used a biological outcome and all asked about peers in general rather than about specific relationships. Studies were heterogeneous in their use of theoretical frameworks and means of operationalizing peer influence concepts. All studies found evidence for an association between peers and sexual behaviour for at least one peer exposure/outcome/sub-group association. Of all 37 outcome/exposure/sub-group associations tested, there was evidence for 19 (51%). There were no clear patterns by type of peer exposure, outcome or adolescent sub-group. There is a lack conclusive evidence about the role of peers in adolescent sexual behaviour in Sub-Saharan. We argue that longitudinal designs, use of biological outcomes and approaches from social network analysis are priorities for future studies

Changes in nutritional status associated with unresectable pancreatic cancer.

Weight loss is common in patients with pancreatic cancer; however, the nature and progress of their nutritional depletion are not well documented. In this study, pre-illness weight and duration of weight loss were recorded in 20 patients with histologically confirmed unresectable cancer of the pancreas. Patients then underwent nutritional analysis at monthly intervals until death. The median period of assessment was 27 weeks (interquartile range 22.5-38.0 weeks). At the time of diagnosis, all patients had lost weight [median 14.2% (10.0-20.0%) of pre-illness stable weight], and this weight loss was progressive, increasing to a median of 24.5% by the time of the last assessment (P =0.0004). Body mass index was significantly reduced from a pre-illness median value of 24.9 kg m-2 (22.4-27.4 kg m-2) to 20.7 kg m-2 (19.5-23.6 kg m-2) at the time of diagnosis and further to 17.7 kg m-2 (16.6-23.1 kg m-2) just before death (P =0.0003). Further evidence of tissue depletion was evident from the significant reductions in lean body mass [43.4 kg (36.9-53.0 kg) to 40.1 kg (33.5-50.7 kg) P =0.008] and fat mass [12.5 kg (8.9-17.8 kg) to 9.6 kg (6.3-15.1 kg) P =0.03). This study confirms that the majority of patients with unresectable pancreatic cancer have already undergone significant weight loss by the time of diagnosis and that the natural history of this process is one of inexorable progression. These results highlight the need for selective non-toxic therapeutic intervention to attenuate cachexia and indicate that such interventions should be instituted early in the course of the disease

Dystrophin glycoprotein complex dysfunction:a regulatory link between muscular dystrophy and cancer cachexia

SummaryCachexia contributes to nearly a third of all cancer deaths, yet the mechanisms underlying skeletal muscle wasting in this syndrome remain poorly defined. We report that tumor-induced alterations in the muscular dystrophy-associated dystrophin glycoprotein complex (DGC) represent a key early event in cachexia. Muscles from tumor-bearing mice exhibited membrane abnormalities accompanied by reduced levels of dystrophin and increased glycosylation on DGC proteins. Wasting was accentuated in tumor mdx mice lacking a DGC but spared in dystrophin transgenic mice that blocked induction of muscle E3 ubiquitin ligases. Furthermore, DGC deregulation correlated positively with cachexia in patients with gastrointestinal cancers. Based on these results, we propose that, similar to muscular dystrophy, DGC dysfunction plays a critical role in cancer-induced wasting

Friendships Among Young South African Women, Sexual Behaviours and Connections to Sexual Partners (HPTN 068).

Friends could be influential on young women's sexual health via influences on sexual behaviours and as connections to sexual partners, but are understudied in sub-Saharan Africa. We cross-sectionally surveyed 2326 13-20 year-old young women eligible for grades 8-11 in rural South Africa about their sexual behaviour and up to three sexual partners. Participants each described five specific but unidentified friends and the relationships between them in an 'egocentric' network analysis design. We used logistic regression to investigate associations between friendship characteristics and participants' reports of ever having had sex (n = 2326) and recent condom use (n = 457). We used linear regression with random effects by participant to investigate friendship characteristics and age differences with sexual partners (n = 633 participants, 1051 partners). We found that it was common for friends to introduce young women to those who later became sexual partners, and having older friends was associated with having older sexual partners, (increase of 0.37 years per friend at least 1 year older, 95% CI 0.21-0.52, adjusted). Young women were more likely to report ever having had sex when more friends were perceived to be sexually active (adjusted OR 1.85, 95% CI 1.72-2.01 per friend) and when they discussed sex, condoms and HIV with friends. Perception of friends' condom use was not associated with participants' reported condom use. While this study is preliminary and unique in this population and further research should be conducted, social connections between friends and sexual partners and perceptions of friend sexual behaviours could be considered in the design of sexual health interventions for young women in South Africa

Silencing the GUCA2A-GUCY2C tumor suppressor axis in CIN, serrated, and MSI colorectal neoplasia.

Colorectal cancers (CRCs) initiate through distinct mutations, including in APC pathway components leading to tubular adenomas (TAs); in BRAF, with epigenetic silencing of CDX2, leading to serrated adenomas (SAs); and in the DNA mismatch repair machinery driving microsatellite instability (MSI). Transformation through the APC pathway involves loss of the hormone GUCA2A that silences the tumor-suppressing receptor GUCY2C. Indeed, oral hormone replacement is an emerging strategy to reactivate GUCY2C and prevent CRC initiation and progression. Moreover, retained expression by tumors arising from TAs has established GUCY2C as a diagnostic and therapeutic target to prevent and treat metastatic CRC. Here, we defined the potential role of the GUCA2A-GUCY2C axis and its suitability as a target in tumors arising through the SA and MSI pathways. GUCA2A hormone expression was eliminated in TAs, SAs, and MSI tumors compared to their corresponding normal adjacent tissues. In contrast to the hormone, the tumor-suppressing receptor GUCY2C was retained in TA and MSI tumors. Surprisingly, GUCY2C expression was nearly eliminated in SAs, reflecting loss of the transcription factor CDX2. Changes in the GUCA2A-GUCY2C axis in human SAs and MSI tumors were precisely recapitulated in genetic mouse models. These data reveal the possibility of GUCA2A loss silencing GUCY2C in the pathophysiology of, and oral hormone replacement to restore GUCY2C signaling to prevent, MSI tumors. Also, they highlight the potential for targeting GUCY2C to prevent and treat metastases arising from TA and MSI tumors. In contrast, loss of GUCY2C excludes patients with SAs as candidates for GUCY2C-based prevention and therapy

