Unraveling female communication through scent marks in the Norway rat.

Chemical communication by females remains poorly understood, with most attention focused on female advertisement of sexual receptivity to males or mother-offspring communication. However, in social species, scents are likely to be important for mediating competition and cooperation between females determining individual reproductive success. Here, we explore chemical signaling by female laboratory rats (Rattus norvegicus) to test i) whether females target their deployment of scent information differentially according to their sexual receptivity and the genetic identity of both female and male conspecifics signaling in the local environment and ii) whether females are attracted to gain the same or different information from female scents compared to males. Consistent with targeting of scent information to colony members of similar genetic background, female rats increased scent marking in response to scents from females of the same strain. Females also suppressed scent marking in response to male scent from a genetically foreign strain while sexually receptive. Proteomic analysis of female scent deposits revealed a complex protein profile, contributed from several sources but dominated by clitoral gland secretion. In particular, female scent marks contained a series of clitoral-derived hydrolases and proteolytically truncated major urinary proteins (MUPs). Manipulated blends of clitoral secretion and urine from estrus females were strongly attractive to both sexes, while voided urine alone stimulated no interest. Our study reveals that information about female receptive status is shared between females as well as with males, while clitoral secretions containing a complex set of truncated MUPs and other proteins play a key role in female communication.

CyVerse: Cyberinfrastructure for open science.

CyVerse, the largest publicly-funded open-source research cyberinfrastructure for life sciences, has played a crucial role in advancing data-driven research since the 2010s. As the technology landscape evolved with the emergence of cloud computing platforms, machine learning and artificial intelligence (AI) applications, CyVerse has enabled access by providing interfaces, Software as a Service (SaaS), and cloud-native Infrastructure as Code (IaC) to leverage new technologies. CyVerse services enable researchers to integrate institutional and private computational resources, custom software, perform analyses, and publish data in accordance with open science principles. Over the past 13 years, CyVerse has registered more than 124,000 verified accounts from 160 countries and was used for over 1,600 peer-reviewed publications. Since 2011, 45,000 students and researchers have been trained to use CyVerse. The platform has been replicated and deployed in three countries outside the US, with additional private deployments on commercial clouds for US government agencies and multinational corporations. In this manuscript, we present a strategic blueprint for creating and managing SaaS cyberinfrastructure and IaC as free and open-source software.

Renin and renin blockade have no role in complement activity.

Renin, an aspartate protease, regulates the renin-angiotensin system by cleaving its only known substrate angiotensinogen to angiotensin. Recent studies have suggested that renin may also cleave complement component C3 to activate complement or contribute to its dysregulation. Typically, C3 is cleaved by C3 convertase, a serine protease that uses the hydroxyl group of a serine residue as a nucleophile. Here, we provide seven lines of evidence to show that renin does not cleave C3. First, there is no association between renin plasma levels and C3 levels in patients with C3 Glomerulopathies (C3G) and atypical Hemolytic Uremic Syndrome (aHUS), implying that serum C3 consumption is not increased in the presence of high renin. Second, in vitro tests of C3 conversion to C3b do not detect differences when sera from patients with high renin levels are compared to sera from patients with normal/low renin levels. Third, aliskiren, a renin inhibitor, does not block abnormal complement activity introduced by nephritic factors in the fluid phase. Fourth, aliskiren does not block dysregulated complement activity on cell surfaces. Fifth, recombinant renin from different sources does not cleave C3 even after 24 hours of incubation at 37 °C. Sixth, direct spiking of recombinant renin into sera samples of patients with C3G and aHUS does not enhance complement activity in either the fluid phase or on cell surfaces. And seventh, molecular modeling and docking place C3 in the active site of renin in a position that is not consistent with a productive ground state complex for catalytic hydrolysis. Thus, our study does not support a role for renin in the activation of complement.

Sexual Violence, Genital Cytokines, and Colposcopy Findings: A Cross-Sectional Study of Women Engaged in Sex Work in Mombasa, Kenya.

