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• New fin pattern for liquid-cooled heat sink is generated by topology optimization. • Performance of fin patterns with different spanwise lengths of design domain are compared. • Three rows of sectional fins reduced the overall pressure drop in present TO design. • Topology design required 54 % lower pumping power compared to straight channels. • Topology design delivered 3 to 4 °C lower junction temperature compared to existing designs. Topology optimization generate promising 'heat sink fin layouts' to satisfy the thermo-hydraulic objectives with lightweight designs. This article evaluates the performance of topology-optimized liquid-cooled heat sinks with different spanwise length-based design domains. A reduced-scale model (with 1/8th the width of the full-scale heat sink model) is selected and optimized with 'pressure drop' and 'average junction temperature' as objective functions and constraints, respectively. Fin layouts consisting of non-continuous fins are derived for different inlet flow velocities and temperature constraints using an accurate two-dimensional (2D) mathematical model, mimicking a three-dimensional (3D) heat sink geometry. Three-dimensional CFD simulation is used to compare the performance of the present fin layout with a reference topology-optimized design (with 1/16th the width of the full-scale model) and an augmented straight channel-based heat sink. To cool the heat sink to an average junction temperature of 50 °C, the present design requires 17 % and 54 % lower pumping power compared to the reference design and straight channel with significantly reduced material volume. Flow phenomena such as secondary flow-induced mixing and frequent reinitialization of boundary layers at leading edges of fins are observed during numerical investigation which are illustrated using velocity and temperature contours. The optimized fin layout's overall performance is compared with existing fin designs of heat sinks such as step fins, offset strip fins, oblique fins, and oblique and trapezoidal fins. Oblique and trapezoidal fin and oblique fin compete with topology optimized design which outperforms at lower flow rates (for velocity ranging from 0.05 m/s to 0.175 m/s). The average junction temperature using Oblique and trapezoidal fins and oblique fins are 63 °C and 61.22 °C, respectively compared to 58.5 °C for topology-optimized design with a similar pressure drop of 300 Pa. [ABSTRACT FROM AUTHOR]

• Transmission of non-prion disease causing deaths in cadaveric pituitary hormone recipients. • Deaths from intra-cerebral haemorrhage, potentially related to cerebral amyloid angiopathy, were increased. • Despite limitations, there was no evidence of increased non-prion neurodegeneration-related deaths. Recent scientific reports and epidemiological studies have engendered mounting concerns regarding the potential human-to-human transmissibility of non-prion neurodegenerative and related diseases. This study investigated whether recipients of cadaveric pituitary hormone treatments are at increased risk of death from non-prion neurodegenerative and related diseases. A retrospective national cohort study based on death certificates of recipients of the cadaveric pituitary hormone treatments (n = 184) as part of the Australian Human Pituitary Hormone Program (AHPHP; n = 2940) 1967–1985. Standardised mortality ratios (SMR) from non-prion neurodegenerative and other diseases were estimated based on the Australian population. Allowing for potential diagnostic mis-attributions, there was no significant increase in the SMR from non-prion central nervous system (CNS) neurodegenerative disease, especially dementia and/or Alzheimer's disease (0.47; [95% CI: 0.19, 1.12] P = 0.081). The SMR for intra-cerebral haemorrhage, potentially related to cerebral amyloid angiopathy (CAA), was increased (2.77; [95% CI: 1.12–5.75] P = 0.009), although accommodation of possible mis-diagnosis through conflation of this category with other stroke causes of death emphasising likely intra-cranial haemorrhage showed no persisting significant increase in mortality in cadaveric pituitary hormone recipients, including all deaths recorded as due to intra-cranial haemorrhage (1.72; [95% CI: 0.80, 3.26] P = 0.123). In the setting of recent evidence strongly supporting the likelihood of brain-to-brain horizontal transmission and subsequent propagation and deposition of abnormally folded proteins associated with non-prion neurodegenerative and related disorders, this study offers further tentative support for deaths directly stemming from transmission of non-prion disease related to cadaveric pituitary hormone treatment. Acknowledging the limitations of the present study, however, ongoing detailed assessments of this potential risk are necessary. [ABSTRACT FROM AUTHOR]

