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Duchenne muscular dystrophy is a devastating neuromuscular disorder characterized by the loss of dystrophin, inevitably leading to cardiomyopathy. Despite publications on prophylaxis and treatment with cardiac medications to mitigate cardiomyopathy progression, gaps remain in the specifics of medication initiation and optimization.
Method:
This document is an expert opinion statement, addressing a critical gap in cardiac care for Duchenne muscular dystrophy. It provides thorough recommendations for the initiation and titration of cardiac medications based on disease progression and patient response. Recommendations are derived from the expertise of the Advance Cardiac Therapies Improving Outcomes Network and are informed by established guidelines from the American Heart Association, American College of Cardiology, and Duchenne Muscular Dystrophy Care Considerations. These expert-derived recommendations aim to navigate the complexities of Duchenne muscular dystrophy-related cardiac care.
Results:
Comprehensive recommendations for initiation, titration, and optimization of critical cardiac medications are provided to address Duchenne muscular dystrophy-associated cardiomyopathy.
Discussion:
The management of Duchenne muscular dystrophy requires a multidisciplinary approach. However, the diversity of healthcare providers involved in Duchenne muscular dystrophy can result in variations in cardiac care, complicating treatment standardization and patient outcomes. The aim of this report is to provide a roadmap for managing Duchenne muscular dystrophy-associated cardiomyopathy, by elucidating timing and dosage nuances crucial for optimal therapeutic efficacy, ultimately improving cardiac outcomes, and improving the quality of life for individuals with Duchenne muscular dystrophy.
Conclusion:
This document seeks to establish a standardized framework for cardiac care in Duchenne muscular dystrophy, aiming to improve cardiac prognosis.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
Results
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Conclusions
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Preliminary animal and human data suggest that angiotensin-converting enzyme inhibition has a role in pulmonary vascular remodelling. We sought to assess the effect of ACEi versus placebo on pulmonary artery pressure and transpulmonary gradient amongst infants undergoing single-ventricle palliation.
Materials and methods:
Using the publicly available Pediatric Heart Network Infant Single-Ventricle trial dataset, we compared mean PA pressure at pre-superior cavopulmonary connection catheterisation (primary outcome), transpulmonary gradient, pulmonary-to-systemic flow ratio, and post-SCPC oxygen saturation (secondary outcomes) in infants receiving enalapril versus placebo.
Results:
A total of 179 infants underwent pre-SCPC catheterisation, of which 85 (47%) received enalapril. There was no difference between the enalapril and placebo group in the primary and the secondary outcomes. Mean PA pressure in the enalapril group was 13.1 ± 2.9 compared to 13.7 ± 3.4 mmHg in the placebo group. The transpulmonary gradient was 6.7 ± 2.5 versus 6.9 ± 3.2 mmHg in the enalapril and placebo groups, respectively. The pulmonary-to-systemic flow ratio was 1.1 ± 0.5 in the enalapril group versus 1.0 ± 0.5 in the placebo group and the post-SCPC saturation was 83.1 ± 5.0% in the enalapril group versus 82.2 ± 5.3% in the placebo group. In the pre-specified subgroup analyses comparing enalapril and placebo according to ventricular morphology and shunt type, there was no difference in the primary and secondary outcomes.
Conclusion:
ACEi did not impact mean pulmonary artery pressure or transpulmonary gradient amongst infants with single-ventricle physiology prior to SCPC palliation.
