Completing a systematic review and unsure where to start or what path to take? Set out on your journey confidently with this practical guide written by a team of experienced academics. With a ...friendly, accessible style, the book covers every step of the systematic review process, from planning to dissemination. This book will help you to: Work with qualitative, quantitative and mixed methods data Understand the how-to of systematic reviews with a range of real-life examples and case studies Learn from students who have been in your shoes with FAQs taken from actual supervision meetings. This book will not only support you to overcome common challenges and pitfalls, it will give you the knowledge and skills to produce an excellent review and you might even enjoy the journey! Alongside updated examples and case studies, this edition also includes two new chapters to help you write and register your review protocol and understand and synthesise data from correlational and experimental studies. The book is accompanied by an online guide for teaching, including videos, example documents, further reading, software recommendations and weblinks.
Copy-number analysis to detect disease-causing losses and gains across the genome is recommended for the evaluation of individuals with neurodevelopmental disorders and/or multiple congenital ...anomalies, as well as for fetuses with ultrasound abnormalities. In the decade that this analysis has been in widespread clinical use, tremendous strides have been made in understanding the effects of copy-number variants (CNVs) in both affected individuals and the general population. However, continued broad implementation of array and next-generation sequencing-based technologies will expand the types of CNVs encountered in the clinical setting, as well as our understanding of their impact on human health.
To assist clinical laboratories in the classification and reporting of CNVs, irrespective of the technology used to identify them, the American College of Medical Genetics and Genomics has developed the following professional standards in collaboration with the National Institutes of Health (NIH)-funded Clinical Genome Resource (ClinGen) project.
This update introduces a quantitative, evidence-based scoring framework; encourages the implementation of the five-tier classification system widely used in sequence variant classification; and recommends "uncoupling" the evidence-based classification of a variant from its potential implications for a particular individual.
These professional standards will guide the evaluation of constitutional CNVs and encourage consistency and transparency across clinical laboratories.
Computational modeling of cardiovascular flow is a growing and useful field, but such simulations usually require the researcher to guess the flow's inlet and outlet conditions since they are ...difficult and expensive to measure. It is critical to determine the amount of uncertainty introduced by these assumptions in order to evaluate the degree to which cardiovascular flow simulations are accurate. Our work begins to address this question by examining the sensitivity of flow to several different assumed velocity inlet and outlet conditions in a patient-specific aorta model.
We examined the differences between plug flow, parabolic flow, linear shear flows, skewed cubic flow profiles, and Womersley flow at the inlet. Only the shape of the inlet velocity profile was varied-all other parameters were identical among these simulations. Secondary flow in the form of a counter-rotating pair of vortices was also added to parabolic axial flow to study its effect on the solution. In addition, we examined the differences between two-element Windkessel, three element Windkessel and the outflow boundary conditions. In these simulations, only the outlet boundary condition was varied.
The results show axial and in-plane velocities are considerably different close to the inlet for the cases with different inlet velocity profile shapes. However, the solutions are qualitatively similar beyond 1.75D, where D is the inlet diameter. This trend is also observed in other quantities such as pressure and wall shear stress. Normalized root-mean-square deviation, a measure of axial velocity magnitude differences between the different cases, generally decreases along the streamwise coordinate. The linear shear inlet velocity boundary condition and plug velocity boundary condition solution exhibit the highest time-averaged wall shear stress, approximately Formula: see text higher than the parabolic inlet velocity boundary condition. Upstream of 1D from the inlet, adding secondary flow has a significant impact on temporal wall shear stress distributions. This is especially observable during diastole, when integrated wall shear stress magnitude varies about Formula: see text between simulations with and without secondary flow. The results from the outlet boundary condition study show the Windkessel models differ from the outflow boundary condition by as much as Formula: see text in terms of time-averaged wall shear stress. Furthermore, normalized root-mean-square deviation of axial velocity magnitude, a measure of deviation between Windkessel and the outflow boundary condition, increases along the streamwise coordinate indicating larger variations near outlets.