Antiretroviral monotherapy and treatment interruption are potential strategies for perinatally HIV-infected adolescents (PHIVA) who face challenges maintaining effective combination antiretroviral therapy (ART). We assessed the use and outcomes for adolescents receiving monotherapy or undergoing treatment interruption in a regional Asian cohort. Regional Asian data (2001–2016) were analyzed to describe PHIVA who experienced ≥2 weeks of lamivudine or emtricitabine monotherapy or treatment interruption and trends in CD4 count and HIV viral load during and after episodes. Survival analyses were used for World Health Organization (WHO) stage III/IV clinical and immunologic event-free survival during monotherapy or treatment interruption, and a Poisson regression to determine factors associated with monotherapy or treatment interruption. Of 3,448 PHIVA, 84 (2.4%) experienced 94 monotherapy episodes, and 147 (4.3%) experienced 174 treatment interruptions. Monotherapy was associated with older age, HIV RNA >400 copies/mL, younger age at ART initiation, and exposure to ≥2 combination ART regimens. Treatment interruption was associated with CD4 count <350 cells/μL, HIV RNA ≥1,000 copies/mL, ART adverse event, and commencing ART age ≥10 years compared with age <3 years. WHO clinical stage III/IV 1-year event-free survival was 96% and 85% for monotherapy and treatment interruption cohorts, respectively. WHO immunologic stage III/IV 1-year event-free survival was 52% for both cohorts. Those who experienced monotherapy or treatment interruption for more than 6 months had worse immunologic and virologic outcomes. Until challenges of treatment adherence, engagement in care, and combination ART durability/tolerability are met, monotherapy and treatment interruption will lead to poor long-term outcomes. [ABSTRACT FROM AUTHOR]

Background & Aims Delayed hepatitis B virus (HBV) or hepatitis C virus (HCV) diagnosis may increase risk of advanced liver disease complications, including decompensated cirrhosis (DC) and hepatocellular carcinoma (HCC). The aim of this study was to characterise “late hepatitis notification” among people with an HBV/HCV notification and advanced liver disease in New South Wales, Australia. Methods HBV/HCV notifications 1995–2012 were linked to cancer registry and hospital admissions. Late hepatitis notification was defined by a notification after, at the time, or within two years before DC/HCC diagnosis. Results HBV and HCV cohorts comprised 50,958 and 79,727 individuals, respectively. Among people with DC (n = 3869), late HBV notification declined from 64% (88/138) during 2001–2002 to 31% (46/149) in 2011–2012 ( p <0.001), and late HCV notification declined from 52% (179/341) during 2001–2002 to 22% (134/605) in 2011–2012 ( p <0.001). Among people with HCC (n = 1656), late HBV notification declined from 68% (59/87) during 2001–2002 to 29% (37/128) in 2011–2012 ( p <0.001), and late HCV notification declined from 51% (40/79) during 2001–2002 to 17% (49/288) in 2011–2012 ( p <0.001). Conclusions Despite significant declines in late hepatitis notification since early 2000s, efforts to enhance hepatitis screening, particularly for HBV, are required. Late hepatitis notification as described in this study could be used as a measure of population-level HBV/HCV screening. Lay summary Delayed hepatitis B virus (HBV) or hepatitis C virus (HCV) diagnosis may increase the risk of advanced liver disease complications, including decompensated cirrhosis (DC) and hepatocellular carcinoma (HCC). The aim of this study was to characterise “late hepatitis notification” among people with an HBV or HCV notification in New South Wales, Australia. Late hepatitis notifications have significantly declined since early 2000s; however, efforts to enhance hepatitis screening, particularly for HBV, are required. Late hepatitis notification as described in this study could be used as a measure of population-level HBV/HCV screening. [ABSTRACT FROM AUTHOR]

The oblique-finned structure has been proven to exhibit significant enhancements in heat transfer in both single-phase and two-phase modes of operation coupled with slight increment in pressure drop. These enhancements come with the mitigation of two-phase flow instability compared to the conventional straight-finned microchannels, which encourages further parametric studies on the fin geometry. In the present work, flow boiling experiments are conducted in oblique-finned microchannels using the FC-72 dielectric fluid with varying secondary channel widths to investigate its effects on two-phase heat transfer, pressure drop and flow boiling instabilities. Three different secondary channel widths of 0.15 mm, 0.30 mm and 0.45 mm are tested with mass fluxes ranging from 197 kg/m 2 s to 394 kg/m 2 s, and effective heat fluxes from 14.9 W/cm 2 to 70.2 W/cm 2 with the aid of high-speed visualisations. From the experiments and flow visualisations, it is found that increasing the width of the secondary channels has adverse effect on heat transfer performance and critical heat flux limit due to the inability of the microchannels to suppress flow boiling instabilities. Pressure drop penalty of the larger secondary channel configurations are higher as a result of greater amount of flow diversion, which amplifies flow migration from the draining edge to the filling edge of the oblique-finned array. [ABSTRACT FROM AUTHOR]

