Tropical tree mortality has increased with rising atmospheric water stress.

Evidence exists that tree mortality is accelerating in some regions of the tropics1,2, with profound consequences for the future of the tropical carbon sink and the global anthropogenic carbon budget left to limit peak global warming below 2 °C. However, the mechanisms that may be driving such mortality changes and whether particular species are especially vulnerable remain unclear3-8. Here we analyse a 49-year record of tree dynamics from 24 old-growth forest plots encompassing a broad climatic gradient across the Australian moist tropics and find that annual tree mortality risk has, on average, doubled across all plots and species over the last 35 years, indicating a potential halving in life expectancy and carbon residence time. Associated losses in biomass were not offset by gains from growth and recruitment. Plots in less moist local climates presented higher average mortality risk, but local mean climate did not predict the pace of temporal increase in mortality risk. Species varied in the trajectories of their mortality risk, with the highest average risk found nearer to the upper end of the atmospheric vapour pressure deficit niches of species. A long-term increase in vapour pressure deficit was evident across the region, suggesting that thresholds involving atmospheric water stress, driven by global warming, may be a primary cause of increasing tree mortality in moist tropical forests.

Oxygen uptake and heart rate responses to 4 weeks of RPE-guided handcycle training.

PURPOSE: To investigate the efficacy of using Ratings of Perceived Exertion (RPE) to prescribe and regulate a 4-week handcycle training intervention. METHODS: Thirty active adults, untrained in upper body endurance exercise, were divided into three groups to complete a 4-week intervention: (i) RPE-guided training (n = 10; 2 female), (ii) power output (PO)-guided (n = 10; 2 female) training, or (iii) non-training control (n = 10; 4 female). Training groups performed three sessions of handcycling each week. Oxygen uptake ([Formula: see text]), heart rate (HR), and Feeling Scale (FS) rating were collected during training sessions. RPE-guided training was performed at RPE 13. PO-guided training was matched for percentage of peak PO per session, based upon that achieved by the RPE-guided training group. RESULTS: There were no differences in percentage of peak [Formula: see text] (66 ± 13% vs 61 ± 9%, p = 0.22), peak HR (75 ± 8% vs 71 ± 6%, p = 0.11) or FS rating (1.2 ± 1.9 vs 0.8 ± 1.6, p = 0.48) between RPE- and PO-guided training, respectively. The average coefficient of variation in percentage of peak HR between consecutive training sessions was 2.8% during RPE-guided training, and 3.4% during PO-guided training. CONCLUSION: Moderate-vigorous intensity handcycling exercise can be prescribed effectively using RPE across a chronic training intervention, suggesting utility for practitioners in a variety of rehabilitation settings.

Stakeholders' Consensus to Guide the Minimum Impairment Criteria in Wheelchair Basketball.

The International Paralympic Committee athlete classification code mandates sports to have defined minimum impairment criteria, describing the minimum level of an eligible impairment an athlete must possess, to be able to participate in that sport. The aim of this study was to establish stakeholders' consensus for the minimum impairment criteria in wheelchair basketball. From a pool of 48 expert stakeholders (identified via an international medical and scientific working group), 39 completed a 4-round Delphi survey. Questions were answered on the method of assessing each eligible impairment, and the level of impairment that should constitute the minimum impairment criteria. This study indicated where stakeholder consensus existed and noted that consensus was developed for impaired muscle power, impaired passive range of motion, leg length difference, hypertonia and ataxia. No consensus was found for limb deficiency and athetosis. Participants raised concerns with using subjective measurement scales for assessing certain impairments, whilst also calling for more quantitative research to be conducted into the level of impairment that should constitute the minimum impairment criteria. For these research findings to form practical minimum impairment criteria that are part of a wheelchair basketball classification system, it is required to examine their feasibility by conducting further research.

Tropical tree growth sensitivity to climate is driven by species intrinsic growth rate and leaf traits.

