Miracle-dz/UniFAR-FTUs huggingface dataset:
Paralimbic and lateral prefrontal encoding of reward value during intertemporal choice in attempted suicide

Background Alongside impulsive suicide attempts, clinicians encounter highly premeditated suicidal acts, particularly in older adults. We have previously found that in contrast to the more impulsive suicide attempters’ inability to delay gratification, serious and highly planned suicide attempts were associated with greater willingness to wait for larger rewards. This study examined neural underpinnings of intertemporal preference in suicide attempters. We expected that impulsivity and suicide attempts, particularly poorly planned ones, would predict altered paralimbic subjective value representations. We also examined lateral prefrontal and paralimbic correlates of premeditation in suicidal behavior. Method A total of 48 participants aged 46–90 years underwent extensive clinical and cognitive characterization and completed the delay discounting task in the scanner: 26 individuals with major depression (13 with and 13 without history of suicide attempts) and 22 healthy controls. Results More impulsive individuals displayed greater activation in the precuneus/posterior cingulate cortex (PCC) to value difference favoring the delayed option. Suicide attempts, particularly better-planned ones, were associated with deactivation of the lateral prefrontal cortex (lPFC) in response to value difference favoring the immediate option. Findings were robust to medication exposure, depression severity and possible brain damage from suicide attempts, among other confounders. Finally, in suicide attempters longer reward delays were associated with diminished parahippocampal responses. Conclusions Impulsivity was associated with an altered paralimbic (precuneus/PCC) encoding of value difference during intertemporal choice. By contrast, better-planned suicidal acts were associated with altered lPFC representations of value difference. The study provides preliminary evidence of impaired decision processes in both impulsive and premeditated suicidal behavior.
Mastering Each New Direction (MEND): A Biopsychosocial Intervention for Pediatric Chronic Illness

It is estimated that 30% of all school-aged children suffer from some form of chronic illness (Pai & Ostendorf, 2011). Unfortunately, compared to the general population, children with chronic illness experience multiple stressors such as painful treatments, uncomfortable side effects of treatment, disruptions in social and academic schedules, and changes in the systemic functioning of their families (Rolland, 1994; Sexson & Madan-Swain, 1993). Together these stressors lead to these children having twice the rate of psychological, developmental, and educational problems (Weiland, Pless, & Roghmann, 1992). For these children, a crucial developmental step is gaining independence in the self-management of their treatment regimen. Unfortunately, this process can be challenging for parents of chronically ill children, and ultimately creates an additional layer of stress for the child (Armstrong, Mackey, & Streisand, 2011; Carpentier, Mullins, Wagner, Wolfe-Christensen, & Chaney, 2007).
The structure of adolescent psychopathology: a symptom-level analysis

Background Most empirical studies into the covariance structure of psychopathology have been confined to adults. This work is not developmentally informed as the meaning, age-of-onset, persistence and expression of disorders differ across the lifespan. This study investigates the underlying structure of adolescent psychopathology and associations between the psychopathological dimensions and sex and personality risk profiles for substance misuse and mental health problems. Method This study analyzed data from 2175 adolescents aged 13.3 years. Five dimensional models were tested using confirmatory factor analysis and the external validity was examined using a multiple-indicators multiple-causes model. Results A modified bifactor model, with three correlated specific factors (internalizing, externalizing, thought disorder) and one general psychopathology factor, provided the best fit to the data. Females reported higher mean levels of internalizing, and males reported higher mean levels of externalizing. No significant sex differences emerged in liability to thought disorder or general psychopathology. Liability to internalizing, externalizing, thought disorder and general psychopathology was characterized by a number of differences in personality profiles. Conclusions This study is the first to identify a bifactor model including a specific thought disorder factor. The findings highlight the utility of transdiagnostic treatment approaches and the importance of restructuring psychopathology in an empirically based manner.
Dual MEK/AKT inhibition with trametinib and GSK2141795 does not yield clinical benefit in metastatic NRAS‐mutant and wild‐type melanoma

