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Background In integrated community case management (iCCM) care, community health workers (CHWs) provide home-based management of fever, diarrhea and fast breathing for children aged <5 y. The iCCM protocol recommends that children with danger signs for severe illness are referred by CHWs to health facilities within their catchment area. This study examines the management of danger signs by CHWs implementing iCCM in a rural context. Methods A retrospective observational study that examined clinical records for all patients with danger signs evaluated by CHWs from March 2014 to December 2018 was conducted. Results In total, 229 children aged <5 y had been recorded as having a danger sign during 2014–2018. Of these children, 56% were males with a mean age of 25 (SD 16.9) mo, among whom 78% were referred by the CHWs as per the iCCM protocol. The age category of 12 to 35 mo had the highest numbers of prereferred and referred cases (54% and 46%, respectively). Conclusions CHWs play a key role in early symptomatic detection, prereferral treatment and early referral of children aged <5 y. Danger signs among children aged <5 y, if left untreated, can result in death. A high proportion of the children with danger signs were referred as per the iCCM protocol. Continuous CHW training is emphasized to reduce the number of referral cases that are missed. More studies need to focus on children aged 12–35 mo and why they are the most referred category. Policymakers should occasionally revise iCCM guidelines to detail the types of danger signs and how CHWs can address these. [ABSTRACT FROM AUTHOR]

Background: Pre-referral treatment aims to stabilize the child's condition before transferring them to a higher level of healthcare. This study explored pre-referral treatment for diarrhea, malaria and pneumonia in children U5. The study aims to assess pre-referral treatment practices among community health workers (CHWs) for children aged 2 to 59 months diagnosed with malaria, diarrhea, and pneumonia. Methods: Conducted in 2023, this study employed a quantitative retrospective analysis of secondary data gathered from March 2014 to December 2018. Among the subjects, 171 patients received pre-referral treatment, serving as the foundation for categorical data analysis, presenting proportions and 95% confidence intervals across different categories. Results: In this cohort, 90 (53%) of the 177 children U5 were male, and age distribution showed 39 (23%), 70 (41%), and 62 (36%) in the 2–11 months, 12–35 months, and 36–60 months categories, respectively. Rapid Diagnostic Test (RDT) malaria results indicated a negative outcome in 83(60%) and positive in 55 (40%) of cases. Symptomatically, 45 (26%) had diarrhea, 52 (30%) exhibited fast breathing, and 109 (63%) presented with fever. Furthermore, 59 (35%) displayed danger signs, while 104 (61%) sought medical attention within 24 h. Conclusion: The study analyzed a sample of 171 children under 5 years old to assess various characteristics and variables related to pre-referral treatment. The findings reveal notable proportions in gender distribution, age categories, RDT results, presence of diarrhea, fast breathing, fever, danger signs, and timely medical visits. The results highlight the need to strengthen pre-referral treatment interventions and enhance iCCM programs. [ABSTRACT FROM AUTHOR]

Fillet discolouration, commonly known as bruising, is an unintended and undesirable consequence in many commercial fishing operations. The purpose of this study was to develop a method to objectively measure and characterize the size and location of discolouration patterns that are currently observed in the fillets of commercially harvested yellowtail flounder ( Limanda ferruginea) on the east coast of Canada. To accomplish this, an image processing program was developed to analyse fillet discolouration patterns. Total discoloured area and percent fillet coverage were measured and compared to total bruise weight and percent bruise weight attained from manual assessment. Results revealed that bruising was evident in 86.5% of the fish sampled. Of all the parameters measured, fish weight was the only parameter correlated with bruise weight. Bruise area ranged from 0 to 124.5 cm 2 , with a mean of 12.1 cm 2 (s.d. = 21.4), and accounted for an average of 4.3% of fillet area. Bruises were not uniformly distributed on any of the fillet sides. Results revealed a strong tendency for bruising to occur at the anterior dorsal region of the fillet, commonly known as the “nape”. Functional explanations for this finding are provided, including recommendations for future research. [ABSTRACT FROM AUTHOR]

The article offers the author's insights on the importance of good critical thinking skills for all students which results to deeper comprehension. The author mentions the methods which can be used to foster critical thinking skills in intermediate gifted readers such as the literature discussions and critical literacy. She also mentions the characteristics of gifted readers including literature variety, reading habits, and higher-level thinking skills.

