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  1. George C, Yesoda A, Jayakumar B, Lal L
    J Clin Pharm Ther, 2009 Feb;34(1):33-40.
    PMID: 19125901 DOI: 10.1111/j.1365-2710.2008.00988.x
    This prospective, observational, study evaluates the clinical outcomes, drug utilization patterns, and adherence to treatment of patients on highly active anti retroviral therapy (HAART) at a government institution in Kerala, India.
  2. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2017;77(5):294.
    PMID: 28579921 DOI: 10.1140/epjc/s10052-017-4787-8
    A search for new phenomena is performed in final states containing one or more jets and an imbalance in transverse momentum in pp collisions at a centre-of-mass energy of 13[Formula: see text]. The analysed data sample, recorded with the CMS detector at the CERN LHC, corresponds to an integrated luminosity of 2.3[Formula: see text]. Several kinematic variables are employed to suppress the dominant background, multijet production, as well as to discriminate between other standard model and new physics processes. The search provides sensitivity to a broad range of new-physics models that yield a stable weakly interacting massive particle. The number of observed candidate events is found to agree with the expected contributions from standard model processes, and the result is interpreted in the mass parameter space of fourteen simplified supersymmetric models that assume the pair production of gluinos or squarks and a range of decay modes. For models that assume gluino pair production, masses up to 1575 and 975[Formula: see text] are excluded for gluinos and neutralinos, respectively. For models involving the pair production of top squarks and compressed mass spectra, top squark masses up to 400[Formula: see text] are excluded.
  3. George CR, O'Neill BJ, Garth JM
    Med J Aust, 1971 May 22;1(21):1110-3.
    PMID: 4932319
  4. Haagsma JA, James SL, Castle CD, Dingels ZV, Fox JT, Hamilton EB, et al.
    Inj Prev, 2020 Oct;26(Supp 1):i12-i26.
    PMID: 31915273 DOI: 10.1136/injuryprev-2019-043296
    BACKGROUND: The epidemiological transition of non-communicable diseases replacing infectious diseases as the main contributors to disease burden has been well documented in global health literature. Less focus, however, has been given to the relationship between sociodemographic changes and injury. The aim of this study was to examine the association between disability-adjusted life years (DALYs) from injury for 195 countries and territories at different levels along the development spectrum between 1990 and 2017 based on the Global Burden of Disease (GBD) 2017 estimates.

    METHODS: Injury mortality was estimated using the GBD mortality database, corrections for garbage coding and CODEm-the cause of death ensemble modelling tool. Morbidity estimation was based on surveys and inpatient and outpatient data sets for 30 cause-of-injury with 47 nature-of-injury categories each. The Socio-demographic Index (SDI) is a composite indicator that includes lagged income per capita, average educational attainment over age 15 years and total fertility rate.

    RESULTS: For many causes of injury, age-standardised DALY rates declined with increasing SDI, although road injury, interpersonal violence and self-harm did not follow this pattern. Particularly for self-harm opposing patterns were observed in regions with similar SDI levels. For road injuries, this effect was less pronounced.

    CONCLUSIONS: The overall global pattern is that of declining injury burden with increasing SDI. However, not all injuries follow this pattern, which suggests multiple underlying mechanisms influencing injury DALYs. There is a need for a detailed understanding of these patterns to help to inform national and global efforts to address injury-related health outcomes across the development spectrum.

  5. Global Burden of Disease Child and Adolescent Health Collaboration, Kassebaum N, Kyu HH, Zoeckler L, Olsen HE, Thomas K, et al.
    JAMA Pediatr, 2017 Jun 01;171(6):573-592.
    PMID: 28384795 DOI: 10.1001/jamapediatrics.2017.0250
    IMPORTANCE: Comprehensive and timely monitoring of disease burden in all age groups, including children and adolescents, is essential for improving population health.

    OBJECTIVE: To quantify and describe levels and trends of mortality and nonfatal health outcomes among children and adolescents from 1990 to 2015 to provide a framework for policy discussion.

