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AbstractAs the potential for human-AI design collaboration increases, understanding the role of artificial intelligence (AI) in the design process becomes more important. How does AI currently support the design process and how could it do so in the future? To answer this question, we categorized existing AI design support systems (DSS) according to the Double-Diamond design process model, and found that they are mostly used in the later stages of the design process, focusing on generating design solutions. In contrast, very few systems focus on the early stages of the process, which include discovering and defining design problems. To explore this finding’s alignment with designers’ expectations in real-world design, we present a case study involving emerging AI technologies such as ChatGPT and robots. This study proposes that AI agents can potentially assist designers by providing inspirations, defining design problems with constraints, offering grounded metaphors, and exploring design materials. [ABSTRACT FROM AUTHOR]

The relationship between body mass index (BMI) and melanoma and other skin cancers remains unclear. The objective of this study was to employ the Mendelian randomization (MR) approach to evaluate the effects of genetically predicted childhood adiposity on the risk of developing skin cancer later in life. Two-sample MR analyses were conducted using summary data from genome-wide association study (GWAS) meta-analyses of childhood BMI, melanoma, cutaneous squamous cell carcinoma (cSCC), and basal cell carcinoma (BCC). We used the inverse-variance-weighted (IVW) methods to obtain a pooled estimate across all genetic variants for childhood BMI. We performed multiple sensitivity analyses to evaluate the potential influence of various assumptions on our findings. We found no evidence that genetically predicted childhood BMI was associated with risks of developing melanoma, cSCC, or BCC in adulthood (OR, 95% CI: melanoma: 1.02 (0.93–1.13), cSCC 0.94 (0.79–1.11), BCC 0.97 (0.84–1.12)). Our findings do not support the conclusions from observational studies that childhood BMI is associated with increased risks of melanoma, cSCC, or BCC in adulthood. Intervening on childhood adiposity will not reduce the risk of common skin cancers later in life. [ABSTRACT FROM AUTHOR]

Observational studies have suggested that smoking may increase the risk of cutaneous squamous cell carcinoma (cSCC) while decreasing the risks of basal cell carcinoma (BCC), and melanoma. However, it remains possible that confounding by other factors may explain these associations. The aim of this investigation was to use Mendelian randomization (MR) to test whether smoking is associated with skin cancer, independently of other factors. Two-sample MR analyses were conducted to determine the causal effect of smoking measures on skin cancer risk using genome-wide association study (GWAS) summary statistics. We used the inverse-variance-weighted estimator to derive separate risk estimates across genetic instruments for all smoking measures. A genetic predisposition to smoking initiation was associated with lower risks of all skin cancer types, although none of the effect estimates reached statistical significance (OR 95% CI BCC 0.91, 0.82–1.01; cSCC 0.82, 0.66–1.01; melanoma 0.91, 0.82–1.01). Results for other measures were similar to smoking initiation with the exception of smoking intensity which was associated with a significantly reduced risk of melanoma (OR 0.67, 95% CI 0.51–0.89). Our findings support the findings of observational studies linking smoking to lower risks of melanoma and BCC. However, we found no evidence that smoking is associated with an elevated risk of cSCC; indeed, our results are most consistent with a decreased risk, similar to BCC and melanoma. [ABSTRACT FROM AUTHOR]

Observational studies have suggested that smoking may increase the risk of cutaneous squamous cell carcinoma (cSCC) while decreasing the risks of basal cell carcinoma (BCC), and melanoma. However, it remains possible that confounding by other factors may explain these associations. The aim of this investigation was to use Mendelian randomization (MR) to test whether smoking is associated with skin cancer, independently of other factors. Two-sample MR analyses were conducted to determine the causal effect of smoking measures on skin cancer risk using genome-wide association study (GWAS) summary statistics. We used the inverse-variance-weighted estimator to derive separate risk estimates across genetic instruments for all smoking measures. A genetic predisposition to smoking initiation was associated with lower risks of all skin cancer types, although none of the effect estimates reached statistical significance (OR 95% CI BCC 0.91, 0.82–1.01; cSCC 0.82, 0.66–1.01; melanoma 0.91, 0.82–1.01). Results for other measures were similar to smoking initiation with the exception of smoking intensity which was associated with a significantly reduced risk of melanoma (OR 0.67, 95% CI 0.51–0.89). Our findings support the findings of observational studies linking smoking to lower risks of melanoma and BCC. However, we found no evidence that smoking is associated with an elevated risk of cSCC; indeed, our results are most consistent with a decreased risk, similar to BCC and melanoma. [ABSTRACT FROM AUTHOR]

Introduction: Viral load (VL) testing is still challenging to monitor treatment responses of antiretroviral therapy (ART) for HIV treatment programme in Asia. We assessed the association between routine VL testing and virological failure (VF) and determine factors associated with switching to second‐line regimen. Methods: Among 21 sites from the TREAT Asia HIV Observational Database (TAHOD), people living with HIV (PLHIV) aged ≥18 years initiating ART from 2003 to 2021 were included. We calculated the average number of VL tests per patient per year between the date of ART initiation and the most recent visit. If the median average number of VL tests was ≥ 0.80 per patient per year, the site was classified as a routine VL site. A site with a median < 0.80 was classified into the non‐routine VL sites. VF was defined as VL ≥1000 copies/ml during first‐line therapy. Factors associated with VF were analysed using generalized estimating equations with Poisson distribution. Results: Of 6277 PLHIV starting ART after 2003, 3030 (48%) were from 11 routine VL testing sites and 3247 (52%) were from 10 non‐routine VL testing sites. The median follow‐up was 9 years (IQR 5–13). The median age was 35 (30–42) years; 68% were male and 5729 (91%) started non‐nucleoside reverse‐transcriptase inhibitor‐based regimen. The median pre‐ART CD4 count in PLHIV from routine VL sites was lower compared to non‐routine VL sites (144 vs. 156 cells/mm3, p <0.001). Overall, 1021 subsequent VF at a rate of 2.15 (95% CI 2.02–2.29) per 100 person‐years (PY). VF was more frequent at non‐routine VL sites (adjusted incidence rate ratio 2.85 [95% CI 2.27–3.59]) compared to routine VL sites. Other factors associated with an increased rate of VF were age <50 years and CD4 count <350 cells/mm3. A total of 817 (13%) patients switched to second‐line regimen at a rate of 1.44 (95% CI 1.35–1.54) per 100 PY. PLHIV at routine VL monitoring sites were at higher risk of switching than those at non‐routine VL sites (adjusted sub‐hazard ratio 1.78 95% CI [1.17–2.71]). Conclusions: PLHIV from non‐routine VL sites had a higher incidence of persistent VF and a low switching regimen rate, reflecting possible under‐utilized VL testing. [ABSTRACT FROM AUTHOR]

