Previous research suggests that various types of childhood maltreatment frequently co-occur and confer risk for attempting suicide. However, it is unknown whether the effect of childhood maltreatment ...on this risk occurs through diverse, specific mechanisms or through a generalized liability, independently of psychopathology. Although these competing explanations have different implications for intervention, they have never been evaluated empirically.
Structural equation modeling was used to examine the effect of different types of childhood maltreatment (ie, sexual abuse, physical and emotional abuse and neglect) on suicide attempt risk, and on age at first suicide attempt and repeated suicide attempts among attempters. Analyses controlled for demographic characteristics and DSM-IV Axis I and Axis II disorders. Data were drawn from a nationally representative survey of US adults, the 2004-2005 National Epidemiologic Survey on Alcohol and Related Conditions (N = 34,653).
Childhood maltreatment was associated with an increased risk for attempting suicide and an earlier age at first suicide attempt among attempters, independently of psychopathology (P < .005). These associations operated mainly through the latent variable representing effects shared by the different types of childhood maltreatment, although sexual abuse had an additional, direct effect on the risk of suicide attempt. Childhood maltreatment types were not significantly associated with a history of multiple suicide attempts (all P values > .05).
The association between childhood maltreatment and suicide attempt operates mainly through a single broad liability, suggesting that the mechanisms underlying this dimension should be considered as an important therapeutic target for suicide prevention.
Mucinous ovarian tumors are an unusual group of rare neoplasms with an apparently clear progression from benign to borderline to carcinoma, yet with a controversial cell of origin in the ovarian ...surface epithelium. They are thought to be molecularly distinct from other ovarian tumors but there have been no exome-level sequencing studies performed to date.
To understand the genetic etiology of mucinous ovarian tumors and assess the presence of novel therapeutic targets or pathways, we undertook exome sequencing of 24 tumors encompassing benign (5), borderline (8) and carcinoma (11) histologies and also assessed a validation cohort of 58 tumors for specific gene regions including exons 4-9 of TP53.
The predominant mutational signature was of C>T transitions in a NpCpG context, indicative of deamination of methyl-cytosines. As well as mutations in known drivers (KRAS, BRAF and CDKN2A), we identified a high percentage of carcinomas with TP53 mutations (52 %), and recurrent mutations in RNF43, ELF3, GNAS, ERBB3 and KLF5.
The diversity of mutational targets suggests multiple routes to tumorigenesis in this heterogeneous group of tumors that is generally distinct from other ovarian subtypes.
A battery has normally a high energy density with low power density, while an ultracapacitor has a high power density but a low energy density. Therefore, this paper has been proposed to associate ...more than one storage technology generating a hybrid energy storage system (HESS), which has battery and ultracapacitor, whose objective is to improve the electric vehicle (EV) driving range. The HESS parameters have been evaluated in a configuration of EV powered by two in-wheel electric motors, coupled straight into the front wheels, and by a unique EM, connected to a differential transmission to drive the rear wheels. Moreover, this paper considers a real-world drive cycle based on the urban driving behavior of Campinas city, one of the most populous cities in Brazil. Aiming to minimize the HESS size and enhance the EV driving range, an optimization problem was formulated and solved using a genetic algorithm technique, in which the EV drivetrain parameters and HESS components and control are optimized. Finally, the obtained Pareto frontier defines the optimum EV configurations, in which the best-selected configurations were able to perform up to 188 km with a 418 kg HESS (maximum drive range solution), or 82.75 km with a 146.58 kg HESS (minimum HESS solution) and 319 km with a 188.43 kg HESS (best trade-off solution), without presenting performance losses.
The influence of left ventricular outflow tract obstruction on the clinical outcome of hypertrophic cardiomyopathy remains unresolved.
We assessed the effect of outflow tract obstruction on morbidity ...and mortality in a large cohort of patients with hypertrophic cardiomyopathy who were followed for a mean (+/-SD) of 6.3+/-6.2 years.
Of the 1101 consecutive patients, 273 (25 percent) had obstruction of left ventricular outflow under basal (resting) conditions with a peak instantaneous gradient of at least 30 mm Hg. A total of 127 patients (12 percent) died of hypertrophic cardiomyopathy, and 216 surviving patients (20 percent) had severe, disabling symptoms of progressive heart failure (New York Heart Association NYHA functional class III or IV). The overall probability of death related to hypertrophic cardiomyopathy was significantly greater among patients with outflow tract obstruction than among those without obstruction (relative risk, 2.0; P=0.001). The risk of progression to NYHA class III or IV or death specifically from heart failure or stroke was also greater among patients with obstruction (relative risk, 4.4; P<0.001), particularly among patients 40 years of age or older (P<0.001). Age-adjusted multivariate analysis confirmed that outflow tract obstruction was independently associated with an increased risk of both death related to hypertrophic cardiomyopathy (relative risk, 1.6; P=0.02) and progression to NYHA class III or IV or death from heart failure or stroke (relative risk, 2.7; P<0.001). The likelihood of severe symptoms and death related to outflow tract obstruction did not increase as the gradient increased above the threshold of 30 mm Hg.
