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We report of a 26-year-old female patient who was referred to our centre with congestive heart failure (CHF). Acute myocarditis with a high Parvovirus B19 virus load was diagnosed by myocardial biopsy. CHF improved after start of ramipril 5 mg/d, metoprolol, diuretics, immunoglobins, and a 24-hour infusion of levosimendan. Soon after initiation of medical therapy, the patient started to expectorate bronchial casts with varying frequencies (three times per week to five times daily). Thorough pneumological workup, including histology of the casts, microbiology, and a CT scan of the lungs, did not reveal any cause for bronchial cast formation. Inhalative corticoids were started without any benefit. Two years later, cardiac catheterisation demonstrated normalised left ventricular function. LV end-diastolic pressure, however, was still elevated at 14 mmHg. Endomyocardial biopsies at this time were negative for virus genome. Finally, we changed afterload reduction therapy from ramipril to candesartan. Within 24 hours, expectoration of bronchial casts terminated. Four weeks later, re-exposition to ramipril prompted immediate re-appearance of cast formation, which again stopped with switching back to candesartan. Finally, we were to prove that treatment with ramipril resulted in bronchial cast formation in this patient.
This article examines candidate emails from the 2016–17 Conservative Party of Canada leadership race to explore how candidates communicated with party supporters on issues of moral traditionalism (for example, abortion and sexuality diversity) and minority religious accommodation. We find that the level of public support for a given policy position shaped how overtly candidates signalled their views, with those supporting moral traditionalism or restrictions on religious minorities tending to express their views covertly and vice versa. Message overtness also changed following the deadline for new members to join the party before the vote. This article marks the first systematic study of how party leadership candidates attempt to solicit support from particular party factions and how candidates’ appeals evolve throughout a campaign. The results also show that the high-profile debate around minority religious accommodation during the leadership race did not displace contestation between candidates over issues such as sexual or reproductive rights.
Stream reasoning systems are designed for complex decision-making from possibly infinite, dynamic streams of data. Modern approaches to stream reasoning are usually performing their computations using stand-alone solvers, which incrementally update their internal state and return results as the new portions of data streams are pushed. However, the performance of such approaches degrades quickly as the rates of the input data and the complexity of decision problems are growing. This problem was already recognized in the area of stream processing, where systems became distributed in order to allocate vast computing resources provided by clouds. In this paper we propose a distributed approach to stream reasoning that can efficiently split computations among different solvers communicating their results over data streams. Moreover, in order to increase the throughput of the distributed system, we suggest an interval-based semantics for the LARS language, which enables significant reductions of network traffic. Performed evaluations indicate that the distributed stream reasoning significantly outperforms existing stand-alone LARS solvers when the complexity of decision problems and the rate of incoming data are increasing.
Individuals with depression often do not respond to medication or psychotherapy. Radically open dialectical behaviour therapy (RO DBT) is a new treatment targeting overcontrolled personality, common in refractory depression.
To compare RO DBT plus treatment as usual (TAU) for refractory depression with TAU alone (trial registration: ISRCTN 85784627).
RO DBT comprised 29 therapy sessions and 27 skills classes over 6 months. Our completed randomised trial evaluated RO DBT for refractory depression over 18 months in three British secondary care centres. Of 250 adult participants, we randomised 162 (65%) to RO DBT. The primary outcome was the Hamilton Rating Scale for Depression (HRSD), assessed masked and analysed by treatment allocated.
After 7 months, immediately following therapy, RO DBT had significantly reduced depressive symptoms by 5.40 points on the HRSD relative to TAU (95% CI 0.94–9.85). After 12 months (primary end-point), the difference of 2.15 points on the HRSD in favour of RO DBT was not significant (95% CI –2.28 to 6.59); nor was that of 1.69 points on the HRSD at 18 months (95% CI –2.84 to 6.22). Throughout RO DBT participants reported significantly better psychological flexibility and emotional coping than controls. However, they reported eight possible serious adverse reactions compared with none in the control group.
The RO DBT group reported significantly lower HRSD scores than the control group after 7 months, but not thereafter. The imbalance in serious adverse reactions was probably because of the controls' limited opportunities to report these.
