The effect of supplementary grass silage and standard concentrate on milk fat fatty acid composition and iodine value when cows are fed a whole rapeseed-based concentrate at pasture

peer-reviewedThe use of grass silage and concentrates to supplement fresh grass intake is commonly practised in dairy systems. However, the effects of such supplementation within a dietary regime designed to produce a spreadable butter are unknown. Sixteen Holstein Friesian cows were used in an incomplete changeover design to investigate the effect on milk fat of supplementation with grass silage (GS) or standard concentrate (SC) when offering a concentrate based on whole rapeseed at pasture (RC+G). A control diet of fresh grass and standard concentrate (SC+G) was also included. Diet had no effect (P > 0.05) on milk yield or on the lactose concentration of milk. The iodine value (IV; grams of iodine per 100 g milk fat) of milk fat with the RC+G diet was greater (43.9, P < 0.05) than with the SC+G diet (39.9). The iodine value of milk fat was reduced (P < 0.05) when RC+G+GS was offered (41.5 g/100g), but not when RC+G+SC was offered (43.1 g/100g), compared with when RC+G was offered. The proportion of unsaturated fatty acids in milk fat was higher (P < 0.05) when the RC+G diet was offered compared with either RC+G+GS or RC+G+SC. If supplementary feedstuffs are to be used in combination with a wholerapeseed- based concentrate and pasture, then inclusion of standard concentrate would be preferred over grass silage because the negative impact on the iodine value of milk fat was less. However, further research is required to investigate the effect on IV of milk fat when a standard concentrate supplement is offered at levels that increase milk yield

Sample Size Calculations for Population Size Estimation Studies Using Multiplier Methods With Respondent-Driven Sampling Surveys.

BACKGROUND: While guidance exists for obtaining population size estimates using multiplier methods with respondent-driven sampling surveys, we lack specific guidance for making sample size decisions. OBJECTIVE: To guide the design of multiplier method population size estimation studies using respondent-driven sampling surveys to reduce the random error around the estimate obtained. METHODS: The population size estimate is obtained by dividing the number of individuals receiving a service or the number of unique objects distributed (M) by the proportion of individuals in a representative survey who report receipt of the service or object (P). We have developed an approach to sample size calculation, interpreting methods to estimate the variance around estimates obtained using multiplier methods in conjunction with research into design effects and respondent-driven sampling. We describe an application to estimate the number of female sex workers in Harare, Zimbabwe. RESULTS: There is high variance in estimates. Random error around the size estimate reflects uncertainty from M and P, particularly when the estimate of P in the respondent-driven sampling survey is low. As expected, sample size requirements are higher when the design effect of the survey is assumed to be greater. CONCLUSIONS: We suggest a method for investigating the effects of sample size on the precision of a population size estimate obtained using multipler methods and respondent-driven sampling. Uncertainty in the size estimate is high, particularly when P is small, so balancing against other potential sources of bias, we advise researchers to consider longer service attendance reference periods and to distribute more unique objects, which is likely to result in a higher estimate of P in the respondent-driven sampling survey

Statistical design and analysis plan for an impact evaluation of an HIV treatment and prevention intervention for female sex workers in Zimbabwe: a study protocol for a cluster randomised controlled trial.

BACKGROUND: Pragmatic cluster-randomised trials should seek to make unbiased estimates of effect and be reported according to CONSORT principles, and the study population should be representative of the target population. This is challenging when conducting trials amongst 'hidden' populations without a sample frame. We describe a pair-matched cluster-randomised trial of a combination HIV-prevention intervention to reduce the proportion of female sex workers (FSW) with a detectable HIV viral load in Zimbabwe, recruiting via respondent driven sampling (RDS). METHODS: We will cross-sectionally survey approximately 200 FSW at baseline and at endline to characterise each of 14 sites. RDS is a variant of chain referral sampling and has been adapted to approximate random sampling. Primary analysis will use the 'RDS-2' method to estimate cluster summaries and will adapt Hayes and Moulton's '2-step' method to adjust effect estimates for individual-level confounders and further adjust for cluster baseline prevalence. We will adapt CONSORT to accommodate RDS. In the absence of observable refusal rates, we will compare the recruitment process between matched pairs. We will need to investigate whether cluster-specific recruitment or the intervention itself affects the accuracy of the RDS estimation process, potentially causing differential biases. To do this, we will calculate RDS-diagnostic statistics for each cluster at each time point and compare these statistics within matched pairs and time points. Sensitivity analyses will assess the impact of potential biases arising from assumptions made by the RDS-2 estimation. DISCUSSION: We are not aware of any other completed pragmatic cluster RCTs that are recruiting participants using RDS. Our statistical design and analysis approach seeks to transparently document participant recruitment and allow an assessment of the representativeness of the study to the target population, a key aspect of pragmatic trials. The challenges we have faced in the design of this trial are likely to be shared in other contexts aiming to serve the needs of legally and/or socially marginalised populations for which no sampling frame exists and especially when the social networks of participants are both the target of intervention and the means of recruitment. The trial was registered at Pan African Clinical Trials Registry (PACTR201312000722390) on 9 December 2013