Background: Repeated use, coitus-independent microbicide gels that do not contain antiretroviral agents also used as first line HIV therapy are urgently needed to curb HIV spread. Current formulations require high doses (millimolar range) of antiretroviral drugs and typically only provide short-term protection in macaques. We used the macaque model to test the efficacy of a novel combination microbicide gel containing zinc acetate and micromolar doses of the novel non-nucleoside reverse transcriptase inhibitor MIV-150 for up to 24 h after repeated gel application. Methods and Findings: Rhesus macaques were vaginally challenged with SHIV-RT up to 24 h after repeated administration of microbicide versus placebo gels. Infection status was determined by measuring virologic and immunologic parameters. Combination microbicide gels containing 14 mM zinc acetate dihydrate and 50 μM MIV-150 afforded full protection (21 of 21 animals) for up to 24 h after 2 weeks of daily application. Partial protection was achieved with the MIV-150 gel (56% of control at 8 h after last application, 11% at 24 h), while the zinc acetate gel afforded more pronounced protection (67% at 8-24 h). Marked protection persisted when the zinc acetate or MIV-150/zinc acetate gels were applied every other day for 4 weeks prior to challenge 24 h after the last gel was administered (11 of 14 protected). More MIV-150 was associated with cervical tissue 8 h after daily dosing of MIV-150/zinc acetate versus MIV-150, while comparable MIV-150 levels were associated with vaginal tissues and at 24 h. Conclusions: A combination MIV-150/zinc acetate gel and a zinc acetate gel provide significant protection against SHIV-RT infection for up to 24 h. This represents a novel advancement, identifying microbicides that do not contain anti-viral agents used to treat HIV infection and which can be used repeatedly and independently of coitus, and underscores the need for future clinical testing of their safety and ability to prevent HIV transmission in humans. [ABSTRACT FROM AUTHOR]

Introduction: We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids' quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium. Methods: Following a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for the centralized handling, dermatopathology review and histology-guided coextraction of RNA and DNA. Samples are distributed for evaluation of somatic mutations using next gen sequencing (NGS) with the MSK-IMPACTTM assay, methylation-profiling (Infinium MethylationEPIC arrays), and miRNA expression (Nanostring nCounter Human v3 miRNA Expression Assay). Results: Sufficient material was obtained for screening of miRNA expression in 683/685 (99%) eligible melanomas, methylation in 467 (68%), and somatic mutations in 560 (82%). In 446/685 (65%) cases, aliquots of RNA/DNA were sufficient for testing with all three platforms. Among samples evaluated by the time of this analysis, the mean NGS coverage was 249x, 59 (18.6%) samples had coverage below 100x, and 41/414 (10%) failed methylation QC due to low intensity probes or insufficient Meta-Mixed Interquartile (BMIQ)- and single sample (ss)- Noob normalizations. Six of 683 RNAs (1%) failed Nanostring QC due to the low proportion of probes above the minimum threshold. Age of the FFPE tissue blocks (p<0.001) and time elapsed from sectioning to co-extraction (p = 0.002) were associated with methylation screening failures. Melanin reduced the ability to amplify fragments of 200bp or greater (absent/lightly pigmented vs heavily pigmented, p<0.003). Conversely, heavily pigmented tumors rendered greater amounts of RNA (p<0.001), and of RNA above 200 nucleotides (p<0.001). Conclusion: Our experience with many archival tissues demonstrates that with careful management of tissue processing and quality control it is possible to conduct multi-omic studies in a complex multi-institutional setting for investigations involving minute quantities of FFPE tumors, as in studies of early-stage melanoma. The study describes, for the first time, the optimal strategy for obtaining archival and limited tumor tissue, the characteristics of the nucleic acids co-extracted from a unique cell lysate, and success rate in downstream applications. In addition, our findings provide an estimate of the anticipated attrition that will guide other large multicenter research and consortia. [ABSTRACT FROM AUTHOR]

