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Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
Summary: In this paper we build on work investigating the feasibility of human immunodeficiency virus (HIV) testing in emergency departments (EDs), estimating the prevalence of hepatitis B, C and HIV infections among persons attending two inner-London EDs, identifying factors associated with testing positive in an ED. We also undertook molecular characterisation to look at the diversity of the viruses circulating in these individuals, and the presence of clinically significant mutations which impact on treatment and control.
Blood-borne virus (BBV) testing in non-traditional settings is feasible, with emergency departments (ED) potentially effective at reaching vulnerable and underserved populations. We investigated the feasibility of BBV testing within two inner-London EDs. Residual samples from biochemistry for adults (⩾18 years) attending The Royal Free London Hospital (RFLH) or the University College London Hospital (UCLH) ED between January and June 2015 were tested for human immunodeficiency virus (HIV)Ag/Ab, anti-hepatitis C (HCV) and HBsAg. PCR and sequence analysis were conducted on reactive samples. Sero-prevalence among persons attending RFH and UCLH with residual samples (1287 and 1546), respectively, were 1.1% and 1.0% for HBsAg, 1.6% and 2.3% for anti-HCV, 0.9% and 1.6% for HCV RNA, and 1.3% and 2.2% for HIV. For RFH, HBsAg positivity was more likely among persons of black vs. white ethnicity (odds ratio 9.08; 95% confidence interval 2.72–30), with anti-HCV positivity less likely among females (0.15, 95% CI 0.04–0.50). For UCLH, HBsAg positivity was more likely among non-white ethnicity (13.34, 95% CI 2.20–80.86 (Asian); 8.03, 95% CI 1.12–57.61 (black); and 8.11, 95% CI 1.13–58.18 (other/mixed)). Anti-HCV positivity was more likely among 36–55 year olds vs. ⩾56 years (7.69, 95% CI 2.24–26.41), and less likely among females (0.24, 95% CI 0.09–0.65). Persons positive for HIV-markers were more likely to be of black vs. white ethnicity (4.51, 95% CI 1.63–12.45), and less likely to have one ED attendance (0.39, 95% CI 0.17–0.88), or female (0.12, 95% CI 0.04–0.42). These results indicate that BBV-testing in EDs is feasible, providing a basis for further studies to explore provider and patient acceptability, referral into care and cost-effectiveness.
Evaluation of post-operative donor site disability remains unaddressed in radial forearm free flap cases. This study aimed to assess donor site dysfunction following radial forearm free flap harvest using validated general, disease-specific and site-specific disability questionnaires.
In this retrospective case series of 24 patients at a tertiary academic medical centre, patients were assessed using the Short Form 36 Health Survey, Short Musculoskeletal Function Assessment questionnaire, and Disabilities of the Arm, Shoulder and Hand questionnaire. One-sample z-tests were performed, comparing means of the cohort to controls.
Compared to population controls, the cohort had higher mean scores for the Disabilities of the Arm, Shoulder and Hand questionnaire (18.22 vs 10.1, p < 0.01), and Short Musculoskeletal Function Assessment questionnaire bothersome index (21.44 vs 13.77, p = 0.04), and a lower mean score for the Short Form 36 Health Survey physical component (38.88 vs 50, p < 0.01), indicating a greater disability for the cohort compared to controls.
Radial forearm free flap harvest causes significant long-term donor site disability in head and neck tumour patients. The Disabilities of the Arm, Shoulder and Hand questionnaire is a concise tool for measuring this dysfunction.
Patient-reported outcomes and preferences rely on reports of the status of a patient’s health condition that comes directly from the patient, without interpretation or qualification by clinicians or investigators. Patient-reported outcomes and preferences have become an accepted approach in drug development. As part of this effort, we assessed the relative importance to patients with schizophrenia of trying a new antipsychotic that might improve symptoms in the context of common antipsychotic side effects, especially weight gain. Information from surveys such as this one can provide pilot guidance about what might be acceptable versus unacceptable trade-offs when considering new therapies for schizophrenia.
We prospectively administered a cross-sectional survey to 250 patients with clinical diagnoses of schizophrenia or schizoaffective disorder, aged ≥18 years, from five US outpatient community clinics, regarding the importance of efficacy and side effects on treatment decisions involving medications. Sixty-four percent (n=160) of the patients were male; mean age was 43 years (range: 18–72 years); mean weight was 91 kg (range: 49–182 kg); and mean body mass index was 30.3 kg/m2 (range: 15.3–63.3 kg/m2).