BACKGROUND: Sexual violence (SV) increases HIV susceptibility in a sustained manner. This study evaluated genital cytokines and colposcopy findings in women reporting both recent and more remote SV.Methods: A cross-sectional study of HIV-1 negative Kenyan women who engage in sex work (WESW) was performed. Cervicovaginal fluid was collected by menstrual cup and cytokines (IFNγ, TNFα, IL-1ß, IL-6, IL-10, MIP-1α, MIP-1ß and CXCL10) measured using chemiluminescence. Cervical injury was assessed by colposcopy. Associations between recent (≤30 days prior), more remote (>30 days prior) and no (reference category) SV exposure and cytokine concentrations were evaluated using linear regression. RESULTS: Among 282 participants, 25 (8.9%) reported recent SV and 123 (43.6%) reported more remote SV. Only two cytokines (IL-10 and CXCL10) were associated with the 3-category SV variable in bivariable modeling at the pre-specified cut-off (p < 0.2) and carried forward. In multivariable analyses, more remote SV (ß = 0.72, 95% CI 0.06, 1.38; p = 0.03), but not recent SV (ß = 0.20, 95%CI -0.99, 1.39; p = 0.74) was associated with cervicovaginal IL-10 compared to no SV. Recent (ß = 0.36, 95% CI -0.94, 1.67; p = 0.58) and more remote (ß = 0.51, 95% CI -0.21, 1.24; p = 0.16) SV were not associated with CXCL10 compared to no SV. Cervical epithelial friability (χ2 = 1.3, p = 0.51), erythema (χ2 = 2.9, p = 0.24), vascular disruption (χ2 = 1.4; p = 0.50), epithelial disruption (χ2 = 2.6, p = 0.27), or any colposcopy finding (χ2 = 1.2, p = 0.54) were not associated with SV category by chi-square test. CONCLUSIONS: The mechanism linking SV to sustained increases in HIV susceptibility may not be related to persistent genital inflammation or injury.

Feasibility and Acceptability of the Novel Tu'Washindi Intervention to Increase PrEP Use among Adolescent Girls and Young Women in Siaya County, Kenya.

The Tu'Washindi intervention addressed intimate partner violence (IPV) and relationship dynamics to increase PrEP use among adolescent girls and young women (AGYW) in Siaya County, Kenya. We evaluated feasibility and acceptability in a cluster-randomized trial in six DREAMS Safe Spaces. The multilevel intervention, delivered over 6 months, included three components delivered by DREAMS staff with support from the study team: an 8-session structured support club; community sensitization of male partners; and a couples PrEP education and health fair ("Buddy Day"). Feasibility and acceptability assessments included implementation process measures, questionnaires, and focus group discussions with AGYWs and post-intervention questionnaires with intervention providers. The study included 103 AGYWs aged 17 to 24 (N = 49 intervention), with 97% retention. Median age was 22, 54% were married, and 84% were mothers. At enrollment, 45% used PrEP and 61% reported lifetime IPV. All intervention participants attended at least one support club session (mean = 5.2 of 8) and 90% attended Buddy Day. At 6 months, most participants perceived Tu'Washindi to be effective: all agreed (with 54% reporting "strongly agree") that the intervention improved partner communication and 60% agreed they were better able to gain partner support for their PrEP use. Providers believed the intervention resonated with community values. Tu'Washindi was highly acceptable and feasible and it was perceived by AGYW participants and providers as being effective in improving partner relationships and supporting PrEP use.

Correlates of Adherence to Oral and Vaginal Pre-exposure Prophylaxis (PrEP) Among Adolescent Girls and Young Women (AGYW) Participating in the MTN-034/REACH Trial.