Background: The control of malaria, pneumonia, and diarrhoea is important for the reduction in morbidity and mortality among children under 5 years. Uganda has adopted the Integrated Community Case Management strategy using Community Health Workers (CHWs) to address this challenge. The extent and trend of these three conditions managed by the CHWs are not well documented. This study was done to describe the epidemiology and trends of the three common illnesses treated by the CHWs in Bugoye Sub-County in rural Uganda. Methods: A retrospective review of monthly morbidity data for children less than 5 years of age for the period April 2014–December 2018 for CHWs in rural Bugoye Sub-County in Kasese district, Uganda was done. The total number reviewed was 18,430 records. The data were analysed using STATA version 14. Results: In total male were 50.2% of the sample, pneumonia was the highest cause of illness among the infants (< 1 year), while malaria was the highest among the children 1 year–59 months. Infection with a single illness was the commonest recorded cause of presentation but there were some children recorded with multiple illnesses. All the CHWs were managing the three common illnesses among children under 5 years. The trend of the three common illnesses was changing from malaria to pneumonia being the commonest. Children aged 12–24 months and 25–59 months were at 2.1 times (95% CI 1.7–2.4) and 5.2 times (95% CI 4.6–5.9), respectively, more likely to get malaria but less likely to get pneumonia and diarrhoea. Conclusion: Community Health Workers in rural Uganda are contributing significantly to the management of all the three commonest illnesses among under-5 years-old children. The trend of the commonest illness is changing from malaria to pneumonia. Children under 1 year are at a higher risk of getting pneumonia and diarrhoea and at a lower risk of getting malaria. [ABSTRACT FROM AUTHOR]

Background: There is widespread agreement that the integration of cessation services in lung cancer screening (LCS) is essential for achieving the full benefits of LCS with low-dose computed tomography (LDCT). There is a formidable knowledge gap about how to best design feasible, effective, and scalable cessation services in LCS facilities. A collective of NCI-funded clinical trials addressing this gap is the Smoking Cessation at Lung Examination (SCALE) Collaboration.Methods: The Cessation and Screening to Save Lives (CASTL) trial seeks to advance knowledge about the reach, effectiveness, and implementation of tobacco treatment in lung cancer screening. We describe the rationale, design, evaluation plan, and interventions tested in this multiphase optimization strategy trial (MOST). A total of 1152 screening-eligible current smokers are being recruited from 18 LCS sites (n = 64/site) in both academic and community settings across the USA. Participants receive enhanced standard care (cessation advice and referral to the national Quitline) and are randomized to receive additional tobacco treatment components (motivational counseling, nicotine replacement patches/lozenges, message framing). The primary outcome is biochemically validated, abstinence at 6 months follow-up. Secondary outcomes are self-reported smoking abstinence, quit attempts, and smoking reduction at 3 and 6 months. Guided by the Implementation Outcomes Framework (IOF), our evaluation includes measurement of implementation processes (reach, fidelity, acceptability, appropriateness, sustainability, and cost).Conclusion: We will identify effective treatment components for delivery by LCS sites. The findings will guide the assembly of an optimized smoking cessation package that achieves superior cessation outcomes. Future trials can examine the strategies for wider implementation of tobacco treatment in LDCT-LCS sites.Trial Registration: ClinicalTrials.gov NCT03315910. [ABSTRACT FROM AUTHOR]

Prevalent infection with human herpes simplex 2 (HSV-2) or human papillomavirus (HPV) is associated with increased human immunodeficiency virus (HIV) acquisition. Microbicides that target HIV as well as these sexually transmitted infections (STIs) may more effectively limit HIV incidence. Previously, we showed that a microbicide gel (MZC) containing MIV-150, zinc acetate (ZA) and carrageenan (CG) protected macaques against simian-human immunodeficiency virus (SHIV-RT) infection and that a ZC gel protected mice against HSV-2 infection. Here we evaluated a modified MZC gel (containing different buffers, co-solvents, and preservatives suitable for clinical testing) against both vaginal and rectal challenge of animals with SHIV-RT, HSV-2 or HPV. MZC was stable and safe in vitro (cell viability and monolayer integrity) and in vivo (histology). MZC protected macaques against vaginal (p<0.0001) SHIV-RT infection when applied up to 8 hours (h) prior to challenge. When used close to the time of challenge, MZC prevented rectal SHIV-RT infection of macaques similar to the CG control. MZC significantly reduced vaginal (p<0.0001) and anorectal (p = 0.0187) infection of mice when 106 pfu HSV-2 were applied immediately after vaginal challenge and also when 5×103 pfu were applied between 8 h before and 4 h after vaginal challenge (p<0.0248). Protection of mice against 8×106 HPV16 pseudovirus particles (HPV16 PsV) was significant for MZC applied up to 24 h before and 2 h after vaginal challenge (p<0.0001) and also if applied 2 h before or after anorectal challenge (p<0.0006). MZC provides a durable window of protection against vaginal infection with these three viruses and, against HSV-2 and HPV making it an excellent candidate microbicide for clinical use. [ABSTRACT FROM AUTHOR]