Patients rated both efficacy and side effects as important attributes of medication for schizophrenia treatment, with 88.5% identifying the ability to think more clearly as an important property of their medication. Patients identified efficacy and side effects as important drivers to take their prescribed medicine (endorsed as very or most important by 94.3% and 84.0% of patients, respectively). Patients identified weight gain, physical restlessness and somnolence as significant side effects of current treatments for schizophrenia (very/most important by 61.5%, 60.4%, and 58.9%, respectively). When asked about willingness to change antipsychotics, anticipated weight gain had a strong negative influence on willingness to try a new antipsychotic, with 44.9% of patients declining to try a medication that would lead to a weight gain of 3–5 kg, and 70.8% of patients declining for an anticipated weight gain of 5–9kg.
Patients living with schizophrenia or schizoaffective disorder are influenced by many factors when considering whether to take their prescribed medication, including efficacy and side effects. It is important for clinicians to assess patient-specific concerns and develop a comprehensive treatment plan to maximize adherence to prescribed therapies.
Funding Acknowledgements: This study was funded by Alkermes, Inc.
This study aimed to evaluate the presence of subjective post-operative donor site morbidity after fibula free flap reconstruction in head and neck cancer patients, utilising three validated instruments: the 36-item Short Form Health Survey, the Short Musculoskeletal Function Assessment questionnaire and the Lower Limb Core Scale.
In this retrospective study, all head and neck cancer patients who underwent fibula free flap reconstruction between January 2009 and July 2014 were identified. All questionnaires and their respective subcomponents were scored.
Twenty-one cases were included. Patients were found to have a higher Short Musculoskeletal Function Assessment bothersome index (22.42 vs 13.77, p = 0.03), a lower Short Form 36 Health Survey Physical Component Summary score (42.44 vs 50, p < 0.01) and a decreased Lower Limb Core Scale score (47.08 vs 90.52, p < 0.01), compared to US population norms. The Short Form 36 Health Survey Mental Component Summary scores and Short Musculoskeletal Function Assessment function index failed to demonstrate significant differences. Gender affected overall disability.
In this study, significant long-term disability was demonstrated after fibular flap reconstruction, as measured by the Lower Limb Core Scale.
Good education requires student experiences that deliver lessons about practice as well as theory and that encourage students to work for the public good—especially in the operation of democratic institutions (Dewey 1923; Dewy 1938). We report on an evaluation of the pedagogical value of a research project involving 23 colleges and universities across the country. Faculty trained and supervised students who observed polling places in the 2016 General Election. Our findings indicate that this was a valuable learning experience in both the short and long terms. Students found their experiences to be valuable and reported learning generally and specifically related to course material. Postelection, they also felt more knowledgeable about election science topics, voting behavior, and research methods. Students reported interest in participating in similar research in the future, would recommend other students to do so, and expressed interest in more learning and research about the topics central to their experience. Our results suggest that participants appreciated the importance of elections and their study. Collectively, the participating students are engaged and efficacious—essential qualities of citizens in a democracy.
Slender liquid jets that have a curved trajectory have been examined in a range of papers using a method introduced in Wallwork et al. (Proc. IUTAM Symp. on Free-Surface Flows, 2000, Kluwer; J. Fluid Mech., vol. 459, 2002, pp. 43–65) and Decent et al. (J. Engng Maths, vol. 42, 2002, pp. 265–282), for jets that emerge from an orifice on the surface of a rotating cylindrical container, successfully comparing computational results to measurements arising from laboratory experiments. Wallwork et al. (2000, 2002) and Decent et al. (2002) based their analyses on the slenderness of the jet, and neglected the torsion of the centreline of the jet, which is valid since in most situations examined the torsion is zero or small. Shikhmurzaev & Sisoev (J. Fluid Mech., vol. 819, 2017, pp. 352–400) used differential geometry and incorporated the torsion. This paper shows that these two methods produce identical results at leading order when the torsion is zero or when the torsion is
, in an asymptotic framework based upon the slenderness of the jet, and shows that the method of Wallwork et al. (2000, 2002) and Decent et al. (2002) is accurate for parameters corresponding to scenarios previously examined and also when the torsion is
. It is shown that the method of Shikhmurzaev & Sisoev (2017) should be used when the torsion is asymptotically large or when the jet is not slender.