    EVIDENCE REVIEW: Cause-specific mortality and nonfatal health outcomes were analyzed for 195 countries and territories by age group, sex, and year from 1990 to 2015 using standardized approaches for data processing and statistical modeling, with subsequent analysis of the findings to describe levels and trends across geography and time among children and adolescents 19 years or younger. A composite indicator of income, education, and fertility was developed (Socio-demographic Index [SDI]) for each geographic unit and year, which evaluates the historical association between SDI and health loss.

    FINDINGS: Global child and adolescent mortality decreased from 14.18 million (95% uncertainty interval [UI], 14.09 million to 14.28 million) deaths in 1990 to 7.26 million (95% UI, 7.14 million to 7.39 million) deaths in 2015, but progress has been unevenly distributed. Countries with a lower SDI had a larger proportion of mortality burden (75%) in 2015 than was the case in 1990 (61%). Most deaths in 2015 occurred in South Asia and sub-Saharan Africa. Global trends were driven by reductions in mortality owing to infectious, nutritional, and neonatal disorders, which in the aggregate led to a relative increase in the importance of noncommunicable diseases and injuries in explaining global disease burden. The absolute burden of disability in children and adolescents increased 4.3% (95% UI, 3.1%-5.6%) from 1990 to 2015, with much of the increase owing to population growth and improved survival for children and adolescents to older ages. Other than infectious conditions, many top causes of disability are associated with long-term sequelae of conditions present at birth (eg, neonatal disorders, congenital birth defects, and hemoglobinopathies) and complications of a variety of infections and nutritional deficiencies. Anemia, developmental intellectual disability, hearing loss, epilepsy, and vision loss are important contributors to childhood disability that can arise from multiple causes. Maternal and reproductive health remains a key cause of disease burden in adolescent females, especially in lower-SDI countries. In low-SDI countries, mortality is the primary driver of health loss for children and adolescents, whereas disability predominates in higher-SDI locations; the specific pattern of epidemiological transition varies across diseases and injuries.

    CONCLUSIONS AND RELEVANCE: Consistent international attention and investment have led to sustained improvements in causes of health loss among children and adolescents in many countries, although progress has been uneven. The persistence of infectious diseases in some countries, coupled with ongoing epidemiologic transition to injuries and noncommunicable diseases, require all countries to carefully evaluate and implement appropriate strategies to maximize the health of their children and adolescents and for the international community to carefully consider which elements of child and adolescent health should be monitored.

  6. Abdul-Razak S, Azzopardi PS, Patton GC, Mokdad AH, Sawyer SM
    J Adolesc Health, 2017 Oct;61(4):424-433.
    PMID: 28838752 DOI: 10.1016/j.jadohealth.2017.05.014
    PURPOSE: A rapid epidemiological transition in developing countries in Southeast Asia has been accompanied by major shifts in the health status of children and adolescents. In this article, mortality estimates in Malaysian children and adolescents from 1990 to 2013 are used to illustrate these changes.

    METHODS: All-cause and cause-specific mortality estimates were obtained from the 2013 Global Burden of Disease Study. Data were extracted from 1990 to 2013 for the developmental age range from 1 to 24 years, for both sexes. Trends in all-cause and cause-specific mortality for the major epidemiological causes were estimated.

    RESULTS: From 1990 to 2013, all-cause mortality decreased in all age groups. Reduction of all-cause mortality was greatest in 1- to 4-year-olds (2.4% per year reduction) and least in 20- to 24-year-olds (.9% per year reduction). Accordingly, in 2013, all-cause mortality was highest in 20- to 24-year-old males (129 per 100,000 per year). In 1990, the principal cause of death for 1- to 9-year boys and girls was vaccine preventable diseases. By 2013, neoplasms had become the major cause of death in 1-9 year olds of both sexes. The major cause of death in 10- to 24-year-old females was typhoid in 1990 and neoplasms in 2013, whereas the major cause of death in 10- to 24-year-old males remained road traffic injuries.

    CONCLUSIONS: The reduction in mortality across the epidemiological transition in Malaysia has been much less pronounced for adolescents than younger children. The contribution of injuries and noncommunicable diseases to adolescent mortality suggests where public health strategies should focus.