It was found that the selection of inlet velocity conditions significantly affects only the flow region close to the inlet of the aorta. Beyond two diameters distal to the inlet, differences in flow solution are small. Although additional studies must be performed to verify this result, the data suggest that it is important to use patient-specific inlet conditions primarily if the researcher is concerned with the details of the flow very close to the inlet. Similarly, the selection of outlet conditions significantly affects the flow in the vicinity of the outlets. Upstream of five diameters proximal to the outlet, deviations between the outlet boundary conditions examined are insignificant. Although the inlet and outlet conditions only affect the flow significantly in their respective neighborhoods, our study indicates that outlet conditions influence a larger percentage of the solution domain.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
The objectives of this work were to (1) determine whether higher doses of motor therapy in chronic poststroke hemiparesis result in better outcomes, compared to lower doses, and (2) ...evaluate potential modifiers of the dose‐response relationship.
Methods
Eighty‐five adults with upper extremity paresis ≥6 months poststroke were randomized to one of four dose groups in this single‐blind, parallel, randomized, control trial. The dosing parameter manipulated was amount of task‐specific training, as indexed by the number of task repetitions. Groups received 3,200, 6,400, 9,600, or individualized maximum (IM) repetitions, during 1‐hour sessions, 4 days/week for 8 weeks. The intervention was an individualized, progressive, task‐specific upper‐limb training program designed to improve upper‐limb functional motor capacity. The primary outcome was the slope of the Action Research Arm Test (ARAT) during the intervention. Effects of dose and potential modifiers of the dose‐response relationship were evaluated with hierarchical linear models.
Results
ARAT scores for the 3,200, 9,600, and IM groups improved over time as indicated by slopes (ΔARAT/week, mean ± standard errors) of 0.40 ± 0.15, 0.31 ± 0.16, and 0.66 ± 0.14, respectively (p < 0.05). The slope of the 6,400 group was smaller (−0.05 ± 0.15) and significantly different from the 3,200 and IM groups (p < 0.001). Initial motor capacity, neglect, and other tested characteristics did not modify the dose‐response relationship.
Interpretation
Overall, treatment effects were small. There was no evidence of a dose‐response effect of task‐specific training on functional capacity in people with long‐standing upper‐limb paresis poststroke. Ann Neurol 2016;80:342–354
Automated Lymph Node (LN) detection is an important clinical diagnostic task but very challenging due to the low contrast of surrounding structures in Computed Tomography (CT) and to their varying ...sizes, poses, shapes and sparsely distributed locations. State-of-the-art studies show the performance range of 52.9% sensitivity at 3.1 false-positives per volume (FP/vol.), or 60.9% at 6.1 FP/vol. for mediastinal LN, by one-shot boosting on 3D HAAR features. In this paper, we first operate a preliminary candidate generation stage, towards -100% sensitivity at the cost of high FP levels (-40 per patient), to harvest volumes of interest (VOI). Our 2.5D approach consequently decomposes any 3D VOI by resampling 2D reformatted orthogonal views N times, via scale, random translations, and rotations with respect to the VOI centroid coordinates. These random views are then used to train a deep Convolutional Neural Network (CNN) classifier. In testing, the CNN is employed to assign LN probabilities for all N random views that can be simply averaged (as a set) to compute the final classification probability per VOI. We validate the approach on two datasets: 90 CT volumes with 388 mediastinal LNs and 86 patients with 595 abdominal LNs. We achieve sensitivities of 70%/83% at 3 FP/vol. and 84%/90% at 6 FP/vol. in mediastinum and abdomen respectively, which drastically improves over the previous state-of-the-art work.