Changes in engagement in HIV prevention and care services among female sex workers during intensified community mobilization in 3 sites in Zimbabwe, 2011-2015

Introduction - ‘Sisters with a Voice’, Zimbabwe’s nationally-scaled comprehensive program for female sex workers (FSWs), intensified community mobilisation activities in three sites to increase protective behaviors and utilization of clinical services. We compare indicators among FSWs at the beginning and after implementation. Methods – We used mixed methods to collect data at three sites: in-depth interviews (n=22) in 2015, routine clinical data from 2010 to 2015, and two respondent driven sampling surveys in 2011 and 2015, in which participants completed an interviewer-administered questionnaire and provided a finger prick blood sample for HIV antibody testing. Estimates were weighted using RDS-1 and estimate convergence assessed in both years. We assessed differences in six indicators between 2011 and 2015 using logistic regression adjusted for age, duration in sex work and education. Results - 870 FSWs were recruited from the three sites in 2011 and 915 in 2015. Using logistic regression to adjust for socio-demographic differences, we found differences in the estimates of the proportion of HIV positive FSWs and HIV positive FSWs who knew their status and reported being on ART in Mutare and Victoria Fallsbetween 2011 and 2015. Reported condom use with clients was similar at both time points; however, condom use with regular partners different in 2015 in Mutare and Hwange. Reported HIV testing in the last 6 months among HIV negative FSWs was different at all sites for instance in Victoria Falls it was 13.4% (95% CI 8.7 – 19.9%) in 2011 and 80.8% (95% CI 74.0-87.7) in 2015. FSWs described positive perceptions of the Sisters program, ease of engaging with health services, and improved solidarity among peers. Program data showed increases in services use by 2015 across all sites. Conclusion – Improvements in key HIV care engagement indicators were observed among FSWs in two sites and in testing and prevention indicators across the three sites after implementation of an intensified community mobilisation intervention. Engagement with services for FSWs is critical for countries to reach 90.90.90 targets

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

Dissection of drug resistance mechanisms in FGFR2 mutant endometrial cancer.

PhDMutations in FGFR2 are common in a subset of endometrial carcinomas. Given the emergence of small molecule inhibitors specific to this receptor tyrosine kinase, FGFR2 is an attractive therapeutic target. However, compensatory and adaptation mechanisms limit the clinical utility of compounds that target nodes in the receptor tyrosine kinase network. Here, we analysed the impact of FGFR inhibition in endometrial cancer cells and observed the emergence of a resistant population in an FGFR2-mutant cell line. To understand the mechanisms underlying this adaptation response, we used a phosphoproteomics approach to measure the kinase network in an unbiased manner. These experiments led to the identification of an AKT-related compensatory mechanism underpinning this resistance. Further dissection of this resistance mechanism utilising gene expression analysis showed PHLDA1, a negative regulator of AKT, was significantly down-regulated in resistant cells. This was further confirmed at the protein level. siRNA knockdown of PHLDA1 conferred immediate drug resistance in the FGFR2-mutant endometrial cancer cell line. Therefore, we identified PHLDA1 down-regulation as a mediator of drug resistance in FGFR2 mutant cancer cells, the first demonstration of the role of PHLDA1 in the acquisition and maintenance of drug resistance. Using a 3D physiomimetic model, we demonstrated that AKT inhibition alone also led to generation of a drug-resistant population. Most importantly, dual-drug therapy inhibited proliferation and induced cell death. Our data highlight how mass spectrometry and microarray gene expression analysis can complement each other in the identification of novel resistance mechanisms in cancer cells. These data suggest that combination treatment of FGFR2-mutant endometrial cancers, targeting both FGFR2 and AKT, represents a promising therapeutic approach.Cancer Research U

Public target interventions to reduce the inappropriate use of medicines or medical procedures: a systematic review.

BACKGROUND: An epidemic of health disorders can be triggered by a collective manifestation of inappropriate behaviors, usually systematically fueled by non-medical factors at the individual and/or societal levels. This study aimed to (1) landscape and assess the evidence on interventions that reduce inappropriate demand of medical resources (medicines or procedures) by triggering behavioral change among healthcare consumers, (2) map out intervention components that have been tried and tested, and (3) identify the "active ingredients" of behavior change interventions that were proven to be effective in containing epidemics of inappropriate use of medical resources. METHODS: For this systematic review, we searched MEDLINE, EMBASE, the Cochrane Library, and PsychINFO from the databases' inceptions to May 2019, without language restrictions, for behavioral intervention studies. Interventions had to be empirically evaluated with a control group that demonstrated whether the effects of the campaign extended beyond trends occurring in the absence of the intervention. Outcomes of interest were reductions in inappropriate or non-essential use of medicines and/or medical procedures for clinical conditions that do not require them. Two reviewers independently screened titles, abstracts, and full text for inclusion and extracted data on study characteristics (e.g., study design), intervention development, implementation strategies, and effect size. Data extraction sheets were based on the checklist from the Cochrane Handbook for Systematic Reviews. RESULTS: Forty-three studies were included. The behavior change technique taxonomy v1 (BCTTv1), which contains 93 behavioral change techniques (BCTs), was used to characterize components of the interventions reported in the included studies. Of the 93 BCTs, 15 (16%) were identified within the descriptions of the selected studies targeting healthcare consumers. Interventions consisting of education messages, recommended behavior alternatives, and a supporting environment that incentivizes or encourages the adoption of a new behavior were more likely to be successful. CONCLUSIONS: There is a continued tendency in research reporting that mainly stresses the effectiveness of interventions rather than the process of identifying and developing key components and the parameters within which they operate. Reporting "negative results" is likely as critical as reporting "active ingredients" and positive findings for implementation science. This review calls for a standardized approach to report intervention studies. TRIAL REGISTRATION: PROSPERO registration number CRD42019139537

