AIDS-associated Kaposi's sarcoma is linked to advanced disease and high mortality in a primary care HIV programme in South Africa

BACKGROUND: AIDS-associated Kaposi's sarcoma is an important, life-threatening opportunistic infection among people living with HIV/AIDS in resource-limited settings. In western countries, the introduction of combination antiretroviral therapy (cART) and new chemotherapeutic agents has resulted in decreased incidence and improved prognosis of AIDS-associated Kaposi's sarcoma. In African cohorts, however, mortality remains high. In this study, we describe disease characteristics and risk factors for mortality in a public sector HIV programme in South Africa. METHODS: We analysed data from an observational cohort study of HIV-infected adults with AIDS-associated Kaposi's sarcoma, enrolled between May 2001 and January 2007 in three primary care clinics. Paper records from primary care and tertiary hospital oncology clinics were reviewed to determine the site of Kaposi's sarcoma lesions, immune reconstitution inflammatory syndrome stage, and treatment. Baseline characteristics, cART use and survival outcomes were extracted from an electronic database maintained for routine monitoring and evaluation. Cox regression was used to model associations with mortality. RESULTS: Of 6292 patients, 215 (3.4%) had AIDS-associated Kaposi's sarcoma. Lesions were most commonly oral (65%) and on the lower extremities (56%). One quarter of patients did not receive cART. The mortality and lost-to-follow-up rates were, respectively, 25 (95% CI 19-32) and eight (95% CI 5-13) per 100 person years for patients who received cART, and 70 (95% CI 42-117) and 119 (80-176) per 100 person years for patients who did not receive cART. Advanced T stage (adjusted HR, AHR = 5.3, p < 0.001), advanced S stage (AHR = 5.1, p = 0.008), and absence of chemotherapy (AHR = 2.4, p = 0.012) were associated with mortality.Patients with AIDS-associated Kaposi's sarcoma presented with advanced disease and high rates of mortality and loss to follow up. Risk factors for mortality included advanced Kaposi's sarcoma disease and lack of chemotherapy use. Contributing factors to the high mortality for patients with AIDS-associated Kaposi's sarcoma likely included late diagnosis of HIV disease, late accessibility to cART, and sub-optimal treatment of advanced Kaposi's sarcoma. CONCLUSIONS: These findings confirm the importance of early access to both cART and chemotherapy for patients with AIDS-associated Kaposi's sarcoma. Early diagnosis and improved treatment protocols in resource-poor settings are essential

Safety Outcomes During Pediatric GH Therapy : Final Results From the Prospective GeNeSIS Observational Program

Altres ajuts: Financial Support: GeNeSIS was sponsored by Eli Lilly and Company (Indianapolis, IN). In compliance with the Uniform Requirements for Manuscripts, established by the International Committee of Medical Journal Editors, the sponsor of this study did not impose any impediment, directly or indirectly, on the publication of the study's results. Disclosure Summary: C.J.C. and N.J. are employees and stockholders ofEliLilly and Company (Indianapolis, IN).W.F.B. and A.G.Z. are former employees and are stockholders of Lilly. C.L.D., T.H., M.M., and R.G.R. are former members of the GeNeSIS International Advisory Board; S.L., J.P.S., A.R.-U., and M.P. have served as regional advisors. B.P. has consulted for Eli Lilly Italia SpA, and E.C. has received grant support from Lilly. W.F.B. also reports heis aconsultant forAmmonett Pharma,Lilly Germany, and Merck KGaA Darmstadt. C.L.D. also reports receipt of grants, consultancy honoraria, and speaker fees from Lilly,EMD Serono, and Sandoz; grants fromOpko Prolor, Pfizer, and Versatis; honoraria and speaker fees from Roche; honoraria from Pfizer; and speaker fees from Novo Nordisk. The remaining authors have nothing to disclose.Safety concerns have been raised regarding premature mortality, diabetes, neoplasia, and cerebrovascular disease in association with GH therapy. To assess incidence of key safety outcomes. Prospective, multinational, observational study (1999 to 2015). A total of 22,311 GH-treated children from 827 investigative sites in 30 countries. Children with growth disorders. GH treatment. Standardized mortality ratio (SMR) and standardized incidence ratio (SIR) with 95% CIs for mortality, diabetes, and primary cancer using general population registries. Predominant short stature diagnoses were GH deficiency (63%), idiopathic short stature (13%), and Turner syndrome (8%), with mean ± SD follow-up of 4.2 ± 3.2 years (∼92,000 person-years [PY]). Forty-two deaths occurred in patients with follow-up, with an SMR (95% CI) of 0.61 (0.44, 0.82); the SMR was elevated for patients with cancer-related organic GH deficiency [5.87 (3.21, 9.85)]. Based on 18 cases, type 2 diabetes mellitus (T2DM) risk was elevated [SIR: 3.77 (2.24, 5.96)], but 72% had risk factors. In patients without cancer history, 14 primary cancers were observed [SIR: 0.71 (0.39, 1.20)]. Second neoplasms occurred in 31 of 622 cancer survivors [5.0%; 10.7 (7.5, 15.2) cases/1000 PY] and intracranial tumor recurrences in 67 of 823 tumor survivors [8.1%; 16.9 (13.3, 21.5) cases/1000 PY]. All three hemorrhagic stroke cases had risk factors. GeNeSIS (Genetics and Neuroendocrinology of Short Stature International Study) data support the favorable safety profile of pediatric GH treatment. Overall risk of death or primary cancer was not elevated in GH-treated children, and no hemorrhagic strokes occurred in patients without risk factors. T2DM incidence was elevated compared with the general population, but most cases had diabetes risk factors. Safety of GH therapy was assessed in a pediatric observational study. Death and primary cancer rates were not higher than in the general population; T2DM rate was higher owing to risk factors

