Froude supercritical flow processes and sedimentary structures: new insights from experiments with a wide range of grain sizes

Recognition of Froude supercritical flow deposits in environments that range from rivers to the ocean floor has triggered a surge of interest in their flow processes, bedforms and sedimentary structures. Interpreting these supercritical flow deposits is especially important because they often represent the most powerful flows in the geological record. Insights from experiments are key to reconstruct palaeo‐flow processes from the sedimentary record. So far, all experimentally produced supercritical flow deposits are of a narrow grain‐size range (fine to medium sand), while deposits in the rock record often consist of a much wider grain‐size distribution. This paper presents results of supercritical‐flow experiments with a grain‐size distribution from clay to gravel. These experiments show that cyclic step instabilities can produce more complex and a larger variety of sedimentary structures than the previously suggested backsets and ‘scour and fill’ structures. The sedimentary structures are composed of irregular lenses, mounds and wedges with backsets and foresets, as well as undulating planar to low‐angle upstream and downstream dipping laminae. The experiments also demonstrate that the Froude number is not the only control on the sedimentary structures formed by supercritical‐flow processes. Additional controls include the size and migration rate of the hydraulic jump and the substrate cohesion. This study further demonstrates that Froude supercritical flow promotes suspension transport of all grain sizes, including gravels. Surprisingly, it was observed that all grain sizes were rapidly deposited just downstream of hydraulic jumps, including silt and clay. These results expand the range of dynamic mud deposition into supercritical‐flow conditions, where local transient shear stress reduction rather than overall flow waning conditions allow for deposition of fines. Comparison of the experimental deposits with outcrop datasets composed of conglomerates to mudstones, shows significant similarities and highlights the role of hydraulic jumps, rather than overall flow condition changes, in producing lithologically and geometrically complex stratigraphy

Viral Load Status Before Switching to Dolutegravir-Containing Antiretroviral Therapy and Associations With Human Immunodeficiency Virus Treatment Outcomes in Sub-Saharan Africa

Background: Dolutegravir is being rolled out globally as part of preferred antiretroviral therapy (ART) regimens, including among treatment-experienced patients. The role of viral load (VL) testing before switching patients already on ART to a dolutegravir-containing regimen is less clear in real-world settings. Methods: We included patients from the International epidemiology Databases to Evaluate AIDS consortium who switched from a nevirapine- or efavirenz-containing regimen to one with dolutegravir. We used multivariable cause-specific hazards regression to estimate the association of the most recent VL test in the 12 months before switching with subsequent outcomes. Results: We included 36 393 patients at 37 sites in 5 countries (Democratic Republic of the Congo, Kenya, Rwanda, Tanzania, Uganda) who switched to dolutegravir from July 2017 through February 2020, with a median follow-up of approximately 11 months. Compared with those who switched with a VL <200 copies/mL, patients without a recent VL test or with a preswitch VL ≥1000 copies/mL had significantly increased hazards of an incident VL ≥1000 copies/mL (adjusted hazard ratio [aHR], 2.89; 95% confidence interval [CI], 1.99-4.19 and aHR, 6.60; 95% CI, 4.36-9.99, respectively) and pulmonary tuberculosis or a World Health Organization clinical stage 4 event (aHR, 4.78; 95% CI, 2.77-8.24 and aHR, 13.97; 95% CI, 6.62-29.50, respectively). Conclusions: A VL test before switching to dolutegravir may help identify patients who need additional clinical monitoring and/or adherence support. Further surveillance of patients who switched to dolutegravir with an unknown or unsuppressed VL is needed

Temporal trends in co-trimoxazole use among children on antiretroviral therapy and the impact of co-trimoxazole on mortality rates in children without severe immunodeficiency

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

Mortality and losses to follow-up among adolescents living with HIV in the IeDEA global cohort collaboration

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

Global estimates of viral suppression in children and adolescents and adults on antiretroviral therapy adjusted for missing viral load measurements: a multiregional, retrospective cohort study in 31 countries