The aim of this report is to describe our experience in endovascular treatment of May-Thurner syndrome. We report three cases of iliocaval stenosis treated endovascularly at our institution. We included three patients age range from 41 to 85 years with two presenting with acute deep vein thrombosis and associated limb swelling and one with chronic lower limb symptoms. We reviewed the technical success, complications, and stent patency on follow-up, latter was monitored be serial imaging. The three cases of iliocaval stenosis were treated with endovascular stenting with follow-up imaging follow-up period ranged from 6 to 13 months (mean 5.6 months) with two out of the three cases maintaining stent patency. One case was complicated by intraprocedural reopening of previously venous bleed. Clinical symptoms resolved with no recurrence in two out of three cases. One case experienced symptomatic in-stent thrombosis following endovascular treatment. Endovascular treatment of iliocaval stenosis appears effective in immediate technical success. Periprocedural attention to anticoagulation and stent position are important in preventing in-stent restenosis. [ABSTRACT FROM AUTHOR]

• 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]

Objectives: We investigated weight changes following antiretroviral therapy (ART) initiation, the development of metabolic syndrome (MetS) and its association with all‐cause mortality among Asian adults living with HIV. Methods: Participants enrolled in a regional Asian HIV‐infected cohort with weight and height measurements at ART initiation were eligible for inclusion in the analysis. Factors associated with weight changes and incident MetS (according to the International Diabetic Federation (IDF) definition) were analysed using linear mixed models and Cox regression, respectively. Competing‐risk regression models were used to investigate the association of MetS with all‐cause mortality. Results: Among 4931 people living with HIV (PLWH), 66% were male. At ART initiation, the median age was 34 [interquartile range (IQR) 29–41] years, and the median (IQR) weight and body mass index (BMI) were 55 (48–63) kg and 20.5 (18.4–22.9) kg/m2, respectively. At 1, 2 and 3 years of ART, overall mean (± standard deviation) weight gain was 2.2 (±5.3), 3.0 (±6.2) and 3.7 (±6.5) kg, respectively. Participants with baseline CD4 count ≤ 200 cells/µL [weight difference (diff) = 2.2 kg; 95% confidence interval (CI) 1.9–2.5 kg] and baseline HIV RNA ≥ 100 000 HIV‐1 RNA copies/mL (diff = 0.6 kg; 95% CI 0.2–1.0 kg), and those starting with integrase strand transfer inhibitor (INSTI)‐based ART (diff = 2.1 kg; 95% CI 0.7–3.5 kg vs. nonnucleoside reverse transcriptase inhibitors) had greater weight gain. After exclusion of those with abnormal baseline levels of MetS components, 295/3503 had incident MetS [1.18 (95% CI 1.05–1.32)/100 person‐years (PY)]. The mortality rate was 0.7 (95% CI 0.6–0.8)/100 PY. MetS was not significantly associated with all‐cause mortality in the adjusted model (P = 0.236). Conclusions: Weight gain after ART initiation was significantly higher among those initiating ART with lower CD4 count, higher HIV RNA and an INSTI‐based regimen after controlling for baseline BMI. Greater efforts to identify and manage MetS among PLWH are needed. [ABSTRACT FROM AUTHOR]

Background Co-trimoxazole is recommended for all children with human immunodeficiency virus. In this analysis, we evaluate trends in pediatric co-trimoxazole use and survival on co-trimoxazole in children using antiretroviral therapy (ART). Methods We used data collected between January 1, 2006, and March 31, 2016, from the International Epidemiology Databases to Evaluate AIDS. Logistic regression was used to evaluate factors associated with using co-trimoxazole at ART initiation. Competing risk regression was used to assess factors associated with death. Results A total of 54113 children were included in this study. The prevalence of co-trimoxazole use at ART initiation increased from 66.5% in 2006 to a peak of 85.6% in 2010 and then declined to 48.5% in 2015–2016. A similar trend was observed among children who started ART with severe immunodeficiency. After adjusting for year of ART initiation, younger age (odds ratio [OR], 1.18 for <1 vs 1 to <5 years of age [95% confidence interval (CI), 1.09–1.28]), lower height-for-age z score (OR, 1.15 for less than −3 vs greater than −2 [95% CI, 1.08–1.22]), anemia (OR, 1.08 [95% CI, 1.02–1.15]), severe immunodeficiency (OR, 1.25 [95% CI, 1.18–1.32]), and receiving care in East Africa (OR, 8.97 vs Southern Africa [95% CI, 8.17–9.85]) were associated with a high prevalence of co-trimoxazole use. Survival did not differ according to co-trimoxazole use in children without severe immunodeficiency (hazard ratio, 1.01 for nonusers versus users [95% CI, 0.77–1.34]). Conclusions Recent declines in co-trimoxazole use may not be linked to the current shift toward early ART initiation. Randomized trial data might be needed to establish the survival benefit of co-trimoxazole in children without severe immunodeficiency. [ABSTRACT FROM AUTHOR]

Background: Previous observational studies have suggested that coffee intake may be associated with a reduction in cancer risk. Mendelian randomization (MR) studies can help clarify whether the observed associations are likely to be causal. Here we evaluated whether coffee intake is associated with: (i) overall risk of being diagnosed with/dying from any cancer; and (ii) risk of individual cancers.Methods: We identified 46 155 cases (of which 6998 were fatal) and 270 342 controls of White British ancestry from the UK Biobank cohort (UKB), based on ICD10 diagnoses. Individuals with benign tumours were excluded. Coffee intake was self-reported and recorded based on cup/day consumption. We conducted both observational and summary data MR analyses.Results: There was no observational association between coffee intake and overall cancer risk [odds ratio (OR) per one cup/day increase = 0.99, 95% confidence interval (CI) 0.98, 1.00] or cancer death (OR = 1.01, 0.99, 1.03); the estimated OR from MR is 1.01 (0.94, 1.08) for overall cancer risk and 1.11 (0.95, 1.31) for cancer death. The relationship between coffee intake and individual cancer risks were consistent with a null effect, with most cancers showing little or no associations with coffee. Meta-analysis of our MR findings with publicly available summary data on various cancers do not support a strong causal relationship between coffee and risk of breast, ovarian, lung or prostate cancer, upon correction for multiple testing.Conclusions: Taken together, coffee intake is not associated with overall risk of being diagnosed with or dying from cancer in UKB. For individual cancers, our findings were not statistically inconsistent with earlier observational studies, although for these we were unable to rule out a small effect on specific types of cancer. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: People living with HIV (PLWH) experience a higher cardiovascular disease (CVD) risk. Yet, traditional algorithms are often used to estimate CVD risk. We evaluated the performance of 4 commonly used algorithms. Setting: The Netherlands. Methods: We used data from 16,070 PLWH aged ≥18 years, who were in care between 2000 and 2016, had no pre-existing CVD, had initiated first combination antiretroviral therapy >1 year ago, and had available data on CD4 count, smoking status, cholesterol, and blood pressure. Predictive performance of 4 algorithms [Data Collection on Adverse Effects of Anti-HIV Drugs Study (D:A:D); Systematic COronary Risk Evaluation adjusted for national data (SCORE-NL); Framingham CVD Risk Score (FRS); and American College of Cardiology and American Heart Association Pooled Cohort Equations (PCE)] was evaluated using a Kaplan–Meier approach. Model discrimination was assessed using Harrell's C-statistic. Calibration was assessed using observed-versus-expected ratios, calibration plots, and Greenwood-Nam-D'Agostino goodness-of-fit tests. Results: All algorithms showed acceptable discrimination (Harrell's C-statistic 0.73–0.79). On a population level, D:A:D, SCORE-NL, and PCE slightly underestimated, whereas FRS slightly overestimated CVD risk (observed-versus-expected ratios 1.35, 1.38, 1.14, and 0.92, respectively). D:A:D, FRS, and PCE best fitted our data but still yielded a statistically significant lack of fit (Greenwood-Nam-D'Agostino χ2 ranged from 24.57 to 34.22, P < 0.05). Underestimation of CVD risk was particularly observed in low-predicted CVD risk groups. Conclusions: All algorithms perform reasonably well in PLWH, with SCORE-NL performing poorest. Prediction algorithms are useful for clinical practice, but clinicians should be aware of their limitations (ie, lack of fit and slight underestimation of CVD risk in low-risk groups). [ABSTRACT FROM AUTHOR]

