2,177 research outputs found

    Development of a Retrospective Measure of Child Abuse for Heterosexual and LGBTQ Mexican Adults

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    Child abuse is a phenomenon that affects a large proportion of the world’s population and has important effects on their mental health. Although several instruments exist to measure it, they present some difficulties that require improvement. The present study started from an instrument previously developed for Mexican population (Esparza-Del Villar et al., Journal of Interpersonal Violence, 2020) to construct a new retrospective measure of abuse: the Child Abuse Scale for Adults (EAIA, Spanish initials). We worked with a total sample of 810 individuals, consisting mainly of women (> 70%) and young adults (mean age around 23 years). We conducted both traditional (exploratory and confirmatory factor analysis) and advanced (exploratory graph analysis, item response theory) procedures to obtain a short self-report measure of child abuse experiences. The EAIA evidenced a clear factor structure (CFI = .96, RSMEA = .06), as well as adequate reliability for its three subscales: sexual (ω = .91), physical (ω = .88) and emotional abuse (ω = .93). In addition, it showed partial scalar invariance between sexes. At the item level, it was observed that the items of the sexual and physical abuse subscales had greater informative capacity at high levels of maltreatment, while the items of the emotional abuse subscale showed better psychometric quality at average levels of the construct. Finally, associations were found in the expected direction between the three subscales of the EAIA and a set of psychopathological variables (depression, anxiety and suicidal ideation). In conclusion, the EAIA constitutes a promising alternative to retrospectively measure child abuse in the Mexican adult population

    Water sufficiency for cacao production in the Sierra Nevada de Santa Marta (SNSM) region, Colombia

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    Study region: Sierra Nevada de Santa Marta (SNSM) region of Colombia. Study focus: This research was conducted as a case study to generate relevant, quantitative information to support cacao farmer decision-making processes concerning water management in the SNSM. It involved the development and evaluation of a spatial dataset of precipitation and temperature, integration of digital soil mapping with a modification of the Thornthwaite and Mather water balance model, and finally an assessment of water sufficiency for cacao production. We elaborated site-specific and spatially-distributed analyses to generate information that will be shared with technicians who assist cacao growers in the SNSM. New hydrological insights for the region: Under the climate conditions for the analysis period (1989–2018), rainfall was not enough to prevent cacao yield losses for 10 out of the 27 farms evaluated. The location of farms in two departments with contrasting climate conditions showed the importance of spatial analysis of water availability when providing recommendations of management practices to cacao growers. The results revealed that farms facing less frequent water stress are characterized by higher rainfalls and lower temperatures, soils that contain more organic matter, and are located at higher elevations with steeper slopes. Temporally, water stress is highest in the months February-August, with special interest in March-April as the dry season ends and July-August just before the peak rainy season

    PanDrugs: a novel method to prioritize anticancer drug treatments according to individual genomic data

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    BACKGROUND: Large-sequencing cancer genome projects have shown that tumors have thousands of molecular alterations and their frequency is highly heterogeneous. In such scenarios, physicians and oncologists routinely face lists of cancer genomic alterations where only a minority of them are relevant biomarkers to drive clinical decision-making. For this reason, the medical community agrees on the urgent need of methodologies to establish the relevance of tumor alterations, assisting in genomic profile interpretation, and, more importantly, to prioritize those that could be clinically actionable for cancer therapy. RESULTS: We present PanDrugs, a new computational methodology to guide the selection of personalized treatments in cancer patients using the variant lists provided by genome-wide sequencing analyses. PanDrugs offers the largest database of drug-target associations available from well-known targeted therapies to preclinical drugs. Scoring data-driven gene cancer relevance and drug feasibility PanDrugs interprets genomic alterations and provides a prioritized evidence-based list of anticancer therapies. Our tool represents the first drug prescription strategy applying a rational based on pathway context, multi-gene markers impact and information provided by functional experiments. Our approach has been systematically applied to TCGA patients and successfully validated in a cancer case study with a xenograft mouse model demonstrating its utility. CONCLUSIONS: PanDrugs is a feasible method to identify potentially druggable molecular alterations and prioritize drugs to facilitate the interpretation of genomic landscape and clinical decision-making in cancer patients. Our approach expands the search of druggable genomic alterations from the concept of cancer driver genes to the druggable pathway context extending anticancer therapeutic options beyond already known cancer genes. The methodology is public and easily integratable with custom pipelines through its programmatic API or its docker image. The PanDrugs webtool is freely accessible at http://www.pandrugs.org .The authors thank Joaquín Dopazo, Patricia León, and José Carbonell for kindly providing the modelled pathways employed in PanDrugs implementation; and Michael Tress for his helpful comments and suggestions in the earlier version of the manuscript.S

