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The SCN5A gene is implicated in many arrhythmogenic and cardiomyopathic processes. We identified a novel SCN5A variant in a family with significant segregation in individuals affected with progressive sinus and atrioventricular nodal disease, atrial arrhythmia, dilated cardiomyopathy, and early sudden cardiac arrest.
A patient pedigree was created following the clinical evaluation of three affected individuals, two monozygotic twins and a paternal half-brother, which lead to the evaluation of a paternal half-sister (four siblings with the same father and three mothers) all of whom experienced varying degrees of atrial arrhythmias, conduction disease, and dilated cardiomyopathy in addition to a paternal history of unexplained death in his 50s with similar autopsy findings. The index male underwent sequencing of 58 genes associated with cardiomyopathies. Sanger sequencing was used to provide data for bases with insufficient coverage and for bases in some known regions of genomic segmental duplications. All clinically significant and novel variants were confirmed by independent Sanger sequencing.
All relatives tested were shown to have the same SCN5A variant of unknown significance (p. Asp197His) and the monozygotic twins shared a co-occurring NEXN (p. Glu575*). Segregation analysis demonstrates likely pathogenic trait for the SCN5A variant with an additional possible role for the NEXN variant in combination.
There is compelling clinical evidence suggesting that the SCN5A variant p. Asp197His may be re-classified as likely pathogenic based on the segregation analysis of our family of interest. Molecular mechanism studies are pending.
In this paper we continue the examination of inventory control in which the inventory is modeled by a diffusion process and a long-term average cost criterion is used to make decisions. The class of such models under consideration has general drift and diffusion coefficients, and boundary points that are consistent with the notion that demand should tend to reduce the inventory level. The conditions on the cost functions are greatly relaxed from those in Helmes et al. (2017). Characterization of the cost of a general (s, S) policy as a function of two variables naturally leads to a nonlinear optimization problem over the ordering levels s and S. Existence of an optimizing pair (s*, S*) is established for these models under very weak conditions; nonexistence of an optimizing pair is also discussed. Using average expected occupation and ordering measures and weak convergence arguments, weak conditions are given for the optimality of the (s*, S*) ordering policy in the general class of admissible policies. The analysis involves an auxiliary function that is globally C2 and which, together with the infimal cost, solves a particular system of linear equations and inequalities related to but different from the long-term average Hamilton‒Jacobi‒Bellman equation. This approach provides an analytical solution to the problem rather than a solution involving intricate analysis of the stochastic processes. The range of applicability of these results is illustrated on a drifted Brownian motion inventory model, both unconstrained and reflected, and on a geometric Brownian motion inventory model under two different cost structures.
The objective of the present study was to evaluate the growth and tolerance in healthy, term infants consuming a synbiotic formula with daily weight gain as the primary outcome. In a randomised, controlled, double-blind, multicentre, intervention study infants were assigned to an extensively hydrolysed formula containing a specific combination of Bifidobacterium breve M-16V and a prebiotic mixture (short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides in a 9:1 ratio; scGOS/lcFOS; synbiotic group), or the same formula without this synbiotic concept for 13 weeks (control group). Anthropometry, formula intake, tolerance, stool characteristics, blood parameters, faecal microbiota and metabolic faecal profile were assessed. Medically confirmed adverse events were recorded throughout the study. Equivalence in daily weight gain was demonstrated for the intention-to-treat (ITT) population (n 211). In the per-protocol (PP) population (n 102), the 90 % CI of the difference in daily weight gain slightly crossed the lower equivalence margin. During the intervention period, the mean weight-for-age and length-for-age values were close to the median of the WHO growth standards in both groups, indicating adequate growth. The number of adverse events was not different between both groups. No relevant differences were observed in blood parameters indicative for liver and renal function. At 13 weeks, an increased percentage of faecal bifidobacteria (60 v. 48 %) and a reduced percentage of Clostridium lituseburense/C. histolyticum (0·2 v. 2·6 %) were observed in the synbiotic group (n 19) compared with the control group (n 27). In conclusion, this study demonstrates that an extensively hydrolysed formula with B. breve M-16V and the prebiotic mixture scGOS/lcFOS (9:1) supports an adequate infant growth.