A long section of depleted mantle peridotite

Comunicación oral presentada en The 7th Orogenic Lherzolite Meeting, del 30 de septiembre al 6 de octubre de 2024, celebrado en Oviedo (España)The depleted mantle is a principal component of the upper mantle and drives significant volcanism. However, our knowledge of the depleted mantle has remained limited due to its severely restricted accessibility, with only local exposure of abyssal peridotites along slow- and ultraslow-spreading mid-ocean ridges and transform faults. Although abyssal peridotites have yielded important insights into mantle composition and melting, the vast majority of these rocks have been obtained by dredging. Hence, they lack the context, spatial continuity, and orientation information critical for understanding a range of processes, including the spatial scale of compositional variations, melt migration and mantle flow. As a result, many properties of the depleted mantle have been inferred from the study of its melting products: mid-ocean ridge basalts. Here, we report the recovery of a long (1268 m) section of serpentinized abyssal mantle peridotite, interleaved with thin gabbroic intrusions, from Atlantis Massif (Mid-Atlantic Ridge) during IODP Expedition 399. The nearly continuous recovery in the principal hole (U1601C) provides an opportunity to obtain a robust and quantitative lithological, mineralogical, and structural inventory of the upper mantle. The peridotites are dominated by harzburgite (82%; Fig. 1), with significant dunite (18%); lherzolite is rare, as are ultramafic veins (wehrlite, orthopyroxenite, (olivine) websterite). Mineralogically and geochemically, the peridotites are depleted: harzburgites have low orthopyroxene content (average 15.9%) and often lack clinopyroxene altogether. Geochemically, the peridotites have high MgO/SiO2 and low Al2O3/SiO2, falling on the depleted end of the array defined by global mantle rocks. Orthopyroxene abundance varies significantly on scales ranging from the centimeter to hundreds of meters, forming a continuum from 0-30%. Dunite occurs as zones in harzburgite and, more frequently, in orthopyroxene-bearing dunite, and are typically tens of centimeters thick. Contacts between dunite and the surrounding peridotites are nearly always gradational, and well-defined dunite zones are an endmember of a continuum of variations in orthopyroxene content in the mantle rocks, with the full spectrum of harzburgite to dunite preserved in the core. We posit that the observed variations in mineralogy and therefore lithology are controlled by melt migration and the associated dissolution of orthopyroxene and precipitation of olivine, superimposed on the residues of relatively high degrees of melting. The geometry of melt flow is captured by the orientation of the dunite zones. Harzburgite-dunite contacts have predominantly intermediate dips and record a ~40° discordance with the mantle fabrics. This is consistent with the formation of a network of dunite channels with variable but predominantly intermediate dips oblique to mantle upwelling as a result of melt focusing toward the ridge axis. Going forward, the comprehensive rock record obtained during Expedition 399 provides a wealth of opportunities to make fundamental advances on our understanding of the oceanic upper mantle. This includes a determination of mantle heterogeneity on the centimeter to kilometer scale and investigations of the role of previous depletion in governing mantle composition and melting. The continuous nature of the core, and its re-orientation, will also be instrumental in studies of spatial variations in melting and melt transport, as well as research into mantle flow and the associated deformation mechanisms

