Interhemispheric facilitation of gesturing: A combined theta burst stimulation and diffusion tensor imaging study

BackgroundImaging studies point to a posture (finger vs. hand) and domain-specific neural basis of gestures. Furthermore, modulation of gestures by theta burst stimulation (TBS) may depend on interhemispheric disinhibition.Objective/HypothesisIn this randomized sham-controlled study, we hypothesized that dual site continuous TBS over left inferior frontal gyrus (IFG-L) and right inferior parietal gyrus (IPL-R) predominantly affects pantomime of finger postures. Furthermore, we predicted that dual cTBS improves imitation of hand gestures if the effect correlates with measures of callosal connectivity.MethodsForty-six healthy subjects participated in this study and were targeted with one train of TBS in different experimental sessions: baseline, sham, single site IFG-L, dual IFG-L/IPL-R, single site IPL-R. Gestures were evaluated by blinded raters using the Test for Upper Limb Apraxia (TULIA) and Postural Imitation Test (PIT). Callosal connectivity was analyzed by diffusion tensor imaging (DTI).ResultsDual cTBS significantly improved TULIA_total (F [3, 28] = 4.118, p = .009), but did not affect TULIA_pantomime. The beneficial effect was driven by the cTBS over IPL-R, which improved TULIA_imitation (p = .038). Furthermore, TULIA_imitation significantly correlated with the microstructure (fractional anisotropy) of the splenium (r = 0.420, p = .026), corrected for age and whole brain volume.ConclusionsThe study suggests that inhibition of IPL-R largely accounted for improved gesturing, possibly through transcallosal facilitation of IPL-L. Therefore, the findings may be relevant for the treatment of apraxic stroke patients. Gesture pantomime and postural gestures escaped the modulation by dual cTBS, suggesting a more widespread and/or variable neural representation.     

The role and interpretation of pilot studies in clinical research

Pilot studies represent a fundamental phase of the research process. The purpose of conducting a pilot study is to examine the feasibility of an approach that is intended to be used in a larger scale study. The roles and limitations of pilot studies are described here using a clinical trial as an example. A pilot study can be used to evaluate the feasibility of recruitment, randomization, retention, assessment procedures, new methods, and implementation of the novel intervention.A pilot study is not a hypothesis testing study. Safety, efficacy and effectiveness are not evaluated in a pilot. Contrary to tradition, a pilot study does not provide a meaningful effect size estimate for planning subsequent studies due to the imprecision inherent in data from small samples. Feasibility results do not necessarily generalize beyond the inclusion and exclusion criteria of the pilot design.A pilot study is a requisite initial step in exploring a novel intervention or an innovative application of an intervention. Pilot results can inform feasibility and identify modifications needed in the design of a larger, ensuing hypothesis testing study. Investigators should be forthright in stating these objectives of a pilot study. Grant reviewers and other stakeholders should expect no more.     

On Mathematicians' Different Standards When Evaluating Elementary Proofs

In this article, we report a study in which 109 research‐active mathematicians were asked to judge the validity of a purported proof in undergraduate calculus. Significant results from our study were as follows: (a) there was substantial disagreement among mathematicians regarding whether the argument was a valid proof, (b) applied mathematicians were more likely than pure mathematicians to judge the argument valid, (c) participants who judged the argument invalid were more confident in their judgments than those who judged it valid, and (d) participants who judged the argument valid usually did not change their judgment when presented with a reason raised by other mathematicians for why the proof should be judged invalid. These findings suggest that, contrary to some claims in the literature, there is not a single standard of validity among contemporary mathematicians.     

欺诈性医疗行为的认定与举证责任分配

欺诈性医疗行为是指医务人员以欺诈手段使患者产生错误认识,并在此基础上实施的诊疗活动.分析了欺诈性医疗与欺诈性医疗纠纷的不同,指出了其中的民事法律责任,并介绍了欺诈性医疗的举证责任分配,旨在讨论欺诈性医疗民事责任中的举证责任问题.     

Granularity Analysis for Mathematical Proofs

Mathematical proofs generally allow for various levels of detail and conciseness, such that they can be adapted for a particular audience or purpose. Using automated reasoning approaches for teaching proof construction in mathematics presupposes that the step size of proofs in such a system is appropriate within the teaching context. This work proposes a framework that supports the granularity analysis of mathematical proofs, to be used in the automated assessment of students' proof attempts and for the presentation of hints and solutions at a suitable pace. Models for granularity are represented by classifiers, which can be generated by hand or inferred from a corpus of sample judgments via machine‐learning techniques. This latter procedure is studied by modeling granularity judgments from four experts. The results provide support for the granularity of assertion‐level proofs but also illustrate a degree of subjectivity in assessing step size.     

Impact of responder definition on the enriched enrollment randomized withdrawal trial design for establishing proof of concept in neuropathic pain

The objective of this study was to evaluate how enrichment for responders increases assay sensitivity in an enriched enrollment randomized withdrawal (EERW) proof-of-concept (POC) study in neuropathic pain. Adults with moderate to severe peripheral neuropathic pain entered a 3- to 4-day screening period, followed by a 12-day titration to the highest tolerated dose that provided pain control (pregabalin 50-200 mg t.i.d.), and then a 9-day maintenance period. Subjects were stratified as primary responders (?30%), secondary responders (?10% to <30%), or nonresponders (<10%) based on decrease in pain intensity and were randomized to placebo or pregabalin during the randomized withdrawal period. The primary endpoint was mean of average 24-h pain intensity during the last 3 days of treatment period relative to the 3 days before randomization. Time-to-efficacy-failure was the key secondary endpoint. Other features included not requiring discontinuation of current analgesic therapies and blinding investigators to study design elements that could contribute to non-treatment-related responses. Effect size (ES) (mean treatment difference/SD) was used to measure assay sensitivity. Pregabalin-treated subjects (n = 52) had significantly less pain than those receiving placebo (n = 51) (P ? .003). Effect size of the primary endpoint was 0.72 for primary responders and decreased if secondary and nonresponders were included in the analysis. The highest ES (1.68) was demonstrated for the endpoint time-to-efficacy-failure seen in primary responders with painful diabetic neuropathy. The EERW trial design using time-to-efficacy-failure may provide a sensitive and efficient method to conduct POC studies of novel therapies in patients with neuropathic pain.     

Immunhistologischer Nachweis hautsensibilisierender Antikörper bei Penicillinallergie vom Typ der Serumkrankheit

Ohne Zusammenfassung

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对医疗侵权诉讼中"专家辅助人"制度的设想

最高人民法院在《关于民事诉讼证据的若干规定》中,首次将医疗侵权案件列入"举证责任倒置"的范畴。文章分析了新的证据规则对医疗侵权诉讼的影响,并结合参与医疗侵权诉讼的经验,提出了在诉讼中构建"专家辅助人"制度的设想。