Secondary containment system for a high tritium research cryostat

A 4.2- to 300-K liquid helium cryostat was constructed for cryogenic samples of D-T containing up to 4 x 10$sup 14$ dis/s (10,000 Ci) of tritium radioactivity. The cryostat is enclosed in a secondary box, which acts as the ultimate container in case of a tritium release. Dry argon is flushed through the box, and the box atmosphere is monitored for tritium, oxygen, and water vapor. A rupture disk and abort tank protect the box atmosphere in case the sample cell breaks. If tritium breaks into the box, a powdered uranium getter trap reduces the 4 x 10$sup 14$ dis/s (10,000 Ci) to 4 x 10$sup 9$ dis/s (0.1 Ci) in 24 h. A backup palladium-zeolite getter system goes into operation if an overabundance of oxygen contaminates the uranium getter. (auth

Routinely used interventions to improve attachment in infants and young children: a national survey and two systematic reviews.

BACKGROUND: Attachment refers to an infant's innate tendency to seek comfort from their caregiver. Research shows that attachment is important in promoting healthy social and emotional development. Many parenting interventions have been developed to improve attachment outcomes for children. However, numerous interventions used in routine practice have a limited evidence base, meaning that we cannot be sure if they are helpful or harmful. OBJECTIVES: This research aimed to conduct a large-scale survey to identify what interventions are being used in UK services to improve child attachment; conduct a systematic review to evaluate the evidence for parenting attachment interventions; and develop recommendations for future research and practice. DESIGN AND METHODS: We worked closely with our Expert Reference Group to plan a large-scale survey focused on relevant UK services. We then conducted two systematic reviews. One searched for all randomised controlled trial evidence for any attachment parenting intervention. The second searched for all research for the top 10 routinely used interventions identified from the survey. RESULTS: The survey collected 625 responses covering 734 UK services. The results identified the 10 most commonly used interventions. The responses showed a limited use of validated measures and a wide variety of definitions of attachment. For the first review, seven studies were included from 2516 identified records. These were combined with results from previous reviews conducted by the team. Meta-analyses showed that, overall, parenting interventions are effective in reducing disorganised attachment (pooled odds ratio 0.54, 95% confidence interval 0.39 to 0.77) and increasing secure attachment (pooled odds ratio 1.85, 95% confidence interval 1.36 to 2.52). The second review searched the literature for the top 10 routinely used interventions identified by the survey; 61 studies were included from 1198 identified records. The results showed that many of the most commonly used interventions in UK services have a weak evidence base and those with the strongest evidence base are not as widely used. CONCLUSIONS: There is a need for better links between research and practice to ensure that interventions offered to families are safe and effective. Possible reasons for the disparity include the cost and accessibility of training. There is also a need for improved understanding by professionals regarding the meaning of attachment. LIMITATIONS: Although the survey had good geographical spread, most respondents were based in England. For review 2 we were unable to access a large number of papers; however, we conducted extensive reference checking to account for this. FUTURE WORK: There is a need for robust research to test the efficacy of routinely used attachment interventions. Research could also explore why routinely used interventions are not consistently subject to thorough evaluation; how to embed dissemination, cost-effectiveness, fidelity and sustainability into research; and how to keep clinical practice up to date with research developments. STUDY REGISTRATION: This study is registered as PROSPERO CRD42019137362. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 2. See the NIHR Journals Library website for further project information

Associations between friendship characteristics and HIV and HSV-2 status amongst young South African women in HPTN-068.

INTRODUCTION: Prevalence of HIV among young women in South Africa remains extremely high. Adolescent peer groups have been found to be an important influence on a range of health behaviours. The characteristics of young women's friendships might influence their sexual health and HIV risk via connections to sexual partners, norms around sexual initiation and condom use, or provision of social support. We investigated associations between young women's friendships and their Herpes Simplex Virus Type 2 (HSV-2) and HIV infection status in rural South Africa. METHODS: Our study is a cross-sectional, egocentric network analysis. In 2011 to 2012, we tested 13- to 20-year-old young women for HIV and HSV-2, and collected descriptions of five friendships for each. We generated summary measures describing friend socio-demographic characteristics and the number of friends perceived to have had sex. We used logistic regression to analyse associations between friend characteristics and participant HIV and HSV-2 infection, excluding likely perinatal HIV infections. RESULTS: There were 2326 participants included in the study sample, among whom HIV and HSV-2 prevalence were 3.3% and 4.6% respectively. Adjusted for participant and friend socio-demographic characteristics, each additional friend at least one year older than the participant was associated with raised odds of HIV (odds ratio (OR) = 1.37, 95% CI 1.03 to 1.82) and HSV-2 (adjusted OR=1.41, 95% CI 1.18 to 1.69). Each additional friend perceived to have ever had sex also raised the odds of HIV (OR = 1.29, 95% CI 1.03 to 1.63) and HSV-2 (OR=1.18, 95% CI 1.03 to 1.35). DISCUSSION: We found good evidence that a greater number of older friends and friends perceived to have had sex were associated with increased risk for HSV-2 and HIV infection among young women. CONCLUSIONS: The characteristics of young women's friendships could contribute to their risk of HIV infection. The extent to which policies or programmes influence age-mixing and young women's normative environments should be considered