The study of intermediate-mass black holes (IMBHs) is a young and promising field of research. If IMBHs exist, they could explain the rapid growth of supermassive black holes by acting as seeds in the early stage of galaxy formation. Formed by runaway collisions of massive stars in young and dense stellar clusters, intermediate-mass black holes could still be present in the centers of globular clusters, today. Our group investigated the presence of intermediate-mass black holes for a sample of 10 Galactic globular clusters. We measured the inner kinematic profiles with integral-field spectroscopy and determined masses or upper limits of central black holes in each cluster. In combination with literature data we further studied the positions of our results on known black-hole scaling relations (such as M• − σ) and found a similar but flatter correlation for IMBHs. Applying cluster evolution codes, the change in the slope could be explained with the stellar mass loss occurring in clusters in a tidal field over its life time. Furthermore, we present results from several numerical simulations on the topic of IMBHs and integral field units (IFUs). We ran N-body simulations of globular clusters containing IMBHs in a tidal field and studied their effects on mass-loss rates and remnant fractions and showed that an IMBH in the center prevents core collapse and ejects massive objects more rapidly. These simulations were further used to simulate IFU data cubes. For the specific case of NGC 6388 we simulated two different IFU techniques and found that velocity dispersion measurements from individual velocities are strongly biased towards lower values due to blends of neighboring stars and background light. In addition, we use the Astrophysical Multipurpose Software Environment (AMUSE) to combine gravitational physics, stellar evolution and hydrodynamics to simulate the accretion of stellar winds onto a black hole.
Metacognitive training (MCT) for patients with psychosis is a psychological group intervention that aims to educate patients about common cognitive biases underlying delusion formation and maintenance, and to highlight their negative consequences in daily functioning.
In this randomized controlled trial, 154 schizophrenia spectrum patients with delusions were randomly assigned to either MCT + treatment as usual (TAU) or TAU alone. Both groups were assessed at baseline, and again after 8 and 24 weeks. The trial was completed fully by 111 patients. Efficacy was measured with the Psychotic Symptom Rating Scales (PSYRATS) Delusions Rating Scale (DRS), and with specific secondary measures referring to persecutory ideas and ideas of social reference (the Green Paranoid Thoughts Scale, GPTS), cognitive insight (the Beck Cognitive Insight Scale, BCIS), subjective experiences of cognitive biases (the Davos Assessment of Cognitive Biases Scale, DACOBS) and metacognitive beliefs (the 30-item Metacognitions Questionnaire, MCQ-30). Economic analysis focused on the balance between societal costs and health outcomes (quality-adjusted life years, QALYs).
Both conditions showed a decrease of delusions. MCT was not more efficacious in terms of reducing delusions, nor did it change subjective paranoid thinking and ideas of social reference, cognitive insight or subjective experience of cognitive biases and metacognitive beliefs. The results of the economic analysis were not in favour of MCT + TAU.
In the present study, MCT did not affect delusion scores and self-reported cognitive insight, or subjective experience of cognitive biases and metacognitive beliefs. MCT was not cost-effective.
The growing movement of biologically inspired design is driven in part by the need for sustainable development and in part by the recognition that nature could be a source of innovation. Biologically inspired design by definition entails cross-domain analogies from biological systems to problems in engineering and other design domains. However, the practice of biologically inspired design at present typically is ad hoc, with little systemization of either biological knowledge for the purposes of engineering design or the processes of transferring knowledge of biological designs to engineering problems. In this paper we present an intricate episode of biologically inspired engineering design that unfolded over an extended period of time. We then analyze our observations in terms of why, what, how, and when questions of analogy. This analysis contributes toward a content theory of creative analogies in the context of biologically inspired design.
Vanadium dioxide (VO2) displays a well-known metal-insulator (MI) transition at a temperature of 68°C. In this study we use terahertz time-domain spectroscopy (THz-TDS) to investigate the optical properties of VO2 thin films in the vicinity of the MI transition temperature in the frequency range 0.1 – 1.5 THz. We observe the interesting effect that the phase of the transmitted THz field through the conducting VO2 film is delayed in comparison to the phase of the same THz signal transmitted through the insulating VO2 film. This is in contrast to the expected behavior of a homogeneous, conducting film. This observation shows that even at temperatures significantly above the transition temperature, the formation of a homogeneous, conducting film is incomplete. We demonstrate that effective-medium theory (EMT) in combination with a Drude model accounting for the conductivity of metallic domains formed in the VO2 film accounts for all our observations. We show that the Maxwell-Garnett EMT is consistent with our observations, whereas the Bruggeman EMT fails to account for our observations.
The risks of ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage are not increased in the 9 months of gestation except for a high risk in the 2 days prior and 1 day postpartum. The remaining 6 weeks postpartum also have an increased risk of ischemic stroke and intracerebral hemorrhage, though less than the peripartum period. Although there are some rare causes of stroke specific to pregnancy and the postpartum period, eclampsia, cardiomyopathy, postpartum cerebral venous thrombosis, and, possibly, paradoxical embolism warrant special consideration. The diagnostic and therapeutic approaches to stroke during pregnancy and the postpartum period are similar to the approaches in the nonpregnant woman with some minor modifications based on consideration of the welfare of the fetus. There is a theoretical risk of magnetic resonance imaging exposure during the first and second trimester but the benefit to the mother of obtaining the information may outweigh the risk. Available evidence suggests that low-dose aspirin (<150 mg/day) during the second and third trimesters is safe for both mother and fetus. Postpartum use of low-dose aspirin by breast-feeding mother is also safe for infant. While proper counseling is imperative, a history of pregnancy-related stroke should not be a contraindication for subsequent pregnancy.