Flow boiling experiments are conducted in oblique-finned microchannels with different oblique angles to investigate its effects on two-phase heat transfer, pressure drop and instabilities. These studies are carried out with FC-72 dielectric fluid at three different oblique angles of 10°, 30° and 50°. Three mass fluxes ranging from 194 kg/m 2 s to 386 kg/m 2 s, and effective heat fluxes from 14.9 W/cm 2 to 70.0 W/cm 2 are tested with high-speed flow visualisations to explore the physical boiling phenomenon in the microchannels. Results show that heat transfer performance increases with oblique angles from 10° to 50° due to the increase in secondary channels which promote flow mixing. This causes an increase in pressure drop from 10° to 30° oblique angles due to the increase in flow separation and flow diversion. Pressure drop, however, is almost negligible when the oblique angles are increased from 30° to 50°. As a result, the 50° oblique-finned microchannels presents an attractive option for further parametric studies. [ABSTRACT FROM AUTHOR]

The thermal and hydraulic performances of an air-cooled heat sink channel design have been numerically investigated in 2D computational domains in ANSYS Fluent. The channel expansion ratio (ER) is the key parameter to control the flow restriction, therefore the rate of flow mixing. As the channel ER is increased, Nu number increases with an accompanying increase in the pressure drop penalty. The heat transfer enhancement is attributed to two main phenomena: flow mixing, and thermal boundary layer (TBL) disruption and reinitialization. Thanks to flow mixing, air temperature builds up more uniformly in the direction of flow and TBL disruption and reinitialization decreases the thermal resistance on the channel walls. Despite the increase in the pressure drop penalty with increasing channel ER; it is possible to enhance thermal resistance by 40% with the same pressure drop of a straight channel heat sink. [ABSTRACT FROM AUTHOR]

Flow boiling experiments are conducted in straight- and oblique-finned microchannels with similar channel dimensions and operating conditions using the FC-72 dielectric fluid. Both the test pieces are made from a copper block with a footprint area of 25 mm × 25 mm and 40 parallel microchannels. The oblique cuts are created at a nominal oblique angle of 10° with a nominal width which is half of that of the parallel microchannels. Two mass fluxes at 175 kg/m 2 s and 370 kg/m 2 s, with heat fluxes from 14 W/cm 2 to 42 W/cm 2 are tested. Wall temperature and pressure fluctuations during the flow boiling process are presented in this article. It is found that the oblique-finned configuration considerably mitigates temperature and pressure instabilities at various operating conditions, apart from augmentation in heat transfer performance. The increased flow stability is attributed to the ability of the oblique fins in reducing flow reversal. These results show that the oblique-finned microchannels present an interesting thermal management technique for stabilised two-phase cooling. [ABSTRACT FROM AUTHOR]

Flow boiling experiments are conducted in straight-finned and oblique-finned microchannels with similar channel dimensions and operating conditions using the FC-72 dielectric fluid. Both heat sink geometries consist of 40 parallel microchannels, and are fabricated on a copper block with a footprint area of 25 mm × 25 mm. The oblique fins are produced by introducing diagonal cuts with angle of 27° and width which is half of that of the parallel microchannels. The comparative study with straight fins shows significant augmentation in heat transfer and the delay in the onset of critical heat flux for the oblique-finned microchannels. This is due to enhancement in the flow boiling stability offered by the oblique fins in terms of reduced wall temperature gradients and pressure fluctuations. Flow visualisations performed on both microchannel geometries show increased bubbles generation in the nucleate boiling region and a continuously developing thin liquid-film in the convective boiling region for the oblique fins, which is believed to be the primary factor in heat transfer enhancement. However, the improved heat transfer performance incurs a higher pressure drop penalty compared to its straight-finned counterpart. This drawback could possibly be overcome by careful modifications in the oblique-finned geometry, so as to control the amount of secondary flow. [ABSTRACT FROM AUTHOR]