We present experimental data providing evidence for the formation of transient (${\sim }20\ \mathrm {\mu }\textrm {s}$) plasmas that are simultaneously weakly magnetized (i.e. Hall magnetization parameter $\omega \tau > 1$) and dominated by thermal pressure (i.e. ratio of thermal-to-magnetic pressure $\beta > 1$). Particle collisional mean free paths are an appreciable fraction of the overall system size. These plasmas are formed via the head-on merging of two plasmas launched by magnetized coaxial guns. The ratio $\lambda _{\textrm {gun}}=\mu _0 I_{\textrm {gun}}/\psi _{\textrm {gun}}$ of gun current $I_{\textrm {gun}}$ to applied magnetic flux $\psi _{\textrm {gun}}$ is an experimental knob for exploring the parameter space of $\beta$ and $\omega \tau$. These experiments were conducted on the Big Red Ball at the Wisconsin Plasma Physics Laboratory. The transient formation of such plasmas can potentially open up new regimes for the laboratory study of weakly collisional, magnetized, high-$\beta$ plasma physics; processes relevant to astrophysical objects and phenomena; and novel magnetized plasma targets for magneto-inertial fusion.
Although testing is widely regarded as critical to fighting the COVID-19 pandemic, what measure and level of testing best reflects successful infection control remains unresolved. Our aim was to compare the sensitivity of two testing metrics – population testing number and testing coverage – to population mortality outcomes and identify a benchmark for testing adequacy. We aggregated publicly available data through 12 April on testing and outcomes related to COVID-19 across 36 OECD (Organization for Economic Development) countries and Taiwan. Spearman correlation coefficients were calculated between the aforementioned metrics and following outcome measures: deaths per 1 million people, case fatality rate and case proportion of critical illness. Fractional polynomials were used to generate scatter plots to model the relationship between the testing metrics and outcomes. We found that testing coverage, but not population testing number, was highly correlated with population mortality (rs = −0.79, P = 5.975 × 10−9vs. rs = −0.3, P = 0.05) and case fatality rate (rs = −0.67, P = 9.067 × 10−6vs. rs = −0.21, P = 0.20). A testing coverage threshold of 15–45 signified adequate testing: below 15, testing coverage was associated with exponentially increasing population mortality; above 45, increased testing did not yield significant incremental mortality benefit. Taken together, testing coverage was better than population testing number in explaining country performance and can serve as an early and sensitive indicator of testing adequacy and disease burden.
To assess the safety of, and subsequent allergy documentation associated with, an antimicrobial stewardship intervention consisting of test-dose challenge procedures prompted by an electronic guideline for hospitalized patients with reported β-lactam allergies.
Design:
Retrospective cohort study.
Setting:
Large healthcare system consisting of 2 academic and 3 community acute-care hospitals between April 2016 and December 2017.
Methods:
We evaluated β-lactam antibiotic test-dose outcomes, including adverse drug reactions (ADRs), hypersensitivity reactions (HSRs), and electronic health record (EHR) allergy record updates. HSR predictors were examined using a multivariable logistic regression model. Modification of the EHR allergy record after test doses considered relevant allergy entries added, deleted, and/or specified.
Results:
We identified 1,046 test-doses: 809 (77%) to cephalosporins, 148 (14%) to penicillins, and 89 (9%) to carbapenems. Overall, 78 patients (7.5%; 95% confidence interval [CI], 5.9%–9.2%) had signs or symptoms of an ADR, and 40 (3.8%; 95% CI, 2.8%–5.2%) had confirmed HSRs. Most HSRs occurred at the second (ie, full-dose) step (68%) and required no treatment beyond drug discontinuation (58%); 3 HSR patients were treated with intramuscular epinephrine. Reported cephalosporin allergy history was associated with an increased odds of HSR (odds ratio [OR], 2.96; 95% CI, 1.34–6.58). Allergies were updated for 474 patients (45%), with records specified (82%), deleted (16%), and added (8%).
Conclusion:
This antimicrobial stewardship intervention using β-lactam test-dose procedures was safe. Overall, 3.8% of patients with β-lactam allergy histories had an HSR; cephalosporin allergy histories conferred a 3-fold increased risk. Encouraging EHR documentation might improve this safe, effective, and practical acute-care antibiotic stewardship tool.