Childhood emotional maltreatment (CEM) increases the likelihood of developing an anxiety disorder in adulthood, but the neural processes underlying conferment of this risk have not been established. Here, we test the potential for neuroimaging the adult brain to inform understanding of the mechanism linking CEM to adult anxiety symptoms.
One hundred eighty-two adults (148 females, 34 males) with a normal-to-clinical range of anxiety symptoms underwent structural and functional magnetic resonance imaging while completing an emotion-processing paradigm with facial expressions of fear, anger, and happiness. Participants completed self-report measures of CEM and current anxiety symptoms. Voxelwise mediation analyses on gray-matter volumes and activation to each emotion condition were used to identify candidate brain mechanisms relating CEM to anxiety in adulthood.
During processing of fear and anger faces, greater amygdala and less right dorsolateral prefrontal (dlPFC) activation partially mediated the positive relationship between CEM and anxiety symptoms. Greater right posterior insula activation to fear also partially mediated this relationship, as did greater ventral anterior cingulate (ACC) and less dorsal ACC activation to anger. Responses to happy faces in these regions did not mediate the CEM-anxiety relationship. Smaller right dlPFC gray-matter volumes also partially mediated the CEM-anxiety relationship.
Activation patterns of the adult brain demonstrate the potential to inform mechanistic accounts of the CEM conferment of anxiety symptoms. Results support the hypothesis that exaggerated limbic activation to negative valence facial emotions links CEM to anxiety symptoms, which may be consequent to a breakdown of cortical regulatory processes.
We examine the roles of actuaries in UK life offices, along with trends, challenges to and opportunities for actuaries. We carry out an analysis of senior roles in life offices, a questionnaire survey and interviews with relevant senior personnel. We find that actuaries occupy many important roles in life offices and are regarded as having good industry knowledge and technical skills, especially in financial modelling. There are fewer executive directors and more non-executive directors of life offices who are actuaries compared with the position in 1990. A higher proportion of reserved roles is outsourced to consultants than was the case in 1990. Only a small number of Actuarial Function Holders are directors. Actuaries are more siloed than was the case in the past, although actuaries are well represented in the finance and risk functions of many offices. Although actuarial work in connection with the preparation for Solvency II will decline, there will be important ongoing requirements for actuaries following Solvency II implementation. We also see opportunities for actuaries in four areas: in risk management, in financial analysis and management based on Solvency II and international financial reporting standards, in connection with “big data”, and in product development and the customer proposition. There are implications for the examination syllabus, continuing professional development and research.
Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism contributes to the development of depression (major depressive disorder, MDD), but it is unclear whether neural effects observed in healthy individuals are sustained in MDD.
To investigate BDNF Val66Met effects on key regions in MDD neurocircuitry: amygdala, anterior cingulate, middle frontal and orbitofrontal regions.
Magnetic resonance imaging scans were acquired in 79 persons with MDD (mean age 49 years) and 74 healthy volunteers (mean age 50 years). Effects on surface area and cortical thickness were examined with multiple comparison correction.
People who were Met allele carriers showed reduced caudal middle frontal thickness in both study groups. Significant interaction effects were found in the anterior cingulate and rostral middle frontal regions, in which participants in the MDD group who were Met carriers showed the greatest reduction in surface area.
Modulatory effects of the BDNF Val66Met polymorphism on distinct subregions in the prefrontal cortex in MDD support the neurotrophin model of depression.
Although evidence exists for abnormal brain function across various
anxiety disorders, direct comparison of neural function across diagnoses
is needed to elicit abnormalities common across disorders and those
distinct to a particular diagnosis.
To delineate common and distinct abnormalities within generalised anxiety
(GAD), panic and social anxiety disorder (SAD) during affective
Fifty-nine adults (15 with GAD, 15 with panic disorder, 14 with SAD, and
15 healthy controls) underwent functional magnetic resonance imaging
while completing a facial emotion matching task with fearful, angry and
Greater differential right amygdala activation to matching fearful
v. happy facial expressions related to greater
negative affectivity (i.e. trait anxiety) and was heightened across all
anxiety disorder groups compared with controls. Collapsing across
emotional face types, participants with panic disorder uniquely displayed
greater posterior insula activation.