Background: In some areas of Uganda, village health workers (VHW) deliver Integrated Community Case Management (iCCM) care, providing initial assessment of children under 5 years of age as well as protocol-based treatment of malaria, pneumonia, and diarrhoea for eligible patients. Little is known about community perspectives on or satisfaction with iCCM care. This study examines usage of and satisfaction with iCCM care as well as potential associations between these outcomes and time required to travel to the household's preferred health facility. Methods: A cross-sectional household survey was administered in a rural subcounty in western Uganda during December 2016, using a stratified random sampling approach in villages where iCCM care was available. Households were eligible if the household contained one or more children under 5 years of age. Results: A total of 271 households across 8 villages were included in the final sample. Of these, 39% reported that it took over an hour to reach their preferred health facility, and 73% reported walking to the health facility; 92% stated they had seen a VHW for iCCM care in the past, and 55% had seen a VHW in the month prior to the survey. Of respondents whose households had sought iCCM care, 60% rated their overall experience as "very good" or "excellent," 97% stated they would seek iCCM care in the future, and 92% stated they were "confident" or "very confident" in the VHW's overall abilities. Longer travel time to the household's preferred health facility did not appear to be associated with higher propensity to seek iCCM care or higher overall satisfaction with iCCM care. Conclusions: In this setting, community usage of and satisfaction with iCCM care for malaria, pneumonia, and diarrhoea appears high overall. Ease of access to facility-based care did not appear to impact the choice to access iCCM care or satisfaction with iCCM care. [ABSTRACT FROM AUTHOR]

Background: Village health workers (VHWs) in five villages in Bugoye subcounty (Kasese District, Uganda) provide integrated community case management (iCCM) services, in which VHWs evaluate and treat malaria, pneumonia, and diarrhoea in children under 5 years of age. VHWs use a “Sick Child Job Aid” that guides them through the evaluation and treatment of these illnesses. A retrospective observational study was conducted to measure the quality of iCCM care provided by 23 VHWs in 5 villages in Bugoye subcounty over a 2-year period. Methods: Patient characteristics and clinical services were summarized using existing aggregate programme data. Lot quality assurance sampling of individual patient records was used to estimate adherence to the iCCM algorithm, VHW-level quality (based on adherence to the iCCM protocol), and change over time in quality of care (using generalized estimating equations regression modelling). Results: For each of 23 VHWs, 25 patient visits were randomly selected from a 2-year period after iCCM care initiation. In these visits, 97% (150) of patients with diarrhoea were treated with oral rehydration and zinc, 95% (216) of patients with pneumonia were treated with amoxicillin, and 94% (240) of patients with malaria were treated with artemisininbased combination therapy or rectal artesunate. However, only 44% (44) of patients with a negative rapid test for malaria were appropriately referred to a health facility. Overall, 75% (434) of patients received all the correct evaluation and management steps. Only 9 (39%) of the 23 VHWs met the pre-determined LQAS threshold for high-quality care over the 2-year observation period. Quality of care increased significantly in the first 6 months after initiation of iCCM services (p = 0.003), and then plateaued during months 7–24. Conclusions: Quality of care was high for uncomplicated malaria, pneumonia and diarrhoea. Overall quality of care was lower, in part because VHWs often did not follow the guidelines to refer patients with fever who tested negative for malaria. Quality of care appears to improve in the initial months after iCCM implementation, as VHWs gain initial experience in iCCM care. [ABSTRACT FROM AUTHOR]