Abstract: Oblique fins are modified from its conventional straight fins counterpart via the introduction of oblique cuts at specific locations, leaving obliquely-shaped fins with secondary microchannels. The benefits of having these secondary microchannels have been conclusively demonstrated in single-phase mode, however, they have yet to be tested in two-phase mode, which forms the motivation behind this study. Flow boiling experiments are conducted in the oblique-finned microchannel heat sink, made from a copper block with a footprint area of 25×25mm2. 40 parallel microchannels, each with a nominal width of 0.3mm are machined with wire-cut electro-discharge machining process. The nominal width of the oblique cuts, on the other hand, is half of that of the parallel microchannels. Tests are performed with FC-72 dielectric fluid with an inlet temperature of 29.5°C, with a range of mass fluxes from 175kg/m2 s to 350kg/m2 s and heat fluxes from 6W/cm2 to 120W/cm2. Flow boiling results and discussion on its heat transfer performance and pressure drop characteristics are presented in this paper. It is found that nucleate boiling is the dominant heat transfer mechanism at low heat fluxes, with a transition to convective boiling-dominant via thin-film evaporation occurring at medium heat fluxes. A full convective boiling mechanism is observed thereafter prior to CHF. These observations agreed well with high-speed flow visualisation images. Inlet pressure fluctuations within the oblique-finned microchannels are extremely small, indicating that the oblique fins are able to considerably stabilise the flow boiling process. [Copyright &y& Elsevier]

Genetic linkage and candidate gene studies have identified a number of genes involved in melanoma susceptibility, such as MC1R and CDKN2A, via the endophenotypes of pigmentation and nevus proliferation. A series of genome-wide association studies (GWASs) in 2008 and 2009 showed that a handful of additional genes (e.g., ASIP, TYR, and PLA2G6) influencing these endophenotypes also affected melanoma risk. The most recent wave of melanoma GWASs has uncovered genes functioning independently of the known melanoma-associated phenotypes, highlighting the role of processes such as DNA repair and cell cycle control. We take this opportunity to summarize these new and exciting findings and integrate them into the current framework of our understanding of melanoma genetics. [ABSTRACT FROM AUTHOR]

Abstract: Detailed data and modeling of cyclohexane flames establish that a mixture of pathways contributes to benzene formation and that this mixture changes with stoichiometry. Mole-fraction profiles are mapped for more than 40 species in a fuel-rich, premixed flat flame (ϕ =2.0, cyclohexane/O2/30% Ar, 30Torr, 50.0cm/s) using molecular-beam mass spectrometry with VUV-photoionization at the Advanced Light Source of the Lawrence Berkeley National Laboratory. The use of a newly constructed set of reactions leads to an excellent simulation of this flame and an earlier stoichiometric flame (M.E. Law et al., Proc. Combust. Inst. 31 (2007) 565–573), permitting analysis of the contributing mechanistic pathways. Under stoichiometric conditions, benzene formation is found to be dominated by stepwise dehydrogenation of the six-membered ring with cyclohexadienyl⇄benzene+H being the final step. This finding is in accordance with recent literature. Dehydrogenation of the six-membered ring is also found to be a dominant benzene-formation route under fuel-rich conditions, at which H2 elimination from 1,3-cyclohexadiene contributes even more than cyclohexadienyl decomposition. Furthermore, at the fuel-rich condition, additional reactions make contributions, including the direct route via 2C3H3 ⇄benzene and more importantly the H-assisted isomerization of fulvene formed from i-/n-C4H5 +C2H2, C3H3 +allyl, and C3H3 +C3H3. Smaller contributions towards benzene formation arise from C4H3 +C2H3, 1,3-C4H6 +C2H3, and potentially via n-C4H5 +C2H2. This diversity of pathways is shown to result nominally from the temperature and the concentrations of benzene precursors present in the benzene-formation zone, which are ultimately due to the feed stoichiometry. [Copyright &y& Elsevier]