A better understanding of how climate affects growth in tree species is essential for improved predictions of forest dynamics under climate change. Long-term climate averages (mean climate) drive spatial variations in species' baseline growth rates, whereas deviations from these averages over time (anomalies) can create growth variation around the local baseline. However, the rarity of long-term tree census data spanning climatic gradients has so far limited our understanding of their respective role, especially in tropical systems. Furthermore, tree growth sensitivity to climate is likely to vary widely among species, and the ecological strategies underlying these differences remain poorly understood. Here, we utilize an exceptional dataset of 49 years of growth data for 509 tree species across 23 tropical rainforest plots along a climatic gradient to examine how multiannual tree growth responds to both climate means and anomalies, and how species' functional traits mediate these growth responses to climate. We show that anomalous increases in atmospheric evaporative demand and solar radiation consistently reduced tree growth. Drier forests and fast-growing species were more sensitive to water stress anomalies. In addition, species traits related to water use and photosynthesis partly explained differences in growth sensitivity to both climate means and anomalies. Our study demonstrates that both climate means and anomalies shape tree growth in tropical forests and that species traits can provide insights into understanding these demographic responses to climate change, offering a promising way forward to forecast tropical forest dynamics under different climate trajectories.

Effects of Perceptually Regulated Exercise Training on Cardiorespiratory Fitness and Peak Power Output in Adults With Spinal Cord Injury: A Systematic Review and Meta-analysis.

OBJECTIVE: To analyze and summarize the effect of regulating exercise training interventions with subjective measures of intensity on cardiorespiratory fitness, measured by peak oxygen uptake (V̇O2peak) and peak power output (POpeak) in adults with spinal cord injury (SCI). DATA SOURCES: Four databases (MEDLINE, Embase, PsycINFO, SPORTDiscus) were searched from inception up until September 1, 2020, and updated November 18, 2021. STUDY SELECTION: Searches combined keywords relating to the topics: SCI, subjective measures of exercise intensity, and exercise. DATA EXTRACTION: Two reviewers independently conducted eligibility screening, data extraction, and assessed the risk of bias. Nine studies were included in the systematic review and meta-analysis, resulting in the inclusion of data from 95 adults with SCI representing both sexes and a diverse range of age, time since injury, lesion level, and lesion completeness classifications. DATA SYNTHESIS: Data were extracted and added to summary tables with 3 outcomes: V̇O2peak, POpeak, and Other. Mean and SD values for V̇O2peak and POpeak were extracted from pre- and post-perceptually regulated exercise training. CONCLUSIONS: All studies used ratings of perceived exertion scale to prescribe exercise intensity. Seven of 8 studies concluded an improvement in V̇O2peak, and 5 studies of 7 concluded an improvement in POpeak. In the outcome Other, 5 studies concluded an improvement, and 3 studies concluded no change. There was evidence for an improvement in cardiorespiratory fitness, measured by V̇O2peak and POpeak after perceptually regulated exercise training in adults with SCI (Grading of Recommendations, Assessment, Development, and Evaluation ratings: Low) (mean difference [MD], 2.92mL/kg/min; 95% confidence interval [CI], 1.30-4.54; P=.0004 and MD, 9.8W; 95% CI, 5.5-14.3; P<.0001, respectively). This review provides critically appraised, cumulative evidence on the use of perceptually regulated exercise training in individuals with SCI.

Rethinking aerobic exercise intensity prescription in adults with spinal cord injury: time to end the use of "moderate to vigorous" intensity?