Researchers have studied psychological disorders extensively from a common cause perspective, in which symptoms are treated as independent indicators of an underlying disease. In contrast, the causal systems perspective seeks to understand the importance of individual symptoms and symptom-to-symptom relationships. In the current study, we used network analysis to examine the relationships between and among depression and anxiety symptoms from the causal systems perspective.
Method
We utilized data from a large psychiatric sample at admission and discharge from a partial hospital program (N = 1029, mean treatment duration = 8 days). We investigated features of the depression/anxiety network including topology, network centrality, stability of the network at admission and discharge, as well as change in the network over the course of treatment.
Results
Individual symptoms of depression and anxiety were more related to other symptoms within each disorder than to symptoms between disorders. Sad mood and worry were among the most central symptoms in the network. The network structure was stable both at admission and between admission and discharge, although the overall strength of symptom relationships increased as symptom severity decreased over the course of treatment.
Conclusions
Examining depression and anxiety symptoms as dynamic systems may provide novel insights into the maintenance of these mental health problems.
Taiwan is a young and seismically active mountain belt, where a series of strong earthquakes (M>7) have occurred over the past hundred years. Identifying historical earthquakes around Taiwan is a key to better constrain the geodynamic of this active region. Sedimentological and geochemical analyses of surface sediments from one station offshore east Taiwan revealed the presence of coarse-grained layers interpreted as turbidites. The age of these layers have been determined by 210Pb, 137Cs, and 241Am chronology. Dating of the three most recent turbidites provides ages of AD 2001±3, AD 1950±5, and AD 1928±10. The results show striking temporal correspondence of turbidite layers to large (M≥6.8) earthquakes recorded in the region since the 20th century. The chronologies of sediment layers lead us to believe that turbidites resulted from the 2003 Taitung earthquake (M 6.8), the 1951 Chengkong earthquake (M 7.1), and the 1935 Lutao earthquake (M 7.0), respectively. Such a good correlation between turbidites and high-magnitude (M≥6.8) historical and instrumental seismic events suggests that turbidite paleoseismology constitutes a valuable tool for earthquake assessment in the eastern Taiwan margin. Moreover, the modern reservoir radiocarbon age and the regional marine reservoir correction (ΔR) of the Kuroshio Current off Taiwan were estimated by comparing accelerator mass spectrometry (AMS) 14C ages with ages derived from corrected 210Pb profiles and historical accounts of identifiable seismic events. Such a determination is important to calibrate the 14C ages of marine materials for accurate comparison of marine and continental geological records. Our calculated mean ΔR value of 232±54 14C yr (n=2) is higher than its modern value of 86±40 14C yr. This high value can be explained by the presence of local upwelling cells and turbulence in the Kuroshio Current, north of Green Island. These upwelling cells bring 14C-depleted water to the surface, resulting in an increase of the modern ΔR value in this portion of the Kuroshio Current.
Recent meta-analyses of resting-state networks in major depressive disorder (MDD) implicate network disruptions underlying cognitive and affective features of illness. Heterogeneity of findings to date may stem from the relative lack of data parsing clinical features of MDD such as phase of illness and the burden of multiple episodes.
Method
Resting-state functional magnetic resonance imaging data were collected from 17 active MDD and 34 remitted MDD patients, and 26 healthy controls (HCs) across two sites. Participants were medication-free and further subdivided into those with single v. multiple episodes to examine disease burden. Seed-based connectivity using the posterior cingulate cortex (PCC) seed to probe the default mode network as well as the amygdala and subgenual anterior cingulate cortex (sgACC) seeds to probe the salience network (SN) were conducted.
Results
Young adults with remitted MDD demonstrated hyperconnectivity of the left PCC to the left inferior frontal gyrus and of the left sgACC to the right ventromedial prefrontal cortex (PFC) and left hippocampus compared with HCs. Episode-independent effects were observed between the left PCC and the right dorsolateral PFC, as well as between the left amygdala and right insula and caudate, whereas the burden of multiple episodes was associated with hypoconnectivity of the left PCC to multiple cognitive control regions as well as hypoconnectivity of the amygdala to large portions of the SN.