We evaluated correlates of adherence to PrEP, including daily oral tenofovir disoproxil fumarate in combination emtricitabine (oral FTC/TDF) and the monthly dapivirine ring (ring)among adolescent girls and young women (AGYW) in the MTN-034/REACH study. We enrolled 247 AGYW aged 16-21 years in South Africa, Uganda and Zimbabwe (ClinicalTrials.gov: NCT03074786). Participants were randomized to the order of oral FTC/TDF or ring use for 6 months each in a crossover period, followed by a 6-month choice period. We assessed potential adherence correlates-individual, interpersonal, community, study, and product-related factors-quarterly via self-report. We measured biomarkers of adherence monthly; high adherence was defined as > 4 mg dapivirine released from returned rings or intracellular tenofovir diphosphate levels ≥ 700 fmol/punch from dried blood spots (DBS). We tested associations between correlates and objective measures of high adherence using generalized estimating equations. High adherence to oral FTC/TDF was significantly associated with having an older primary partner (p = 0.04), not having exchanged sex in the past 3 months (p = 0.02), and rating oral FTC/TDF as highly acceptable (p = 0.003). High ring adherence was significantly associated with unstable housing (p = 0.01), disclosing ring use to a male family member (p = 0.01), and noting a social benefit from study participation (p = 0.03). All associations were moderate, corresponding to about 6%-10% difference in the proportion with high adherence. In our multinational study, correlates of adherence among African AGYW differed for oral FTC/TDF and the ring, highlighting the benefit of offering multiple PrEP options.

Associations between alcohol taxes and varied health outcomes among women of reproductive age and infants.

OBJECTIVE: No studies have examined whether alcohol taxes may be relevant for reducing harms related to pregnant people's drinking. METHOD: We examined how beverage-specific ad valorem, volume-based, and sales taxes are associated with outcomes across three data sets. Drinking outcomes came from women of reproductive age in the 1990-2020 US National Alcohol Surveys (N = 11 659 women $\le$ 44 years); treatment admissions data came from the 1992-2019 Treatment Episode Data Set: Admissions (N = 1331 state-years; 582 436 pregnant women admitted to treatment); and infant and maternal outcomes came from the 2005-19 Merative Marketscan® database (1 432 979 birthing person-infant dyads). Adjusted analyses for all data sets included year fixed effects, state-year unemployment and poverty, and accounted for clustering by state. RESULTS: Models yield no robust significant associations between taxes and drinking. Increased spirits ad valorem taxes were robustly associated with lower rates of treatment admissions [adjusted IRR = 0.95, 95% CI: 0.91, 0.99]. Increased wine and spirits volume-based taxes were both robustly associated with lower odds of infant morbidities [wine aOR = 0.98, 95% CI: 0.96, 0.99; spirits aOR = 0.99, 95% CI: 0.98, 1.00] and lower odds of severe maternal morbidities [wine aOR = 0.91, 95% CI: 0.86, 0.97; spirits aOR = 0.95, 95% CI: 0.92, 0.97]. Having an off-premise spirits sales tax was also robustly related to lower odds of severe maternal morbidities [aOR = 0.78, 95% CI: 0.64, 0.96]. CONCLUSIONS: Results show protective associations between increased wine and spirits volume-based and sales taxes with infant and maternal morbidities. Policies that index tax rates to inflation might yield more public health benefits, including for pregnant people and infants.

Comparative Efficacy and Safety of Wakefulness-Promoting Agents for Excessive Daytime Sleepiness in Patients With Obstructive Sleep Apnea : A Systematic Review and Network Meta-analysis.