• Prior to the introduction of DAA therapy, the disease burden of HCV was rising in New South Wales. • DAA scale-up has had a major population-level impact on HCV morbidity and mortality. • The World Health Organization has set a 65% HCV mortality reduction target by 2030. • To achieve this target, enhanced efforts are required to continue DAA scale-up. • In the DAA era, the impact of heavy alcohol use on liver disease should be monitored. Population-level evidence for the impact of direct-acting antiviral (DAA) therapy on hepatitis C virus (HCV)-related disease burden is lacking. We aimed to evaluate trends in HCV-related decompensated cirrhosis and hepatocellular carcinoma (HCC) hospitalisation, and liver-related and all-cause mortality in the pre-DAA (2001–2014) and DAA therapy (2015–2017) eras in New South Wales, Australia. HCV notifications (1993–2016) were linked to hospital admissions (2001–2017) and mortality (1995–2017). Segmented Poisson regressions and Poisson regression were used to assess the impact of DAA era and factors associated with liver-related mortality, respectively. Among 99,910 people with an HCV notification, 3.8% had a decompensated cirrhosis diagnosis and 1.8% had an HCC diagnosis, while 3.3% and 10.5% died of liver-related and all-cause mortality, respectively. In the pre-DAA era, the number of decompensated cirrhosis and HCC diagnoses, and liver-related and all-cause mortality consistently increased (incidence rate ratios 1.04 [95% CI 1.04–1.05], 1.08 [95% CI 1.07–1.08], 1.07 [95% CI 1.06–1.07], and 1.05 [95% CI 1.04–1.05], respectively) over each 6-monthly band. In the DAA era, decompensated cirrhosis diagnosis and liver-related mortality numbers declined (incidence rate ratios 0.97 [95% CI 0.95–0.99] and 0.96 [95% CI 0.94–0.98], respectively), and HCC diagnosis and all-cause mortality numbers plateaued (incidence rate ratio 1.00 [95% CI 0.97–1.03] and 1.01 [95% CI 1.00–1.02], respectively) over each 6-monthly band. In the DAA era, alcohol-use disorder (AUD) was common in patients diagnosed with decompensated cirrhosis and HCC (65% and 46% had a history of AUD, respectively). AUD was independently associated with liver-related mortality (incidence rate ratio 3.35; 95% CI 3.14–3.58). In the DAA era, there has been a sharp decline in liver disease morbidity and mortality in New South Wales, Australia. AUD remains a major contributor to HCV-related liver disease burden, highlighting the need to address comorbidities. Rising hepatitis C-related morbidity and mortality is a major public health issue. However, development of highly effective medicines against hepatitis C (called direct-acting antivirals or DAAs) means hepatitis C could be eliminated as a public health threat by 2030. This study shows a sharp decline in liver disease morbidity and mortality since the introduction of DAAs in New South Wales, Australia. Despite this, heavy alcohol use remains an important risk factor for liver disease among people with hepatitis C. To ensure that the benefits of new antiviral treatments are not compromised, management of major comorbidities, including heavy alcohol use must improve among people with hepatitis C. [ABSTRACT FROM AUTHOR]

Background: Direct acting antivirals are expected to drastically reduce the burden of hepatitis C virus (HCV) in people living with Human Immunodeficiency Virus (HIV). However, rates of HCV testing, re-testing and incident infection in this group remain uncertain in Australia. We assessed trends in HCV testing, re-testing and incident infection among HIV-positive individuals, and evaluated factors associated with HCV re-testing and incident infection.Methods: The study population consisted of HIV-positive individuals who visited a sexual health service involved in the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance (ACCESS) between 2007 and 2015. Poisson regression was used to assess trends and to evaluate factors associated with HCV re-testing and incident HCV infection.Results: There were 9227 HIV-positive individuals included in our testing rate analysis. Of 3799 HIV-positive/HCV-negative people that attended an ACCESS sexual health service more than once, 2079 (54.7%) were re-tested for HCV and were therefore eligible for our incidence analysis. The rate of HCV testing increased from 17.1 to 51.4 tests per 100 patient years between 2007 and 2015 (p for trend <0.01). Over the same period, HCV re-testing rates increased from 23.9 to 79.7 tests per 100 person years (p for trend <0.01). A clear increase in testing and re-testing began after 2011. Patients who identified as men who have sex with men and those with a history of injecting drug use experienced high rates of HCV re-testing over the course of the study period. Among those who re-tested, 157 incident HCV infections occurred at a rate of 2.5 events per 100 person years. Between 2007 and 2009, 2010-2011, 2012-2013 and 2014-2015, rates of incident HCV were 0.8, 1.5, 3.9 and 2.7 events per 100 person years, respectively (p for trend <0.01). Incident HCV was strongly associated with a history of injecting drug use.Conclusions: High rates of HCV testing and re-testing among HIV-positive individuals in Australia will assist strategies to achieve HCV elimination through rapid treatment scale up. Continued monitoring of HCV incidence in this population is essential for guiding both HCV prevention and treatment strategies. [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]

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]

