Global, Regional, and National Sex-Specific Burden and Control of the HIV Epidemic, 1990-2019, for 204 Countries and Territories: The Global Burden of Diseases Study 2019

Background The sustainable development goals (SDGs) aim to end HIV/AIDS as a public health threat by 2030. Understanding the current state of the HIV epidemic and its change over time is essential to this effort. This study assesses the current sex-specific HIV burden in 204 countries and territories and measures progress in the control of the epidemic. Methods To estimate age-specific and sex-specific trends in 48 of 204 countries, we extended the Estimation and Projection Package Age-Sex Model to also implement the spectrum paediatric model. We used this model in cases where age and sex specific HIV-seroprevalence surveys and antenatal care-clinic sentinel surveillance data were available. For the remaining 156 of 204 locations, we developed a cohort-incidence bias adjustment to derive incidence as a function of cause-of-death data from vital registration systems. The incidence was input to a custom Spectrum model. To assess progress, we measured the percentage change in incident cases and deaths between 2010 and 2019 (threshold \u3e75% decline), the ratio of incident cases to number of people living with HIV (incidence-to-prevalence ratio threshold \u3c0.03), and the ratio of incident cases to deaths (incidence-to-mortality ratio threshold \u3c1.0). Findings In 2019, there were 36.8 million (95% uncertainty interval [UI] 35.1-38.9) people living with HIV worldwide. There were 0.84 males (95% UI 0.78-0.91) per female living with HIV in 2019, 0.99 male infections (0.91-1.10) for every female infection, and 1.02 male deaths (0.95-1.10) per female death. Global progress in incident cases and deaths between 2010 and 2019 was driven by sub-Saharan Africa (with a 28.52% decrease in incident cases, 95% UI 19.58-35.43, and a 39.66% decrease in deaths, 36.49-42.36). Elsewhere, the incidence remained stable or increased, whereas deaths generally decreased. In 2019, the global incidence-to-prevalence ratio was 0.05 (95% UI 0.05-0.06) and the global incidence-to-mortality ratio was 1.94 (1.76-2.12). No regions met suggested thresholds for progress. Interpretation Sub-Saharan Africa had both the highest HIV burden and the greatest progress between 1990 and 2019. The number of incident cases and deaths in males and females approached parity in 2019, although there remained more females with HIV than males with HIV. Globally, the HIV epidemic is far from the UNAIDS benchmarks on progress metrics

The salinity normalization of marine inorganic carbon chemistry data

Normalization to a constant salinity (S) is widely used for the adjustment of marine inorganic carbon chemistry data such as total alkalinity (AT) and total dissolved inorganic carbon (CT). This procedure traces back to the earliest studies in marine chemistry, but ignores the influence of riverine input of alkalinity and of dissolution of biogenic carbonates in the ocean. We tested different adjustment possibilities for AT and conclude that in most parts of the surface ocean the normalization concept does not reflect relationships which represent reality. In this paper, we propose a salinity adjustment based on a constant and region-specific term for S = 0, which expresses river run off, upwelling from below the lysocline, calcification, and lateral sea surface water exchange. One application of the normalization concept is its extension to AT and also CT predictions and implementation in models. We give a brief discussion on the usage of such extensions

Anthropogenic CO₂ Inventory of the Indian Ocean

This study presents basin-wide anthropogenic CO2 inventory estimates for the Indian Ocean based on measurements from the World Ocean Circulation Experiment/Joint Global Ocean Flux Study global survey. These estimates employed slightly modified ΔC* and time series techniques originally proposed by Gruber et al. [1996] and Wallace [1995], respectively. Together, the two methods yield the total oceanic anthropogenic CO2 and the carbon increase over the past 2 decades. The highest concentrations and the deepest penetrations of anthropogenic carbon are associated with the Subtropical Convergence at around 30° to 40°S. With both techniques, the lowest anthropogenic CO2 column inventories are observed south of 50°S. The total anthropogenic CO2 inventory north of 35°S was 13.6±2 Pg C in 1995. The inventory increase since GEOSECS (Geochemical Ocean Sections Program) was 4.1±1 Pg C for the same area. Approximately 6.7±1 Pg C are stored in the Indian sector of the Southern Ocean, giving a total Indian Ocean inventory of 20.3 ±3 Pg C for 1995. These estimates are compared to anthropogenic CO2 inventories estimated by the Princeton ocean biogeochemistry model. The model predicts an Indian Ocean sink north of 35°S that is only 0.61–0.68 times the results presented here; while the Southern Ocean sink is nearly 2.6 times higher than the measurement-based estimate. These results clearly identify areas in the models that need further examination and provide a good baseline for future studies of the anthropogenic inventory

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Global, regional, and national sex-specific burden and control of the HIV epidemic, 1990-2019, for 204 countries and territories: the Global Burden of Diseases Study 2019