Pediatric malignancies presenting as a possible infectious disease

<p>Abstract</p> <p>Background</p> <p>The clinical, laboratory, and radiological features of malignancy can overlap with those of infection. The purpose of this study was to determine the findings in children who were initially thought to have an infectious disease but ultimately proved to have a malignancy.</p> <p>Methods</p> <p>The database of patients diagnosed with a malignancy in the Northern Alberta Children's Cancer Program (NACCP) January 1, 1993 to December 31, 2003 was merged with the database of inpatients referred to the infectious diseases service at the Stollery Children's Hospital and charts were reviewed on all patients referred to the infectious diseases consult service prior to the diagnosis of malignancy.</p> <p>Results</p> <p>An infectious diseases consultation for diagnosis was requested in 21 of 561 patients prior to the confirmation of malignancy, and 3 of these 21 patients had both infection and malignancy (leukemia (N = 13), lymphoma (N = 3), rhabdomyosarcoma (N = 1), Langerhan's cell histiocytosis (N = 1), fibrous histicocytosis (N = 1), ependymoma (N = 1), and neuroblastoma (N = 1). The most common reason for infectious diseases consultation was suspected muskuloskeletal infection (N = 9). A palpable or radiographically enlarged spleen was noted in 11 patients (52%). All but 2 patients had abnormal hematologic parameters while an elevated lactate dehydrogenase (LDH) occurred in 10 patients (48%). Delay of diagnosis because of investigation or therapy for an infectious disease occurred in only 2 patients.</p> <p>Conclusion</p> <p>It is not common for treatment of pediatric malignancies to be delayed because infection is thought to be the primary diagnosis. However, pediatric infectious diseases physicians should consider malignancy in the differential diagnosis when they see patients with fever and bone pain, unexplained splenomegaly or abnormal complete blood cell counts. Other clues may include hepatomegaly or elevated LDH.</p

Prevalence of adolescent mental disorders in Kenya, Indonesia, and Viet Nam measured by the National Adolescent Mental Health Surveys (NAMHS):a multi-national cross-sectional study