Myeloid dendritic cells (mDCs) contribute to both HIV pathogenesis and elicitation of antiviral immunity. Understanding how mDC responses to stimuli shape HIV infection outcomes will inform HIV prevention and treatment strategies. The long double-stranded RNA (dsRNA) viral mimic, polyinosinic polycytidylic acid (polyIC, PIC) potently stimulates DCs to focus Th1 responses, triggers direct antiviral activity in vitro, and boosts anti-HIV responses in vivo. Stabilized polyICLC (PICLC) is being developed for vaccine adjuvant applications in humans, making it critical to understand how mDC sensing of PICLC influences HIV infection. Using the monocyte-derived DC (moDC) model, we sought to describe how PICLC (vs. other dsRNAs) impacts HIV infection within DCs and DC-T cell mixtures. We extended this work to in vivo macaque rectal transmission studies by administering PICLC with or before rectal SIVmac239 (SIVwt) or SIVmac239ΔNef (SIVΔNef) challenge. Like PIC, PICLC activated DCs and T cells, increased expression of α4β7 and CD169, and induced type I IFN responses in vitro. The type of dsRNA and timing of dsRNA exposure differentially impacted in vitro DC-driven HIV infection. Rectal PICLC treatment similarly induced DC and T cell activation and pro- and anti-HIV factors locally and systemically. Importantly, this did not enhance SIV transmission in vivo. Instead, SIV acquisition was marginally reduced after a single high dose challenge. Interestingly, in the PICLC-treated, SIVΔNef-infected animals, SIVΔNef viremia was higher, in line with the importance of DC and T cell activation in SIVΔNef replication. In the right combination anti-HIV strategy, PICLC has the potential to limit HIV infection and boost HIV immunity. [ABSTRACT FROM AUTHOR]

Background: In Uganda, over half of under-five child mortality is attributed to three infectious diseases: malaria, pneumonia and diarrhoea. Integrated community case management (iCCM) trains village health workers (VHWs) to provide in-home diagnosis and treatment of these common childhood illnesses. For severely ill children, iCCM relies on a functioning referral system to ensure timely treatment at a health facility. However, referral completion rates vary widely among iCCM programmes and are difficult to monitor. The Bugoye Integrated Community Case Management Initiative (BIMI) is an iCCM programme operating in Bugoye sub-county, Uganda. This case study describes BIMI's experience with monitoring referral completion at Bugoye Health Centre III (BHC), and outlines improvements to be made within iCCM referral systems. Methods: This study triangulated multiple data sources to evaluate the strengths and gaps in the BIMI referral system. Three quantitative data sources were reviewed: (1) VHW report of referred patients, (2) referral forms found at BHC, and (3) BHC patient records. These data sources were collated and triangulated from January-December 2014. The goal was to determine if patients were completing their referrals and if referrals were adequately documented using routine data sources. Results: From January-December 2014, there were 268 patients referred to BHC, as documented by VHWs. However, only 52 of these patients had referral forms stored at BHC. Of the 52 referral forms found, 22 of these patients were also found in BHC register books recorded by clinic staff. Thus, the study found a mismatch between VHW reports of patient referrals and the referral visits documented at BHC. This discrepancy may indicate several gaps: (1) referred patients may not be completing their referral, (2) referral forms may be getting lost at BHC, and, (3) referred patients may be going to other health facilities or drug shops, rather than BHC, for their referral. Conclusions: This study demonstrates the challenges of effectively monitoring iCCM referral completion, given identified limitations such as discordant data sources, incomplete record keeping and lack of unique identifiers. There is a need to innovate and improve the ways by which referral compliance is monitored using routine data, in order to improve the percentage of referrals completed. Through research and field experience, this study proposes programmatic and technological solutions to rectify these gaps within iCCM programmes facing similar challenges. With improved monitoring, VHWs will be empowered to increase referral completion, allowing critically ill children to access needed health services. [ABSTRACT FROM AUTHOR]