Purpose: First-pass perfusion cardiovascular magnetic resonance (CMR) is increasingly being utilized in both clinical practice and research. However, the reproducibility of this technique remains incompletely evaluated, particularly in patients with severe coronary artery disease (CAD). The purpose of this study was to determine the inter-study reproducibility of adenosine stress CMR in patients with symptomatic multi-vessel CAD and those at low risk for CAD. Methods: Twenty patients (10 with CAD, 10 low risk CAD) underwent two CMR scans 8 ± 2 days apart. Basal, mid and apical left ventricular short axis slices were acquired using gadolinium 0.05 mmol/kg at peak stress (adenosine, 140 μ/ kg/min, 4 min) and rest. Myocardial perfusion was evaluated qualitatively by assessing the number of ischemic segments, and semi-quantitatively by determining the myocardial perfusion reserve index (MPRi) using a normalized upslope method. Inter-study and observer reproducibility were assessed--the latter being defined by the coefficient of variation (CoV), which was calculated from the standard deviation of the differences of the measurements, divided by the mean. Additionally, the percentage of myocardial segments with perfect agreement and inter- and intra-observer MPRi correlation between studies, were also determined. Results: The CoV for the number of ischemic segments was 31% with a mean difference of -0.15 ± 0.88 segments and 91% perfect agreement between studies. MPRi was lower in patients with CAD (1.13 ± 0.21) compared to those with low risk CAD (1.59 ± 0.58), p = 0.02. The reproducibility of MPRi was 19% with no significant difference between patients with CAD and those with low risk CAD (p = 0.850). Observer reproducibility for MPRi was high: inter-observer CoV 9%, r = 0.93 and intra-observer CoV 5%, r = 0.94. For trials using perfusion CMR as an endpoint, an estimated sample size of 12 subjects would be required to detect a two-segment change in the number of ischemic segments (power 0.9, a 0.05). Conclusions: Adenosine stress CMR, by qualitative and semi-quantitative normalized upslope analyses are reproducible techniques in both patients with multi-vessel CAD and those without known CAD. The robust inter-study reproducibility of perfusion CMR supports its clinical and research application. [ABSTRACT FROM AUTHOR]

Abstract: It has consistently been reported that patients with schizophrenia have an increased risk of type-2 diabetes. To investigate a genetic link between these two diseases, the combined effects of the PLA2G4A, PTGS2 and PPARG genes were tested among 221 British nuclear families consisting of fathers, mothers and affected offspring with schizophrenia. A total of 10 single nucleotide polymorphisms (SNPs) were tested and the likelihood-based association analysis for nuclear families was used to analyse the genotyping data. Eight SNPs detected across the PPARG gene did not show allelic association with schizophrenia; a weak association was detected at rs2745557 in the PTGS2 locus (χ 2=4.19, p=0.041) and rs10798059 in the PLA2G4A locus (χ 2=4.28, p=0.039) but these associations did not survive after 10,000 permutations to correct the p-value (global p=0.246). The gene–gene interaction test did not show any evidence of either cis-phase interactions for the PLA2G4A and PTGS2 combinations or a trans-phase interaction for the PLA2G4A and PPARG combinations. The PPARG gene has been reported to be strongly associated with type-2 diabetes, but the present study did not support the hypothesis that the PPARG gene may also play an important role in the development of schizophrenia. [Copyright &y& Elsevier]

Abstract: Flame-sampling photoionization mass spectrometry is used for measurements of the absolute molar composition of fuel-rich (ϕ =1.8) low-pressure laminar flames of allene and propyne. The experiment combines molecular-beam mass spectrometry with photoionization by tunable vacuum–ultraviolet synchrotron radiation. This approach provides selective detection of individual isomers and unambiguous identifications of other flame species of near-equal mass by near threshold photoionization efficiency measurements. Mole fraction profiles for more than 30 flame species with ion masses ranging from 2 to 78 are presented. The isomeric composition is resolved for most intermediates, for example, mole fraction profiles are presented for both benzene and the fulvene isomer. The results are compared with predictions based on current kinetic models. The mole fractions of the major species are predicted quite accurately, however, some discrepancies are observed for minor species. [Copyright &y& Elsevier]

Abstract: Benzene formation was found to be dominated by stepwise radical dehydrogenation of cyclohexane in a stoichiometric flat flame of cyclohexane/O2/32.5% Ar, 30.00Torr pressure, and 35.0cms−1 feed velocity. This route, involving H-abstractions and β-scissions, is in contrast to conventional propargyl routes. Three types of analyses lead to this conclusion: identification of key flame species by mass and ionization energy; measurement and use of mole-fraction profiles in the flat flame; and mechanistic reactive-flow modeling of the flame, interpreted by analyzing the dominant reaction steps giving rise to the prediction. For relevant species, profiles of mole fraction were mapped by molecular-beam mass spectrometry in separate apparatuses with identical burners using electron ionization (UMass Amherst) and synchrotron VUV photoionization (LBNL ALS), respectively. In the latter, recently developed apparatus, ionization energies can be measured with greatly enhanced resolution, yielding improvements in species identification that include precise resolution of hydrocarbon isomers, crucial to the findings of this study. [Copyright &y& Elsevier]