BackgroundMental disorders are the leading global cause of health burden among adolescents. However, prevalence data for mental disorders among adolescents in low-income and middle-income countries are scarce with often limited generalisability. This study aimed to generate nationally representative prevalence estimates for mental disorders in adolescents in Kenya, Indonesia, and Viet Nam.MethodsAs part of the National Adolescent Mental Health Surveys (NAMHS), a multinational cross-sectional study, nationally representative household surveys were conducted in Kenya, Indonesia, and Viet Nam between March and December, 2021. Adolescents aged 10–17 years and their primary caregiver were interviewed from households selected randomly according to sampling frames specifically designed to elicit nationally representative results. Six mental disorders (social phobia, generalised anxiety disorder, major depressive disorder, post-traumatic stress disorder, conduct disorder, and attention-deficit hyperactivity disorder) were assessed with the Diagnostic Interview Schedule for Children, Version 5. Suicidal behaviours and self-harm in the past 12 months were also assessed. Prevalence in the past 12 months and past 4 weeks was calculated for each mental disorder and collectively for any mental disorder (ie, of the six mental disorders assessed). Prevalence of suicidal behaviours (ie, ideation, planning, and attempt) and self-harm in the past 12 months was calculated, along with adjusted odds ratios (aORs) to show the association with prevalence of any mental disorder in the past 12 months. Inverse probability weighting was applied to generate national estimates with corresponding 95% CIs.FindingsFinal samples consisted of 5155 households (ie, adolescent and primary caregiver pairs) from Kenya, 5664 households from Indonesia, and 5996 households from Viet Nam. In Kenya, 2416 (46·9%) adolescents were male and 2739 (53·1%) were female; in Indonesia, 2803 (49·5%) adolescents were male and 2861 (50·5%) were female; and in Viet Nam, 3151 (52·5%) were male and 2845 (47·4%) were female. Prevalence of any mental disorder in the past 12 months was 12·1% (95% CI 10·9–13·5) in Kenya, 5·5% (4·3–6·9) in Indonesia, and 3·3% (2·7–4·1) in Viet Nam. Prevalence in the past 4 weeks was 9·4% (8·3–10·6) in Kenya, 4·4% (3·4–5·6) in Indonesia, and 2·7% (2·2–3·3) in Viet Nam. The prevalence of suicidal behaviours in the past 12 months was low in all three countries, with suicide ideation ranging from 1·4% in Indonesia (1·0–2·0) and Viet Nam (1·0–1·9) to 4·6% (3·9–5·3) in Kenya, suicide planning ranging from 0·4% in Indonesia (0·3–0·8) and Viet Nam (0·2–0·6) to 2·4% (1·9–2·9) in Kenya, and suicide attempts ranging from 0·2% in Indonesia (0·1–0·4) and Viet Nam (0·1–0·3) to 1·0% (0·7–1·4) in Kenya. The prevalence of self-harm in the past 12 months was also low in all three countries, ranging from 0·9% (0·6–1·3) in Indonesia to 1·2% (0·9–1·7) in Kenya. However, the prevalence of suicidal behaviours and self-harm in the past 12 months was significantly higher among those with any mental disorder in the past 12 months than those without (eg, aORs for suicidal ideation ranged from 7·1 [3·1–15·9] in Indonesia to 14·7 [7·5–28·6] in Viet Nam).InterpretationNAMHS provides the first national adolescent mental disorders prevalence estimates for Kenya, Indonesia, and Viet Nam. These data can inform mental health and broader health policies in low-income and middle-income countries.FundingThe University of Queensland in America (TUQIA) through support from Pivotal Ventures, a Melinda French Gates company. Previous article in issu

Preliminary Target Selection for the DESI Milky Way Survey (MWS)

International audienceThe DESI Milky Way Survey (MWS) will observe $\ge$8 million stars between $16 < r < 19$ mag, supplemented by observations of brighter targets under poor observing conditions. The survey will permit an accurate determination of stellar kinematics and population gradients; characterize diffuse substructure in the thick disk and stellar halo; enable the discovery of extremely metal-poor stars and other rare stellar types; and improve constraints on the Galaxy's 3D dark matter distribution from halo star kinematics. MWS will also enable a detailed characterization of the stellar populations within 100 pc of the Sun, including a complete census of white dwarfs. The target catalog from the preliminary selection described here is public

Man against machine reloaded : performance of a market-approved convolutional neural network in classifying a broad spectrum of skin lesions in comparison with 96 dermatologists working under less artificial conditions

Copyright © 2019 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.Background: Convolutional neural networks (CNNs) efficiently differentiate skin lesions by image analysis. Studies comparing a market-approved CNN in a broad range of diagnoses to dermatologists working under less artificial conditions are lacking. Materials and methods: One hundred cases of pigmented/non-pigmented skin cancers and benign lesions were used for a two-level reader study in 96 dermatologists (level I: dermoscopy only; level II: clinical close-up images, dermoscopy, and textual information). Additionally, dermoscopic images were classified by a CNN approved for the European market as a medical device (Moleanalyzer Pro, FotoFinder Systems, Bad Birnbach, Germany). Primary endpoints were the sensitivity and specificity of the CNN's dichotomous classification in comparison with the dermatologists’ management decisions. Secondary endpoints included the dermatologists’ diagnostic decisions, their performance according to their level of experience, and the CNN's area under the curve (AUC) of receiver operating characteristics (ROC). Results: The CNN revealed a sensitivity, specificity, and ROC AUC with corresponding 95% confidence intervals (CI) of 95.0% (95% CI 83.5% to 98.6%), 76.7% (95% CI 64.6% to 85.6%), and 0.918 (95% CI 0.866–0.970), respectively. In level I, the dermatologists’ management decisions showed a mean sensitivity and specificity of 89.0% (95% CI 87.4% to 90.6%) and 80.7% (95% CI 78.8% to 82.6%). With level II information, the sensitivity significantly improved to 94.1% (95% CI 93.1% to 95.1%; P < 0.001), while the specificity remained unchanged at 80.4% (95% CI 78.4% to 82.4%; P = 0.97). When fixing the CNN's specificity at the mean specificity of the dermatologists’ management decision in level II (80.4%), the CNN's sensitivity was almost equal to that of human raters, at 95% (95% CI 83.5% to 98.6%) versus 94.1% (95% CI 93.1% to 95.1%); P = 0.1. In contrast, dermatologists were outperformed by the CNN in their level I management decisions and level I and II diagnostic decisions. More experienced dermatologists frequently surpassed the CNN's performance. Conclusions: Under less artificial conditions and in a broader spectrum of diagnoses, the CNN and most dermatologists performed on the same level. Dermatologists are trained to integrate information from a range of sources rendering comparative studies that are solely based on one single case image inadequate.publishersversionPeer reviewe

