Electromyography Data Processing Impacts Muscle Synergies during Gait for Unimpaired Children and Children with Cerebral Palsy

Muscle synergies calculated from electromyography (EMG) data identify weighted groups of muscles activated together during functional tasks. Research has shown that fewer synergies are required to describe EMG data of individuals with neurologic impairments. When considering potential clinical applications of synergies, understanding how EMG data processing impacts results and clinical interpretation is important. The aim of this study was to evaluate how EMG signal processing impacts synergy outputs during gait. We evaluated the impacts of two common processing steps for synergy analyses: low pass (LP) filtering and unit variance scaling. We evaluated EMG data collected during barefoot walking from five muscles of 113 children with cerebral palsy (CP) and 73 typically-developing (TD) children. We applied LP filters to the EMG data with cutoff frequencies ranging from 4 to 40 Hz (reflecting the range reported in prior synergy research). We also evaluated the impact of normalizing EMG amplitude by unit variance. We found that the total variance accounted for (tVAF) by a given number of synergies was sensitive to LP filter choice and decreased in both TD and CP groups with increasing LP cutoff frequency (e.g., 9.3 percentage points change for one synergy between 4 and 40 Hz). This change in tVAF can alter the number of synergies selected for further analyses. Normalizing tVAF to a z-score (e.g., dynamic motor control index during walking, walk-DMC) reduced sensitivity to LP cutoff. Unit variance scaling caused comparatively small changes in tVAF. Synergy weights and activations were impacted less than tVAF by LP filter choice and unit variance normalization. These results demonstrate that EMG signal processing methods impact outputs of synergy analysis and z-score based measures can assist in reporting and comparing results across studies and clinical centers

Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5

The 5'-cap-structures of higher eukaryote mRNAs are ribose 2'-O-methylated. Likewise, a number of viruses replicating in the cytoplasm of eukayotes have evolved 2'-O-methyltransferases to modify autonomously their mRNAs. However, a defined biological role of mRNA 2'-O-methylation remains elusive. Here we show that viral mRNA 2'-O-methylation is critically involved in subversion of type-I-interferon (IFN-I) induction. We demonstrate that human and murine coronavirus 2'-O-methyltransferase mutants induce increased IFN-I expression, and are highly IFN-I sensitive. Importantly, IFN-I induction by 2'-O-methyltransferase-deficient viruses is dependent on the cytoplasmic RNA sensor melanoma differentiation-associated gene 5 (MDA5). This link between MDA5-mediated sensing of viral RNA and mRNA 2'-O-methylation suggests that RNA modifications, such as 2'-O-methylation, provide a molecular signature for the discrimination of self and non-self mRNA

Rescue therapy for vasospasm following aneurysmal subarachnoid hemorrhage:a propensity score-matched analysis with machine learning

OBJECTIVE Rescue therapies have been recommended for patients with angiographic vasospasm (aVSP) and delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH). However, there is little evidence from randomized clinical trials that these therapies are safe and effective. The primary aim of this study was to apply game theory-based methods in explainable machine learning (ML) and propensity score matching to determine if rescue therapy was associated with better 3-month outcomes following post-SAH aVSP and DCI. The authors also sought to use these explainable ML methods to identify patient populations that were more likely to receive rescue therapy and factors associated with better outcomes after rescue therapy. METHODS Data for patients with aVSP or DCI after SAH were obtained from 8 clinical trials and 1 observational study in the Subarachnoid Hemorrhage International Trialists repository. Gradient boosting ML models were constructed for each patient to predict the probability of receiving rescue therapy and the 3-month Glasgow Outcome Scale (GOS) score. Favorable outcome was defined as a 3-month GOS score of 4 or 5. Shapley Additive Explanation (SNAP) values were calculated for each patient-derived model to quantify feature importance and interaction effects. Variables with high S HAP importance in predicting rescue therapy administration were used in a propensity score-matched analysis of rescue therapy and 3-month GOS scores. RESULTS The authors identified 1532 patients with aVSP or DCI. Predictive, explainable ML models revealed that aneurysm characteristics and neurological complications, but not admission neurological scores, carried the highest relative importance rankings in predicting whether rescue therapy was administered. Younger age and absence of cerebral ischemia/ infarction were invariably linked to better rescue outcomes, whereas the other important predictors of outcome varied by rescue type (interventional or noninterventional). In a propensity score-matched analysis guided by SHAP-based variable selection, rescue therapy was associated with higher odds of 3-month GOS scores of 4-5 (OR 1.63, 95% CI 1.22-2.17). CONCLUSIONS Rescue therapy may increase the odds of good outcome in patients with aVSP or DCI after SAH. Given the strong association between cerebral ischemia/infarction and poor outcome, trials focusing on preventative or therapeutic interventions in these patients may be most able to demonstrate improvements in clinical outcomes. Insights developed from these models may be helpful for improving patient selection and trial design