In patients with hypertrophic cardiomyopathy, left ventricular outflow tract obstruction at rest is a strong, independent predictor of progression to severe symptoms of heart failure and of death.
This article develops a model of a forest owner operating in a small, open-city environment where the rent for developed land is increasing concave in nearby preserved open space and is rising over ...time, reflecting an upward trend in households' income. Within this framework we examine how changes in nearby preserved open space and alternative development constraints affect an individual private landowner's decisions regarding both regeneration harvests and conversion dates. We also examine how such policies affect development density once conversion from forestry to residential use occurs. We show that when residential rents change over time, the nature of the timber problem at the urban-forest interface changes because it forces us to allow for the possibility of changes in land use from timber to residential use. As a result, the traditional Faustmann setup is not suitable to study forest management decisions at this interface. We also find that in the presence of rising income, increases in permanently preserved open space hasten regeneration and conversion cuts of a neighboring parcel currently under forest use and leads to lower density development once conversion takes place compared to the case where income is constant. We also find that both a binding development moratorium and a binding minimum-lot-size policy can postpone regeneration and conversion cut dates and thus help to protect open space, even if only temporarily. However, the policies do not have the same effects on development density of converted forestland. While the former leads to high-density development, the latter encourages low-density development.
Prostate cancer develops through a stochastic mechanism whereby precancerous lesions on occasion progress to multifocal adenocarcinoma. Analysis of human benign and cancer prostate tissues revealed ...heterogeneous loss of TGF-β signaling in the cancer-associated stromal fibroblastic cell compartment. To test the hypothesis that prostate cancer progression is dependent on the heterogeneous TGF-β responsive microenvironment, a tissue recombination experiment was designed in which the ratio of TGF-β responsive and nonresponsive stromal cells was varied. Although 100% TGF-β responsive stromal cells supported benign prostate growth and 100% TGF-β nonresponsive stromal cells resulted in precancerous lesions, only the mixture of TGF-β responsive and nonresponsive stromal cells resulted in adenocarcinoma. A computational model was used to resolve a mechanism of tumorigenic progression in which proliferation and invasion occur in two independent steps mediated by distinct stromally derived paracrine signals produced by TGF-β nonresponsive and responsive stromal cells. Complex spatial relationships of stromal and epithelial cells were incorporated into the model on the basis of experimental data. Informed by incorporation of experimentally derived spatial parameters for complex stromal-epithelial relationships, the computational model indicated ranges for the relative production of paracrine factors by each cell type and provided bounds for the diffusive range of the molecules. Because SDF-1 satisfied model predictions for an invasion-promoting paracrine factor, a more focused computational model was subsequently used to investigate whether SDF-1 was the invasion signal. Simulations replicating SDF-1 expression data revealed the requirement for cooperative SDF-1 expression, a prediction supported biologically by heterotypic stromal interleukin-1β signaling between fibroblastic cell populations. The cancer stromal field effect supports a functional role for the unaltered fibroblasts as a cooperative mediator of cancer progression.
Postoperative cognitive decline (pCD) occurs frequently (6 to 30%) after carotid endarterectomy (CEA), although there are no exact estimates and risk factors are still unclear.
The objective of this ...study was to determine pCD incidence and risk factors in CEA patients.
We performed a systematic review and meta-analysis of both randomised and nonrandomised trials following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
We searched Cochrane, PubMed/Medline and Embase databases from the date of database inception to 1 December 2018.
We selected longitudinal studies including CEA patients with both pre-operative and postoperative cognitive assessments. Primary outcome was pCD incidence, differentiating delayed neurocognitive recovery (dNCR) and postoperative neurocognitive disorder (pNCD). dNCR and pNCD incidences were expressed as proportions of cases on total CEA sample and pooled as weighted estimates from proportions. Postoperative delirium was excluded from the study design. Secondary outcomes were patient-related (i.e. age, sex, diabetes, hypertension, contralateral stenosis, pre-operative symptoms, dyslipidaemia and statin use) and procedure-related (i.e. hyperperfusion, cross-clamping duration and shunting placement) risk factors for pCD. We estimated odds ratios (ORs) and mean differences through a random effects model by using STATA 13.1 and RevMan 5.3.
Our search identified 5311 publications and 60 studies met inclusion criteria reporting a total of 4823 CEA patients. dNCR and pNCD incidence were 20.5% 95% confidence interval (CI), 17.1 to 24.0 and 14.1% (95% CI, 9.5 to 18.6), respectively. pCD risk was higher in patients experiencing hyperperfusion during surgery (OR, 35.68; 95% CI, 16.64 to 76.51; P < 0.00001; I = 0%), whereas dNCR risk was lower in patients taking statins before surgery (OR, 0.56; 95% CI, 0.41 to 0.77; P = 0.0004; I = 19%). Sensitivity analysis revealed that longer cross-clamping duration was a predictor for dNCR (mean difference, 5.25 min; 95% CI, 0.87 to 9.63; P = 0.02; I = 49%).
