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Pathological worry is a hallmark feature of generalised anxiety disorder (GAD), associated with dysfunctional emotional processing. The ventromedial prefrontal cortex (vmPFC) is involved in the regulation of such processes, but the link between vmPFC emotional responses and pathological v. adaptive worry has not yet been examined.
To study the association between worry and vmPFC activity evoked by the processing of learned safety and threat signals.
In total, 27 unmedicated patients with GAD and 56 healthy controls (HC) underwent a differential fear conditioning paradigm during functional magnetic resonance imaging.
Compared to HC, the GAD group demonstrated reduced vmPFC activation to safety signals and no safety–threat processing differentiation. This response was positively correlated with worry severity in GAD, whereas the same variables showed a negative and weak correlation in HC.
Poor vmPFC safety–threat differentiation might characterise GAD, and its distinctive association with GAD worries suggests a neural-based qualitative difference between healthy and pathological worries.
We critically evaluate arguments in a recent Journal of Law, Medicine & Ethics article by Svoboda, Adler, and Van Howe disputing the 2012 affirmative infant male circumcision policy recommendations of the American Academy of Pediatrics. We provide detailed evidence in explaining why the extensive claims by these opponents are not supported by the current strong scientific evidence. We furthermore show why their legal and ethical arguments are contradicted by a reasonable interpretation of current U.S. and international law and ethics. After all considerations are taken into account it would be logical to conclude that failure to recommend male circumcision early in infancy may be viewed as akin to failure to recommend childhood vaccination to parents. In each case, parental consent is required and the intervention is not compulsory. Our evaluation leads us to dismiss the arguments by Svoboda et al. Instead, based on the evidence, infant male circumcision is both ethical and lawful.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
Self-report questionnaires are frequently used in clinical and epidemiologic studies to assess post-traumatic stress disorder (PTSD). A number of studies have evaluated these scales relative to clinician administered structured interviews; however, there has been no formal evaluation of their performance relative to non-clinician administered epidemiologic assessments such as the Composite International Diagnostic Interview (CIDI). We examined the diagnostic performance of two self-report PTSD scales, the PTSD checklist (PCL) and the Vietnam Era Twin Registry (VET-R) PTSD scale, compared to the CIDI.
Data were derived from a large epidemiologic follow-up study of PTSD in 5141 Vietnam Era Veterans. Measures included the PCL, VET-R PTSD scale and CIDI. For both the PCL and VET-R PTSD scale, ROC curves, areas under the curve (AUC), sensitivity, specificity, % correctly classified, likelihood ratios, predictive values and quality estimates were generated based on the CIDI PTSD diagnosis.
For the PCL and VET-R PTSD scale the AUCs were 89.0 and 87.7%, respectively. Optimal PCL cutpoints varied from the 31–33 range (when considering sensitivity and specificity) to the 36–56 range (when considering quality estimates). Similar variations were found for the VET-R PTSD, ranging from 31 (when considering sensitivity and specificity) to the 37–42 range (when considering quality estimates).
The PCL and VET-R PTSD scale performed similarly using a CIDI PTSD diagnosis as the criterion. There was a range of acceptable cutpoints, depending on the metric used, but most metrics suggested a lower PCL cutpoint than in previous studies in Veteran populations.
In countries maintaining national hepatitis C virus (HCV) surveillance systems, a substantial proportion of individuals report no risk factors for infection. Our goal was to estimate the proportion of diagnosed HCV antibody-positive persons in Scotland (1991–2010) who probably acquired infection through injecting drug use (IDU), by combining data on IDU risk from four linked data sources using log-linear capture–recapture methods. Of 25 521 HCV-diagnosed individuals, 14 836 (58%) reported IDU risk with their HCV diagnosis. Log-linear modelling estimated a further 2484 HCV-diagnosed individuals with IDU risk, giving an estimated prevalence of 83. Stratified analyses indicated variation across birth cohort, with estimated prevalence as low as 49% in persons born before 1960 and greater than 90% for those born since 1960. These findings provide public-health professionals with a more complete profile of Scotland's HCV-infected population in terms of transmission route, which is essential for targeting educational, prevention and treatment interventions.