Introduction: HIV prevention strategies are moving towards reducing plasma HIV RNA viral load in all HIV-positive persons, including those undiagnosed, treatment naïve, on or off antiretroviral therapy. A proxy population for those undiagnosed are patients that present late to care with advanced HIV. The objectives of this analysis are to examine factors associated with patients presenting with advanced HIV, and establish rates of treatment interruption and modification after initiating ART. Methods: We deterministically linked records from the Australian HIV Observational Database to the Australian National HIV Registry to obtain information related to HIV diagnosis. Logistic regression was used to identify factors associated with advanced HIV diagnosis. We used survival methods to evaluate rates of ART initiation by diagnosis CD4 count strata and by calendar year of HIV diagnosis. Cox models were used to determine hazard of first ART treatment interruption (duration >30 days) and time tofirst major ART modification. Results: Factors associated (p<0.05) with increased odds of advanced HIV diagnosis were sex, older age, heterosexual mode of HIV exposure, born overseas and rural-regional care setting. Earlier initiation of ART occurred at higher rates in later periods (2007-2012) in all diagnosis CD4 count groups. We found an 83% (69, 91%) reduction in the hazard of first treatment interruption comparing 2007-2012 versus 1996-2001 (p<0.001), and no difference in ART modification for patients diagnosed with advanced HIV. Conclusions: Recent HIV diagnoses are initiating therapy earlier in all diagnosis CD4 cell count groups, potentially lowering community viral load compared to earlier time periods. We found a marked reduction in the hazard of first treatment interruption, and found no difference in rates of major modification to ART by HIV presentation status in recent periods. [ABSTRACT FROM AUTHOR]

Background: Mental health and substance use disorders are common among people living with HIV and are associated with high-risk sexual behaviors, such as unprotected sex and multiple sexual partners, but Asia-Pacific data are limited. Methods: Adults living with HIV in care at 5 Asia-Pacific HIV clinics were enrolled at routine clinic visits between July 2019 and June 2020. Depression, substance use, sexual practice, and sociodemographic data were collected using the Patient Health Questionnaire-9, Alcohol, Smoking, and Substance Involvement Screening Test, and a study-specific questionnaire. Clinical data were accessed from medical records. Risk factors for medium-to high-risk sexual practices, defined based on total scores from the sexual practice questionnaire assessing number of sexual partners and condom use, were analyzed using logistic regression. Moderate-to-severe depression was defined as a Patient Health Questionnaire-9 score >9 and moderate- to high-risk substance use as an Alcohol, Smoking, and Substance Involvement Screening Test score ≥11 for alcohol or ≥4 for other substances. Results: Among 723 participants, the median age was 38 years, 89% were men, 99% were on antiretroviral therapy and 37% had medium- to high-risk sexual practices. Medium- to high-risk sexual practices were more common among those ≤30 years old, unemployed, and those with HIV status disclosed and were more likely in participants with moderate-to-severe depression (aOR 2.09, 95% CI: 1.17 to 3.74) compared with none-to-minimal depression, and moderate- to high-risk substance use (aOR 1.73, 95% CI: 1.23 to 2.44) compared with those without. Conclusions: Further integration of comprehensive sexual risk reduction strategies, mental health services, and substance use harm reduction within HIV clinical settings in the region is needed. [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]

Background: Recent papers have suggested that expanded combination antiretroviral treatment (cART) through lower viral load may be a strategy to reduce HIV transmission at a population level. We assessed calendar trends in detectable viral load in patients recruited to the Australian HIV Observational Database who were receiving cART. Methods: Patients were included in analyses if they had started cART (defined as three or more antiretrovirals) and had at least one viral load assessment after 1 January 1997. We analyzed detectable viral load (>400 copies/ml) in the first and second six months of each calendar year while receiving cART. Repeated measures logistic regression methods were used to account for within and between patient variability. Rates of detectable viral load were predicted allowing for patients lost to follow up. Results: Analyses were based on 2439 patients and 31,339 viral load assessments between 1 January 1997 and 31 March 2009. Observed detectable viral load in patients receiving cART declined to 5.3% in the first half of 2009. Predicted detectable viral load based on multivariate models, allowing for patient loss to follow up, also declined over time, but at higher levels, to 13.8% in 2009. Conclusions: Predicted detectable viral load in Australian HIV Observational Database patients receiving cART declined over calendar time, albeit at higher levels than observed. However, over this period, HIV diagnoses and estimated HIV incidence increased in Australia. [ABSTRACT FROM AUTHOR]

The article presents an analysis of the statement that individuals who have received effective antiretroviral therapy are sexually non-infectious. The authors found that the risk in heterosexual couples is low but non-zero, and that the risk of transmission in male homosexual couples is high over repeated exposures. The authors also note that if condoms are rejected because an individual believes him or herself sexually non-infectious, then there is potential for marked increases in HIV transmission. The authors provide charts and graphs to support their analysis.

Background: Hepatitis B virus (HBV) is the major cause of chronic liver disease in Vietnam. This study aimed to estimate and project chronic HBV prevalence and HBV-related liver cirrhosis (LC) and hepatocellular carcinoma (HCC) for the period 1990–2025. Method: The Vietnamese population for the period 1990–1999 was derived from census data to 1999 and from 2000 to 2025 based on projection data from the United States Census Bureau. Population chronic HBV prevalence for males and females was estimated based on age-specific HBV prevalence from Vietnamese community-based studies. Universal infant HBV vaccination from 2003 was assumed to reduce HBV infection by 90% in subsequent birth cohorts. Incidences of HBV-related LC and HCC by HBV DNA levels from the Taiwanese REVEAL studies were applied to the chronic HBV population to estimate and project HBV-related liver disease burden. Results: Estimated chronic HBV prevalence increased from 6.4 million cases in 1990 to around 8.4 million cases in 2005 and was projected to decrease to 8.0 million by 2025. Estimated HBV-related LC and HCC incidence increased linearly from 21 900 and 9400 in 1990 to 58 650 and 25 000 in 2025. Estimated HBV-related mortality increased from 12 600 in 1990 to 40 000 in 2025. Conclusion: Over the next two decades, universal infant HBV vaccination will reduce chronic HBV prevalence in Vietnam but HBV-related liver disease burden will continue to rise. A national HBV strategy is required to address this expanding burden of liver disease. [ABSTRACT FROM AUTHOR]

Pavlovian cues associated with reward exert a powerful motivational influence on the performance of goal-directed actions. This motivational process depends critically on the ventral striatum, although little is known about the cellular and molecular mechanisms that mediate it. In the current experiments we examined the role of calcium calmodulin-dependent kinase II (CaMKII) by using transgenic mice that express a constitutively active form of this kinase. We found that controlled expression of active CaMKII in the striatum did not affect learning but did impair the motivation of goal-directed actions by Pavlovian cues associated with reward. Mutant mice learned to lever press for reward, remained sensitive to outcome devaluation and contingency degradation manipulations, and were able to acquire Pavlovian responses to cues paired with reward. However, Pavlovian cues were completely unable to motivate lever pressing in mutant mice. This was true even in mice trained with the CaMKII transgene turned off and then tested with it turned on. We were also able to suppress transgene expression in impaired mutants and fully restore the motivational effects of reward cues in these animals. Therefore, the current experiments demonstrate that normal CaMKII activity in the striatum is essential for the motivational effects of reward cues on goal-directed actions. [ABSTRACT FROM AUTHOR]