STUDY DESIGN: Cohort study. OBJECTIVES: To investigate and critique different methods for aerobic exercise intensity prescription in adults with spinal cord injury (SCI). SETTING: University laboratory in Loughborough, UK. METHODS: Trained athletes were split into those with paraplegia (PARA; n = 47), tetraplegia (TETRA; n = 20) or alternate health condition (NON-SCI; n = 67). Participants completed a submaximal step test with 3 min stages, followed by graded exercise test to exhaustion. Handcycling, arm crank ergometry or wheelchair propulsion were performed depending on the sport of the participant. Oxygen uptake (V̇O2), heart rate (HR), blood lactate concentration ([BLa]) and ratings of perceived exertion (RPE) on Borg's RPE scale were measured throughout. Lactate thresholds were identified according to log-V̇O2 plotted against log-[BLa] (LT1) and 1.5 mmol L-1 greater than LT1 (LT2). These were used to demarcate moderate (LT1, < LT2) and severe (>LT2) exercise intensity domains. RESULTS: Associations between percentage of peak V̇O2 (%V̇O2peak) and HR (%HRpeak) with RPE differed between PARA and TETRA. At LT1 and LT2, %V̇O2peak and %HRpeak were significantly greater in TETRA compared to PARA and NON-SCI (P < 0.05). The variation in %V̇O2peak and %HRpeak at lactate thresholds resulted in large variability in the domain distribution at fixed %V̇O2peak and %HRpeak. CONCLUSIONS: Fixed %V̇O2peak and %HRpeak should not be used for aerobic exercise intensity prescription in adults with SCI as the method does not lead to uniform exercise intensity domain distribution.

We Must Talk about Sex and Focal Dystonia.

In a recent workshop on "Defining research priorities in dystonia,", there was absolutely no reference to sex as a factor in disease pathogenesis. In this viewpoint paper, we argue that the most distinctive aspects of adult onset isolated focal dystonia are the marked sex-related differences demonstrated by epidemiological, clinical, and laboratory studies in patients with adult onset dystonia, particularly in cervical dystonia, the most common presentation. We propose that the future focus of research should be on neurobiological mechanisms underlying the profound sexual dimorphism in this disorder. Targeting research into gamma aminobutyric acid (GABA)ergic function, which also shows similar sexual dimorphism, would be most productive in elucidating the pathogenesis of adult onset dystonia. © 2021 International Parkinson and Movement Disorder Society.

Impact of obstructive sleep apnoea on cognitive function in multiple sclerosis: A longitudinal study.

Cognitive impairment (CI) and fatigue are common in people with multiple sclerosis (MS), with well-known profound effects on quality of life. Sleep disorders, including obstructive sleep apnoea (OSA), are also common in MS patients. The presence of CI has previously been shown to strongly correlate with OSA diagnosed using polysomnography in MS. Treatment of OSA has not previously been investigated as a potential modality to improve cognition in MS patients. Therefore, we sought to investigate the potential effects of OSA treatment on both cognitive function and fatigue in MS patients. Twenty-three participants with MS reporting significant fatigue were enrolled. CI was assessed by the Brief International Cognitive Assessment in MS and the 3-second Paced Auditory Serial Addition Test. All participants underwent overnight polysomnography to assess for possible OSA. Cognitive and fatigue measures were repeated in those subsequently treated for OSA and in a comparative untreated sample. Seven participants (30%) had a diagnosis of OSA based on an apnoea-hypopnea index greater than 5 per hour, with no correlation between the presence of CI and OSA. Verbal learning at follow-up assessment was seen to improve significantly in those treated for OSA, compared with those who were not treated for a sleep disorder. This small study demonstrates the potential for OSA treatment to improve verbal learning in people with MS, larger studies are indicated to further investigate the potential for cognitive and fatigue improvement in people with MS through treatment of comorbid OSA.

Comparison of two Borg exertion scales for monitoring exercise intensity in able-bodied participants, and those with paraplegia and tetraplegia.