Aberrant MAPK and PI3K pathway signaling may drive the malignant phenotype in NRAS‐mutant and BRAFWT NRASWT metastatic melanoma. To target these pathways, NRAS‐mutant and BRAFWT NRASWT patients received oral trametinib at 1.5 mg daily and GSK2141795 at 50 mg daily in a two‐cohort Simon two‐stage design. Participants had adequate end‐organ function and no more than two prior treatment regimens. Imaging assessments were performed at 8‐week intervals. A total of 10 NRAS‐mutant and 10 BRAFWT NRASWT patients were enrolled. No objective responses were noted in either cohort. The median PFS and OS were 2.3 and 4.0 months in the NRAS‐mutant cohort and 2.8 and 3.5 months in the wild‐type cohort. Grade 3 and grade 4 adverse events, primarily rash, were observed in 25% of patients. We conclude that the combination of trametinib and GSK2141795 does not have significant clinical activity in NRAS‐mutant or BRAFWT NRASWT melanoma.
Clostridium difficile infection: update on diagnosis, epidemiology, and treatment strategies.

BACKGROUND Clostridium difficile infection (CDI) has increased in incidence and severity over the past quarter century, and is now considered a major cause of healthcare-associated infections. METHODS Review of the pertinent English-language medical literature. RESULTS There has been a substantial change in the management of CDI. The emergence of the NAP1/BI/O27 strain in the early to mid-2000s has been associated with more severe forms of CDI. The pathophysiology, epidemiology, clinical manifestations and diagnosis, as well as new strategies for medical and surgical management are discussed in this review. CONCLUSIONS Clostridium difficile infection can range from benign diarrhea to severe disease associated with substantial morbidity and mortality. Treatment modalities vary based on disease severity and timing of onset. The mainstay of medical treatment remains metronidazole and oral/rectal vancomycin. New management strategies are evolving, including adjunctive treatments such as monoclonal antibodies, vaccination, and fecal transplant. In patients with severe disease or clinical deterioration, early surgical consultation for total colectomy or loop ileostomy may be life-saving. Infection control measures are vital to mitigating the spread of CDI.
The relationship between longevity and healthy life expectancy

What is the relationship between longevity and health? Health expectancies were developed more than 30 years ago specifically to answer this question. It may therefore be the time to try to answer this question, though it is worth noting that the question implies a unidirectional relationship. Almost no one questions the positive association between health and longevity. It is expected that healthy, robust people will live, on average, longer than frail people. This heterogeneity in terms of robustness/frailty may explain the shape of the mortality trajectory with age, ie. the oldest old seem to follow a lower mortality schedule (Vaupel et al, 1979). On the other hand, many people wonder about the relationship between longevity and health. Are we living longer because we are in better health? Are we living longer in good health? Or are we merely surviving longer whatever our health status? In other words, can we live in good health as long as we can survive? And this is exactly the purpose of health expectancies: monitoring how long people live in various health statuses (Sanders, 1964; Sullivan, 1971; Robine et al, 2003a).
Parental suicide attempt and offspring educational attainment during adolescence in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort

Background Few studies have investigated the impact of parental suicide attempt (SA) on offspring outcomes other than mental health. We investigated the association of parental SA with offspring educational attainment in the Avon Longitudinal Study of Parents and Children (ALSPAC). Method Parental SA was prospectively recorded from pregnancy until the study children were 11 years old. National school test results (ages 11–16 years) were obtained by record linkage. Multilevel regression models quantified the association between parental SA and offspring outcomes. Results Data were available for 6667 mother–child and 3054 father–child pairs. Adolescents whose mothers had attempted suicide were less likely than their peers to achieve the expected educational level by age 14 years [adjusted odds ratio (aOR) 0.63, 95% confidence interval (CI) 0.41–0.95] in models controlling for relevant confounders, including parental education and depression. At age 16 years, adolescents whose mothers had attempted suicide were less likely to obtain the expected educational level (five or more qualifications at grade A*–C) (aOR 0.66, 95% CI 0.43–1.00) in models controlling for relevant confounders and parental education; however, after additionally controlling for maternal depression the results were consistent with chance (aOR 0.74, 95% CI 0.48–1.13). Findings in relation to paternal SA were consistent with those of maternal SA but power was limited due to lower response rate amongst fathers. Conclusions Maternal SA was associated with diminished educational performance at age 14 years. Educational attainment during adolescence can have substantial effect on future opportunities and well-being and these offspring may benefit from interventions.
Temporal reproduction and its neuroanatomical correlates in adults with attention deficit hyperactivity disorder and their unaffected first-degree relatives