  7. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, et al.
    Eur Phys J C Part Fields, 2015 06 26;75(6):288.
    PMID: 26146483
    The inclusive jet cross section for proton-proton collisions at a centre-of-mass energy of 7[Formula: see text] was measured by the CMS Collaboration at the LHC with data corresponding to an integrated luminosity of 5.0[Formula: see text]. The measurement covers a phase space up to 2[Formula: see text] in jet transverse momentum and 2.5 in absolute jet rapidity. The statistical precision of these data leads to stringent constraints on the parton distribution functions of the proton. The data provide important input for the gluon density at high fractions of the proton momentum and for the strong coupling constant at large energy scales. Using predictions from perturbative quantum chromodynamics at next-to-leading order, complemented with electroweak corrections, the constraining power of these data is investigated and the strong coupling constant at the Z boson mass [Formula: see text] is determined to be [Formula: see text], which is in agreement with the world average.
  8. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, et al.
    Eur Phys J C Part Fields, 2015 07 17;75(7):325.
    PMID: 26213486
    Stringent limits are set on the long-lived lepton-like sector of the phenomenological minimal supersymmetric standard model (pMSSM) and the anomaly-mediated supersymmetry breaking (AMSB) model. The limits are derived from the results presented in a recent search for long-lived charged particles in proton-proton collisions, based on data collected by the CMS detector at a centre-of-mass energy of 8 TeV at the Large Hadron Collider. In the pMSSM parameter sub-space considered, 95.9 % of the points predicting charginos with a lifetime of at least 10 ns are excluded. These constraints on the pMSSM are the first obtained at the LHC. Charginos with a lifetime greater than 100 ns and masses up to about 800 GeV in the AMSB model are also excluded. The method described can also be used to set constraints on other models.
  9. GBD 2017 Child and Adolescent Health Collaborators, Reiner RC, Olsen HE, Ikeda CT, Echko MM, Ballestreros KE, et al.
    JAMA Pediatr, 2019 06 01;173(6):e190337.
    PMID: 31034019 DOI: 10.1001/jamapediatrics.2019.0337
    Importance: Understanding causes and correlates of health loss among children and adolescents can identify areas of success, stagnation, and emerging threats and thereby facilitate effective improvement strategies.

    Objective: To estimate mortality and morbidity in children and adolescents from 1990 to 2017 by age and sex in 195 countries and territories.

    Design, Setting, and Participants: This study examined levels, trends, and spatiotemporal patterns of cause-specific mortality and nonfatal health outcomes using standardized approaches to data processing and statistical analysis. It also describes epidemiologic transitions by evaluating historical associations between disease indicators and the Socio-Demographic Index (SDI), a composite indicator of income, educational attainment, and fertility. Data collected from 1990 to 2017 on children and adolescents from birth through 19 years of age in 195 countries and territories were assessed. Data analysis occurred from January 2018 to August 2018.

    Exposures: Being under the age of 20 years between 1990 and 2017.

    Main Outcomes and Measures: Death and disability. All-cause and cause-specific deaths, disability-adjusted life years, years of life lost, and years of life lived with disability.

    Results: Child and adolescent deaths decreased 51.7% from 13.77 million (95% uncertainty interval [UI], 13.60-13.93 million) in 1990 to 6.64 million (95% UI, 6.44-6.87 million) in 2017, but in 2017, aggregate disability increased 4.7% to a total of 145 million (95% UI, 107-190 million) years lived with disability globally. Progress was uneven, and inequity increased, with low-SDI and low-middle-SDI locations experiencing 82.2% (95% UI, 81.6%-82.9%) of deaths, up from 70.9% (95% UI, 70.4%-71.4%) in 1990. The leading disaggregated causes of disability-adjusted life years in 2017 in the low-SDI quintile were neonatal disorders, lower respiratory infections, diarrhea, malaria, and congenital birth defects, whereas neonatal disorders, congenital birth defects, headache, dermatitis, and anxiety were highest-ranked in the high-SDI quintile.

    Conclusions and Relevance: Mortality reductions over this 27-year period mean that children are more likely than ever to reach their 20th birthdays. The concomitant expansion of nonfatal health loss and epidemiological transition in children and adolescents, especially in low-SDI and middle-SDI countries, has the potential to increase already overburdened health systems, will affect the human capital potential of societies, and may influence the trajectory of socioeconomic development. Continued monitoring of child and adolescent health loss is crucial to sustain the progress of the past 27 years.