Background: As countries move towards the UNAIDS's 95-95-95 targets and with strong evidence that undetectable equals untransmittable, it is increasingly important to assess whether those with HIV who are receiving antiretroviral therapy (ART) achieve viral suppression. We estimated the proportions of children and adolescents and adults with viral suppression at 1, 2, and 3 years after initiating ART. Methods: In this retrospective cohort study, seven regional cohorts from the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium contributed data from individuals initiating ART between Jan 1, 2010, and Dec 31, 2019, at 148 sites in 31 countries with annual viral load monitoring. Only people with HIV who started ART after the time a site started routine viral load monitoring were included. Data up to March 31, 2020, were analysed. We estimated the proportions of children and adolescents (aged <18 years at ART initiation) and adults (aged ≥18 years at ART initiation) with viral suppression (viral load <1000 copies per mL) at 1, 2, and 3 years after ART initiation using an intention-to-treat approach and an adjusted approach that accounted for missing viral load measurements. Findings: 21 594 children and adolescents (11 812 [55%] female, 9782 [45%] male) from 106 sites in 22 countries and 255 662 adults (163 831 [64%] female, 91 831 [36%] male) from 143 sites in 30 countries were included. Using the intention-to-treat approach, the proportion of children and adolescents with viral suppression was 7303 (36%) of 20 478 at 1 year, 5709 (30%) of 19 135 at 2 years, and 4287 (24%) of 17 589 at 3 years after ART initiation; the proportion of adults with viral suppression was 106 541 (44%) of 240 600 at 1 year, 79 141 (36%) of 220 925 at 2 years, and 57 970 (29%) of 201 124 at 3 years after ART initiation. After adjusting for missing viral load measurements among those who transferred, were lost to follow-up, or who were in follow-up without viral load testing, the proportion of children and adolescents with viral suppression was 12 048 (64% [plausible range 43–81]) of 18 835 at 1 year, 10 796 (62% [41–77]) of 17 553 at 2 years, and 9177 (59% [38–91]) of 15 667 at 3 years after ART initiation; the proportion of adults with viral suppression was 176 964 (79% [53–80]) of 225 418 at 1 year, 145 552 (72% [48–79]) of 201 238 at 2 years, and 115 260 (65% [43–69]) of 178 458 at 3 years after ART initiation. Interpretation: Although adults with HIV are approaching the global target of 95% viral suppression, progress among children and adolescents is much slower. Substantial efforts are still needed to reach the viral suppression target for children and adolescents. Funding: US National Institutes of Health

Growth and CD4 patterns of adolescents living with perinatally acquired HIV worldwide, a CIPHER cohort collaboration analysis

Introduction: Adolescents living with HIV are subject to multiple co-morbidities, including growth retardation and immunodeficiency. We describe growth and CD4 evolution during adolescence using data from the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) global project. Methods: Data were collected between 1994 and 2015 from 11 CIPHER networks worldwide. Adolescents with perinatally acquired HIV infection (APH) who initiated antiretroviral therapy (ART) before age 10 years, with at least one height or CD4 count measurement while aged 10–17 years, were included. Growth was measured using height-for-age Z-scores (HAZ, stunting if &lt;-2 SD, WHO growth charts). Linear mixed-effects models were used to study the evolution of each outcome between ages 10 and 17. For growth, sex-specific models with fractional polynomials were used to model non-linear relationships for age at ART initiation, HAZ at age 10 and time, defined as current age from 10 to 17 years of age. Results: A total of 20,939 and 19,557 APH were included for the growth and CD4 analyses, respectively. Half were females, two-thirds lived in East and Southern Africa, and median age at ART initiation ranged from &lt;3 years in North America and Europe to &gt;7 years in sub-Saharan African regions. At age 10, stunting ranged from 6% in North America and Europe to 39% in the Asia-Pacific; 19% overall had CD4 counts &lt;500 cells/mm3. Across adolescence, higher HAZ was observed in females and among those in high-income countries. APH with stunting at age 10 and those with late ART initiation (after age 5) had the largest HAZ gains during adolescence, but these gains were insufficient to catch-up with non-stunted, early ART-treated adolescents. From age 10 to 16 years, mean CD4 counts declined from 768 to 607 cells/mm3. This decline was observed across all regions, in males and females. Conclusions: Growth patterns during adolescence differed substantially by sex and region, while CD4 patterns were similar, with an observed CD4 decline that needs further investigation. Early diagnosis and timely initiation of treatment in early childhood to prevent growth retardation and immunodeficiency are critical to improving APH growth and CD4 outcomes by the time they reach adulthood

Hemorrhagic Transformation in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Time to Initiation of Oral Anticoagulant Therapy and Outcomes.

Background In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation ( HT ). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT , (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores &gt;2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT . Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3-8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0-6.0) of those without HT ; 53.1% of patients with  HT were deceased or disabled compared with 35.8% of those without HT . On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24-2.35). Conclusions In patients with HT , anticoagulation was initiated about 12 days later than patients without HT . This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability

The post-pediatric HIV generation in Asia: Adolescent HIV care, treatment, and transitions into adult life

The trajectory of pediatric HIV infection, care, and treatment varies from that of adults on multiple levels, including by geography. In Asia, pediatric antiretroviral treatment was slowly scaled up from the early 2000s, and those with perinatally acquired HIV now live with the legacies of local delays in diagnosis and treatment. Sustained treatment adherence is central to HIV control, but growing up with HIV and the associated stigma make this especially challenging. When treatment fails, children are at greater risk of opportunistic infections, often leading to pneumonia and sepsis, which are the most common causes of death in Asian adolescents living with HIV. Life-long HIV also is associated with other conditions, such as persistent infection with human papillomavirus, which leads to abnormal cervical cytology and risk of anogenital cancer. Compounding the medical challenges are HIV-related stigma and discrimination, which can lead to social isolation from a young age. Data from Southeast Asian youth soon after transition from pediatric to adult HIV care have shown that most hide their HIV status from others. Their fear of disclosure escalates as they become more socially exposed in their communities, and shapes their daily interactions. In addition to the policy and practice changes needed to improve the quality of global and national HIV surveillance data and comprehensiveness of clinical care, research on treatment outcomes of Asian adolescents with perinatally acquired HIV should include studying co-morbidities and co-infections to better understand how related risks and behaviors intersect to impact HIV viral suppression, retention, and survival