Summary Background Hepatitis B and hepatitis C virus infections are common causes of death related to liver disease. In this large study, we aimed to investigate all cause mortality of the viruses in a community-based setting. Methods In the study population, 39 109 people had hepatitis B, 75 834 had hepatitis C, and 2604 had hepatitis B and hepatitis C co-infection, notified to the New South Wales state health department, Australia, between 1990 and 2002. Their data were probabilistically linked to the National Death Index. Standardised mortality ratios for all causes of death were calculated and adjusted for age, sex, and calendar year. Results The number of deaths identified by the linkage were 1233 (3·2%) for hepatitis B, 4008 (5·3)% for hepatitis C, and 186 (7·1)% for hepatitis B and C co-infection. Raised risk of liver-related death (standardised mortality ratios 12·2, 95% CI 10·7-13·9; 16·8, 15·4-18·3, and 32·9, 23·1-46·7, for hepatitis B, hepatitis C, and hepatitis B and C co-infected patients, respectively) and drug-induced death (1·4, 1·0-2·0; 19·3, 18·1-20·5; and 24·7, 18·2-33·5, respectively) were detected. In people with hepatitis C, raised risk of dying from drug-related causes was significantly greater than from liver-related causes (p=0·012), with the greatest excess risk in women aged 15-24 years (56·9, 39·2-79·9). Interpretation All groups had increased risk of liver-related death compared with the standard population, with the greatest excess in people diagnosed with hepatitis B and hepatitis C co-infection. Our data highlight that young people with hepatitis C and with co-infection face a higher mortality risk from continued drug use than from their infection, whereas the main cause of hepatitis B death was liver related. [ABSTRACT FROM AUTHOR]

We have therefore undertaken further analyses to clarify the role of monitoring trends in "late HCV diagnosis" and to highlight key differences in the epidemiology of HCV and population-level HCV screening in New South Wales (NSW) and Ontario. In our original study, we had proposed a definition of "late HCV diagnosis", to monitor population-level HCV screening, particularly among older people and those with longer duration of HCV who are at higher risk of advanced liver disease. In our study, HCV diagnoses 1995-1999 comprised 47% of all diagnoses and were included to reduce overestimation of late HCV diagnosis in the early 2000s; however, the look-back observation time was shorter for people with a DC and HCC diagnosis in the early 2000s, compared to the later time periods. [Extracted from the article]

The purpose of this qualitative single case study is to explore one grandmother's experience with voluntary kinship care and child welfare services. Voluntary kinship care is pursued as a viable option when out-of-home placement is imminent. Research indicates that voluntary kinship care, as an alternative living arrangement, helps to maintain familial and community attachments as well as to minimize trauma and upheaval in a child's life. This case study identifies four major themes relating to the participant's experiences: life altering events, gaining control, daily challenges, and looking to the future. Implications for public and child welfare practice are discussed. [ABSTRACT FROM AUTHOR]

Objective: To examine the effectiveness of needle and syringe programmes (NSPs) in preventing HIV transmission among injecting drug users (IDUs).Methods: An ecological study design was used to determine change in HIV prevalence among injecting drug users between cities with and without NSPs. Several data sources, such as electronic journal databases, surveillance reports, websites, and index review of relevant journals, were used to identify studies of HIV seroprevalence among IDUs, and presence of NSPs. The rate of change in HIV prevalence was estimated by regression analysis.Results: There were 778 years of data from 99 cities globally included in the analysis. HIV prevalence decreased by 18.6% per annum in cities that introduce NSPs, and increased by 8.1% in cities that had never introduced NSPs (mean difference −24.7% [95% CI: −43.8, 0.5%], P=0.06). The mean difference was –33% when comparison was weighted to one over the variance of the regression estimator (29% decrease in cities with NSPs and 5% increase in cities without NSPs, P<0.001). When analysis was restricted to cities with first HIV seroprevalence less than 10%, the average annual change in seroprevalence was 18% lower in cities with NSPs (P=0.03).Conclusions: Despite the inherent limitations within an ecological study design, the study provides additional evidence that NSPs reduce transmission of HIV infection. The rapid spread of HIV among IDU populations and increasing rates of injecting in many countries calls for scaling up of NSPs as well as other harm reduction strategies. [Copyright &y& Elsevier]

Describes an objective lipodystrophy severity grading scale derived from the lipodystrophy case definition score (LCDS). LDCD score as the best objective measure of lipodystrophy severity; Data showing that the LDCD score and its derived lipodystrophy grading scale merit prospective evaluation.

Background: Since the discovery in 1989 of hepatitis C virus (HCV) as the infectious agent responsible for the vast majority of post-transfusion non-A non-B hepatitis the patterns of transmission and clinical consequences of this highly prevalent flavivirus have been widely studied. Objective: This paper reviews available evidence on the epidemiology of HCV infection in Australia, including HCV notification data obtained through public health surveillance systems, HCV seroprevalence surveys among high risk populations, and models for estimating and projecting HCV transmission and long-term consequences of chronic HCV infection. Results: Over the period 1990–2000 approximately 160 000 notifications of HCV infection were received by State and Territory health jurisdictions making it the most commonly notified communicable disease in Australia. Approximately 210 000 people are estimated to be living with HCV infection in Australia, with an estimated 80% having acquired their infection through injecting drug use. Less than 500 cases of newly acquired HCV infection are notified each year, however, an estimated 16 000 new infections occur annually. Despite the widespread introduction of needle and syringe programmes in the late 1980s, HCV transmission continues at high levels among current injecting drug users (IDUs) with incidence and prevalence estimates of 10–20/100 person years and 50–55%, respectively. Levels of HCV transmission are particularly high in both younger and incarcerated IDUs. In contrast to HCV infection, prevalence of HIV among current IDUs has remained below 2% since 1995. Although a small minority of people with chronic HCV infection will develop liver failure or hepatocellular carcinoma, the incidence of these advanced disease complications is estimated to double over the next decade. Conclusion: The epidemic of HCV infection continues to escalate in Australia, predominantly through transmission related to injecting drug use. As the population of people with chronic HCV infection and progressive liver disease expands the public health burden of advanced disease complications will be considerable. [Copyright &y& Elsevier]

Aims. To plan an appropriate response to heroin use in Australia, good estimates are needed of the numbers of dependent heroin users, the group who are most in need of treatment, most at risk of fatal opioid overdose and most at risk of contracting and transmitting blood-borne viruses. Methods. Back-projection methods were used to estimate the numbers of people starting dependent heroin injecting in Australia between 1960 and 1997. Separate analyses were based on national opioid overdose deaths and numbers of new entrants to methadone treatment in New South Wales (NSW). Estimates of the rates at which dependent heroin users cease heroin use, commence methadone treatment or die from opioid overdoses were estimated from external data sources. Results. Back-projection estimates derived from opioid overdose deaths indicated that there were 104 000 (lower limit of 72 000 and upper limit of 157 000) people who were heroin dependent in Australia between 1960 and 1997. Of these it was estimated that 67 000 (39 000-120 000) were still heroin dependent at the end of 1997. Back-projection estimates based on numbers of new entrants to methadone treatment in NSW indicated that there were 108 000 (82 000-141 000) heroin-dependent people in Australia between 1960 and 1997, of whom 71 000 (47 000-109 000) were estimated to be heroin dependent at the end of 1997. Both analyses indicated that the number of heroin-dependent people in Australia has increased substantially from the early 1970s onwards. Conclusions. Back-projection estimates based on analyses of treatment entries and opioid overdose deaths provide an additional method for estimating the numbers of heroin-dependent people in the population. The addition of these methods to existing methods, using different data sources and statistical methods, should improve consensus estimates of the numbers of heroin-dependent people. [ABSTRACT FROM AUTHOR]