Numerical integration of mathematical models of heart cell electrophysiology provides an important computational tool for studying cardiac arrhythmias, but the abundance of available models ...complicates selecting an appropriate model. We study the behavior of two recently published models of human ventricular action potentials, the Grandi-Pasqualini-Bers (GPB) and the O'Hara-Virág-Varró-Rudy (OVVR) models, and compare the results with four previously published models and with available experimental and clinical data. We find the shapes and durations of action potentials and calcium transients differ between the GPB and OVVR models, as do the magnitudes and rate-dependent properties of transmembrane currents and the calcium transient. Differences also occur in the steady-state and S1-S2 action potential duration and conduction velocity restitution curves, including a maximum conduction velocity for the OVVR model roughly half that of the GPB model and well below clinical values. Between single cells and tissue, both models exhibit differences in properties, including maximum upstroke velocity, action potential amplitude, and minimum diastolic interval. Compared to experimental data, action potential durations for the GPB and OVVR models agree fairly well (although OVVR epicardial action potentials are shorter), but maximum slopes of steady-state restitution curves are smaller. Although studies show alternans in normal hearts, it occurs only in the OVVR model, and only for a narrow range of cycle lengths. We find initiated spiral waves do not progress to sustained breakup for either model. The dominant spiral wave period of the GPB model falls within clinically relevant values for ventricular tachycardia (VT), but for the OVVR model, the dominant period is longer than periods associated with VT. Our results should facilitate choosing a model to match properties of interest in human cardiac tissue and to replicate arrhythmia behavior more closely. Furthermore, by indicating areas where existing models disagree, our findings suggest avenues for further experimental work.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this paper, we present the measurement of the energy spectra of carbon and oxygen in cosmic rays based on observations with the Calorimetric Electron Telescope on the International Space Station ...from October 2015 to October 2019. Analysis, including the detailed assessment of systematic uncertainties, and results are reported. The energy spectra are measured in kinetic energy per nucleon from 10 GeV/n to 2.2 TeV/n with an all-calorimetric instrument with a total thickness corresponding to 1.3 nuclear interaction length. The observed carbon and oxygen fluxes show a spectral index change of ∼0.15 around 200 GeV/n established with a significance > 3σ. They have the same energy dependence with a constant C/O flux ratio 0.911 ± 0.006 above 25 GeV/n. The spectral hardening is consistent with that measured by AMS-02, but the absolute normalization of the flux is about 27% lower, though in agreement with observations from previous experiments including the PAMELA spectrometer and the calorimetric balloon-borne experiment CREAM.
Abstract
Over the past 3 decades, the volume of human motor learning research has grown enormously. As such, the understanding of motor learning (ie, sustained change in motor behavior) has evolved. ...It has been learned that there are multiple mechanisms through which motor learning occurs, each with distinctive features. These mechanisms include use-dependent, instructive, reinforcement, and sensorimotor adaptation-based motor learning. It is now understood that these different motor learning mechanisms contribute in parallel or in isolation to drive desired changes in movement, and each mechanism is thought to be governed by distinct neural substrates. This expanded understanding of motor learning mechanisms has important implications for physical therapy. It has the potential to facilitate the development of new, more precise treatment approaches that physical therapists can leverage to improve human movement. This Perspective describes scientific advancements related to human motor learning mechanisms and discusses the practical implications of this work for physical therapist practice and education.
Abstract
Recruitment to key positions in institutions can be viewed as one way to introduce strategic reforms; however, little research has been conducted as to the effectiveness of the practice ...within parliaments. Even less has been written about the recruitment practices for non-elected parliamentary actors. Applying a feminist discursive institutionalist analysis, this article highlights the main discourses prominent in discussions around the recruitment to the Clerk of the House of Commons in 2014. It is argued that there are three discourses that rhetorically de-gendered career structures in the UK House of Commons, while two discourses explicitly gendered the applicant to the position of Clerk. The article discusses the broader significance of these insights for analysing parliaments as gendered workplaces, and for member engagement with parliamentary administrations.
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