Good news for sex workers in Zimbabwe: how a court order improved safety in the absence of decriminalization.

As highlighted in the JIAS special issue on the role of police in the global HIV pandemic, legal policy and its enforcement both reflect and shape social attitudes toward key populations including sex workers, men who have sex with men, drug users and other marginalised groups [1]. How the police interpret and implement legal restrictions on specific behaviours influences local risk environments by sharpening or mitigating the laws’ impact [2-4]. This paper summarises recent legal action in Zimbabwe that has positively influenced female sex workers’ (FSW) safety and, if sustained, is likely to translate into reduced HIV risk

Decisions to use antibiotics for upper respiratory tract infections across China: a large-scale cross-sectional survey among university students.

OBJECTIVES: To investigate the decision-making process of Chinese university students with respect to antibiotic use for upper respiratory tract infections (URTIs). DESIGN: A cross-sectional questionnaire study. SETTING: The participants recruited from six universities across all Chinese regions from September to November 2015. PARTICIPANTS: A total of 2834 university students sampled across six Chinese regions who self-reported experiencing symptoms of URTI within the past month completed the survey. OUTCOME MEASURES: The prevalence of decisions for treatment and antibiotic use for URTIs as well as knowledge about antibiotic use were measured by a self-administrated questionnaire. Using regular and multinomial logistic regression a nd adapted health belief model, we identified and measured a number of variables as potential risk factors for antibiotic misuse behaviours in order to explain and predict people's treatment decisions and antibiotic use including knowledge, perceptions, access to antibiotics and cues to action. RESULTS: Of the 2834 university students who self-diagnosed a URTI, 947 (33.4%) self-reported having taken antibiotics; among them, 462 (48.8%) used non-prescription antibiotics, which came principally from left-over prescriptions (29.0%) and over-the-counter purchases at retail pharmacies (67.3%). One in four who sought care pressured their doctors for antibiotics; all received them. Those who perceived greater severity of the disease, had access to antibiotics, perceived benefits of using antibiotics (for the common cold: adjusted OR (aOR)=2.55, 95% CI 1.93 to 3.38 or as anti-inflammatory drugs: aOR=1.35, 95% CI 1.12 to 1.63), and were cued to action (eg, seeing presence of fever: aOR=2.05, 95% CI 1.62 to 2.60 or self-diagnosing their current infection as severe: aOR=1.86, 95% CI 1.41 to 2.45), keeping antibiotics at home (aOR=2.27, 95% CI 1.83 to 2.81) and access to over-the-counter antibiotics (aOR=2.00, 95% CI 1.63 to 2.45), were more likely to misuse antibiotics. CONCLUSIONS: Misconceptions of antibiotic efficacy and easy access to antibiotics-with or without a prescription-were associated with antibiotic misuse among Chinese university students, which calls for context-appropriate multifaceted interventions in order to effectively reduce antibiotic misuse

Relationship between the Mediterranean dietary pattern and musculoskeletal health in children, adolescents, and adults: systematic review and evidence map

Context: An understanding of the modifiable effects of diet on bone and skeletal muscle mass and strength over the life course will help inform strategies to reduce age-related fracture risk. The Mediterranean diet is rich in nutrients that may be important for optimal musculoskeletal health. Objective: The aim of this systematic review was to investigate the relationship between a Mediterranean diet and musculoskeletal outcomes (fracture, bone density, osteoporosis, sarcopenia) in any age group. Data Sources: Ten electronic databases were searched. Study Selection: Randomized controlled trials and prospective cohort studies that investigated a traditional Mediterranean diet, published in any language, were eligible. Studies using other designs or other definitions of the Mediterranean diet were collated separately in an evidence map. Data Extraction: Details on study design, methods, population, dietary intervention or exposure, length of follow-up, and effect on or association with musculoskeletal outcomes were extracted. Results: The search yielded 1738 references. Data from eligible randomized controlled trials (n = 0) and prospective cohort studies (n = 3) were synthesized narratively by outcome for the systematic review. Two of these studies reported on hip fracture incidence, but results were contradictory. A third study found no association between the Mediterranean diet and sarcopenia incidence. Conclusions: Overall, the systematic review and evidence map demonstrate a lack of research to understand the relationship between the Mediterranean diet and musculoskeletal health in all ages. Systematic Review Registration: PROSPERO registration number IDCRD42016037038