Abstract: Flame-sampling photoionization mass spectrometry, using continuously tunable synchrotron radiation, offers important advantages for studies of flame chemistry. Mole fraction profile measurements for 24 flame species are presented for a fuel-rich low-pressure premixed laminar C3H8/O2/Ar flame. Near-threshold photoionization efficiency measurements provide selective detection of individual isomers and unambiguous identifications of other flame species of near-equal mass. The absolute molar composition of the allene and propyne isomers of C3H4 was determined. Absolute cross-sections for photoionization of C2H2, C2H4, CH3OH, C3H4 (propyne), CH3CHO, (CH3)2CO, and C6H6 were used to determine molecular beam mass discrimination factors valid for ion masses ranging from 26 to 78amu. [Copyright &y& Elsevier]

A letter to the editor is presented which discusses a meta-analysis of the risk of melanoma from the influences of the telomerase reverse transcriptase (TERT)-cleft lip and palate transmembrane protein 1-like protein (CLPTM1L) locus.

High HCV treatment uptake among people at most risk of transmission is essential to achieve elimination. We aimed to characterise subpopulations of people with HCV based on drug dependence, to estimate direct-acting antiviral (DAA) uptake in an unrestricted treatment era, and to evaluate factors associated with treatment uptake among people with recent drug dependence. HCV notifications in New South Wales, Australia (1995-2017) were linked to opioid agonist therapy (OAT), hospitalisations, incarcerations, HIV notifications, deaths, and prescription databases. Drug dependence was defined as hospitalisation due to injectable drugs or receipt of OAT, with indicators in 2016-2018 considered recent. Records were weighted to account for spontaneous clearance. Logistic regression was used to analyse factors associated with treatment uptake among those with recent drug dependence. 57,467 people were estimated to have chronic HCV throughout the DAA era. Treatment uptake was highest among those with recent (47%), compared to those with distant (38%), and no (33%) drug dependence. Among those with recent drug dependence, treatment was more likely among those with HIV (adjusted odds ratio [aOR] 1.71; 95% CI 1.24–2.36), recent incarceration (aOR 1.10; 95% CI 1.01–1.19), and history of alcohol use disorder (aOR 1.22; 95% CI 1.13–1.31). Treatment was less likely among women (aOR 0.78; 95% CI 0.72–0.84), patients of Indigenous ethnicity (aOR 0.75; 95% CI 0.69–0.81), foreign-born individuals (aOR 0.86; 95% CI 0.78–0.96), those with outer-metropolitan notifications (aOR 0.90; 95% CI 0.82–0.98), HBV coinfection (aOR 0.69; 95% CI 0.59–0.80), and >1 recent hospitalisation (aOR: 0.91; 95% CI 0.84–0.98). These data provide evidence of high DAA uptake among people with recent drug dependence, including those who are incarcerated. Enhancing this encouraging initial uptake among high-risk populations will be essential to achieve HCV elimination. To facilitate HCV elimination, those at highest risk of infection and transmission are a treatment priority. This study shows the successes of Australia's universal provision of DAA therapy in reducing the barriers to treatment which have historically persisted among people who inject drugs. Despite higher DAA therapy uptake among those with recent drug dependence, gaps remain. Strategies which aim to reduce marginalisation and increase treatment uptake to ensure equitable HCV elimination must be advanced. • People who inject drugs are a key population for hepatitis C elimination. • Australia has provided universal access to direct-acting antiviral therapy since 2016. • Data linkage was used to assess population-level direct-acting antiviral uptake. • Those with evidence of recent drug dependence had the highest treatment uptake. • Despite higher direct-acting antiviral uptake among those with recent drug dependence, gaps remain. [ABSTRACT FROM AUTHOR]