Women urgently need a self-initiated, multipurpose prevention technology (MPT) that simultaneously reduces their risk of acquiring HIV-1, HSV-2, and HPV (latter two associated with increased risk of HIV-1 acquisition) and prevents unintended pregnancy. Here, we describe a novel core–matrix intravaginal ring (IVR), the MZCL IVR, which effectively delivered the MZC combination microbicide and a contraceptive. The MZCL IVR contains four active pharmaceutical ingredients (APIs): M IV-150 (targets HIV-1), zinc acetate ( Z A; targets HIV-1 and HSV-2), carrageenan ( C G; targets HPV and HSV-2), and levonorgestrel ( L NG; targets unintended pregnancy). The elastomeric IVR body (matrix) was produced by hot melt extrusion of the non-water swellable elastomer, ethylene vinyl acetate (EVA-28), containing the hydrophobic small molecules, MIV-150 and LNG. The solid hydrophilic core, embedded within the IVR by compression, contained the small molecule ZA and the macromolecule CG. Hydrated ZA/CG from the core was released by diffusion via a pore on the IVR while the MIV-150/LNG diffused from the matrix continuously for 94 days (d) in vitro and up to 28d (study period) in macaques. The APIs released in vitro and in vivo were active against HIV-1 ADA-M , HSV-2, and HPV16 PsV in cell-based assays. Serum LNG was at levels associated with local contraceptive effects. The results demonstrate proof-of-concept of a novel core–matrix IVR for sustained and simultaneous delivery of diverse molecules for the prevention of HIV, HSV-2 and HPV acquisition, as well as unintended pregnancy. [ABSTRACT FROM AUTHOR]

Several studies suggest that progesterone and estrogens may affect HIV transmission in different, possibly opposing ways. Nonetheless, a direct comparison of their effects on the mucosal immune system has never been done. We hypothesize that sex hormones might impact the availability of cells and immune factors important in early stages of mucosal transmission, and, in doing so influence the risk of HIV acquisition. To test this hypothesis, we employed 15 ovarectomized rhesus macaques: 5 were treated with Depot Medroxy Progesterone Acetate (DMPA), 6 with 17-β estradiol (E2) and 4 were left untreated. All animals were euthanized 5 weeks after the initiation of hormone treatment, a time post-DMPA injection associated with high susceptibility to SIV infection. We found that DMPA-treated macaques exhibited higher expression of integrin α4β7 (α4β7) on CD4+ T cells, the gut homing receptor and a marker of cells highly susceptible to HIV, in the endocervix than did the E2-treated animals. In contrast, the frequency of CCR5+ CD4+ T cells in DMPA-treated macaques was higher than in the E2-treated group in vaginal tissue, but lower in endocervix. α4β7 expression on dendritic cells (DCs) was higher in the DMPA-treated group in the endocervical tissue, but lower in vaginal tissue and on blood DCs compared with the E2-treated animals. Soluble MAdCAM-1, the α4β7 ligand, was present in the vaginal fluids of the control and E2-treated groups, but absent in the fluids from DMPA-treated animals. Both hormones modulated the expression and release of inflammatory factors and modified the distribution of sialomucins in the endocervix. In summary, we found that sex hormones profoundly impact mucosal immune factors that are directly implicated in HIV transmission. The effect is particularly significant in the endocervix. This may increase our understanding of the potential hormone-driven modulation of HIV susceptibility and potentially guide contraceptive policies in high-risk settings. [ABSTRACT FROM AUTHOR]

Background There are no existing data on alcoholic beverage prices and ethanol ( EtOH) content at the level of alcohol brand. A comprehensive understanding of alcohol prices and EtOH content at the brand level is essential for the development of effective public policy to reduce alcohol use among underage youth. The purpose of this study was to comprehensively assess alcoholic beverage prices and EtOH content at the brand level. Methods Using online alcohol price data from 15 control states and 164 online alcohol stores, we estimated the average alcohol price and percent alcohol by volume for 900 brands of alcohol, across 17 different alcoholic beverage types, in the United States in 2011. Results There is considerable variation in both brand-specific alcohol prices and EtOH content within most alcoholic beverage types. For many types of alcohol, the within-category variation between brands exceeds the variation in average price and EtOH content among the several alcoholic beverage types. Despite differences in average prices between alcoholic beverage types, in 12 of the 16 alcoholic beverage types, customers can purchase at least 1 brand of alcohol that is under $1 per ounce of EtOH. Conclusions Relying on data or assumptions about alcohol prices and EtOH content at the level of alcoholic beverage type is insufficient for understanding and influencing youth drinking behavior. Surveillance of alcohol prices and EtOH content at the brand level should become a standard part of alcohol research. [ABSTRACT FROM AUTHOR]