BACKGROUND: Excessive daytime sleepiness (EDS) is common among patients with obstructive sleep apnea (OSA). The comparative effectiveness of pharmacologic agents is unknown. PURPOSE: To compare the effectiveness of drugs for EDS in OSA using network meta-analysis. DATA SOURCES: MEDLINE, CENTRAL, EMBASE, and ClinicalTrials.gov to 7 November 2022. STUDY SELECTION: Reviewers identified randomized trials that enrolled patients with EDS-associated OSA on or eligible for conventional therapy assigned to any pharmacologic intervention. DATA EXTRACTION: Paired reviewers independently extracted data addressing effects of drugs on the Epworth Sleepiness Scale (ESS), Maintenance of Wakefulness Test (MWT), and adverse events at the longest reported follow-up. The certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. DATA SYNTHESIS: Fourteen trials (3085 patients) were eligible. At 4 weeks, compared with placebo, solriamfetol improves ESS scores (mean difference [MD], -3.85 [95% CI, -5.24 to -2.50]; high certainty), and armodafinil-modafinil (MD, -2.25 [CI, -2.85 to -1.64]; moderate certainty) and pitolisant-H3-autoreceptor blockers (MD, -2.78 [CI, -4.03 to -1.51]; moderate certainty) probably improve ESS scores. At 4 weeks, compared with placebo, solriamfetol (standardized mean difference [SMD], 0.9 [CI, 0.64 to 1.17]) and armodafinil-modafinil (SMD, 0.41 [CI, 0.27 to 0.55]) improve MWT (both high certainty), whereas pitolisant-H3-autoreceptor blockers probably do not (moderate certainty). At 4 weeks, armodafinil-modafinil probably increases the risk for discontinuation due to adverse events (relative risk [RR], 2.01 [CI, 1.14 to 3.51]; moderate certainty); solriamfetol may increase the risk for discontinuation due to adverse events (RR, 2.07 [CI, 0.67 to 6.25]; low certainty). Low certainty evidence suggests these interventions may not increase the risk for serious adverse events. LIMITATIONS: There is limited evidence on long term or effectiveness among patients nonadherent or with mixed adherence to conventional OSA therapies. CONCLUSION: Solriamfetol, armodafinil-modafinil, and pitolisant reduce daytime sleepiness for patients with OSA already on conventional therapy, with solriamfetol likely superior. Adverse events probably increase the risk for discontinuation of armodafinil-modafinil and may increase the risk for discontinuation with solriamfetol. PRIMARY FUNDING SOURCE: None.

Mechanistic modeling of climate effects on redistribution and population growth in a community of fish species.

Understanding community responses to climate is critical for anticipating the future impacts of global change. However, despite increased research efforts in this field, models that explicitly include important biological mechanisms are lacking. Quantifying the potential impacts of climate change on species is complicated by the fact that the effects of climate variation may manifest at several points in the biological process. To this end, we extend a dynamic mechanistic model that combines population dynamics, such as species interactions, with species redistribution by allowing climate to affect both processes. We examine their relative contributions in an application to the changing biomass of a community of eight species in the Gulf of Maine using over 30 years of fisheries data from the Northeast Fishery Science Center. Our model suggests that the mechanisms driving biomass trends vary across space, time, and species. Phase space plots demonstrate that failing to account for the dynamic nature of the environmental and biologic system can yield theoretical estimates of population abundances that are not observed in empirical data. The stock assessments used by fisheries managers to set fishing targets and allocate quotas often ignore environmental effects. At the same time, research examining the effects of climate change on fish has largely focused on redistribution. Frameworks that combine multiple biological reactions to climate change are particularly necessary for marine researchers. This work is just one approach to modeling the complexity of natural systems and highlights the need to incorporate multiple and possibly interacting biological processes in future models.

Adolescent Girls and Young Women's Experiences with Disclosing Oral PrEP or Dapivirine Vaginal Ring Use: a Multi-Country Qualitative Analysis.

Effective use of oral pre-exposure prophylaxis (PrEP) has been low among adolescent girls and young women (AGYW) in Eastern and Southern Africa, partly due to stigma and opposition from key influencers. Understanding AGYW's experiences of disclosure of different PrEP modalities to key influencers may inform strategies to motivate uptake and adherence. We analyzed qualitative in-depth interviews and focus group discussions data from 119 participants in the MTN-034/REACH (Reversing the Epidemic in Africa with Choices in HIV Prevention) study of oral PrEP and the dapivirine vaginal ring (ring) to explore AGYW's disclosure experiences. We found that AGYW disclosure experiences varied across influencers and product type. The ring was disclosed less often to most influencers, except partners, because it was discreet. Oral PrEP was disclosed more often, because pills were more common and to avoid HIV stigma given that oral PrEP resembled HIV treatment. Ultimately, disclosure typically led most key influencers to support product use through reminders and encouragement. While disclosure yielded positive support from influencers, further community awareness of both PrEP products is essential to reduce potential opposition and perceived stigma.Clinical Trial Number: NCT03593655.

Examining Associations Between Mental Health, IPV Exposure, HIV Risk Behaviors, and PrEP Use in South African Women: An Analysis of Data from the Charisma Study.