State of the climate in 2018

In 2018, the dominant greenhouse gases released into Earth’s atmosphere—carbon dioxide, methane, and nitrous oxide—continued their increase. The annual global average carbon dioxide concentration at Earth’s surface was 407.4 ± 0.1 ppm, the highest in the modern instrumental record and in ice core records dating back 800 000 years. Combined, greenhouse gases and several halogenated gases contribute just over 3 W m−2 to radiative forcing and represent a nearly 43% increase since 1990. Carbon dioxide is responsible for about 65% of this radiative forcing. With a weak La Niña in early 2018 transitioning to a weak El Niño by the year’s end, the global surface (land and ocean) temperature was the fourth highest on record, with only 2015 through 2017 being warmer. Several European countries reported record high annual temperatures. There were also more high, and fewer low, temperature extremes than in nearly all of the 68-year extremes record. Madagascar recorded a record daily temperature of 40.5°C in Morondava in March, while South Korea set its record high of 41.0°C in August in Hongcheon. Nawabshah, Pakistan, recorded its highest temperature of 50.2°C, which may be a new daily world record for April. Globally, the annual lower troposphere temperature was third to seventh highest, depending on the dataset analyzed. The lower stratospheric temperature was approximately fifth lowest. The 2018 Arctic land surface temperature was 1.2°C above the 1981–2010 average, tying for third highest in the 118-year record, following 2016 and 2017. June’s Arctic snow cover extent was almost half of what it was 35 years ago. Across Greenland, however, regional summer temperatures were generally below or near average. Additionally, a satellite survey of 47 glaciers in Greenland indicated a net increase in area for the first time since records began in 1999. Increasing permafrost temperatures were reported at most observation sites in the Arctic, with the overall increase of 0.1°–0.2°C between 2017 and 2018 being comparable to the highest rate of warming ever observed in the region. On 17 March, Arctic sea ice extent marked the second smallest annual maximum in the 38-year record, larger than only 2017. The minimum extent in 2018 was reached on 19 September and again on 23 September, tying 2008 and 2010 for the sixth lowest extent on record. The 23 September date tied 1997 as the latest sea ice minimum date on record. First-year ice now dominates the ice cover, comprising 77% of the March 2018 ice pack compared to 55% during the 1980s. Because thinner, younger ice is more vulnerable to melting out in summer, this shift in sea ice age has contributed to the decreasing trend in minimum ice extent. Regionally, Bering Sea ice extent was at record lows for almost the entire 2017/18 ice season. For the Antarctic continent as a whole, 2018 was warmer than average. On the highest points of the Antarctic Plateau, the automatic weather station Relay (74°S) broke or tied six monthly temperature records throughout the year, with August breaking its record by nearly 8°C. However, cool conditions in the western Bellingshausen Sea and Amundsen Sea sector contributed to a low melt season overall for 2017/18. High SSTs contributed to low summer sea ice extent in the Ross and Weddell Seas in 2018, underpinning the second lowest Antarctic summer minimum sea ice extent on record. Despite conducive conditions for its formation, the ozone hole at its maximum extent in September was near the 2000–18 mean, likely due to an ongoing slow decline in stratospheric chlorine monoxide concentration. Across the oceans, globally averaged SST decreased slightly since the record El Niño year of 2016 but was still far above the climatological mean. On average, SST is increasing at a rate of 0.10° ± 0.01°C decade−1 since 1950. The warming appeared largest in the tropical Indian Ocean and smallest in the North Pacific. The deeper ocean continues to warm year after year. For the seventh consecutive year, global annual mean sea level became the highest in the 26-year record, rising to 81 mm above the 1993 average. As anticipated in a warming climate, the hydrological cycle over the ocean is accelerating: dry regions are becoming drier and wet regions rainier. Closer to the equator, 95 named tropical storms were observed during 2018, well above the 1981–2010 average of 82. Eleven tropical cyclones reached Saffir–Simpson scale Category 5 intensity. North Atlantic Major Hurricane Michael’s landfall intensity of 140 kt was the fourth strongest for any continental U.S. hurricane landfall in the 168-year record. Michael caused more than 30 fatalities and $25 billion (U.S. dollars) in damages. In the western North Pacific, Super Typhoon Mangkhut led to 160 fatalities and$6 billion (U.S. dollars) in damages across the Philippines, Hong Kong, Macau, mainland China, Guam, and the Northern Mariana Islands. Tropical Storm Son-Tinh was responsible for 170 fatalities in Vietnam and Laos. Nearly all the islands of Micronesia experienced at least moderate impacts from various tropical cyclones. Across land, many areas around the globe received copious precipitation, notable at different time scales. Rodrigues and Réunion Island near southern Africa each reported their third wettest year on record. In Hawaii, 1262 mm precipitation at Waipā Gardens (Kauai) on 14–15 April set a new U.S. record for 24-h precipitation. In Brazil, the city of Belo Horizonte received nearly 75 mm of rain in just 20 minutes, nearly half its monthly average. Globally, fire activity during 2018 was the lowest since the start of the record in 1997, with a combined burned area of about 500 million hectares. This reinforced the long-term downward trend in fire emissions driven by changes in land use in frequently burning savannas. However, wildfires burned 3.5 million hectares across the United States, well above the 2000–10 average of 2.7 million hectares. Combined, U.S. wildfire damages for the 2017 and 2018 wildfire seasons exceeded $40 billion (U.S. dollars)