Objective: To assess mortality and loss to follow-up of children with HIV infection who started antiretroviral therapy (ART) through the Universal Coverage Health Program (UC) in Thailand.Study Design: Children with HIV infection who initiated ART at age <15 years through the UC between 2008 and 2013 were included in the analysis. Death was ascertained through linkage with the National Death Registry. A competing-risks method was used to calculate subdistribution hazard ratios (SHRs) of predictors for loss to follow-up. Death was considered a competing risk. Cox proportional hazards models were used to assess predictors of mortality.Results: A total of 4618 children from 497 hospitals in Thailand were included in the study. Median age at ART initiation was 9 years (IQR, 6-12 years), and the median duration of tracking was 4.1 years (a total of 18 817 person-years). Three hundred and ninety-five children (9%) died, for a mortality rate of 2.1 (95% CI, 1.9-2.3) per 100 person-years, and 525 children (11%) were lost to follow-up, for a lost to follow-up rate of 2.9 (95% CI, 2.7-3.2) per 100 person-years. The cumulative incidence of loss to follow-up increased from 4% at 1 year to 8.8% at 3 years. Children who started ART at age ≥12 years were at the greatest risk of loss to follow-up. The probability of death was 3.2% at 6 months and 6.4% at 3 years. Age ≥12 years at ART initiation, lower baseline CD4%, advanced HIV staging, and loss to follow-up were associated with mortality.Conclusion: The Thai national HIV treatment program has been very effective in treating children with HIV infection, with low mortality and modest rates of loss to follow-up. [ABSTRACT FROM AUTHOR]

Abstract: Deterministic dynamic compartmental transmission models (DDCTMs) of human papillomavirus (HPV) transmission have been used in a number of studies to estimate the potential impact of HPV vaccination programs. In most cases, the models were built under the assumption that an individual who cleared HPV infection develops (life-long) natural immunity against re-infection with the same HPV type (this is known as SIR scenario). This assumption was also made by two Australian modelling studies evaluating the impact of the National HPV Vaccination Program to assist in the health-economic assessment of male vaccination. An alternative view denying natural immunity after clearance (SIS scenario) was only presented in one study, although neither scenario has been supported by strong evidence. Some recent findings, however, provide arguments in favour of SIS. We developed HPV transmission models implementing life-time (SIR), limited, and non-existent (SIS) natural immunity. For each model we estimated the herd immunity effect of the ongoing Australian HPV vaccination program and its extension to cover males. Given the Australian setting, we aimed to clarify the extent to which the choice of model structure would influence estimation of this effect. A statistically robust and efficient calibration methodology was applied to ensure credibility of our results. We observed that for non-SIR models the herd immunity effect measured in relative reductions in HPV prevalence in the unvaccinated population was much more pronounced than for the SIR model. For example, with vaccine efficacy of 95% for females and 90% for males, the reductions for HPV-16 were 3% in females and 28% in males for the SIR model, and at least 30% (females) and 60% (males) for non-SIR models. The magnitude of these differences implies that evaluations of the impact of vaccination programs using DDCTMs should incorporate several model structures until our understanding of natural immunity is improved. [Copyright &y& Elsevier]

Background: Hematologic changes that occur with HIV infection and antiretroviral therapy may impact the quality of life of patients and have been associated with morbidity and mortality. The management of anemia and neutropenia has improved survival in persons with HIV.Objectives: This meta-analysis was performed to assess the changes in hemoglobin (Hb) levels and neutrophil counts that occur during thymidine analogue-based triple therapy and to establish whether different regimens of triple therapy are similar in efficacy based on CD4+ T-cell count and viral load changes.Methods: This was a meta-analysis of the impact of zidovudine (AZT) compared with stavudine (d4T) in triple therapy regimens in HIV patients with regard to hematologic parameters and efficacy markers. The peer-reviewed literature was searched with use of MEDLINE, PubMed, EMBASE, and the Cochrane database of systematic reviews (key terms: HIV, antiretroviral therapy, CD4, viral load, three, triple, and highly active antiretroviral therapy [HAART]). Searches were initially not limited by publication type, study design, date, or language but subsequently were sorted to include only studies performed in treatment-naive adult patients; randomized; and comparative of a regimen that included d4T with a regimen that included AZT; to involve regimens that included a minimum of 3 drugs each; and to include hematologic outcomes data. Outcomes were CD4+, viral load, and hematologic parameters.Results: This meta-analysis included 6 studies. Treatment efficacy as measured by changes in CD4+ T-cell counts and viral load did not differ significantly between regimens. Hb levels decreased with AZT treatment by a mean (SE) 0.4 (0.05) g/dL and 0.2 (0.06) g/dL at weeks 24 and 48, respectively, but increased with d4T treatment by 0.45 (0.03) g/dL and 0.58 (0.04) g/dL, respectively. All grades of anemia and neutropenia events were consistently more common with AZT-based regimens relative to d4T-based therapy.Conclusions: AZT-based HAART has a greater negative impact on hematologic parameters relative to d4T-based regimens. AZT recipients are more likely than d4T recipients to experience anemia and neutropenia events of any grade, and AZT is associated with a net decrease in Hb level relative to a net increase with d4T. These factors may influence the choice of drug used in the treatment of certain patient populations. [Copyright &y& Elsevier]

