135 research outputs found
Nexus of Despair: A Network Analysis of Suicidal Ideation among Veterans
The objective of this study was to estimate a network model of risk and resilience factors of suicidal ideation among veterans. Two network models of suicidal ideation among Operation Iraqi Freedom/ Operation Enduring Freedom/Operation New Dawn veterans (N = 276) incorporated key disorders, traumatic stress, and resilience constructs to contextualize suicidal ideation. Childhood trauma was positively connected with suicidal ideation and harassment and inversely connected with social support and distress tolerance. This exemplifies long-lasting associations between childhood trauma and revictimization, emotion regulation, and ability to form supportive social relationships. A subsequent model including lower-order facets indicated that combat trauma was predominantly associated with posttraumatic stress disorder–intrusion symptoms. This study highlights the importance of addressing both risk and resilience to reduce suicide risk among veterans and increases understanding of factors that contribute to suicidal ideation
The Direct and Indirect Influences of Parenting: The Facets of Time-Perspective and Impaired Control along the Alcohol-Related Problems Pathway
Background: Social Learning Theory suggests how one conceptualizes time will be passed from parent to child (Bandura & Walters, 1963). Through the lens of Behavioral Economics Theory (Vuchinich & Simpson, 1998), impaired control may be characterized as consuming alcohol as a form of immediate gratification as a choice over more distal rewards. Because impaired control reflects a self-regulation failure specific to the drinking situation, it may be directly related to time-perspectives. Objectives: This investigation explored whether or not the indirect influences of perceived parenting styles on alcohol use and related problems is mediated by both facets of time-perspective (e.g. hedonism, present-fatalism, future, past-positive, past-negative) and impaired control over drinking. Methods: We examined a structural equation model with 391 (207 women; 184 men) college student drinkers. We used an asymmetric bias-corrected bootstrap technique to conduct mediational analyses (MacKinnon, 2008). Results: Higher levels of past-positive time-perspective were indirectly linked to both less alcohol use and fewer alcohol-related problems through less impaired control. In contrast, higher levels of present-fatalism were indirectly linked to more alcohol use through more impaired control. Higher levels of father permissiveness and mother authoritarianism were indirectly linked to both more impaired control and alcohol use through more present-fatalism. In addition, higher levels of father authoritarianism were indirectly linked to more alcohol use through more hedonism. Conclusions/Implications: Our results support the notion that drinking beyond one’s self-prescribed limits is associated with time-perspectives related to negative aspects of the parent-offspring socialization process, such as fatalism
The Lick AGN Monitoring Project 2011: Dynamical Modeling of the Broad Line Region in Mrk 50
We present dynamical modeling of the broad line region (BLR) in the Seyfert 1
galaxy Mrk 50 using reverberation mapping data taken as part of the Lick AGN
Monitoring Project (LAMP) 2011. We model the reverberation mapping data
directly, constraining the geometry and kinematics of the BLR, as well as
deriving a black hole mass estimate that does not depend on a normalizing
factor or virial coefficient. We find that the geometry of the BLR in Mrk 50 is
a nearly face-on thick disk, with a mean radius of 9.6(+1.2,-0.9) light days, a
width of the BLR of 6.9(+1.2,-1.1) light days, and a disk opening angle of
25\pm10 degrees above the plane. We also constrain the inclination angle to be
9(+7,-5) degrees, close to face-on. Finally, the black hole mass of Mrk 50 is
inferred to be log10(M(BH)/Msun) = 7.57(+0.44,-0.27). By comparison to the
virial black hole mass estimate from traditional reverberation mapping
analysis, we find the normalizing constant (virial coefficient) to be log10(f)
= 0.78(+0.44,-0.27), consistent with the commonly adopted mean value of 0.74
based on aligning the M(BH)-{\sigma}* relation for AGN and quiescent galaxies.
While our dynamical model includes the possibility of a net inflow or outflow
in the BLR, we cannot distinguish between these two scenarios.Comment: Accepted for publication in ApJ. 8 pages, 6 figure
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Related and unrelated donor transplantation for β-thalassemia major: results of an international survey.
We studied 1110 patients with β-thalassemia major aged ≤25 years who received transplants with grafts from HLA-matched related (n = 677; 61%), HLA-mismatched related (n = 78; 7%), HLA-matched unrelated (n = 252; 23%), and HLA-mismatched unrelated (n = 103; 9%) donors between 2000 and 2016. Ninety percent of transplants were performed in the last decade. Eight-five percent of patients received ≥20 transfusions and 88% were inadequately chelated. All patients received myeloablative-conditioning regimen. Overall and event-free survival were highest for patients aged ≤6 years and after HLA-matched related and HLA-matched unrelated donor transplantation. The 5-year probabilities of overall survival for patients aged ≤6 years, 7 to 15 years, and 16 to 25 years, adjusted for donor type and conditioning regimen were 90%, 84%, and 63%, respectively (P < .001). The corresponding probabilities for event-free survival were 86%, 80%, and 63% (P < .001). Overall and event-free survival did not differ between HLA-matched related and HLA-matched unrelated donor transplantation (89% vs 87% and 86% vs 82%, respectively). Corresponding probabilities after mismatched related and mismatched unrelated donor transplantation were 73% vs 83% and 70% vs 78%. In conclusion, if transplantation is considered as a treatment option it should be offered early (age ≤6 years). An HLA-matched unrelated donor is a suitable alternative if an HLA-matched relative is not available
Phosphodiesterase type 5 inhibitors enhance chemotherapy in preclinical models of esophageal adenocarcinoma by targeting cancer-associated fibroblasts
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Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model.