Conclusions
This is the first study of a homogeneous sample of unmedicated young adults with a history of adolescent-onset MDD illustrating brain-based episodic features of illness.
The Helicon-Cathode(HelCat) device is a medium-size linear experiment suitable for a wide range of basic plasma science experiments in areas such as electrostatic turbulence and transport, magnetic relaxation, and high power microwave (HPM)-plasma interactions. The HelCat device is based on dual plasma sources located at opposite ends of the 4 m long vacuum chamber – an RF helicon source at one end and a thermionic cathode at the other. Thirteen coils provide an axial magnetic field B ⩾ 0.220 T that can be configured individually to give various magnetic configurations (e.g. solenoid, mirror, cusp). Additional plasma sources, such as a compact coaxial plasma gun, are also utilized in some experiments, and can be located either along the chamber for perpendicular (to the background magnetic field) plasma injection, or at one of the ends for parallel injection. Using the multiple plasma sources, a wide range of plasma parameters can be obtained. Here, the HelCat device is described in detail and some examples of results from previous and ongoing experiments are given. Additionally, examples of planned experiments and device modifications are also discussed.
To investigate and compare the performance of head mirrors and headlights during otolaryngological examination.
Methods:
The illuminance and illumination field of each device were measured and compared. Visual identification and visual acuity were also measured, in 13 medical students and 10 otolaryngology specialists.
Results:
The illuminance (mean ± standard deviation) of the LumiView, Kimscope 1 W and Kimscope 3 W headlights and a standard head mirror were 352.3 ± 9, 92.3 ± 4.5, 438 ± 15.7 and 68.3 ± 1.2 lux, respectively. The illumination field of the head mirror (mean ± standard deviation) was 348 ± 29.8 grids, significantly greater than that of the Kimscope 3 W headlight (183 ± 9.2 grids) (p = 0.0017). The student group showed no statistically significant difference between visual identification with the best headlight and the head mirror (score means ± standard deviations: 56.2 ± 9 and 53.3 ± 14.1, respectively; p = 0.3). The expert group scored significantly higher for visual identification with head mirrors versus headlights (59.7 ± 3.3 vs 55.2 ± 5.8, respectively; p = 0.0035), but showed no difference for visual acuity.
Conclusion:
Despite the advantages of headlight illumination, head mirrors provided better, shadow-free illumination. Despite no differences amongst students, head mirrors performed better than headlights in experienced hands.
The Boltzmann equation (BE) for gas flows is a time-dependent nonlinear differential-integral equation in 6 dimensions. The current simplified practice is to linearize the collision integral in BE by the BGK model using Maxwellian equilibrium distribution and to approximate the moment integrals by the discrete ordinate method (DOM) using a finite set of velocity quadrature points. Such simplification reduces the dimensions from 6 to 3, and leads to a set of linearized discrete BEs. The main difficulty of the currently used (conventional) numerical procedures occurs when the mean velocity and the variation of temperature are large that requires an extremely large number of quadrature points. In this paper, a novel dynamic scheme that requires only a small number of quadrature points is proposed. This is achieved by a velocity-coordinate transformation consisting of Galilean translation and thermal normalization so that the transformed velocity space is independent of mean velocity and temperature. This enables the efficient implementation of Gaussian-Hermite quadrature. The velocity quadrature points in the new velocity space are fixed while the correspondent quadrature points in the physical space change from time to time and from position to position. By this dynamic nature in the physical space, this new quadrature scheme is termed as the dynamic quadrature scheme (DQS). The DQS was implemented to the DOM and the lattice Boltzmann method (LBM). These new methods with DQS are therefore termed as the dynamic discrete ordinate method (DDOM) and the dynamic lattice Boltzmann method (DLBM), respectively. The new DDOM and DLBM have been tested and validated with several testing problems. Of the same accuracy in numerical results, the proposed schemes are much faster than the conventional schemes. Furthermore, the new DLBM have effectively removed the incompressible and isothermal restrictions encountered by the conventional LBM.