In this paper, a novel set of macros with line/space width from 128nm/128nm, 64nm/64nm to 32nm/32nm was designed and installed on 20nm technology-node hardware. The pitch-dependent pad erosion post Cu CMP was studied by atomic-force microscopy (AFM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) quantitatively on these macros. Two methods were investigated to reduce the difference between pitch- and density-induced CMP non-uniformity. The first is using new scheme of partial Cu plating process followed by SiCNH insulator deposition and then CMP. The second is through the selection of slurries and pads. Both results are discussed in this paper.
Observed co-morbidity among the mood and anxiety disorders has led to the development of increasingly sophisticated dimensional models to represent the common and unique features of these disorders. Patients often present to primary care settings with a complex mixture of anxiety, depression and somatic symptoms. However, relatively little is known about how somatic symptoms fit into existing dimensional models.
We examined the structure of 91 anxiety, depression and somatic symptoms in a sample of 5433 primary care patients drawn from 14 countries. One-, two- and three-factor lower-order models were considered; higher-order and hierarchical variants were studied for the best-fitting lower-order model.
A hierarchical, bifactor model with all symptoms loading simultaneously on a general factor, along with one of three specific anxiety, depression and somatic factors, was the best-fitting model. The general factor accounted for the bulk of symptom variance and was associated with psychosocial dysfunction. Specific depression and somatic symptom factors accounted for meaningful incremental variance in diagnosis and dysfunction, whereas anxiety variance was associated primarily with the general factor.
The results (a) are consistent with previous studies showing the presence and importance of a broad internalizing or distress factor linking diverse emotional disorders, and (b) extend the bounds of internalizing to include somatic complaints with non-physical etiologies.
Density functional theory (DFT) calculations and classical molecular dynamics (MD) simulations have been performed to gain insight into the difference in cycling behaviors between the ethylene carbonate (EC)-based and the propylene carbonate (PC)-based electrolytes in lithium-ion battery cells. DFT calculations for the ternary graphite intercalation compounds (Li+(S)iCn: S=EC or PC), in which the solvated lithium ion Li+(S)i (i=1~3) was inserted into a graphite cell, suggested that Li+(EC)iCn was more stable than Li+(PC)iCn in general. Furthermore, Li+(PC)3Cn was found to be energetically unfavorable, while Li+(PC)2Cn was stable, relative to their corresponding Li+(PC)i in the bulk electrolyte. The calculations also revealed severe structural distortions of the PC molecule in Li+(PC)3Cn, suggesting a rapid kinetic effect on PC decomposition reactions, as compared to decompositions of EC. In addition, MD simulations were carried out to examine the solvation structures at a high salt concentration: 2.45 mo kg-1. The results showed that the solvation structure was significantly interrupted by the counter anions, having a smaller solvation number than that at a lower salt concentration (0.83 mol kg-1). We propose that at high salt concentrations, the lithium desolvation may be facilitated due to the increased contact ion pairs, so that a stable ternary GIC with less solvent molecules can be formed without the destruction of graphite particles, followed by solid-electrolyte-interface film formation reactions. The results from both DFT calculations and MD simulations are consistent with the recent experimental observations.
We estimated the excess risk of in-patient hospitalization in a large cohort of persons diagnosed with hepatitis C virus (HCV) infection, controlling for social deprivation. A total of 20 749 individuals diagnosed with HCV in Scotland by 31 December 2006 were linked to the Scottish hospital discharge database, and indirectly standardized hospitalization rates, adjusting for sex, age, year and deprivation were calculated. We observed significant excess morbidity considering episodes for: any diagnosis [standardized morbidity ratio (SMR) 3·4, 95% CI 3·3–3·5]; liver-related diagnoses (SMR 41·3, 95% CI 39·6–43·0); and only non-liver-related diagnoses (SMR 2·14, 95% CI 2·08–2·19). Cox regression analyses of the 2000–2006 data indicated increased relative risks of hospitalization for males [hazard ratio (HR) 1·1, 95% CI 1·0–1·2], older age (per 10 years) (HR 1·55, 95% CI 1·5–1·6), and those testing HIV-positive (HR 1·6, 95% CI 1·3–1·8). This study has revealed substantial excess all-cause and liver-related morbidity in the Scottish HCV-diagnosed population, even after allowing for deprivation.