Intimate partner violence (IPV) has been associated with poorer mental health outcomes and increased human immunodeficiency virus (HIV) risk behaviors. We examine the relations between IPV, mental health symptomology (defined as psychological distress and alcohol misuse), and engagement in HIV risk behaviors among a sample of South African women who participated in a randomized controlled trial of CHARISMA, an intervention to increase women's agency to use oral pre-exposure prophylaxis (PrEP) safely and consistently as well as mitigate relationship challenges. We also examined the impact of trial participation on women's mental health, as well as the impact of psychological distress on the effectiveness of the CHARISMA intervention. Mental health symptomology and IPV exposure were prevalent and associated with some HIV risk and protective behaviors. Trial participation reduced psychological distress. There was no evidence for mental health symptomology impacting the effectiveness of the CHARISMA intervention.

Integrating Adolescent Mental Health into HIV Prevention and Treatment Programs: Can Implementation Science Pave the Path Forward?

Adolescent mental health (AMH) is a critical driver of HIV outcomes, but is often overlooked in HIV research and programming. The implementation science Exploration, Preparation, Implementation, Sustainment (EPIS) framework informed development of a questionnaire that was sent to a global alliance of adolescent HIV researchers, providers, and implementors working in sub-Saharan Africa with the aim to (1) describe current AMH outcomes incorporated into HIV research within the alliance; (2) identify determinants (barriers/gaps) of integrating AMH into HIV research and care; and (3) describe current AMH screening and referral systems in adolescent HIV programs in sub-Saharan Africa. Respondents reported on fourteen named studies that included AMH outcomes in HIV research. Barriers to AMH integration in HIV research and care programs were explored with suggested implementation science strategies to achieve the goal of integrated and sustained mental health services within adolescent HIV programs.

Intimate Partner Violence and Engagement in the HIV Care Continuum among Women in Sub-Saharan Africa: A Prospective Cohort Study.

Research suggests that women's experience of intimate partner violence (IPV) is associated with poor engagement in HIV care and treatment. However, most studies have been cross-sectional and conducted in North America. We examined the association between physical IPV and HIV care outcomes in a prospective cohort study of women living with HIV (WLHIV) in Malawi, South Africa, Uganda, and Zimbabwe. At enrollment, 15% of the 351 participants self-reported physical IPV. IPV experience was not associated with time to first engagement in HIV care or the proportion virally suppressed after 6 months on ART. Women reporting physical IPV were less likely to initiate ART within 6 months of becoming eligible (adjusted RR 0.74, 95% CI 0.53-1.03). IPV screening is critical to identify survivors and link them to appropriate services. However, addressing IPV may not increase engagement in HIV care or viral load suppression among WLHIV in sub-Saharan Africa.

Integrating Gender-Based Violence Screening and Support into the Research Clinic Setting: Experiences from an HIV Prevention Open-Label Extension Trial in Sub-Saharan Africa.

HIV and gender-based violence (GBV) are syndemic in sub-Saharan Africa and provision of support for participants who disclose GBV constitutes part of comprehensive care. Consequently, a process was undertaken to develop, implement, and evaluate standard operating procedures (SOPs) in MTN-025/HOPE, a study of the dapivirine vaginal ring for HIV prevention. The SOP was developed using needs assessment surveys in addition to World Health Organization (WHO) guidelines and other literature. Sites tailored and implemented the SOP through HOPE implementation. At study end, staff reported increased training 32/35 (91.43%); improved confidence (18/26; 69.23%); and improved vicarious trauma prevention onsite (17/28; 60.71%). Leadership reported increased staff competence in GBV response. Obstacles included limited referral organizations and time for follow-up, continued training needs, and cultural norms. Development and implementation of an SOP is a feasible strategy to build a GBV response to improve health systems and support sustained effective use of HIV prevention products.

Assessing Engagement of Adolescents and Young Adults (AYA) in HIV Research: A Multi-method Analysis of a Crowdsourcing Open Call and Typology of AYA Engagement in Sub-Saharan Africa.