Background: The sustainable development goals (SDGs) aim to end HIV/AIDS as a public health threat by 2030. Understanding the current state of the HIV epidemic and its change over time is essential to this effort. This study assesses the current sex-specific HIV burden in 204 countries and territories and measures progress in the control of the epidemic. Methods: To estimate age-specific and sex-specific trends in 48 of 204 countries, we extended the Estimation and Projection Package Age-Sex Model to also implement the spectrum paediatric model. We used this model in cases where age and sex specific HIV-seroprevalence surveys and antenatal care-clinic sentinel surveillance data were available. For the remaining 156 of 204 locations, we developed a cohort-incidence bias adjustment to derive incidence as a function of cause-of-death data from vital registration systems. The incidence was input to a custom Spectrum model. To assess progress, we measured the percentage change in incident cases and deaths between 2010 and 2019 (threshold >75% decline), the ratio of incident cases to number of people living with HIV (incidence-to-prevalence ratio threshold <0·03), and the ratio of incident cases to deaths (incidence-to-mortality ratio threshold <1·0). Findings: In 2019, there were 36·8 million (95% uncertainty interval [UI] 35·1–38·9) people living with HIV worldwide. There were 0·84 males (95% UI 0·78–0·91) per female living with HIV in 2019, 0·99 male infections (0·91–1·10) for every female infection, and 1·02 male deaths (0·95–1·10) per female death. Global progress in incident cases and deaths between 2010 and 2019 was driven by sub-Saharan Africa (with a 28·52% decrease in incident cases, 95% UI 19·58–35·43, and a 39·66% decrease in deaths, 36·49–42·36). Elsewhere, the incidence remained stable or increased, whereas deaths generally decreased. In 2019, the global incidence-to-prevalence ratio was 0·05 (95% UI 0·05–0·06) and the global incidence-to-mortality ratio was 1·94 (1·76–2·12). No regions met suggested thresholds for progress. Interpretation: Sub-Saharan Africa had both the highest HIV burden and the greatest progress between 1990 and 2019. The number of incident cases and deaths in males and females approached parity in 2019, although there remained more females with HIV than males with HIV. Globally, the HIV epidemic is far from the UNAIDS benchmarks on progress metrics. Funding: The Bill & Melinda Gates Foundation, the National Institute of Mental Health of the US National Institutes of Health (NIH), and the National Institute on Aging of the NIH

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

The OAβ1R receptor is required in peripheral neurons to interpret environmental information

In many species, chemical signals from the environment trigger a variety of possible behavioral responses by an organism including feeding, aggression, and courtship. How neurons located at the periphery receive these signals and mediate the strength of this information before sending it forward to the brain remains unclear. The neuromodulator octopamine (OA, the insect equivalent of norepinephrine) has been shown by experiments from our lab and others to be required to promote male aggression. After OA is released into the extracellular space, it must bind to its receptors to elicit a response. In order to discover how signals from the environment are interpreted to regulate the behaviors of male aggression and courtship, I am making the focus of my project to examine which types of sensory neurons express the Drosophila octopamine receptor, OAβ1R. We are using the UAS/Gal4 system, which comprises of Gal4, a transcriptional activator that binds to UAS, which is an enhancer, in order to increase transcription. We will identify neurons in the periphery that respond to water and sugar. I am removing the legs and mouth parts of males that express a fluorescent marker separately in these different neuron categories as well as expressing a fluorescent reporter for the OAβ1R receptor. I am looking for co-localization between the two markers through examination under a fluorescent microscope and have demonstrated co-localization with pickpocket28, which is a gene coding for an ion channel protein that detects water, as well as gustatory receptor 64, which is a sugar sensing neuron. These results indicate that OAβ1R neurons may be involved in detecting as well as regulating the intake of both water and sugar. Results from my collaborative project will provide necessary information regarding how environmental signals are regulated by octopamine to initiate or modify behavior in any system

Octopamine neuron dependent aggression requires dVGLUT from dual-transmitting neurons

Neuromodulators such as monoamines are often expressed in neurons that also release at least one fast-acting neurotransmitter. The release of a combination of transmitters provides both "classical" and "modulatory" signals that could produce diverse and/or complementary effects in associated circuits. Here, we establish that the majority of Drosophila octopamine (OA) neurons are also glutamatergic and identify the individual contributions of each neurotransmitter on sex-specific behaviors. Males without OA display low levels of aggression and high levels of inter-male courtship. Males deficient for dVGLUT solely in OA-glutamate neurons (OGNs) also exhibit a reduction in aggression, but without a concurrent increase in inter-male courtship. Within OGNs, a portion of VMAT and dVGLUT puncta differ in localization suggesting spatial differences in OA signaling. Our findings establish a previously undetermined role for dVGLUT in OA neurons and suggests that glutamate uncouples aggression from OA-dependent courtship-related behavior. These results indicate that dual neurotransmission can increase the efficacy of individual neurotransmitters while maintaining unique functions within a multi-functional social behavior neuronal network. Author summary Neurons communicate with each other via electrical events and the release of chemical signals. An emerging challenge in understanding neuron communication is the realization that many neurons release more than one type of chemical signal or neurotransmitter. Here we ask how does the release of more than one neurotransmitter from a single neuron impact circuits that control behavior? We determined the monoamine octopamine and the classical transmitter glutamate are co-expressed in the Drosophila adult CNS. By manipulating the release of glutamate in OA-glutamate neurons, we demonstrated glutamate has both separable actions and complementary actions with OA on aggression and reproductive behaviors respectively. Aggression is a behavior that is highly conserved between organisms and present in many human disease states, including depression and Alzheimer's disease. Our results show that aggressive behavior requires the release of both neurotransmitters in dual-transmitting neurons and suggests within this set of neurons, glutamate may provide a new therapeutic target to modulate aggression in pathological conditions