Muscle synergies demonstrate only minimal changes after treatment in cerebral palsy

BACKGROUND: Children with cerebral palsy (CP) have altered synergies compared to typically-developing peers, reflecting different neuromuscular control strategies used to move. While these children receive a variety of treatments to improve gait, whether synergies change after treatment, or are associated with treatment outcomes, remains unknown. METHODS: We evaluated synergies for 147 children with CP before and after three common treatments: botulinum toxin type-A injection (n = 52), selective dorsal rhizotomy (n = 38), and multi-level orthopaedic surgery (n = 57). Changes in synergy complexity were measured by the number of synergies required to explain > 90% of the total variance in electromyography data and total variance accounted for by one synergy. Synergy weights and activations before and after treatment were compared using the cosine similarity relative to average synergies of 31 typically-developing (TD) peers. RESULTS: There were minimal changes in synergies after treatment despite changes in walking patterns. Number of synergies did not change significantly for any treatment group. Total variance accounted for by one synergy increased (i.e., moved further from TD peers) after botulinum toxin type-A injection (1.3%) and selective dorsal rhizotomy (1.9%), but the change was small. Synergy weights did not change for any treatment group (average 0.001 ± 0.10), but synergy activations after selective dorsal rhizotomy did change and were less similar to TD peers (- 0.03 ± 0.07). Only changes in synergy activations were associated with changes in gait kinematics or walking speed after treatment. Children with synergy activations more similar to TD peers after treatment had greater improvements in gait. CONCLUSIONS: While many of these children received significant surgical procedures and prolonged rehabilitation, the minimal changes in synergies after treatment highlight the challenges in altering neuromuscular control in CP. Development of treatment strategies that directly target impaired control or are optimized to an individual's unique control may be required to improve walking function.status: publishe

Associations Between Muscle Synergies and Treatment Outcomes in Cerebral Palsy Are Robust Across Clinical Centers

OBJECTIVE: To determine whether patient-specific differences in motor control quantified using muscle synergy analysis were associated with changes in gait after treatment of cerebral palsy (CP) across 2 clinical centers with different treatments and clinical protocols. DESIGN: Retrospective cohort study. SETTING: Clinical medical center. PARTICIPANTS: Center 1: children with CP (n=473) and typically developing (TD) children (n=84). Center 2: children with CP (n=163) and TD children (n=12). INTERVENTIONS: Standard clinical care at each center. MAIN OUTCOME MEASURES: The Dynamic Motor Control Index During Walking (walk-DMC) was computed from electromyographic data during gait using muscle synergy analysis. Regression analysis was used to evaluate whether pretreatment walking speed or kinematics, muscle synergies, treatment group, prior treatment, or age were associated with posttreatment changes in gait at both clinical centers. RESULTS: Walk-DMC was significantly associated with changes in speed and kinematics after treatment with similar regression models at both centers. Children with less impaired motor control were more likely to have improvements in walking speed and gait kinematics after treatment, independent of treatment group. CONCLUSIONS: Dynamic motor control evaluated with synergy analysis was associated with changes in gait after treatment at both centers, despite differences in treatments and clinical protocols. This study further supports the finding that walk-DMC provides additional information, not captured in traditional gait analysis, that may be useful for treatment planning.status: publishe

Muscle synergy constraints do not improve estimates of muscle activity from static optimization during gait for unimpaired children or children with cerebral palsy