Engagement of adolescents and young adults (AYA) in HIV research is increasing in many settings. We organized a crowdsourcing open call to solicit examples of how AYA have been engaged in HIV research in Africa and to develop an engagement typology. We formed a steering committee, promoted the open call, organized judging and recognized finalists. We used a multi-methods approach to identify emerging themes and measure engagement. We received 95 entries from individuals in 15 countries; 74 met the eligibility criteria. More than three-quarters of entries were from AYA (55/74, 74%). Four themes characterized AYA engagement: (1) AYA were co-creators in the HIV research process. (2) AYA were involved in community-level capacity building. (3) AYA were co-leaders in minor risk research. (4) AYA used digital methods to enhance engagement. Our open call identified diverse methods of AYA engagement, which can enhance strategies used to reach AYA in African HIV studies.

Pregnancy-specific alcohol policies and admissions to substance use disorder treatment for pregnant people in the USA.

AIMS: We examined relationships between pregnancy-specific alcohol policies and admissions to substance use disorder treatment for pregnant people in the USA. METHODS: We merged state-level policy and treatment admissions data for 1992-2019. We aggregated data by state-year to examine effects of nine pregnancy-specific alcohol policies on the number of admissions of pregnant women where alcohol was reported as the primary, secondary, or tertiary substance related to the treatment episode (N = 1331). We fit Poisson models that included all policy variables, state-level controls, fixed effects for state and year, state-specific time trends, and an offset variable of the number of pregnancies in the state-year to account for differences in population size and fertility. RESULTS: When alcohol was reported as the primary substance, civil commitment [incidence rate ratio (IRR) 1.45, 95% CI: 1.10-1.89] and reporting requirements for assessment and treatment purposes [IRR 1.36, 95% CI: 1.04-1.77] were associated with greater treatment admissions. Findings for alcohol as primary, secondary, or tertiary substance were similar for civil commitment [IRR 1.31, 95% CI: 1.08-1.59] and reporting requirements for assessment and treatment purposes [IRR 1.21, 95% CI: 1.00-1.47], although mandatory warning signs [IRR 0.84, 95% CI: 0.72-0.98] and priority treatment for pregnant women [IRR 0.88, 95% CI: 0.78-0.99] were associated with fewer treatment admissions. Priority treatment findings were not robust in sensitivity analyses. No other policies were associated with treatment admissions. CONCLUSIONS: Pregnancy-specific alcohol policies related to greater treatment admissions tend to mandate treatment rather than make voluntary treatment more accessible, raising questions of ethics and effectiveness.

Health care provider reporting practices related to self-managed abortion.

BACKGROUND: Health care providers reporting patients to government authorities is a main way people attempting self-managed abortion (SMA) become exposed to legal risks. Little is known about health care provider decision-making regarding SMA reporting. METHODS: We conducted semi-structured interviews with 37 clinicians who provided care in hospital-based obstetrics or emergency departments (13 obstetricians/gynecologists, two advance practice registered nurses providing obstetrics care, 12 emergency medicine physicians, and 10 family medicine physicians) throughout the United States. The interview guide asked participants to describe one or more cases of caring for a patient who may have attempted SMA and about related reporting decisions. We coded responses to answer two questions: What comes to mind for health care providers when asked to think about experiences caring for a patient who may have attempted SMA? Based on health care provider experiences, how might people who providers suspect may have attempted SMA end up reported? RESULTS: About half of participants had cared for someone who may have attempted SMA for that pregnancy. Only two mentioned SMA with misoprostol. Most participants described cases where they were unsure whether the patient had attempted to end their pregnancy on purpose. In most instances, participants mentioned that that the possibility of reporting never occurred to them nor came up. In some cases, participants described a reporting "adjacent" practice - e.g. beginning processes that could lead to substance use, domestic violence, or self-injury/suicide-related reports - or considered reporting related to a perceived need to report abortion complications. In two cases, hospital staff reported to the police and/or Child Protective Services related to the SMA attempt. These involved passing of a fetus after 20 weeks outside the hospital and a domestic violence incident. CONCLUSION: Reporting patients who may have attempted SMA may occur via provider perception of a need to report abortion complications and fetal demises, particularly at later gestations, and other reporting requirements (e.g. substance use, domestic violence, child maltreatment, suicide/self-harm).

Changes in relationships, HIV risk, and feelings towards PrEP: findings from a qualitative explanatory study among participants in the CHARISMA intervention trial.