A multi-cross-correlation method (MCCM) was developed in a particle image velocimetry (PIV) auto-processing system to reduce spurious vectors and improve accuracy of measurements. This technique is an improvement based on conventional cross-correlation method (CCM). Four typical neighboring interrogation windows were specified to be overlapped and calculated by MCCM. A high cross-correlation value is obtained in which many particle images match up with their corresponding spatially shifted partners, and small cross-correlation peaks due to interference of noises during experiments are reduced. Several parameters such as out-of-plane motions, particle size, and seeding density are considered for checking both MCCM and conventional PIV algorithms. The examination gives authenticity to the merits of MCCM for avoiding particles loss or mistaken velocity vectors.
This study was performed to determine the prevalence, distribution of specimen sources, and antimicrobial susceptibility of the Acinetobacter calcoaceticus–Acinetobacter baumannii (Acb) species complex in Singapore. One hundred and ninety-three non-replicate Acb species complex clinical isolates were collected from six hospitals over a 1-month period in 2006. Of these, 152 (78·7%) were identified as A. baumannii, 18 (9·3%) as ‘Acinetobacter pittii’ [genomic species (gen. sp.) 3], and 23 (11·9%) as ‘Acinetobacter nosocomialis’ (gen. sp. 13TU). Carbapenem resistance was highest in A. baumannii (72·4%), followed by A. pittii (38·9%), and A. nosocomialis (34·8%). Most carbapenem-resistant A. baumannii and A. nosocomialis possessed the blaOXA-23-like gene whereas carbapenem-resistant A. pittii possessed the blaOXA-58-like gene. Two imipenem-resistant strains (A. baumannii and A. pittii) had the blaIMP-like gene. Representatives of carbapenem-resistant A. baumannii were related to European clones I and II.
The previous monolithic active grating bender design met some basic design requirements. However, after a real grating (BM-AGM) had been fabricated and installed for testing, the results showed that the usable length is a mere 60 mm because of the higher-order term error in the surface profile. A method was thus derived to eliminate the higher-order term error by modifying the width of the bender substrate through finite-element method simulation, reducing the residual error from about 100 nm to 6 nm. Owing to the closure of the grating department of Zeiss, ruling the monolithic bender is no longer available and the design has to be modified to a composite-type bender with Si substrate. A prototype was fabricated and assembled to examine all the design situations. The surface roughness of the width-modified Si substrate is around 30 nm before assembly. The residual error after assembly and bending is less than 10 nm. It proves that the design is feasible. However, due to the manufacturing capacity of the vendor, a short-length substrate is required and the design has to be modified. The detailed design modification and testing results are presented in this paper.
The beam position monitors (BPMs) with submicron-level resolution act as the major eyes of storage ring in detecting the position of electron beams and are used for feedback system to guide the beam orbit to the desired track. Compared to major improvements on backend electronics, the physical devices generate and transmit signals had little improvement due to the lack of control on manufacturing processes including all mechanical tolerance requirements. The design started with ANSYS to simulate mechanical deformation. Due to the small size (submillimetre) and complicated assembly of feedthrough structure, it is difficult to achieve 1 % tolerance (submicron) in all aspects including machining and brazing. The smallest tolerance for machining is 5 µ and the overall tolerance will be 30 µm. The influence of the tolerance on mechanical will be shown on time-domain reflectometry measurement. The resulted heat-related issue will also be discussed and addressed since the problem happened at SLAC (private communication with Albert Sheng at Stanford Linear Accelerator Center) and DIAMOND (presented at the RF Button Heating Mini-Workshop at EPAC 2008). Manufacturing steps will be described. The consequence of mismatch on manufacturing will be discussed. All related measurement and simulation data are presented in this paper.