Anti-HIV microbicides are being investigated in clinical trials and understanding how promising strategies work, coincident with demonstrating efficacy in vivo, is central to advancing new generation microbicides. We evaluated CarraguardH and a new generation Carraguard-based formulation containing the non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV- 150 (PC-817). Since dendritic cells (DCs) are believed to be important in HIV transmission, the formulations were tested for the ability to limit DC-driven infection in vitro versus vaginal infection of macaques with RT-SHIV (SIVmac239 bearing HIV reverse transcriptase). Carraguard showed limited activity against cell-free and mature DC-driven RT-SHIV infections and, surprisingly, low doses of Carraguard enhanced infection. However, nanomolar amounts of MIV-150 overcame enhancement and blocked DC-transmitted infection. In contrast, Carraguard impeded infection of immature DCs coincident with DC maturation. Despite this variable activity in vitro, Carraguard and PC-817 prevented vaginal transmission of RT-SHIV when applied 30 min prior to challenge. PC-817 appeared no more effective than Carraguard in vivo, due to the limited activity of a single dose of MIV-150 and the dominant barrier effect of Carraguard. However, 3 doses of MIV-150 in placebo gel at and around challenge limited vaginal infection, demonstrating the potential activity of a topically applied NNRTI. These data demonstrate discordant observations when comparing in vitro and in vivo efficacy of Carraguard-based microbicides, highlighting the difficulties in testing putative anti-viral strategies in vitro to predict in vivo activity. This work also underscores the potential of Carraguard-based formulations for the delivery of anti-viral drugs to prevent vaginal HIV infection. [ABSTRACT FROM AUTHOR]

Background: Uganda has sought to address leading causes of childhood mortality: malaria, pneumonia and diarrhoea, through integrated community case management (iCCM). The success of this approach relies on community health worker (CHW) assessment and referral of sick children to a nearby health centre. This study aimed to determine rates of referral completion in an iCCM programme in rural Uganda. Methods: This was a prospective observational study of referrals made by CHWs in 8 villages in rural western Uganda. All patient referrals by CHWs were tracked and health centre registers were reviewed for documentation of completed referrals. Caregivers of referred patients were invited to complete a survey 2–3 weeks after the referral with questions on the CHW visit, referral completion, and the patient's clinical condition. Results: Among 143 total referrals, 136 (94%) caregivers completed the follow-up survey. Reasons for visiting the CHW were fever/malaria in 111 (82%) cases, cough in 61 (45%) cases, and fast/difficult breathing in 25 (18%) cases. Overall, 121 (89%) caregivers reported taking the referred child for further medical evaluation, of whom 102 (75% overall) were taken to the local public health centre. Ninety per cent of reported referral visits were confirmed in health centre documentation. For the 34 caregivers who did not complete referral at the local health centre, the most common reasons were improvement in child's health, lack of time, ease of going elsewhere, and needing to care for other children. Referrals were slightly more likely to be completed on weekdays versus weekends (p = 0.0377); referral completion was otherwise not associated with child's age or gender, caregiver age, or caregiver relationship to child. One village had a lower rate of referral completion than the others. Improvement in the child's health was not associated with completed referral or timing of the referral visit. Conclusions: A high percentage of children referred to the health centre through iCCM in rural Uganda completed the referral. Barriers to referral completion included improvement in the child's health, time and distance. Interestingly, referral completion at the health centre was not associated with improvement in the child's health. Barriers to referral completion and clinical management at all stages of referral linkages warrant further study. [ABSTRACT FROM AUTHOR]

A correction to the article "Monitoring iCCM referral systems: Bugoye Integrated Community Case Management Initiative (BIMI) in Uganda" that was published in the 2016 issue is presented.