The extant major psychiatric classifications, DSM-IV and ICD-10, are purportedly atheoretical and largely descriptive. Although this achieves good reliability, the validity of a medical diagnosis is greatly enhanced by an understanding of both risk factors and clinical history. In an effort to group mental disorders on the basis of risk factors and clinical manifestations, five clusters have been proposed. The purpose of this paper is to consider the position of bipolar disorder (BPD), which could be either with the psychoses, or with emotional disorders, or in a separate cluster.
We reviewed the literature on BPD, unipolar depression (UPD) and schizophrenia in relation to 11 validating criteria proposed by the DSM-V Task Force Study Group, and then summarized similarities and differences between BPD and schizophrenia on the one hand, and UPD on the other.
There are differences, often substantial and never trivial, for 10 of the 11 validators between BPD and UPD. There are also important differences between BPD and schizophrenia.
BPD has previously been classified together with UPD, but this is the least justifiable place for it. If it is to be recruited to a ‘psychotic cluster’, there are several important respects in which it differs from schizophrenia, so the cluster would have a division within it. The alternative would be to allow it to be in an intermediate position in a cluster of its own.
The extant major psychiatric classifications DSM-IV, and ICD-10, are atheoretical and largely descriptive. Although this achieves good reliability, the validity of a medical diagnosis would be greatly enhanced by an understanding of risk factors and clinical manifestations. In an effort to group mental disorders on the basis of aetiology, five clusters have been proposed. This paper considers the validity of the fourth cluster, emotional disorders, within that proposal.
We reviewed the literature in relation to 11 validating criteria proposed by a Study Group of the DSM-V Task Force, as applied to the cluster of emotional disorders.
An emotional cluster of disorders identified using the 11 validators is feasible. Negative affectivity is the defining feature of the emotional cluster. Although there are differences between disorders in the remaining validating criteria, there are similarities that support the feasibility of an emotional cluster. Strong intra-cluster co-morbidity may reflect the action of common risk factors and also shared higher-order symptom dimensions in these emotional disorders.
Emotional disorders meet many of the salient criteria proposed by the Study Group of the DSM-V Task Force to suggest a classification cluster.
We estimated the extent of undiagnosed hepatitis C virus (HCV) infection in injecting drug users (IDUs) in Scotland. We used record-linkage to determine HCV diagnosis status for 41 062 current/former IDUs attending drug treatment and support services between 1 April 1995 and 31 March 2006; the extent of undiagnosed HCV infection was estimated by comparing the number HCV-diagnosed to the number HCV-infected (estimated from an unlinked anonymous testing survey of 2141 current/former IDUs). In all, 9145 IDUs (22%) were diagnosed HCV antibody-positive since first attendance at drug services (diagnosis rate of 33·6/1000 person-years, 95% CI 32·7–34·4). By 31 March 2006, of the 19 632 current/former IDUs who had attended drug services and were determined to be living with HCV, an estimated 58% (95% CI 45–62) had not been HCV-diagnosed. It is essential that the deployment of resources for identifying at-risk IDUs with a view to offering antiviral therapy is guided by evidence.
Simplicity of construction and operation are advantages of iTMC (ionic transition metal complex) OLEDs compared with multi-layer OLED devices. Unfortunately, lifetimes do not compare favorably with the best multi-layer devices. We have previously shown for Ru(bpy)3(PF6)2 based iTMC OLEDs that electrical drive produces emission-quenching dimers of the active species. We report evidence here that a chemical process may also be implicated in degradation of devices based on Ir(ppy)2(dtb-bpy)PF6 albeit by a very different mechanism. It appears that degradation of operating devices made with this Ir-based complex is related to current-induced heating of the organic layer, resulting in loss of the dtb-bpy ligand. (The dtb-bpy ligand is labile compared with the cyclometallated ppy ligands.) Morphological changes observed in electrically driven Ir(ppy)2(dtb-bpy)PF6 OLEDs provide evidence of substantial heating during device operation. Evidence from UV-vis spectra in the presence of an electric field as well as MALDI-TOF mass spectra of the OLED materials before and after electrical drive add support for this model of the degradation process.