Declaration of interest
Six of the 16 authors have received royalties or fees for RO DBT. R.J.H. is co-owner and director of Radically Open Ltd, the RO DBT training and dissemination company. D.K. reports grants outside the submitted work from NIHR. T.R.L. receives royalties from New Harbinger Publishing for sales of RO DBT treatment manuals, speaking fees from Radically Open Ltd and a grant outside the submitted work from the Medical Research Council. He was codirector of Radically Open Ltd between November 2014 and May 2015 and is married to Erica Smith-Lynch, the principal shareholder and one of two current directors of Radically Open Ltd. H.O’M. reports personal fees from the Charlie Waller Institute and Improving Access to Psychological Therapy. S.C.R. provides RO DBT supervision through S C Rushbrook Ltd. I.T.R. reports grants outside the submitted work from NIHR and Health & Care Research Wales. M.St. reports personal fees from British Isles DBT Training, Stanton Psychological Services Ltd, and Taylor & Francis Ltd. M.Sw. reports personal fees from British Isles DBT Training, Guilford Press, Oxford University Press and Taylor & Francis Ltd. B.W. was codirector of Radically Open Ltd between November 2014 and February 2015.
The late Pleistocene–early Holocene archaeological record of the interior Pacific Northwest is dominated by what has been regionally referred to as the Western Stemmed Tradition (WST). While various efforts have attempted to clarify the chronology of this tradition, these have largely focused on data from the Great Basin and have been disproportionately preoccupied with establishing the beginning of the tradition due to its temporal overlap with Clovis materials. Specifically focusing on the Columbia Plateau, we apply a series of Bayesian chronological models to create concise estimates of the most likely beginning, end, and span of the WST. We then further explore its chronology by modeling its temporal span under various parameters and criteria so as to better identify places in the chronology that need further work and those that are robust regardless of data iteration. Our analysis revealed four major findings: (1) WST conservatively dates between 13,000 and 11,000 cal BP, likely extending to ~13,500 cal BP; (2) the most problematic period for WST is its termination; (3) the WST is incredibly long-lived compared to roughly contemporary Paleoindian traditions; and (4) the WST was seemingly unaffected by the onset of the Younger Dryas.
Inadequate protein quality may be a risk factor for poor growth. To examine the effect of a macronutrient–micronutrient supplement KOKO Plus (KP), provided to infants from 6 to 18 months of age, on linear growth, a single-blind cluster-randomised study was implemented in Ghana. A total of thirty-eight communities were randomly allocated to receive KP (fourteen communities, n 322), a micronutrient powder (MN, thirteen communities, n 329) and nutrition education (NE, eleven communities, n 319). A comparison group was followed cross-sectionally (n 303). Supplement delivery and morbidity were measured weekly and anthropometry monthly. NE education was provided monthly. Baseline, midline and endline measurements at 6, 12 and 18 months included venous blood draws, diet, anthropometry, morbidity, food security and socio-economics. Length-for-age Z-score (LAZ) was the primary outcome. Analyses were intent-to-treat using mixed-effects regressions adjusted for clustering, sex, age and baseline. No differences existed in mean LAZ scores at endline (−1·219 (sd 0·06) KP, −1·211 (sd 0·03) MN, −1·266 (sd 0·03) NE). Acute infection prevalence was lower in the KP than NE group (P = 0·043). Mean serum Hb was higher in KP infants free from acute infection (114·02 (sd 1·87) g/l) than MN (107·8 (sd 2·5) g/l; P = 0·047) and NE (108·8 (sd 0·99) g/l; P = 0·051). Compliance was 84·9 % (KP) and 87·2 % (MN) but delivery 60 %. Adjusting for delivery and compliance, LAZ score at endline was significantly higher in the KP v. MN group (+0·2 LAZ; P = 0·026). A macro- and micronutrient-fortified supplement KP reduced acute infection, improved Hb and demonstrated a dose–response effect on LAZ adjusting consumption for delivery.
One generation's experience of childhood maltreatment is associated with that of the next. However, whether this intergenerational transmission is specific to distinct forms of maltreatment and what factors may contribute to its continuity remains unclear. Borderline personality pathology is predicted by childhood maltreatment and characterized by features (e.g., dysregulated emotion, relationship instability, impulsivity, and inconsistent appraisals of others) that may contribute to its propagation. Among 364 older adults and 573 of their adult children (total n = 937), self-reported exposure to distinct forms of childhood maltreatment (i.e., emotional, physical, and sexual abuse, and emotional and physical neglect as assessed by the Childhood Trauma Questionnaire) showed homotypic and heterotypic associations across generations with little evidence that latent factors unique to specific forms of maltreatment show generational continuity. General nonspecific indices of childhood maltreatment showed evidence of intergenerational transmission after accounting for demographic factors and parent socioeconomic status (b = 0.126, p = 9.21 × 10−4). This continuity was partially mediated by parental borderline personality pathology (assessed longitudinally through a variety of measures and sources, indirect effect: b = 0.031, 95% confidence interval [0.003, 0.060]). The intergenerational continuity of childhood maltreatment may largely represent general risk for nonspecific maltreatment that may, in part, be propagated by borderline personality pathology and/or shared risk factors.