Neuromusculoskeletal simulation provides a promising platform to inform the design of assistive devices or inform rehabilitation. For these applications, a simulation must be able to accurately represent the person of interest, such as an individual with a neurologic injury. If a simulation fails to predict how an individual recruits and coordinates their muscles during movement, it will have limited utility for informing design or rehabilitation. While inverse dynamic simulations have previously been used to evaluate anticipated responses from interventions, like orthopedic surgery or orthoses, they frequently struggle to accurately estimate muscle activations, even for tasks like walking. The simulated muscle activity often fails to represent experimentally measured muscle activity from electromyographic (EMG) recordings. Research has theorized that the nervous system may simplify the range of possible activations used during dynamic tasks, by constraining activations to weighted groups of muscles, referred to as muscle synergies. Synergies are altered after neurological injury, such as stroke or cerebral palsy (CP), and may provide a method for improving subject-specific models of neuromuscular control. The aim of this study was to test whether constraining simulation to synergies could improve estimated muscle activations compared to EMG data. We evaluated modeled muscle activations during gait for six typically developing (TD) children and six children with CP. Muscle activations were estimated with: (1) static optimization (SO), minimizing muscle activations squared, and (2) synergy SO (SynSO), minimizing synergy activations squared using the weights identified from EMG data for two to five synergies. While SynSO caused changes in estimated activations compared to SO, the correlation to EMG data was not higher in SynSO than SO for either TD or CP groups. The correlations to EMG were higher in CP than TD for both SO (CP: 0.48, TD: 0.36) and SynSO (CP: 0.46, TD: 0.26 for five synergies). Constraining activations to SynSO caused the simulated muscle stress to increase compared to SO for all individuals, causing a 157% increase with two synergies. These results suggest that constraining simulated activations in inverse dynamic simulations to subject-specific synergies alone may not improve estimation of muscle activations during gait for generic musculoskeletal models

Muscle synergies demonstrate only minimal changes after treatment in cerebral palsy

Background: Children with cerebral palsy (CP) have altered synergies compared to typically-developing peers, reflecting different neuromuscular control strategies used to move. While these children receive a variety of treatments to improve gait, whether synergies change after treatment, or are associated with treatment outcomes, remains unknown. Methods: We evaluated synergies for 147 children with CP before and after three common treatments: botulinum toxin type-A injection (n = 52), selective dorsal rhizotomy (n = 38), and multi-level orthopaedic surgery (n = 57). Changes in synergy complexity were measured by the number of synergies required to explain > 90% of the total variance in electromyography data and total variance accounted for by one synergy. Synergy weights and activations before and after treatment were compared using the cosine similarity relative to average synergies of 31 typically-developing (TD) peers. Results: There were minimal changes in synergies after treatment despite changes in walking patterns. Number of synergies did not change significantly for any treatment group. Total variance accounted for by one synergy increased (i.e., moved further from TD peers) after botulinum toxin type-A injection (1.3%) and selective dorsal rhizotomy (1.9%), but the change was small. Synergy weights did not change for any treatment group (average 0.001 ± 0.10), but synergy activations after selective dorsal rhizotomy did change and were less similar to TD peers (- 0.03 ± 0.07). Only changes in synergy activations were associated with changes in gait kinematics or walking speed after treatment. Children with synergy activations more similar to TD peers after treatment had greater improvements in gait. Conclusions: While many of these children received significant surgical procedures and prolonged rehabilitation, the minimal changes in synergies after treatment highlight the challenges in altering neuromuscular control in CP. Development of treatment strategies that directly target impaired control or are optimized to an individual's unique control may be required to improve walking function

Comparison of five different methodologies for evaluating ankle–foot orthosis stiffness

Abstract Background The mechanical properties of an ankle–foot orthosis (AFO) play an important role in the gait mechanics of the end user. However, testing methodologies for evaluating these mechanical properties are not standardized. The purpose of this study was to compare five different evaluation frameworks to assess AFO stiffness. Method The same 13 carbon composite AFOs were tested with five different methods. Four previously reported custom test fixtures (the BRUCE, KST, SMApp, and EMPIRE) rotated an AFO into dorsiflexion about a defined axis in the sagittal plane. The fifth method involved quasi-static deflection of AFOs into dorsiflexion by hanging weights (HW) from the footplate. AFO rotational stiffness was calculated as the linear fit of the AFO resistive torque and angular deflection. Differences between methods were assessed using descriptive statistics and a repeated measures Friedman with post-hoc Bonferroni–Holm adjusted Wilcoxon signed-rank tests. Results There were significant differences in measured AFO stiffnesses between test methods. Specifically, the BRUCE and HW methods measured lower stiffness than both the EMPIRE and the KST. Stiffnesses measured by the SMApp were not significantly different than any test method. Stiffnesses were lowest in the HW method, where motion was not constrained to a single plane. The median difference in absolute AFO stiffness across methods was 1.03 Nm/deg with a range of [0.40 to 2.35] Nm/deg. The median relative percent difference, measured as the range of measured stiffness from the five methods over the average measured stiffness was 62% [range 13% to 156%]. When the HW method was excluded, the four previously reported test fixtures produced a median difference in absolute AFO stiffness of 0.52 [range 0.38 to 2.17] Nm/deg with a relative percent difference between the methods of 27% [range 13% to 89%]. Conclusions This study demonstrates the importance of developing mechanical testing standards, similar to those that exist for lower limb prosthetics. Lacking standardization, differences in methodology can result in large differences in measured stiffness, particularly for different constraints on motion. Non-uniform measurement practices may limit the clinical utility of AFO stiffness as a metric in AFO prescription and future research