    Distinct DNA methylomes of newborns and centenarians

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    Human aging cannot be fully understood in terms of the constrained genetic setting. Epigenetic drift is an alternative means of explaining age-associated alterations. To address this issue, we performed whole-genome bisulfite sequencing (WGBS) of newborn and centenarian genomes. The centenarian DNA had a lower DNA methylation content and a reduced correlation in the methylation status of neighboring cytosine--phosphate--guanine (CpGs) throughout the genome in comparison with the more homogeneously methylated newborn DNA. The more hypomethylated CpGs observed in the centenarian DNA compared with the neonate covered all genomic compartments, such as promoters, exonic, intronic, and intergenic regions. For regulatory regions, the most hypomethylated sequences in the centenarian DNA were present mainly at CpG-poor promoters and in tissue-specific genes, whereas a greater level of DNA methylation was observed in CpG island promoters. We extended the study to a larger cohort of newborn and nonagenarian samples using a 450,000 CpG-site DNA methylation microarray that reinforced the observation of more hypomethylated DNA sequences in the advanced age group. WGBS and 450,000 analyses of middle-age individuals demonstrated DNA methylomes in the crossroad between the newborn and the nonagenarian/centenarian groups. Our study constitutes a unique DNA methylation analysis of the extreme points of human life at a single-nucleotide resolution level

    Seafloor Morphology and Processes in the Alboran Sea

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    The seafloor of the Alboran Sea reflects its complex tectonic, sedimentary, and oceanography dynamics as a consequence of the geological context, involving interaction between the Eurasian and African plates, and oceanographic context, as it is where the Atlantic and Mediterranean waters meet. Their physiography has a semi-enclosed configuration characterized by two margins (the Spanish Iberian and North Africa—mostly Moroccan margins) enclosing deep basins. Tectonic activity is mainly attested by folds and faults that predominantly affect the central and eastern seafloor sectors, as well as numerous seamounts and fluid-flow features (pockmarks, mud volcanoes, and diapirs) that dot the seafloor. The sedimentary and oceanographic processes allow us to distinctly define two principal environments in the Alboran Sea: the shallow proximal margin (continental shelf); and the deep distal margin (continental slope and base of the slope) with the adjacent sub-basins. The shelf mostly comprises prodeltaic and infralittoral prograding wedges, with local bedform fields, submarine valleys, and wave-cut terraces. Coastal and fluvio-marine sedimentary processes, acting since the last glacial period, are responsible for these features. The deep marine environment is characterised by the ubiquity of contourites, whose continuity is interrupted by turbidite systems, canyons, and landslides. The alongslope action of the Mediterranean waters and their interfaces with the Atlantic water has been the main process governing transport, seafloor reworking, and sedimentation of contourites. Mass-movement processes are responsible for the formation of: (1) turbidite systems—turbidity flows and mass flows were dominant during the last glacial sea-level lowstand, evolving to dilute gravity flows during present interglacial high stand; and (2) landslides—the main triggering factors comprising over-steepening, seismicity, under consolidation due to overpressure by interstitial fluids, stratigraphy, and high sedimentation rates. Locally, still-undetermined biological activity in the Spanish and coral activity in the Moroccan margin generated fields of mounded bioconstructions. The seafloor morphology of the Alboran Sea offers interesting clues for assessing the main potential geological hazards, with tectonic seismicity and landslides (as well as their related tsunamis) being some of the most important potential hazards affecting coastal populations. In addition, the seafloor morphology in combination with assemblages of habitat-forming species enables habitat identification and mapping.En prens