We found high incidences of dNCR (20.5%) and pNCD (14.1%) after CEA. Hyperperfusion seems to be a risk factor for pCD, whereas the use of statins is associated with a lower risk of dNCR. An increased cross-clamping duration could be a risk factor for dNCR.
This systematic review was registered in the International Prospective Register of Systematic Reviews (CDR42017073633).
Neuroimaging research seeks to identify biomarkers to improve the diagnosis, prognosis, and treatment of attention-deficit/hyperactivity disorder (ADHD), although clinical translation of findings ...remains distant. Resting-state functional magnetic resonance imaging (R-fMRI) is increasingly being used to characterize functional connectivity in the brain. Despite mixed results to date and multiple methodological challenges, dominant hypotheses implicate hyperconnectivity across brain networks in patients with ADHD, which could be the target of pharmacological treatments. We describe the experience and results of the Clínica Universidad de Navarra (Spain) Metilfenidato (CUNMET) pilot study. CUNMET tested the feasibility of identifying R-fMRI markers of clinical response in children with ADHD undergoing naturalistical pharmacological treatments. We analyzed cross-sectional data from 56 patients with ADHD (18 treated with methylphenidate, 18 treated with lisdexamfetamine, and 20 treatment-naive patients). Standard preprocessing and statistical analyses with attention to control for head motion and correction for multiple comparisons were performed. The only results that survived correction were noted in contrasts of children who responded clinically to lisdexamfetamine after long-term treatment vs. treatment-naive patients. In these children, we observed stronger negative correlations (anticorrelations) across nodes in six brain networks, which is consistent with higher across-network functional segregation in patients treated with lisdexamfetamine, i.e., less inter-network interference than in treatment-naive patients. We also note the lessons learned, which could help those pursuing clinically relevant multidisciplinary research in ADHD en route to eventual personalized medicine. To advance reproducible open science, our report is accompanied with links providing access to our data and analytic scripts.
Background
Hematopoietic cell transplantation (HCT) outcomes, including infectious complications, change between centers and countries. Thus, the aim of this study was to report the incidence of ...infections and isolated pathogens among recipients of HCT and the association with mortality at a tertiary referral center in Mexico.
Methods
Two hundred and eighty‐two patients undergoing autologous or allogeneic HCT between January 2005 and December 2018 at the National Institute of Medical Sciences and Nutricion Salvador Zubiran were included.
Results
In autologous HCT (n = 176), within the preengraftment and the early postengraftment, 130 (74%) and 31 (18%) recipients presented infections, respectively. Within the preengraftment, the early postengraftment, and the late postengraftment, 81 (76%), 34 (33%), and 58 (60%) allogeneic HCT recipients presented infections, respectively. Non‐relapse mortality (NRM) as a result of infections occurred in 1 (0.6%) and 5 (5%) autologous and allogeneic HCT recipients, respectively.
Conclusions
Our results demonstrated that despite our limited resources, infections were not a significant burden for NRM among HCT recipients. More importantly, the isolation rates were higher than international studies, which could be explained by the existence of a specialized infectious diseases department and laboratory, which we consider key elements for the establishment of an HCT program worldwide.
Background and Objectives
During the Coronavirus disease 19 (COVID-19) pandemic, isolation and prevention measures to reduce COVID-19 contagions are essential for the care of all people; these ...measures should comply with the principles of inclusion and accessibility for people with disabilities (PWD), with all kinds of deficiencies and levels of dependency. Thereby, the aim of this article is to present the measures adopted for PWD or people with rehabilitation needs, for containment, mitigation, or suppression of the SARS-CoV-2 virus in different countries of all continents and of all income levels.
Methods
A narrative approach was used in this article. First, a broad search was carried out in the 193 member states of the UN, and then 98 countries that issued any document, report, or information related to disability and COVID-19 were selected. Finally, 32 countries were included in this article because they presented official information. We considered official sources, the information available in the government, or on the health ministry page of the country. In this way, the countries that presented information which did not correspond to an official source were excluded. The search was conducted in August 2020 and updated in March 2021.
Results
First, the non-pharmacological general interventions for PWD included informative measures and general recommendations during the stay at home, isolation, and biosecurity measures, contagion prevention, detection of positive cases, mobilization measures, and measures implemented in institutions or residences of PWD. Second, we identified the economic and social benefits provided to PWD during the pandemic. Finally, we identified the measures taken by countries according to the type of impairment (visual, hearing, physical, mental, and cardiopulmonary impairment) during the COVID-19 pandemic.
Conclusion
In response to the COVID-19 pandemic, only 50% of countries from the five world regions created and implemented specific measures for PWD to containment, mitigation, or suppression of the SARS-CoV-2 virus. There is very little specific information available about the measures to continue with the care of people with rehabilitation needs and the long-term follow-up of PWD, and for the prevention and response to violence, especially for women with disabilities.
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