STUDY DESIGN: Cross-sectional cohort study. OBJECTIVES: To compare ratings of perceived exertion (RPE) on Borg's 6-20 RPE scale and Category Ratio 10 (CR10) in able-bodied (AB) participants during upper and lower body exercise, and recreationally active participants with paraplegia (PARA) and athletes with tetraplegia (TETRA) during upper body exercise only. SETTING: University and rehabilitation centre-based laboratories in UK and Netherlands. METHODS: Twenty-four participants were equally split between AB, PARA, and TETRA. AB performed maximal tests using cycle (AB-CYC) and handcycle (AB-HC) ergometry. PARA and TETRA performed maximal handcycle and wheelchair propulsion tests, respectively. Oxygen uptake (V̇O2) and blood lactate concentration were monitored throughout. RPE was rated each stage on Borg's RPE scale and CR10. Thresholds were identified according to log-V̇O2 plotted against log-blood lactate (LT1), and 1.5 mmol L-1 greater than LT1 (LT2). RESULTS: RPE from both scales were best fit against each other using a quadratic model, with high goodness of fit between scales that was independent of exercise mode and participant group (range R2: 0.965-0.970, P < 0.005). Though percentage peak V̇O2 was significantly greater in TETRA (P < 0.005), there was no difference in RPE at LT1 or LT2 between groups on Borg's RPE scale or CR10. CONCLUSION: Strong association between Borg's RPE scale and CR10 suggests they can be used interchangeably. RPE at lactate thresholds were independent of mode of exercise and level of spinal cord injury. However, inter-individual variation precludes from making firm recommendations about using RPE for prescribing homogenous exercise intensity.

Optimising classification of proximal arm strength impairment in wheelchair rugby: A proof of concept study.

This study examined the relationship between proximal arm strength and mobility performance in wheelchair rugby (WR) athletes and examined whether a valid structure for classifying proximal arm strength impairment could be determined. Fifty-seven trained WR athletes with strength impaired arms and no trunk function performed six upper body isometric strength tests and three 10 m sprints in their rugby wheelchair. All strength measures correlated with 2 m and 10 m sprint times (r ≥ -0.43; p ≤ 0.0005) and were entered into k-means cluster analyses with 4-clusters (to mirror the current International Wheelchair Rugby Federation [IWRF] system) and 3-clusters. The 3-cluster structure provided a more valid structure than both the 4-cluster and existing IWRF system, as evidenced by clearer differences in strength (Effect sizes [ES] ≥ 1.0) and performance (ES ≥ 1.1) between adjacent clusters and stronger mean silhouette coefficient (0.64). Subsequently, the 3-cluster structure for classifying proximal arm strength impairment would result in less overlap between athletes from adjacent classes and reduce the likelihood of athletes being disadvantaged due to their impairment. This study demonstrated that the current battery of isometric strength tests and cluster analyses could facilitate the evidence-based development of classifying proximal arm strength impairment in WR.

Measures of impairment applicable to the classification of Paralympic athletes competing in wheelchair sports: A systematic review of validity, reliability and associations with performance.

A fundamental aspect of classification systems in Paralympic sport is having valid and reliable measures of impairment. However, minimal consensus exists for assessing impaired strength, coordination and range of motion. This review aimed to systematically identify measures of upper body strength, coordination and range of motion impairments that meet the requirements for use in evidence-based classification systems in wheelchair sports. Three electronic databases were searched from 2003 until 31 August 2019 for studies that assessed upper body function of participants and used a measurement tool that assessed strength, coordination or range of motion. The body of evidence for each identified measure was appraised using the Grading of Recommendations Assessment, Development and Evaluation framework. Twenty-three studies were included: ten measured strength and coordination, and six measured range of motion. There was "moderate" confidence in using isometric strength for assessing strength impairment. Tapping tasks for the assessment of coordination impairment received a "low" confidence rating. All other identified measures of coordination and range of motion impairment received a "very low" confidence rating. Several potential measures were identified for assessing upper body strength, coordination and range of motion impairments. Further research is warranted to investigate their use for classification in Paralympic wheelchair sports.

Slowed Luminance Reaction Times in Cervical Dystonia: Disordered Superior Colliculus Processing.