Introduction: Females of childbearing age with hepatitis C virus (HCV) face increased marginalisation with intersecting, sex‐specific barriers to direct acting antiviral (DAA) therapy. We assessed the factors associated with uptake of DAA therapy among females of childbearing age, including those with evidence of recent drug dependence. Methods: HCV notifications in New South Wales, Australia (1995–2017) were linked to opioid agonist therapy (OAT), hospitalisations, incarcerations, perinatal, HIV notifications, deaths and prescription databases. Recent drug dependence was defined as hospitalisation due to injectable drugs or receipt of OAT occurring in the DAA era (2016–2018). Logistic regression was used to analyse factors associated with DAA uptake among females of childbearing age (18–44), including those with recent drug dependence. Results: Among 57,467 people with evidence of chronic HCV in the DAA era (2016–2018), 20,161 (35%) were female, including 33% (n = 6563/20,161) of childbearing age (18–44). Among all females of childbearing age (n = 6563) and those with evidence of recent drug dependence (n = 2278/6563, 35%), DAA uptake was lower among those who had given birth in the DAA era (vs. no birth record, all females of childbearing age; aOR: 0.74, 95% CI 0.61, 0.89; those with recent drug dependence; aOR 0.69, 95% CI 0.51, 0.93) and Aboriginal and Torres Strait Islander peoples (all females of childbearing age; aOR 0.81, 95% CI 0.71, 0.93; those with recent drug dependence aOR 0.75, 95% CI 0.62, 0.90). Conclusion: Females of childbearing age should be considered a key population for DAA therapy. Enhancing antenatal and postnatal HCV care may be critical in the pursuit towards elimination. [ABSTRACT FROM AUTHOR]

AbstractIntroduction: In Australia, to the end of 1997, more than 110 000 people have been diagnosed with hepatitis C virus (HCV) antibodies and reported to State/Territory surveillance systems. The available data indicate that the overwhelming majority (around 80%) of people with HCV antibodies were infected through injecting drug use. Methods: Models of the HCV epidemic in Australia were developed based on estimates of the pattern of injecting drug use in Australia. Estimates of HCV infections due to injecting drug use thus obtained were then adjusted to allow for HCV infections resulting from other transmission routes. Projections of cirrhosis and hepatocellular carcinoma (HCC) resulting from HCV were obtained by combining modelled HCV incidence with estimates of the progression rates to these outcomes. Results: Based on the models, it was estimated that there were 196 000 (lower and upper limits of 149 000 and 234 000) people in Australia living with HCV antibodies at the end of 1997, with HCV incidence in 1997 estimated to be 11 000 (8500–13 500). It was estimated that 8500 (4000–13 000) people were living with HCV-related cirrhosis in 1997 and that there were 80 (40–125) incident cases of HCV-related HCC. Discussion: Model-based estimates were broadly consistent with other sources of information on the HCV epidemic in Australia. These models suggest that the prevalence of HCV-related cirrhosis and the incidence of HCV-related HCC will more than double in Australia by 2010. © 1999 Blackwell Science Asia Pty Ltd. [ABSTRACT FROM AUTHOR]

Background People who inject drugs are at greater risk of hepatitis C virus (HCV) infection and hospitalization, yet admissions are not utilized for HCV treatment initiation. We aimed to assess the extent to which people with HCV notification, including those with evidence of recent drug dependence, are hospitalized while eligible for direct-acting antiviral (DAA) therapy, and treatment uptake according to hospitalization in the DAA era. Methods We conducted a longitudinal, population-based cohort study of people living with HCV in the DAA era (March 2016–December 2018) through analysis of linked databases in New South Wales, Australia. Kaplan-Meier estimates were used to report HCV treatment uptake by frequency, length, and cause-specific hospitalization. Results Among 57 467 people, 14 938 (26%) had evidence of recent drug dependence, 50% (n = 7506) of whom were hospitalized while DAA eligible. Incidence of selected cause-specific hospitalization was highest for mental health-related (15.84 per 100 person-years [PY]), drug-related (15.20 per 100 PY), and injection-related infectious disease (9.15 per 100 PY) hospitalizations, and lowest for alcohol use disorder (4.58 per 100 PY) and liver-related (3.13 per 100 PY). In total, 65% (n = 4898) of those who were hospitalized had been admitted ≥2 times, and 46% (n = 3437) were hospitalized ≥7 days. By the end of 2018, DAA therapy was lowest for those hospitalized ≥2 times, for ≥7 days, and those whose first admission was for injection-related infectious disease, mental health disorders, and drug-related complications. Conclusions Among people who have evidence of recent drug dependence, frequent hospitalization—particularly mental health, drug, and alcohol admissions—presents an opportunity for engagement in HCV care. [ABSTRACT FROM AUTHOR]

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.

Abstract: The present study was undertaken to genotype four single nucleotide polymorphisms, which were previously found to be associated with schizophrenia, in 77 patients with schizophrenia and 52 control subjects in order to assess their genotypic association with plasma IL-2 levels. Kruskal–Wallis analysis revealed an association between rs4811528 and plasma IL-2 levels in the patient group (χ2 =7.60, df =2, p =0.022) but not in the control group; binary logistic regression also confirmed the association of rs4811528 with altered IL-2 secretion (χ2 =8.191, df =3, p =0.042) after adjustment for age and sex. TGM2 may be involved in dysfunction of the immune system in schizophrenia. [Copyright &y& Elsevier]

Background Human immunodeficiency virus (HIV) infection leads to chronic immune activation/inflammation that can persist in virally suppressed persons on fully active antiretroviral therapy (ART) and increase risk of malignancies. The prognostic role of low CD4:CD8 ratio and elevated CD8 cell counts on the risk of cancer remains unclear. Methods We investigated the association of CD4:CD8 ratio on the hazard of non-AIDS defining malignancy (NADM), AIDS-defining malignancy (ADM) and most frequent group of cancers in ART-treated people with HIV (PWH) with a CD4 and CD8 cell counts and viral load measurements at baseline. We developed Cox proportional hazard models with adjustment for known confounders of cancer risk and time-dependent cumulative and lagged exposures of CD4:CD8 ratio to account for time-evolving risk factors and avoid reverse causality. Results CD4:CD8 ratios below 0.5, compared to above 1.0, were independently associated with a 12-month time-lagged higher risk of ADM and infection-related malignancies (adjusted hazard ratio 2.61 [95% confidence interval {CI }1.10–6.19] and 2.03 [95% CI 1.24–3.33], respectively). CD4 cell counts below 350 cells/μL were associated with an increased risk of NADMs and ADMs, as did infection, smoking, and body mass index-related malignancies. Conclusions In ART-treated PWH low CD4:CD8 ratios were associated with ADM and infection-related cancers independently from CD4 and CD8 cell counts and may alert clinicians for cancer screening and prevention of NADM. [ABSTRACT FROM AUTHOR]