    DNA Methylation Profiles and Their Relationship with Cytogenetic Status in Adult Acute Myeloid Leukemia

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    Background: Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML) pathophysiology. However, further studies to discuss the prognostic value and the relationship of the epigenetic signatures with defined genomic rearrangements in acute myeloid leukemia are required. Methodology/Principal Findings: We carried out high-throughput methylation profiling on 116 de novo AML cases and we validated the significant biomarkers in an independent cohort of 244 AML cases. Methylation signatures were associated with the presence of a specific cytogenetic status. In normal karyotype cases, aberrant methylation of the promoter of DBC1 was validated as a predictor of the disease-free and overall survival. Furthermore, DBC1 expression was significantly silenced in the aberrantly methylated samples. Patients with chromosome rearrangements showed distinct methylation signatures. To establish the role of fusion proteins in the epigenetic profiles, 20 additional samples of human hematopoietic stem/ progenitor cells (HSPC) transduced with common fusion genes were studied and compared with patient samples carrying the same rearrangements. The presence of MLL rearrangements in HSPC induced the methylation profile observed in the MLL-positive primary samples. In contrast, fusion genes such as AML1/ETO or CBFB/MYH11 failed to reproduce the epigenetic signature observed in the patients. Conclusions/Significance: Our study provides a comprehensive epigenetic profiling of AML, identifies new clinical markers for cases with a normal karyotype, and reveals relevant biological information related to the role of fusion proteins on the methylation signatur

    Infusion reactions after receiving the broadly neutralizing antibody VRC01 or placebo to reduce HIV-1 acquisition : results from the Phase 2b antibody-mediated prevention randomized trials

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    Presented at Conference for Retroviruses and Opportunistic Infections; March 06–10, 2021.BACKGROUND : The antibody-mediated prevention (AMP) studies (HVTN 703/HPTN 081 and HVTN 704/HPTN 085) are harmonized phase 2b trials to assess HIV prevention efficacy and safety of intravenous infusion of anti-gp120 broadly neutralizing antibody VRC01. Antibodies for other indications can elicit infusion-related reactions (IRRs), often requiring premedication and limiting their application. We report on AMP study IRRs. METHODS : From 2016 to 2018, 2699 HIV-uninfected, at-risk men and transgender adults in the Americas and Switzerland (704/085) and 1924 at-risk heterosexual women in sub-Saharan Africa (703/081) were randomized 1:1:1 to VRC01 10 mg/kg, 30 mg/kg, or placebo. Participants received infusions every 8 weeks (n = 10/participant) over 72 weeks, with 104 weeks of follow-up. Safety assessments were conducted before and after infusion and at noninfusion visits. A total of 40,674 infusions were administered. RESULTS : Forty-seven participants (1.7%) experienced 49 IRRs in 704/085; 93 (4.8%) experienced 111 IRRs in 703/081 (P < 0.001). IRRs occurred more frequently in VRC01 than placebo recipients in 703/081 (P < 0.001). IRRs were associated with atopic history (P = 0.046) and with younger age (P = 0.023) in 703/081. Four clinical phenotypes of IRRs were observed: urticaria, dyspnea, dyspnea with rash, and “other.” Urticaria was most prevalent, occurring in 25 (0.9%) participants in 704/085 and 41 (2.1%) participants in 703/081. Most IRRs occurred with the initial infusion and incidence diminished through the last infusion. All reactions were managed successfully without sequelae. CONCLUSIONS : IRRs in the AMP studies were uncommon, typically mild or moderate, successfully managed at the research clinic, and resolved without sequelae. Analysis is ongoing to explore potential IRR mechanisms.Clinical trial funding from Janssen Vaccines.http://www.jaids.comhj2023School of Health Systems and Public Health (SHSPH

    Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

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    This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

    Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

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    One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI
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