  10. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, et al.
    Eur Phys J C Part Fields, 2015 07 01;75(7):302.
    PMID: 26190937
    This paper presents distributions of topological observables in inclusive three- and four-jet events produced in pp collisions at a centre-of-mass energy of 7[Formula: see text] with a data sample collected by the CMS experiment corresponding to a luminosity of 5.1[Formula: see text]. The distributions are corrected for detector effects, and compared with several event generators based on two- and multi-parton matrix elements at leading order. Among the considered calculations, MadGraph interfaced with pythia6 displays the overall best agreement with data.
  11. Gopalakrishna G, Langendam M, Scholten R, Bossuyt P, Leeflang M, Noel-Storr A, et al.
    Diagn Progn Res, 2017;1:11.
    PMID: 31095132 DOI: 10.1186/s41512-017-0011-4
    [This corrects the article DOI: 10.1186/s41512-016-0001-y.].
  12. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2016 03 17;76:155.
    PMID: 27471433
    New sets of parameters ("tunes") for the underlying-event (UE) modelling of the pythia8, pythia6 and herwig++ Monte Carlo event generators are constructed using different parton distribution functions. Combined fits to CMS UE proton-proton ([Formula: see text]) data at [Formula: see text] and to UE proton-antiproton ([Formula: see text]) data from the CDF experiment at lower [Formula: see text], are used to study the UE models and constrain their parameters, providing thereby improved predictions for proton-proton collisions at 13[Formula: see text]. In addition, it is investigated whether the values of the parameters obtained from fits to UE observables are consistent with the values determined from fitting observables sensitive to double-parton scattering processes. Finally, comparisons are presented of the UE tunes to "minimum bias" (MB) events, multijet, and Drell-Yan ([Formula: see text] lepton-antilepton+jets) observables at 7 and 8[Formula: see text], as well as predictions for MB and UE observables at 13[Formula: see text].
  13. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2016;76(6):325.
    PMID: 28280439 DOI: 10.1140/epjc/s10052-016-4156-z
    A measurement of the forward-backward asymmetry [Formula: see text] of oppositely charged lepton pairs ([Formula: see text] and [Formula: see text]) produced via [Formula: see text] boson exchange in pp collisions at [Formula: see text] [Formula: see text] is presented. The data sample corresponds to an integrated luminosity of 19.7[Formula: see text] collected with the CMS detector at the LHC. The measurement of [Formula: see text] is performed for dilepton masses between 40[Formula: see text] and 2[Formula: see text] and for dilepton rapidity up to 5. The [Formula: see text] measurements as a function of dilepton mass and rapidity are compared with the standard model predictions.
  14. Global Burden of Disease 2016 Injury Collaborators, Naghavi M, Marczak LB, Kutz M, Shackelford KA, Arora M, et al.
    JAMA, 2018 Aug 28;320(8):792-814.
    PMID: 30167700 DOI: 10.1001/jama.2018.10060
    IMPORTANCE: Understanding global variation in firearm mortality rates could guide prevention policies and interventions.

    OBJECTIVE: To estimate mortality due to firearm injury deaths from 1990 to 2016 in 195 countries and territories.

    DESIGN, SETTING, AND PARTICIPANTS: This study used deidentified aggregated data including 13 812 location-years of vital registration data to generate estimates of levels and rates of death by age-sex-year-location. The proportion of suicides in which a firearm was the lethal means was combined with an estimate of per capita gun ownership in a revised proxy measure used to evaluate the relationship between availability or access to firearms and firearm injury deaths.

    EXPOSURES: Firearm ownership and access.

    MAIN OUTCOMES AND MEASURES: Cause-specific deaths by age, sex, location, and year.