Background: While national adoption of universal HIV treatment guidelines has led to improved, timely uptake of antiretroviral therapy (ART), longer-term care outcomes are understudied. There is little data from real-world service delivery settings on patient attrition, viral load (VL) monitoring, and viral suppression (VS) at 24 and 36 months after HIV treatment initiation. Methods and findings: For this retrospective cohort analysis, we used observational data from 25 countries in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium's Asia-Pacific, Central Africa, East Africa, Central/South America, and North America regions for patients who were ART naïve and aged ≥15 years at care enrollment between 24 months before and 12 months after national adoption of universal treatment guidelines, occurring 2012 to 2018. We estimated crude cumulative incidence of loss-to-clinic (CI-LTC) at 12, 24, and 36 months after enrollment among patients enrolling in care before and after guideline adoption using competing risks regression. Guideline change–associated hazard ratios of LTC at each time point after enrollment were estimated via cause-specific Cox proportional hazards regression models. Modified Poisson regression was used to estimate relative risks of retention, VL monitoring, and VS at 12, 24, and 36 months after ART initiation. There were 66,963 patients enrolling in HIV care at 109 clinics with ≥12 months of follow-up time after enrollment (46,484 [69.4%] enrolling before guideline adoption and 20,479 [30.6%] enrolling afterwards). More than half (54.9%) were females, and median age was 34 years (interquartile range [IQR]: 27 to 43). Mean follow-up time was 51 months (standard deviation: 17 months; range: 12, 110 months). Among patients enrolling before guideline adoption, crude CI-LTC was 23.8% (95% confidence interval [95% CI] 23.4, 24.2) at 12 months, 31.0% (95% CI [30.6, 31.5]) at 24 months, and 37.2% (95% [CI 36.8, 37.7]) at 36 months after enrollment. Adjusting for sex, age group, enrollment CD4, clinic location and type, and country income level, enrolling in care and initiating ART after guideline adoption was associated with increased hazard of LTC at 12 months (adjusted hazard ratio [aHR] 1.25 [95% CI 1.08, 1.44]; p = 0.003); 24 months (aHR 1.38 [95% CI 1.19, 1.59]; p <.001); and 36 months (aHR 1.34 [95% CI 1.18, 1.53], p <.001) compared with enrollment before guideline adoption, with no before–after differences among patients with no record of ART initiation by end of follow-up. Among patients retained after ART initiation, VL monitoring was low, with marginal improvements associated with guideline adoption only at 12 months after ART initiation. Among those with VL monitoring, VS was high at each time point among patients enrolling before guideline adoption (86.0% to 88.8%) and afterwards (86.2% to 90.3%), with no substantive difference associated with guideline adoption. Study limitations include lags in and potential underascertainment of care outcomes in real-world service delivery data and potential lack of generalizability beyond IeDEA sites and regions included in this analysis. Conclusions: In this study, adoption of universal HIV treatment guidelines was associated with lower retention after ART initiation out to 36 months of follow-up, with little change in VL monitoring or VS among retained patients. Monitoring long-term HIV care outcomes remains critical to identify and address causes of attrition and gaps in HIV care quality. Using real-world service delivery data, Ellen Brazier and team examine long-term HIV care outcomes under universal HIV treatment guidelines across 25 countries. Author summary: Why was this study done?: Although universal HIV treatment recommendations have been adopted in national HIV treatment guidelines, longer-term HIV care outcomes under such guidelines are poorly documented and largely limited to single-country studies with short follow-up times. No multicountry studies using real-world service delivery data have examined long-term HIV care outcomes associated under universal HIV treatment guidelines. What did the researchers do and find?: With data on 66,963 patients enrolling in HIV care at 109 clinics participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) research consortium across 25 countries where universal HIV treatment guidelines were adopted, we estimated the hazard ratios of loss-to-clinic (LTC) at 12, 24, and 36 months after enrollment, comparing those enrolling in HIV care after guideline adoption to those enrolling before guideline adoption. Among 57,615 patients with documented initiation of antiretroviral therapy (ART), we also estimated the relative risks of clinic retention, viral load (VL) monitoring, and viral suppression (VS) at 12, 24, and 36 months after ART initiation, comparing those enrolling after versus before national adoption of universal treatment guidelines. Compared with patients enrolling in HIV care and initiating HIV treatment before national adoption of universal treatment guidelines, those enrolling and initiating treatment after guideline adoption had higher risk of being LTC at 12 months, 24 months, and 36 months after enrollment. Among patients retained in care after ART initiation, those enrolling in HIV care after the adoption of universal HIV treatment guidelines were more likely to have VL monitoring at 12 months after ART initiation and less likely at 36 months, with no difference at 24 months. VS was high at each time point among patients enrolling before and after the adoption of universal HIV treatment guidelines, with no substantive change associated with guideline adoption. What do these findings mean?: Our results raise concerns about long-term retention of patients after ART initiation, as well as the capacity of HIV programs to provide essential aspects of HIV care, including annual VL monitoring for timely identification of adherence problems and treatment failure. Our findings that patient retention in care at the clinic where ART was initiated decreased after the adoption of universal HIV treatment guidelines and that there has been no improvement in annual VL monitoring among patients retained in care should motivate efforts to identify and address factors associated with attrition among patients enrolling in HIV care, as well as barriers to routine VL testing in the era of universal treatment of all people living with HIV. Study limitations include potential underascertainment of patient outcomes in real-world service delivery data, lags in the availability of real-world service delivery data, and the nonrepresentativeness of the clinics and countries reflected in IeDEA datasets available for analysis. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) is a common infection in people living with HIV. However, the risk factors for HIV/TB co-infection in second-line HIV therapy are poorly understood. We aimed to determine the incidence and risk factors for TB co-infection in SECOND-LINE, an international randomized clinical trial of second-line HIV therapy. Methods: We did a cohort analysis of TB cases in SECONDLINE. TB cases included any clinical or laboratory-confirmed diagnoses and/or commencement of treatment for TB after randomization. Baseline factors associated with TB were analyzed using Cox regression stratified by site. Results: TB cases occurred at sites in Argentina, India, Malaysia, Nigeria, South Africa, and Thailand, in a cohort of 355 of the 541 SECOND-LINE participants. Overall, 20 cases of TB occurred, an incidence rate of 3.4 per 100 person-years (95% CI: 2.1 to 5.1). Increased TB risk was associated with a low CD4+-cell count (≤200 cells/mL), high viral load (>200 copies/mL), low platelet count (<150x109/L), and low total serum cholesterol (≤4.5 mmol/L) at baseline. An increased risk of death was associated with TB, adjusted for CD4, platelets, and cholesterol. A low CD4+-cell count was significantly associated with incident TB, mortality, other AIDS diagnoses, and virologic failure. Discussion: The risk of TB remains elevated in PLHIV in the setting of second-line HIV therapy in TB endemic regions. TB was associated with a greater risk of death. Finding that low CD4+ T-cell count was significantly associated with poor outcomes in this population supports the value of CD4+ monitoring in HIV clinical management. [ABSTRACT FROM AUTHOR]

The article discusses the effectiveness and necessity of telephone calls from medical students to victims of elder mistreatment (EM), particularly concerning adult social morbidity before and during the COVID-19 pandemic in the U.S. It examines aspects of EM victims, particularly loneliness, aging, and mental depression.