Background Little is known about time perception, its putative role as cognitive endophenotype, and its neuroanatomical underpinnings in adults with attention deficit hyperactivity disorder (ADHD). Method Twenty adults with ADHD, 20 unaffected first-degree relatives and 20 typically developing controls matched for age and gender undertook structural magnetic resonance imaging scans. Voxel-based morphometry with DARTEL was performed to obtain regional grey-matter volumes. Temporal processing was investigated as a putative cognitive endophenotype using a temporal reproduction paradigm. General linear modelling was employed to examine the relationship between temporal reproduction performances and grey-matter volumes. Results ADHD participants were impaired in temporal reproduction and unaffected first-degree relatives performed in between their ADHD probands and typically developing controls. Increased grey-matter volume in the cerebellum was associated with poorer temporal reproduction performance. Conclusions Adults with ADHD are impaired in time reproduction. Performances of the unaffected first-degree relatives are in between ADHD relatives and controls, suggesting that time reproduction might be a cognitive endophenotype for adult ADHD. The cerebellum is involved in time reproduction and might play a role in driving time performances.
HIV infection and depression

Major depression is highly prevalent among HIV‐positive patients (HIVpp). The prevalence of depression ranges between 18% and 81%, depending on the population studied and the methodology of the study. The etiology of depression in HIVpp is likely determined by: (i) biological factors (alterations in the white matter structure, hypothalamic–pituitary–thyroid dysfunction, Tat‐protein‐induced depressive behavior); (ii) psychosocial factors (HIV stigma, occupational disability, body image changes, isolation and debilitation); (iii) history or comorbidity of psychiatric illness; and (iv) the perinatal period in HIVpp women. Symptomatology of depression differs between HIVpp and HIV‐negative patients (HIVnp). Depression may also alter the function of lymphocytes in HIVpp and decrease natural killer cell activity, contributing to the increased mortality in these patients. Selective serotonin re‐uptake inhibitors are considered the first‐line treatment. Treatment of depression can improve quality of life and lead to a better prognosis of HIV infection.
Transdiagnostic brain responses to disorder-related threat across four psychiatric disorders

Background There is an ongoing debate whether transdiagnostic neural mechanisms are shared by different anxiety-related disorders or whether different disorders show distinct neural correlates. To investigate this issue, studies controlling for design and stimuli across multiple anxiety-related disorders are needed. Method The present functional magnetic resonance imaging study investigated neural correlates of visual disorder-related threat processing across unmedicated patients suffering from panic disorder (n = 20), social anxiety disorder (n = 20), dental phobia (n = 16) and post-traumatic stress disorder (n = 11) relative to healthy controls (HC; n = 67). Each patient group and the corresponding HC group saw a tailor-made picture set with 50 disorder-related and 50 neutral scenes. Results Across all patients, increased activation to disorder-related v. neutral scenes was found in subregions of the bilateral amygdala. In addition, activation of the lateral amygdala to disorder-related v. neutral scenes correlated positively with subjective anxiety ratings of scenes across patients. Furthermore, whole-brain analysis revealed increased responses to disorder-related threat across the four disorders in middle, medial and superior frontal regions, (para-)limbic regions, such as the insula and thalamus, as well as in the brainstem and occipital lobe. We found no disorder-specific brain responses. Conclusions The results suggest that pathologically heightened lateral amygdala activation is linked to experienced anxiety across anxiety disorders and trauma- and stressor-related disorders. Furthermore, the transdiagnostically shared activation network points to a common neural basis of abnormal responses to disorder-related threat stimuli across the four investigated disorders.
Potential role of anticonvulsants in the treatment of obsessive–compulsive and related disorders