Optimization of the Observing Cadence for the Rubin Observatory Legacy Survey of Space and Time: A Pioneering Process of Community-focused Experimental Design

© 2021. The Author(s). Published by the American Astronomical Society. This work may be used under the terms of the Creative Commons Attribution 4.0 licence. https://creativecommons.org/licenses/by/4.0/Vera C. Rubin Observatory is a ground-based astronomical facility under construction, a joint project of the National Science Foundation and the U.S. Department of Energy, designed to conduct a multipurpose 10 yr optical survey of the Southern Hemisphere sky: the Legacy Survey of Space and Time. Significant flexibility in survey strategy remains within the constraints imposed by the core science goals of probing dark energy and dark matter, cataloging the solar system, exploring the transient optical sky, and mapping the Milky Way. The survey’s massive data throughput will be transformational for many other astrophysics domains and Rubin’s data access policy sets the stage for a huge community of potential users. To ensure that the survey science potential is maximized while serving as broad a community as possible, Rubin Observatory has involved the scientific community at large in the process of setting and refining the details of the observing strategy. The motivation, history, and decision-making process of this strategy optimization are detailed in this paper, giving context to the science-driven proposals and recommendations for the survey strategy included in this Focus Issue.Peer reviewedFinal Published versio

Vaccine Platforms Combining Circumsporozoite Protein and Potent Immune Modulators, rEA or EAT-2, Paradoxically Result in Opposing Immune Responses

Malaria greatly impacts the health and wellbeing of over half of the world's population. Promising malaria vaccine candidates have attempted to induce adaptive immune responses to Circumsporozoite (CS) protein. Despite the inclusion of potent adjuvants, these vaccines have limited protective efficacy. Conventional recombinant adenovirus (rAd) based vaccines expressing CS protein can induce CS protein specific immune responses, but these are essentially equivalent to those generated after use of the CS protein subunit based vaccines. In this study we combined the use of rAds expressing CS protein along with rAds expressing novel innate immune response modulating proteins in an attempt to significantly improve the induction of CS protein specific cell mediated immune (CMI) responses.BALB/cJ mice were co-vaccinated with a rAd vectors expressing CS protein simultaneous with a rAd expressing either TLR agonist (rEA) or SLAM receptors adaptor protein (EAT-2). Paradoxically, expression of the TLR agonist uncovered a potent immunosuppressive activity inherent to the combined expression of the CS protein and rEA. Fortunately, use of the rAd vaccine expressing EAT-2 circumvented CS protein's suppressive activity, and generated a fivefold increase in the number of CS protein responsive, IFNγ secreting splenocytes, as well as increased the breadth of T cells responsive to peptides present in the CS protein. These improvements were positively correlated with the induction of a fourfold improvement in CS protein specific CTL functional activity in vivo.Our results emphasize the need for caution when incorporating CS protein into malaria vaccine platforms expressing or containing other immunostimulatory compounds, as the immunological outcomes may be unanticipated and/or counter-productive. However, expressing the SLAM receptors derived signaling adaptor EAT-2 at the same time of vaccination with CS protein can overcome these concerns, as well as significantly improve the induction of malaria antigen specific adaptive immune responses in vivo