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]

Introduction: We assessed mortality and losses to follow‐up (LTFU) during adolescence in routine care settings in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. Methods: Cohorts in the Asia‐Pacific, the Caribbean, Central, and South America, and sub‐Saharan Africa (Central, East, Southern, West) contributed data, and included adolescents living with HIV (ALHIV) enrolled from January 2003 and aged 10 to 19 years (period of adolescence) while under care up to database closure (June 2016). Follow‐up started at age 10 years or the first clinic visit, whichever was later. Entering care at <15 years was a proxy for perinatal infection, while entering care ≥15 years represented infection acquired during adolescence. Competing risk regression was used to assess associations with death and LTFU among those ever receiving triple‐drug antiretroviral therapy (triple‐ART). Results: Of the 61,242 ALHIV from 270 clinics in 34 countries included in the analysis, 69% (n = 42,138) entered care <15 years of age (53% female), and 31% (n = 19,104) entered care ≥15 years (81% female). During adolescence, 3.9% died, 30% were LTFU and 8.1% were transferred. For those with infection acquired perinatally versus during adolescence, the four‐year cumulative incidences of mortality were 3.9% versus 5.4% and of LTFU were 26% versus 69% respectively (both p < 0.001). Overall, there were higher hazards of death for females (adjusted sub‐hazard ratio (asHR) 1.19, 95% confidence interval (CI) 1.07 to 1.33), and those starting treatment at ≥5 years of age (highest asHR for age ≥15: 8.72, 95% CI 5.85 to 13.02), and in care in mostly urban (asHR 1.40, 95% CI 1.13 to 1.75) and mostly rural settings (asHR 1.39, 95% CI 1.03 to 1.87) compared to urban settings. Overall, higher hazards of LTFU were observed among females (asHR 1.12, 95% CI 1.07 to 1.17), and those starting treatment at age ≥5 years (highest asHR for age ≥15: 11.11, 95% CI 9.86 to 12.53), in care at district hospitals (asHR 1.27, 95% CI 1.18 to 1.37) or in rural settings (asHR 1.21, 95% CI 1.13 to 1.29), and starting triple‐ART after 2006 (highest asHR for 2011 to 2016 1.84, 95% CI 1.71 to 1.99). Conclusions: Both mortality and LTFU were worse among those entering care at ≥15 years. ALHIV should be evaluated apart from younger children and adults to identify population‐specific reasons for death and LTFU. [ABSTRACT FROM AUTHOR]

Introduction: Flow cytometry (FCM) is widely used in the diagnosis of mature B‐cell neoplasms (MBN), and FCM data are usually consistent with morphological findings. However, diffuse large B‐cell lymphoma (DLBCL), a common MBN, is sometimes not detected by FCM. This study aimed to explore factors that increase the likelihood of failure to detect DLBCL by FCM. Methods: Cases with a final diagnosis of DLBCL that were analysed by eight‐colour FCM were retrospectively collated. Clinical, FCM, histopathological and genetic data were compared between cases detected and cases not detected by FCM. Results: DLBCL cases from 135 different patients were analysed, of which 22 (16%) were not detected by FCM. In samples not detected by flow cytometry, lymphocytes were a lower percentage of total events (p = 0.02), and T cells were a higher percentage of total lymphocytes (p = 0.01). Cases with high MYC protein expression on immunohistochemistry were less likely to be missed by FCM (p = 0.011). Detection of DLBCL was not different between germinal centre B‐cell (GCB) and non‐GCB subtypes, not significantly affected by the presence of necrosis or fibrosis, and not significantly different between biopsy specimens compared to fine‐needle aspirates, or between samples from nodal compared to extranodal tissue. Conclusion: The study identifies several factors which affect the likelihood of DLBCL being missed by FCM. Even with eight‐colour analysis, FCM fails to detect numerous cases of DLBCL. [ABSTRACT FROM AUTHOR]

Objectives: There is a paucity of data on cardiovascular disease (CVD) among people living with HIV (PLHIV) in resource-limited countries. We assessed factors associated with CVD and the impact of prevalent CVD on all-cause mortality in PLHIV on antiretroviral therapy in Brazil.Methods: Competing risk regression to assess factors associated with CVD and all-cause mortality in the HIV-Brazil Cohort Study between 2003 and 2014.Results: Among 5614 patients, the rate of CVD was 3.5 (95% confidence interval [95% CI] 2.9-4.3) per 1000 person-years. CVD was associated with older age (adjusted hazard ratio [aHR] 6.4 for ≥55 years vs. <35 years, 95% CI: 2.5-16.3, P < 0.01), black race (aHR 1.8 vs. white race, 95% CI: 1.0-3.1, P = 0.04), past CVD (aHR 3.0 vs. no past CVD, 95% CI: 1.4-6.2, P < 0.01), hypertension (aHR 1.8 vs. no hypertension, 95% CI: 1.0-3.1, P = 0.04), high-grade dyslipidemia (aHR 9.3 vs. no high-grade dyslipidemia, 95% CI: 6.0-14.6, P < 0.01), ever smoking (aHR 2.4 vs. never, 95% CI: 1.2-5.0, P = 0.02) and low nadir CD4 cell count (aHR 1.8 for 100-250 cells/mm3 vs. >250 cells/mm3 , 95% CI: 1.0-3.2, P = 0.05). The rate of death was 16.6 (95% CI: 15.1-18.3) per 1000 person-years. Death was strongly associated with having had a past CVD event (aHR 1.7 vs. no past CVD event, 95% CI: 1.1-2.7, P = 0.01).Conclusions: Traditional and HIV-specific factors associated with CVD among PLHIV in Brazil are similar to those identified among PLHIV in high-income countries. PLHIV in Brazil with a history of CVD have a high risk of death. CVD care and treatment remain priorities for PLHIV in Brazil as this population ages and antiretroviral therapy use expands. [ABSTRACT FROM AUTHOR]

The article discusses how ASSP's National Capital Chapter have finished school and are still defining the type of safety professional they will become. It notes that the more eager volunteers are coached and sharpened from the wisdom of experienced leaders, the easier the transition between generations will be. It adds that millennials look for collaborative and consensual responsibility in their working environments and professional organizations.