    RESULTS: Worldwide, it was estimated that 251 000 (95% uncertainty interval [UI], 195 000-276 000) people died from firearm injuries in 2016, with 6 countries (Brazil, United States, Mexico, Colombia, Venezuela, and Guatemala) accounting for 50.5% (95% UI, 42.2%-54.8%) of those deaths. In 1990, there were an estimated 209 000 (95% UI, 172 000 to 235 000) deaths from firearm injuries. Globally, the majority of firearm injury deaths in 2016 were homicides (64.0% [95% UI, 54.2%-68.0%]; absolute value, 161 000 deaths [95% UI, 107 000-182 000]); additionally, 27% were firearm suicide deaths (67 500 [95% UI, 55 400-84 100]) and 9% were unintentional firearm deaths (23 000 [95% UI, 18 200-24 800]). From 1990 to 2016, there was no significant decrease in the estimated global age-standardized firearm homicide rate (-0.2% [95% UI, -0.8% to 0.2%]). Firearm suicide rates decreased globally at an annualized rate of 1.6% (95% UI, 1.1-2.0), but in 124 of 195 countries and territories included in this study, these levels were either constant or significant increases were estimated. There was an annualized decrease of 0.9% (95% UI, 0.5%-1.3%) in the global rate of age-standardized firearm deaths from 1990 to 2016. Aggregate firearm injury deaths in 2016 were highest among persons aged 20 to 24 years (for men, an estimated 34 700 deaths [95% UI, 24 900-39 700] and for women, an estimated 3580 deaths [95% UI, 2810-4210]). Estimates of the number of firearms by country were associated with higher rates of firearm suicide (P 

  15. Global Burden of Disease Pediatrics Collaboration, Kyu HH, Pinho C, Wagner JA, Brown JC, Bertozzi-Villa A, et al.
    JAMA Pediatr, 2016 Mar;170(3):267-87.
    PMID: 26810619 DOI: 10.1001/jamapediatrics.2015.4276
    IMPORTANCE: The literature focuses on mortality among children younger than 5 years. Comparable information on nonfatal health outcomes among these children and the fatal and nonfatal burden of diseases and injuries among older children and adolescents is scarce.

    OBJECTIVE: To determine levels and trends in the fatal and nonfatal burden of diseases and injuries among younger children (aged <5 years), older children (aged 5-9 years), and adolescents (aged 10-19 years) between 1990 and 2013 in 188 countries from the Global Burden of Disease (GBD) 2013 study.

    EVIDENCE REVIEW: Data from vital registration, verbal autopsy studies, maternal and child death surveillance, and other sources covering 14,244 site-years (ie, years of cause of death data by geography) from 1980 through 2013 were used to estimate cause-specific mortality. Data from 35,620 epidemiological sources were used to estimate the prevalence of the diseases and sequelae in the GBD 2013 study. Cause-specific mortality for most causes was estimated using the Cause of Death Ensemble Model strategy. For some infectious diseases (eg, HIV infection/AIDS, measles, hepatitis B) where the disease process is complex or the cause of death data were insufficient or unavailable, we used natural history models. For most nonfatal health outcomes, DisMod-MR 2.0, a Bayesian metaregression tool, was used to meta-analyze the epidemiological data to generate prevalence estimates.

    FINDINGS: Of the 7.7 (95% uncertainty interval [UI], 7.4-8.1) million deaths among children and adolescents globally in 2013, 6.28 million occurred among younger children, 0.48 million among older children, and 0.97 million among adolescents. In 2013, the leading causes of death were lower respiratory tract infections among younger children (905.059 deaths; 95% UI, 810,304-998,125), diarrheal diseases among older children (38,325 deaths; 95% UI, 30,365-47,678), and road injuries among adolescents (115,186 deaths; 95% UI, 105,185-124,870). Iron deficiency anemia was the leading cause of years lived with disability among children and adolescents, affecting 619 (95% UI, 618-621) million in 2013. Large between-country variations exist in mortality from leading causes among children and adolescents. Countries with rapid declines in all-cause mortality between 1990 and 2013 also experienced large declines in most leading causes of death, whereas countries with the slowest declines had stagnant or increasing trends in the leading causes of death. In 2013, Nigeria had a 12% global share of deaths from lower respiratory tract infections and a 38% global share of deaths from malaria. India had 33% of the world's deaths from neonatal encephalopathy. Half of the world's diarrheal deaths among children and adolescents occurred in just 5 countries: India, Democratic Republic of the Congo, Pakistan, Nigeria, and Ethiopia.