BACKGROUND: Pre-eclampsia is a leading cause of maternal deaths. These deaths mainly result from eclampsia, uncontrolled hypertension, or systemic inflammation. We developed and validated the fullPIERS model with the aim of identifying the risk of fatal or life-threatening complications in women with pre-eclampsia within 48 h of hospital admission for the disorder. METHODS: We developed and internally validated the fullPIERS model in a prospective, multicentre study in women who were admitted to tertiary obstetric centres with pre-eclampsia or who developed pre-eclampsia after admission. The outcome of interest was maternal mortality or other serious complications of pre-eclampsia. Routinely reported and informative variables were included in a stepwise backward elimination regression model to predict the adverse maternal outcome. We assessed performance using the area under the curve (AUC) of the receiver operating characteristic (ROC). Standard bootstrapping techniques were used to assess potential overfitting. FINDINGS: 261 of 2023 women with pre-eclampsia had adverse outcomes at any time after hospital admission (106 [5%] within 48 h of admission). Predictors of adverse maternal outcome included gestational age, chest pain or dyspnoea, oxygen saturation, platelet count, and creatinine and aspartate transaminase concentrations. The fullPIERS model predicted adverse maternal outcomes within 48 h of study eligibility (AUC ROC 0·88, 95% CI 0·84-0·92). There was no significant overfitting. fullPIERS performed well (AUC ROC >0·7) up to 7 days after eligibility. INTERPRETATION: The fullPIERS model identifies women at increased risk of adverse outcomes up to 7 days before complications arise and can thereby modify direct patient care (eg, timing of delivery, place of care), improve the design of clinical trials, and inform biomedical investigations related to pre-eclampsia. FUNDING: Canadian Institutes of Health Research; UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development, and Research Training in Human Reproduction; Preeclampsia Foundation; International Federation of Obstetricians and Gynecologists; Michael Smith Foundation for Health Research; and Child and Family Research Institute
MPLEx: a method for simultaneous pathogen inactivation and extraction of samples for multi-omics profiling
The continued emergence and spread of infectious agents is of great concern, and systems biology approaches to infectious disease research can advance our understanding of host–pathogen relationships and facilitate the development of new therapies and vaccines
Crime among irregular immigrants and the influence of internal border control
Both the number of crime suspects without legal status and the number of irregular or undocumented immigrants held in detention facilities increased substantially in theNetherlands between 1997 and 2003. In this period, theDutch state increasingly attempted to exclude irregular immigrants from the formal labour market and public provisions. At the same time the registered crime among irregular migrants rose. The 'marginalisation thesis' asserts that a larger number of migrants have become involved in crime in response to a decrease in conventional life chances. Using police and administrative data, the present study takes four alternative interpretations into consideration based on: 1) reclassification of immigrant statuses by the state and redefinition of the law, 2) criminal migration and crossborder crime, 3) changes in policing, and 4) demographic changes. A combination of factors is found to have caused the rise in crime, but the marginalisation thesis still accounts for at least 28%. These findings accentuate the need for a more thorough discussion on the intended and unintended consequences of border control for immigrant crime
Hydrogen-Deuterium Exchange Mass Spectrometry (HDX-MS) Centroid Data Measured between 3.6 degrees C and 25.4 degrees C for the Fab Fragment of NISTmAb
Expanding the clinical phenotype of IARS2-related mitochondrial disease.
BACKGROUND: IARS2 encodes a mitochondrial isoleucyl-tRNA synthetase, a highly conserved nuclear-encoded enzyme required for the charging of tRNAs with their cognate amino acid for translation. Recently, pathogenic IARS2 variants have been identified in a number of patients presenting broad clinical phenotypes with autosomal recessive inheritance. These phenotypes range from Leigh and West syndrome to a new syndrome abbreviated CAGSSS that is characterised by cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, as well as cataract with no additional anomalies. METHODS: Genomic DNA from Iranian probands from two families with consanguineous parental background and overlapping CAGSSS features were subjected to exome sequencing and bioinformatics analysis. RESULTS: Exome sequencing and data analysis revealed a novel homozygous missense variant (c.2625C > T, p.Pro909Ser, NM_018060.3) within a 14.3 Mb run of homozygosity in proband 1 and a novel homozygous missense variant (c.2282A > G, p.His761Arg) residing in an ~ 8 Mb region of homozygosity in a proband of the second family. Patient-derived fibroblasts from proband 1 showed normal respiratory chain enzyme activity, as well as unchanged oxidative phosphorylation protein subunits and IARS2 levels. Homology modelling of the known and novel amino acid residue substitutions in IARS2 provided insight into the possible consequence of these variants on function and structure of the protein. CONCLUSIONS: This study further expands the phenotypic spectrum of IARS2 pathogenic variants to include two patients (patients 2 and 3) with cataract and skeletal dysplasia and no other features of CAGSSS to the possible presentation of the defects in IARS2. Additionally, this study suggests that adult patients with CAGSSS may manifest central adrenal insufficiency and type II esophageal achalasia and proposes that a variable sensorineural hearing loss onset, proportionate short stature, polyneuropathy, and mild dysmorphic features are possible, as seen in patient 1. Our findings support that even though biallelic IARS2 pathogenic variants can result in a distinctive, clinically recognisable phenotype in humans, it can also show a wide range of clinical presentation from severe pediatric neurological disorders of Leigh and West syndrome to both non-syndromic cataract and cataract accompanied by skeletal dysplasia
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