Background: To address the increasing incidence of gonorrhoea and antimicrobial resistance, we compared the efficacy of Listerine and Biotène mouthwashes for preventing gonorrhoea among men who have sex with men (MSM).Methods: The OMEGA trial was a multicentre, parallel-group, double-blind randomised controlled trial among MSM, done at three urban sexual health clinics and one general practice clinic in Australia. Men were eligible if they were diagnosed with oropharyngeal gonorrhoea by nucleic acid amplification test (NAAT) in the previous 30 days or were aged 16-24 years. They were randomly assigned to receive Listerine (intervention) or Biotène (control) via a computer-generated sequence (1:1 ratio, block size of four). Participants, clinicians, data collectors, data analysts, and outcome adjudicators were masked to the interventions after assignment. Participants were instructed to rinse and gargle with 20 mL of mouthwash for 60 s at least once daily for 12 weeks. Oropharyngeal swabs were collected by research nurses every 6 weeks, and participants provided saliva samples every 3 weeks, to be tested for Neisseria gonorrhoeae with NAAT and quantitative PCR. The primary outcome was proportion of MSM diagnosed with oropharyngeal N gonorrhoeae infection at any point over the 12-week period, defined as a positive result for either oropharyngeal swabs or saliva samples by NAAT, and the cumulative incidence of oropharyngeal gonorrhoea at the week 12 visit. A modified intention-to-treat analysis for the primary outcome was done that included men who provided at least one follow-up specimen over the 12-week study period. The trial was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12616000247471).Findings: Between March 30, 2016, and Oct 26, 2018, 786 MSM were screened and 256 were excluded. 264 MSM were randomly assigned to the Biotène group and 266 to the Listerine group. The analysis population included 227 (86%) men in the Biotène group and 219 (82%) in the Listerine group. Oropharyngeal gonorrhoea was detected in ten (4%) of 227 of MSM in the Biotène group and in 15 (7%) of 219 in the Listerine group (adjusted risk difference 2·5%, 95% CI -1·8 to 6·8). The cumulative incidence of oropharyngeal gonorrhoea at the week 12 visit did not differ between the two mouthwash groups (adjusted risk difference 3·1%, 95% CI -1·4 to 7·7).Interpretation: Listerine did not reduce the incidence of oropharyngeal gonorrhoea compared with Biotène. However, previous research suggests that mouthwash might reduce the infectivity of oropharyngeal gonorrhoea; therefore, further studies of mouthwash examining its inhibitory effect on N gonorrhoeae are warranted to determine if it has a potential role for the prevention of transmission.Funding: Australian National Health and Medical Research Council. [ABSTRACT FROM AUTHOR]

• Patients with sepsis in Myanmar were profoundly socioeconomically disadvantaged. • Limited diagnostic support precluded identification of the pathogen in most cases. • Patients with sepsis were frequently unable to receive the ICU care they required. • Clinical prediction scores had similar prognostic utility to laboratory-based scores. • Their performance in tropical settings was similar to that in high-income settings. To determine the comparative prognostic utility of commonly used disease prediction scores in adults with presumed community-acquired sepsis in a resource-limited tropical setting. This prospective, observational study was performed on the medical ward of a tertiary-referral hospital in Yangon, Myanmar. The ability of the National Early Warning Score 2 (NEWS2), quick NEWS (qNEWS), quick Sequential Organ Failure Assessment (qSOFA) score, Universal Vital Assessment (UVA) and Sequential Organ Failure Assessment (SOFA) scores to predict a complicated inpatient course (death or requirement for intensive care unit (ICU) support) in patients with two or more systemic inflammatory response syndrome criteria was determined. Among the 509 patients, 30 (6%) were HIV-seropositive. The most commonly confirmed diagnoses were tuberculosis (30/509, 5.9%) and measles (26/509, 5.1%). Overall, 75/509 (14.7%) died or required ICU support. All the scores except the qSOFA score, which was inferior, had a similar ability to predict a complicated inpatient course. In this resource-limited tropical setting, disease severity scores calculated at presentation using only vital signs–such as the NEWS2 score–identified high-risk sepsis patient as well as the SOFA score, which is calculated at 24 h and which also requires laboratory data. Use of these simple clinical scores can be used to facilitate recognition of the high-risk patient and to optimise the use of finite resources. [ABSTRACT FROM AUTHOR]