    CONCLUSIONS AND RELEVANCE: Understanding the levels and trends of the leading causes of death and disability among children and adolescents is critical to guide investment and inform policies. Monitoring these trends over time is also key to understanding where interventions are having an impact. Proven interventions exist to prevent or treat the leading causes of unnecessary death and disability among children and adolescents. The findings presented here show that these are underused and give guidance to policy makers in countries where more attention is needed.

  16. James SL, Castle CD, Dingels ZV, Fox JT, Hamilton EB, Liu Z, et al.
    Inj Prev, 2020 10;26(Supp 1):i96-i114.
    PMID: 32332142 DOI: 10.1136/injuryprev-2019-043494
    BACKGROUND: Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries.

    METHODS: We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs).

    FINDINGS: In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505).

    INTERPRETATION: Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.

  17. Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2018 Feb 16;120(7):071802.
    PMID: 29542941 DOI: 10.1103/PhysRevLett.120.071802
    An inclusive search for the standard model Higgs boson (H) produced with large transverse momentum (p_{T}) and decaying to a bottom quark-antiquark pair (bb[over ¯]) is performed using a data set of pp collisions at sqrt[s]=13  TeV collected with the CMS experiment at the LHC. The data sample corresponds to an integrated luminosity of 35.9  fb^{-1}. A highly Lorentz-boosted Higgs boson decaying to bb[over ¯] is reconstructed as a single, large radius jet, and it is identified using jet substructure and dedicated b tagging techniques. The method is validated with Z→bb[over ¯] decays. The Z→bb[over ¯] process is observed for the first time in the single-jet topology with a local significance of 5.1 standard deviations (5.8 expected). For a Higgs boson mass of 125 GeV, an excess of events above the expected background is observed (expected) with a local significance of 1.5 (0.7) standard deviations. The measured cross section times branching fraction for production via gluon fusion of H→bb[over ¯] with reconstructed p_{T}>450  GeV and in the pseudorapidity range -2.5
  18. Jusof FF, Bakmiwewa SM, Weiser S, Too LK, Metz R, Prendergast GC, et al.
    Int J Tryptophan Res, 2017;10:1178646917735098.
    PMID: 29051706 DOI: 10.1177/1178646917735098
    Indoleamine 2,3-dioxygenase-2 (IDO2) is 1 of the 3 enzymes that can catalyze the first step in the kynurenine pathway of tryptophan metabolism. Of the 2 other enzymes, tryptophan 2,3-dioxygenase is highly expressed in the liver and has a role in tryptophan homeostasis, whereas indoleamine 2,3-dioxygenase-1 (IDO1) expression is induced by inflammatory stimuli. Indoleamine 2,3-dioxygenase-2 is reportedly expressed comparatively narrow, including in liver, kidney, brain, and in certain immune cell types, and it does not appear to contribute significantly to systemic tryptophan catabolism under normal physiological conditions. Here, we report the identification of an alternative splicing pattern, including the use of an alternative first exon, that is conserved in the mouse Ido1 and Ido2 genes. These findings prompted us to assess IDO2 protein expression and enzymatic activity in tissues. Our analysis, undertaken in Ido2( +/+) and Ido2(-/-) mice using immunohistochemistry and measurement of tryptophan and kynurenine levels, suggested an even more restricted pattern of tissue expression than previously reported. We found IDO2 protein to be expressed in the liver with a perinuclear/nuclear, rather than cytoplasmic, distribution. Consistent with earlier reports, we found Ido2 (-/-) mice to be phenotypically similar to their Ido2(+/+) counterparts regarding levels of tryptophan and kynurenine in the plasma and liver. Our findings suggest a specialized function or regulatory role for IDO2 associated with its particular subcellular localization.
  19. Haeuser E, Serfes AL, Cork MA, Yang M, Abbastabar H, Abhilash ES, et al.
    BMC Med, 2022 Dec 19;20(1):488.
    PMID: 36529768 DOI: 10.1186/s12916-022-02639-z
    BACKGROUND: Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15-59 years across SSA.

    METHODS: We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units.

    RESULTS: We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group.

    CONCLUSIONS: As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA.

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