We reviewed the extant literature to evaluate the current evidence regarding the efficacy and safety of anticonvulsants in the treatment of obsessive–compulsive and related disorders. Relevant literature was accessed using the Cochrane database, embase and PubMed on 29 October 2013. Prospective studies examining the efficacy of anticonvulsants in obsessive–compulsive and related disorders were included. Case reports, case series, and retrospective studies were excluded. A total of 10 studies were included in this review. The studies of obsessive–compulsive disorder, except for two negative studies, showed favorable efficacy results of anticonvulsants. In one study on body dysmorphic disorder, levetiracetam showed favorable efficacy. In two lamotrigine studies for pathologic skin‐picking, the efficacy findings were inconsistent. In one trichotillomania study, topiramate had reduced hair‐pulling symptoms. Despite limited evidence, our review suggests that anticonvulsants have a potential role in the treatment of obsessive–compulsive and related disorders.
The effect of Low Dye taping upon rearfoot motion and position before and after exercise

SUMMARY. The effect of Low Dye taping was assessed upon rearfoot motion and position of seven excessively pronated individuals (14 feet). A measurement of calcaneal stance position was taken prior to taping and before and after 30 minutes of walking while taped. Taping immediately reduced resting calcaneal stance position significantly (P < 0.05) but this control was lost after exercise. Taping made no significant difference to total pronation or maximum pronation velocity measured during walking. It was concluded that Low Dye taping may still be beneficial to certain specific conditions but its use as a method of reducing dynamic excess pronation or static pronation over a period of time may be inappropriate. fl 2001 Harcourt Publishers Ltd
Do DSM-5 Section II personality disorders and Section III personality trait domains reflect the same genetic and environmental risk factors?

Background DSM-5 includes two conceptualizations of personality disorders (PDs). The classification in Section II is identical to the one found in DSM-IV, and includes 10 categorical PDs. The Alternative Model (Section III) includes criteria for dimensional measures of maladaptive personality traits organized into five domains. The degree to which the two conceptualizations reflect the same etiological factors is not known. Methods We use data from a large population-based sample of adult twins from the Norwegian Institute of Public Health Twin Panel on interview-based DSM-IV PDs and a short self-report inventory that indexes the five domains of the DSM-5 Alternative Model plus a domain explicitly targeting compulsivity. Schizotypal, Paranoid, Antisocial, Borderline, Avoidant, and Obsessive-compulsive PDs were assessed at the same time as the maladaptive personality traits and 10 years previously. Schizoid, Histrionic, Narcissistic, and Dependent PDs were only assessed at the first interview. Biometric models were used to estimate overlap in genetic and environmental risk factors. Results When measured concurrently, there was 100% genetic overlap between the maladaptive trait domains and Paranoid, Schizotypal, Antisocial, Borderline, and Avoidant PDs. For OCPD, 43% of the genetic variance was shared with the domains. Genetic correlations between the individual domains and PDs ranged from +0.21 to +0.91. Conclusion The pathological personality trait domains, which are part of the Alternative Model for classification of PDs in DSM-5 Section III, appears to tap, at an aggregate level, the same genetic risk factors as the DSM-5 Section II classification for most of the PDs.
Genetics of anxiety disorders: Genetic epidemiological and molecular studies in humans

