A Quantitative EMG Assessment of Motor Unit Recruitment in Patients with Ulnar Neuropathy

The aim of the current study was to assess the test – retest reliability of motor unit firing rates with the use of decomposition based quantitative electromyography, and to quantify motor unit firing rates in the first dorsal interosseous of patients with ulnar neuropathy. 8 healthy subjects (mean age 35 ± 10 years) and 8 patients (mean age 48 ± 10 years) with ulnar neuropathy participated in the study. Following the acquisition of a maximum M wave, needle and surface detected EMGs were collected simultaneously during 30-second contractions performed at threshold (1-2% maximum voluntary contraction (MVC)) and 10% MVC- RMS ( maximum voluntary contraction root mean square) to obtain motor unit potential (MUP) trains. From the data collected, motor unit amplitude, duration, area, firing rate, and motor unit number estimates (MUNE) were calculated. Test-retest reliability of MU firing rates in controls was high (ICC =0.85). Motor unit firing rates were found to be moderately correlated with recruitment as rated by experienced clinicians and the MU firing rates were increased in patients with ulnar neuropathy

Investigating the Cortical, Metabolic and Behavioral Effects of Transcranial Direct Current Stimulation in Preparation for Combined Rehabilitation

The goal of this thesis was to determine the cortical reorganization that occurs in patients with cervical spondylotic myelopathy (CSM) after surgical decompression and to implement this knowledge into a new rehabilitation strategy. Transcranial direct current stimulation (tDCS) is a non-invasive technique to modulate human behavior. Due to the novel electrode montage used, it was first pertinent that we determine how tDCS would modulate cortical, metabolic and motor behavior in healthy individuals. We observed the longitudinal functional adaptations that occur in patients with CSM using functional MRI. Enhanced excitation of supplementary motor area (SMA) was observed following surgical decompression and associated with increased function following surgery. This novel finding of enhanced excitation of motivated us to use a bihemispheric tDCS protocol, exciting bilateral motor areas to provide optimal motor enhancement. This novel tDCS electrode montage, targeting the SMA and primary motor cortex (M1) was implemented in healthy older adults to determine its effects on enhancing manual dexterity. Furthermore, to determine the frequency with which to apply tDCS, a single and tri session protocol was used. We observed a differential pattern of action with anti-phase and in-phase motor tasks during multisession tDCS. We used ultra-high field (7T) MRI to examined the metabolic changes that occur following tDCS. After the stimulation period we observed no significant metabolite modulation. A trend towards an increase in the NAA/tCr ratio, with a concomitant decrease in the absolute concentration of tCr was observed. Finally, we examined the functional connectivity before, during and after tDCS with the use of resting-state fMRI at 7T. We observed enhanced connectivity within right sensorimotor area after stimulation compared to during stimulation. This result confirmed that cortical modulations differ during versus after tDCS, signifying that optimal modulation of behaviour may be after the stimulation period. Furthermore, we observed an enhanced correlation between motor regions and the caudate, both during and after stimulation. In conclusion, we observed novel cortical adaptations in CSM patients after surgical decompression, which led us to believe that bihemispheric tDCS of M1-SMA network would result in optimal motor enhancement and warrants further investigation in CSM and other neurological disorders

Many Labs 5:Testing pre-data collection peer review as an intervention to increase replicability

Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect (p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3?9; median total sample = 1,279.5, range = 276?3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (?r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols (r = .05) was similar to that of the RP:P protocols (r = .04) and the original RP:P replications (r = .11), and smaller than that of the original studies (r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00?.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19?.50)

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo

Meeting Abstracts: Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo Clearwater Beach, FL, USA. 9-11 June 201

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Examining long-term trends in politics and culture through language of political leaders and cultural institutions

From many perspectives, the election of Donald Trump was seen as a departure from long-standing political norms. An analysis of Trump’s word use in the presidential debates and speeches indicated that he was exceptionally informal but at the same time, spoke with a sense of certainty. Indeed, he is lower in analytic thinking and higher in confidence than almost any previous American president. Closer analyses of linguistic trends of presidential language indicate that Trump’s language is consistent with long-term linear trends, demonstrating that he is not as much an outlier as he initially seems. Across multiple corpora from the American presidents, non-US leaders, and legislative bodies spanning decades, there has been a general decline in analytic thinking and a rise in confidence in most political contexts, with the largest and most consistent changes found in the American presidency. The results suggest that certain aspects of the language style of Donald Trump and other recent leaders reflect long-evolving political trends. Implications of the changing nature of popular elections and the role of media are discussed

Erratum:Examining long-term trends in politics and culture through language of political leaders and cultural institutions (Proceedings of the National Academy of Sciences of the United States of America (2019)116 (3476–3481) DOI: 10.1073/pnas.1811987116)

Correction for “Examining long-term trends in politics and culture through language of political leaders and cultural institutions,” by Kayla N. Jordan, Joanna Sterling, James W. Pennebaker, and Ryan L. Boyd, which was first published February 11, 2019; 10.1073/ pnas.1811987116 (Proc Natl Acad Sci USA 116:3476–3481). The authors note that their conflict of interest statement was omitted during publication. The authors declare the following: “J.W.P. is the owner of the text analysis program LIWC. All profits from the sales of LIWC are donated to the University of Texas at Austin.

Dual Gain and Loss of Cullin 3 Function Mediates Familial Hyperkalemic Hypertension

Familial hyperkalemic hypertension is caused by mutations in with-no-lysine kinases (WNKs) or in proteins that mediate their degradation, kelch-like 3 (KLHL3) and cullin 3 (CUL3). Although the mechanisms by which WNK and KLHL3 mutations cause the disease are now clear, the effects of the disease-causing CUL3Δ403-459 mutation remain controversial. Possible mechanisms, including hyperneddylation, altered ubiquitin ligase activity, decreased association with the COP9 signalosome (CSN), and increased association with and degradation of KLHL3 have all been postulated. Here, we systematically evaluated the effects of Cul3Δ403-459 using cultured kidney cells. We first identified that the catalytically active CSN subunit jun activation domain-binding protein-1 (JAB1) does not associate with the deleted Cul3 4-helix bundle domain but instead with the adjacent α/β1 domain, suggesting that altered protein folding underlies the impaired binding. Inhibition of deneddylation with JAB1 siRNA increased Cul3 neddylation and decreased KLHL3 abundance, similar to the Cul3 mutant. We next determined that KLHL3 degradation has both ubiquitin ligase-dependent and -independent components. Proteasomal KLHL3 degradation was enhanced by Cul3Δ403-459; however, autophagic degradation was also upregulated by this Cul3 mutant. Finally, to evaluate whether deficient substrate adaptor was responsible for the disease, we restored KLHL3 to wild-type (WT) Cul3 levels. In the absence of WT Cul3, WNK4 was not degraded, demonstrating that Cul3Δ403-459 itself cannot degrade WNK4; conversely, when WT Cul3 was present, as in diseased humans, WNK4 degradation was restored. In conclusion, deletion of exon 9 from Cul3 generates a protein that is itself ubiquitin-ligase defective but also capable of enhanced autophagocytic KLHL3 degradation, thereby exerting dominant-negative effects on the WT allele