The orange coating (varnish) that forms on the undersides (ventral sides) of clasts in desert pavements constitutes a potential relative-age indicator. Using Munsell color notation, we semiquantified the color of the orange, ventral varnish on the undersides of clasts from 15 different alluvial fan and terrace surfaces of various ages ranging from less than 500 to about 25,000 yr. All of the surfaces studied are located along the central portion of the left-lateral Garlock fault, in the Mojave Desert of southern California. The amount of left-lateral offset may be used to determine the relative ages of the surfaces. The previously published slip rate of the fault may also be used to estimate the absolute age of each surface. The color of the ventral varnish is strongly correlated with surface age and appears to be a more reliable age-indicator than the percentage coverage of dorsal varnish. Soil development indices also were not as strongly correlated with age, as were the colors of the ventral varnish. In particular, rubification appears to be more useful than soils for distinguishing relative ages among Holocene surfaces. Humidity sensors indicated that the undersides of clasts condensed moisture nightly for a period of several days to over a week after each rain. These frequent wet-dry cycles may be responsible for the rapid development of clast rubification on Holocene surfaces.
This work initiates an investigation of molecular co-doping to produce p-type centers in (Ga,Al)N with ionization energies lower than Mg. Dopant complexes can be formed between a doubly ionized acceptor such as (Cu, Li or Ag) and a singly ionized donor (silicon). Ion implantation of Cu, Li and Ag into silicon doped GaN films grown by Metalorganic Chemical Vapor Deposition (MOCVD) has been performed. Secondary ion mass spectroscopy (SIMS) data confirmed the simulated depth profile. High resolution X-ray diffraction and Raman spectroscopy were used to characterize the crystalline damage and subsequent recovery upon anneal. A complete recovery was observed after high temperature (700–900°C) annealing. Low temperature (6K) photoluminescence (PL) for Cu-implanted GaN showed bands identified with crystalline lattice damage due to the Cu-implantation. The annealed samples showed recovery of standard crystalline GaN features. Additional donor-acceptor pair features are observed below 3.35 eV indicating the existence of an acceptor state.
Frith et al (1995) and others have hypothesised that disruptions in the connection between left frontal and temporal areas of the brain are a central deficit in schizophrenia. In this paper we examine whether such connectivity as assessed by EEG coherence is related to level of symptoms in patients with schizophrenia.
For 73 patients with schizophrenia, assessments of the EEG coherence between frontal and temporal regions were carried out under conditions of activation by a mathematical task, and between frontal and occipital regions when performing a visuo-spatial task. We then examined the relationship between these coherence measures and the reality distortion, disorganisation and psychomotor poverty dimensions of symptomatology.
Only left frontal -temporal connectivity was found to have a significant negative relationship to symptomatology. This relationship was, however, specific to reality distortion rather than to symptoms of disorganisation or psychomotor poverty, and may be more characteristic of males than females.
Disruption of frontaltemporal connectivity appears to have a specific relationship to reality distortion symptoms in schizophrenia.
On the basis of Liddle's three-syndrome model of schizophrenia, it was predicted that: (1) symptoms of psychomotor poverty would be particularly correlated with impaired performance on neuropsychological tests likely to reflect functioning of the dorsolateral prefrontal cortex; (2) disorganisation would be particularly correlated with impaired performance on tests sensitive to medio-basal prefrontal functioning; and (3) reality distortion would be particularly correlated with measures sensitive to temporal lobe functioning.
The above hypotheses were tested on 87 subjects with a confirmed diagnosis of schizophrenia. Patients' symptoms were scored for each of the three syndromes. Patients completed six neuropsychological tests designed to measure impairment in specific areas of the brain.
There was no support for the first two hypotheses. There was, however, evidence of a specific relationship between reality distortion and neuropsychological performance usually considered to be related to left temporal lobe functioning.
Although not directly supporting the first two hypotheses; the results are, in general, consistent with there being different cortical-subcortical circuits associated with each of psychomotor poverty and disorganisation. Temporal lobe functioning appears to have particular significance for the reality distortion syndrome.
We report here the growth and characterization of intersubband quantum well structures based on the GaAs/AlGaAs material system, designed to emit radiation at approximately 7 micrometers. We present transport behavior, infrared photocurrent spectra, and electroluminescence data. First attempts to fabricate a laser structure from this devices encountered difficulties with the electrical properties of the AIGaAs waveguide cladding layers. Thus, we present measurements with different waveguide concepts as doped AlAs cladding layers and doped superlattice cladding structures.