BACKGROUND: Abnormal temporal discrimination in cervical dystonia is hypothesized to be attributable to disrupted processing in the superior colliculus. The fast, luminance-based, retinotectal pathway, projects to the superior colliculus; chromatic stimuli responses, by the retino-geniculo-calcarine pathway, are up to 30 ms longer. OBJECTIVES: We sought to interrogate visual processing and reaction times in patients with cervical dystonia compared with healthy controls. We hypothesized that cervical dystonia patients would have impaired reaction times to luminance based stimuli accessing the retino-tectal pathway in comparison to healthy control participants. METHODS: In 20 cervical dystonia and 20 age-matched control participants, we compared reaction times to two flashing visual stimuli: (1) a chromatic annulus and (2) a luminant, noncolored annulus. Participants pressed a joystick control when they perceived the annulus flashing. RESULTS: Reaction times in control participants were 20 ms significantly faster in the luminant condition than the chromatic (P = 0.017). Patients with cervical dystonia had no reaction time advantage in response to the luminant stimulus. CONCLUSION: Cervical dystonia patients (compared to control participants) demonstrated no reduction in their reaction time to luminant stimuli, processed through the retinotectal pathway. This finding is consistent with superior colliculus dysfunction in cervical dystonia. © 2020 International Parkinson and Movement Disorder Society.

Division, result and score margin alter the physical and technical performance of elite wheelchair tennis players.

This study determined the physical and technical demands of elite wheelchair tennis (WT) match-play, how the demands differed between divisions (Men, Women, Quad) and the effect that set result and score margin had on these demands. Seventeen WT players were monitored during a singles competition. Physical measures of performance were analysed using an indoor tracking system and inertial measurement units. Technical measures of performance were examined using video analysis. Physical measures of performance differed by division (Men > Women > Quad) for most parameters. Rallies were longer during Men's (P = 0.027) and Women's (P = 0.004) matches compared to Quad's and fewer shots were hit off 2 bounces in Men's matches compared to Women's and Quad's (P ≤ 0.026). High-speed activity (HSA) increased during losing sets (P = 0.043). Most physical measures of performance increased by moderate to large effects during sets with a small score margin (≤3 games differential). Mean speed and HSA were similar during losing sets, regardless of margin, but decreased (large effects) when winning by a large margin. This study demonstrated the physical and technical demands that elite WT players need to be prepared for and how situational factors can influence these demands.

The validity of optimal leaf traits modelled on environmental conditions.

The ratio of leaf intercellular to ambient CO2 (χ) is modulated by stomatal conductance (gs ). These quantities link carbon (C) assimilation with transpiration, and along with photosynthetic capacities (Vcmax and Jmax ) are required to model terrestrial C uptake. We use optimization criteria based on the growth environment to generate predicted values of photosynthetic and water-use efficiency traits and test these against a unique dataset. Leaf gas-exchange parameters and carbon isotope discrimination were analysed in relation to local climate across a continental network of study sites. Sun-exposed leaves of 50 species at seven sites were measured in contrasting seasons. Values of χ predicted from growth temperature and vapour pressure deficit were closely correlated to ratios derived from C isotope (δ13 C) measurements. Correlations were stronger in the growing season. Predicted values of photosynthetic traits, including carboxylation capacity (Vcmax ), derived from δ13 C, growth temperature and solar radiation, showed meaningful agreement with inferred values derived from gas-exchange measurements. Between-site differences in water-use efficiency were, however, only weakly linked to the plant's growth environment and did not show seasonal variation. These results support the general hypothesis that many key parameters required by Earth system models are adaptive and predictable from plants' growth environments.

New versus old: Implications of evolving diagnostic criteria for relapsing-remitting multiple sclerosis.