This review provides a broad overview of the state of research in the genetics of anxiety disorders (AD). Genetic epidemiological studies report a moderate level of familial aggregation (odds ratio: 4–6) and heritability estimates are about 30–50%. Twin studies suggest that the genetic architecture of AD is not isomorphic with their classifications, sharing risk factors with each other. So far, linkage and association studies of AD have produced inconclusive results. Genome‐wide association studies of AD can provide an unbiased survey of common genetic variations across the entire genome. Given the shared causes of AD that transcend our current diagnostic classifications, clustering anxiety phenotypes into broader groups may be a powerful approach to identifying susceptibility locus for AD. Using such a shared genetic risk factor, meta‐analyses of genome‐wide association studies of AD conducted by large consortia are needed. Environmental factors also make a substantial contribution to the cause of AD. Although candidate gene studies of gene by environmental (G × E) interaction have appeared recently, no genome‐wide search for G × E interactions have been performed. Epigenetic modification of DNA appears to have important effects on gene expression mediating environmental influences on disease risk. Given that G × E can be linked to an epigenetic modification, a combination analysis of genome‐wide G × E interaction and methylation could be an alternative method to find risk variants for AD. This genetic research will enable us to utilize more effective strategies for the prevention and treatment of AD in the near future.
Antipsychotic medication and long-term mortality risk in patients with schizophrenia; a systematic review and meta-analysis

Patients with schizophrenia have a higher mortality risk than patients suffering from any other psychiatric disorder. Previous research is inconclusive regarding the association of antipsychotic treatment with long-term mortality risk. To this aim, we systematically reviewed the literature and performed a meta-analysis on the relationship between long-term mortality and exposure to antipsychotic medication in patients with schizophrenia. The objectives were to (i) determine long-term mortality rates in patients with schizophrenia using any antipsychotic medication; (ii) compare these with mortality rates of patients using no antipsychotics; (iii) explore the relationship between cumulative exposure and mortality; and (iv) assess causes of death. We systematically searched the EMBASE, MEDLINE and PsycINFO databases for studies that reported on mortality and antipsychotic medication and that included adults with schizophrenia using a follow-up design of more than 1 year. A total of 20 studies fulfilled our inclusion criteria. These studies reported 23,353 deaths during 821,347 patient years in 133,929 unique patients. Mortality rates varied widely per study. Meta-analysis on a subgroup of four studies showed a consistent trend of an increased long-term mortality risk in schizophrenia patients who did not use antipsychotic medication during follow-up. We found a pooled risk ratio of 0.57 (LL:0.46 UL:0.76 p value <0.001) favouring any exposure to antipsychotics. Statiscal heterogeneity was found to be high (Q = 39.31, I 2 = 92.37%, p value < 0.001). Reasons for the increased risk of death for patients with schizophrenia without antipsychotic medication require further research. Prospective validation studies, uniform measures of antipsychotic exposure and classified causes of death are commendable.
Buffering effects of safe, supportive, and nurturing relationships among women with childhood histories of maltreatment

Background Adults who were victims of childhood maltreatment tend to have poorer health compared with adults who did not experience abuse. However, many are in good health. We tested whether safe, supportive, and nurturing relationships buffer women with a history of childhood maltreatment from poor health outcomes in later life. Methods Participants included women from the Environmental Risk (E-Risk) Longitudinal Twin Study who were involved in an intimate relationship at some point by the time their twin children were 10 years old. Women were initially interviewed in 1999–2000 (mean age = 33 years) and 2, 5, and 7 years later. They reported on their physical and mental health, and their health-risk behaviours. Results Compared with women who did not experience abuse in childhood, women with histories of maltreatment were at elevated risk for mental, physical, and health-risk behaviours, including major depressive disorder, sleep, and substance use problems. Cumulatively, safe, supportive, and nurturing relationships characterized by a lack of violence, emotional intimacy, and social support buffered women with a history of maltreatment from poor health outcomes. Conclusions Our findings emphasize that negative social determinants of health – such as a childhood history of maltreatment – confer risk for psychopathology and other physical health problems. If, however, a woman's current social circumstances are sufficiently positive, they can promote good health, particularly in the face of past adversity.