BACKGROUND: Intimate partner violence (IPV) and other relationship-based challenges have been demonstrated to reduce women's ability to use pre-exposure prophylaxis (PrEP) effectively for HIV prevention. The Community Health Clinical Model for Agency in Relationships and Safer Microbicide Adherence (CHARISMA) intervention was designed to mitigate these challenges and increase South African women's agency to use PrEP. The CHARISMA randomized controlled trial did not identify statistically significant differences in PrEP adherence or relationship dynamics between the intervention and control arms. As such, the aim of this explanatory qualitative sub-study was to understand women's experiences with the CHARISMA trial and explore reasons for the null results. METHODS: Twelve CHARISMA trial participants were purposively selected to participate in serial in-depth interviews, which took place at the trial end and 3 months later. Participants represented individuals who had received each of the three counselling modules, 1) healthy communication counselling, 2) PrEP disclosure counselling, or 3) IPV counselling, as well as those in the control arm who received IPV standard-of-care counselling. RESULTS: A thematic case analysis revealed numerous positive relationship outcomes among intervention participants, including identifying and ending unhealthy relationships, gaining a sense of personal empowerment, and enacting more positive behaviors and HIV risk reduction strategies in subsequent relationships. These positive shifts were occasionally described as contributing to decisions to discontinue PrEP use, which may partly explain the limited impact of the intervention on PrEP adherence. CONCLUSIONS: Future investigations of counselling interventions addressing relationship-based barriers to PrEP use should account for changing risk dynamics and need for PrEP.

Vancomycin use for haemodialysis patients-Development of a new dosing protocol.

AIM: To develop a dosing and monitoring protocol to achieve therapeutic vancomycin levels on intermittent haemodialysis. METHODS: We identified 15 vancomycin treatment courses received by patients on intermittent haemodialysis at a district health board in Auckland, New Zealand. Demographic, biochemical and clinical parameters were gathered from their health records. We subsequently devised and implemented a new vancomycin protocol consisting of weight-based loading dose, and subsequent dose titration according to same-day measured pre-dialysis levels. We then re-audited 16 vancomycin treatment courses to assess the performance of the protocol. RESULTS: A significantly higher proportion of vancomycin levels were within the target range (15-20 mg/L) following the implementation of protocol, from 23% to 46% (p < .005). Additionally, a greater proportion of treatment courses had >50% of pre-dialysis levels within the target range, rising from 13% to 56% (p < .01). In the pre-protocol group, 19 out of 117 doses of vancomycin were withheld during treatment, compared to 1 out of 118 doses in the post-protocol group. A total of 62% of total maintenance doses were administered in adherence to protocol. Length of hospital stay and number of positive blood cultures while on treatment were reduced. CONCLUSIONS: Our initial audit revealed deficiencies in our clinical practice in the absence of a local vancomycin protocol for patients receiving intermittent haemodialysis. Following the implementation of our novel protocol, there was an improvement in therapeutic levels and fewer doses were withheld. Our sample size was too small to allow for interpretation of clinical outcome data.

Changing nutrient cycling in Lake Baikal, the world's oldest lake.

Lake Baikal, lying in a rift zone in southeastern Siberia, is the world's oldest, deepest, and most voluminous lake that began to form over 30 million years ago. Cited as the "most outstanding example of a freshwater ecosystem" and designated a World Heritage Site in 1996 due to its high level of endemicity, the lake and its ecosystem have become increasingly threatened by both climate change and anthropogenic disturbance. Here, we present a record of nutrient cycling in the lake, derived from the silicon isotope composition of diatoms, which dominate aquatic primary productivity. Using historical records from the region, we assess the extent to which natural and anthropogenic factors have altered biogeochemical cycling in the lake over the last 2,000 y. We show that rates of nutrient supply from deep waters to the photic zone have dramatically increased since the mid-19th century in response to changing wind dynamics, reduced ice cover, and their associated impact on limnological processes in the lake. With stressors linked to untreated sewage and catchment development also now impacting the near-shore region of Lake Baikal, the resilience of the lake's highly endemic ecosystem to ongoing and future disturbance is increasingly uncertain.