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.
Workforce shortages in psychiatry are common worldwide. The international literature provides insights into factors influencing decisions to train in psychiatry but is predominately survey based. This national cohort study aimed to identify the characteristics of doctors who were most likely to apply to psychiatry training programmes. The sample comprised doctors who entered UK medical schools in 2007/8 and who made first-time specialty training applications in 2015. The association between application to psychiatry and doctors' sociodemographic and educational characteristics was examined using multivariable logistic regression.
Those most likely to apply were White, privately educated older doctors with below average performance at medical school.
To reduce workforce shortages, psychiatry must make itself more attractive to all doctors, especially those from underrepresented groups such as state-educated Black and minority ethnic individuals. Otherwise, national policies to widen participation in the study of medicine by such groups may exacerbate the current recruitment crisis.
High body fat in apparently lean individuals is a commonly described phenotype in individuals of Asian descent, but very limited consolidated scientific literature is available on this topic. This phenotype is known as ‘normal-weight obesity’ and may explain the large disparity between the prevalence of obesity (as measured by BMI) and diabetes that occurs in these individuals. Routine use of obesity indicators that best predict body fat content would help to identify these individuals in clinical practice. In this debate, we would like to highlight that even though fat and BMI have a good correlation, as suggested by Kryst et al. (2019), clinicians, public health researchers and policymakers should consider the use of these indicators in conjunction with each other rather than individually. Future research is needed on pathogenic mechanisms, diagnostic modalities and therapeutic options in these individuals which will help to further characterize and manage these patients appropriately.
Obesity indicators are useful clinical tools in the measurement of obesity, but it is important for clinicians to appropriately interpret their values in individuals with different ethnicities. Future research is needed to identify optimal cut-offs that can predict the occurrence of cardio-metabolic comorbidities in individuals of different ethnic descent. Assessment of more recently developed indicators like the Edmonton Obesity Staging System and visceral adipose tissue are able to appropriately identify metabolically at-risk individuals.
The shape gradient quantifies the change in some figure of merit resulting from differential perturbations to a shape. Shape gradients can be applied to gradient-based optimization, sensitivity analysis and tolerance calculation. An efficient method for computing the shape gradient for toroidal three-dimensional magnetohydrodynamic (MHD) equilibria is presented. The method is based on the self-adjoint property of the equations for driven perturbations of MHD equilibria and is similar to the Onsager symmetry of transport coefficients. Two versions of the shape gradient are considered. One describes the change in a figure of merit due to an arbitrary displacement of the outer flux surface; the other describes the change in the figure of merit due to the displacement of a coil. The method is implemented for several example figures of merit and compared with direct calculation of the shape gradient. In these examples the adjoint method reduces the number of equilibrium computations by factors of
is the number of parameters used to describe the outer flux surface or coil shapes.
The aviation industry relies on accurate models. These models are used to predict an aircraft system’s outputs, and thus allow an understanding of the parameters involved, which could lead to system improvements. This study focuses on the engine modelling of an aircraft, and on its experimental validation using the Cessna Citation X Research Aircraft Simulator designed by CAE Inc., equipped with a level D Flight Dynamics toolbox. Level D is the highest rank attributed by the Federal Aviation Administration FAA certification authorities for flight dynamics. The proposed model aims to predict the thrust and the fuel consumption for various altitudes, Mach numbers and throttle lever angles (TLA). Different generic static models, which correspond to their steady state, from the literature, were used in this study; however, most of them were validated under restricted hypotheses. An optimisation algorithm was used in order to tune the static model parameters with the set of identification flight test data. Another set of data was then used in order to validate the identified model. Furthermore, a dynamic model corresponding to the transient operations was identified. TLA steps, impulses and ramp perturbations were performed in order to identify the system response, and to validate system dynamic model with other flight tests than the identification tests.