These preliminary results highlight a common neural basis for clinical
anxiety in these diagnoses and also suggest the presence of
We show that the proof-theoretic notion of logical preorder coincides with the process-theoretic notion of barbed preorder for a CCS-like process calculus obtained from the formula-as-process interpretation of a fragment of linear logic. The argument makes use of other standard notions in process algebra, namely simulation and labelled transition systems. This result establishes a connection between an approach to reason about process specifications, the barbed preorder, and a method to reason about logic specifications, the logical preorder.
The amygdala and subgenual anterior cingulate cortex (sACC) are key brain regions for the generation of negative affect. In this longitudinal fMRI study of adolescents we investigated how amygdala–sACC connectivity was correlated with negative affectivity (NA) both cross-sectionally and longitudinally, and examined its relationship to the onset of first-episode depression.
Fifty-six adolescents who were part of a larger longitudinal study of adolescent development were included. They had no history of mental illness at the time of their baseline scan (mean age 16.5 years) and had a follow-up scan 2 years later (mean age 18.8 years). We used resting-state functional-connectivity MRI to investigate whether cross-sectional and change measures of amygdala–sACC connectivity were (i) correlated with NA and its change over time, and (ii) related to the onset of first-episode depression.
The magnitude of amygdala connectivity with sACC showed significant positive correlation with NA at both time-points. Further analysis confirmed that change in amygdala–sACC connectivity between assessments was correlated with change in NA. Eight participants developed a first episode of depression between the baseline and follow-up assessments: they showed increased amygdala–sACC connectivity at follow-up.
Amygdala–sACC connectivity is associated with NA in adolescence, with change in connectivity between these regions showing positive correlation with change in NA. Our observation that the onset of depression was associated with an increase in connectivity between the regions provides support for the neurobiological ‘scar’ hypothesis of depression.
Continuous fiber reinforced composites (RFC) are hierarchal and complex at multiple scales. In this work, tools are developed to automate the 3D characterization and quantification of the overall microstructure. Structure quantification enables accurate representation for material simulation and property prediction for the integrated computation materials engineering (ICME) of RFC based components. Relationships are developed to describe the key attributes of the microstructure at multiple scales including the individual fibers, tows, weave, porosity, and secondary matrix phases, which are treated as 'gestalts' of the structure. Here gestalt refers to the essence of shape or complete form of key features of the microstructure such as those of the tow architecture of the textile. Visualization tools are developed based on an artificial color scheme that allow the visual recognition of whole tows instead of just the collection of simple lines and curves representative of the fibers, which provides means whereby the gestalt of the microstructure can be visualized at the tow scale. These tools are demonstrated using a 3D dataset of the SiNC/SiC S200 ceramic matrix composite material (CMC) obtained via automated serial sectioning. Methods are then demonstrated to generate microstructure models representative of the characterized material for finite element analyses (FEA).
Bipolar disorder (BD) is one of the leading causes of disability worldwide. Patients are further disadvantaged by delays in accurate diagnosis ranging between 5 and 10 years. We applied Gaussian process classifiers (GPCs) to structural magnetic resonance imaging (sMRI) data to evaluate the feasibility of using pattern recognition techniques for the diagnostic classification of patients with BD.
GPCs were applied to gray (GM) and white matter (WM) sMRI data derived from two independent samples of patients with BD (cohort 1: n = 26; cohort 2: n = 14). Within each cohort patients were matched on age, sex and IQ to an equal number of healthy controls.
The diagnostic accuracy of the GPC for GM was 73% in cohort 1 and 72% in cohort 2; the sensitivity and specificity of the GM classification were respectively 69% and 77% in cohort 1 and 64% and 99% in cohort 2. The diagnostic accuracy of the GPC for WM was 69% in cohort 1 and 78% in cohort 2; the sensitivity and specificity of the WM classification were both 69% in cohort 1 and 71% and 86% respectively in cohort 2. In both samples, GM and WM clusters discriminating between patients and controls were localized within cortical and subcortical structures implicated in BD.
Our results demonstrate the predictive value of neuroanatomical data in discriminating patients with BD from healthy individuals. The overlap between discriminative networks and regions implicated in the pathophysiology of BD supports the biological plausibility of the classifiers.