The International Panel on Diagnosis of Multiple Sclerosis (MS) recently revised the 2010 McDonald criteria and made recommendations for revision, allowing for the earliest possible, accurate diagnosis of MS. For relapsing-remitting MS, positive, unmatched cerebrospinal fluid oligoclonal bands may substitute for dissemination in time. Symptomatic lesions, including brainstem and spinal cord, may demonstrate dissemination in space or in time if enhancing (with the exception of the optic nerve). Cortical and juxtacortical lesions are equivalent. In this retrospective analysis, we applied revised criteria to 250 patients previously diagnosed with relapsing-remitting MS according to 2010 criteria and assessed for change in diagnostic times. There was a significant improvement in time to diagnosis between 2010 and 2017 groups ( p < 0.01). Median time to diagnosis according to McDonald 2010 was 7.4 months, compared with 2.3 months for McDonald 2017. Use of cerebrospinal fluid results most frequently resulted in a reduction in time to diagnosis. Symptomatic gadolinium-enhancing lesions led to earliest diagnostic times.

Neuraxial analgesia is not associated with an increased risk of post-partum relapses in MS.

BACKGROUND: Obstetrical analgesia remains a matter of controversy because of the fear of neurotoxicity of local anesthetics on demyelinated fibers or their potential relationship with subsequent relapses. OBJECTIVE: To assess the impact of neuraxial analgesia on the risk of relapse during the first 3 months post-partum, with a focus on women who experienced relapses during pregnancy. METHODS: We analyzed data of women followed-up prospectively during their pregnancies and at least 3 months post-partum, collected in the Pregnancy in Multiple Sclerosis (PRIMS) and Prevention of Post-Partum Relapses with Progestin and Estradiol in Multiple Sclerosis (POPARTMUS) studies between 1992-1995 and 2005-2012, respectively. The association of neuraxial analgesia with the occurrence of a post-partum relapse was estimated by logistic regression analysis. RESULTS: A total of 389 women were included, 215 from PRIMS and 174 from POPARTMUS. In total, 156 women (40%) had neuraxial analgesia. Overall, 24% experienced a relapse during pregnancy and 25% in the 3 months post-partum. Women with a pregnancy relapse were more likely to have a post-partum relapse (odds ratio (OR) = 1.83, p = 0.02), independently of the use of neuraxial analgesia. There was no association between neuraxial analgesia and post-partum relapse (OR = 1.08, p = 0.78). CONCLUSION: Neuraxial analgesia was not associated with an increased risk of post-partum relapses, whatever multiple sclerosis (MS) activity during pregnancy.

Peak oxygen uptake measured during a perceptually-regulated exercise test is reliable in community-based manual wheelchair users.

This study compares test-retest reliability and peak exercise responses from ramp-incremented (RAMP) and maximal perceptually-regulated (PRETmax) exercise tests during arm crank exercise in individuals reliant on manual wheelchair propulsion (MWP). Ten untrained participants completed four trials over 2-weeks (two RAMP (0-40 W + 5-10 W · min-1) trials and two PRETmax. PRETmax consisted of five, 2-min stages performed at Ratings of Perceived Exertion (RPE) 11, 13, 15, 17 and 20). Participants freely changed the power output to match the required RPE. Gas exchange variables, heart rate, power output, RPE and affect were determined throughout trials. The V̇O2peak from RAMP (14.8 ± 5.5 ml · kg-1 · min-1) and PRETmax (13.9 ± 5.2 ml · kg-1 · min-1) trials were not different (P = 0.08). Measurement error was 1.7 and 2.2 ml · kg-1 · min-1 and coefficient of variation 5.9% and 8.1% for measuring V̇O2peak from RAMP and PRETmax, respectively. Affect was more positive at RPE 13 (P = 0.02), 15 (P = 0.01) and 17 (P = 0.01) during PRETmax. Findings suggest that PRETmax can be used to measure V̇O2peak in participants reliant on MWP and leads to a more positive affective response compared to RAMP.

The impact of impairment on kinematic and kinetic variables in Va'a paddling: Towards a sport-specific evidence-based classification system for Para Va'a.

Para Va'a is a new Paralympic sport in which athletes with trunk and/or leg impairment compete over 200 m. The purpose of this study was to examine the impact of impairment on kinematic and kinetic variables during Va'a ergometer paddling. Ten able-bodied and 44 Para Va'a athletes with impairments affecting: trunk and legs (TL), legs bilaterally (BL) or leg unilaterally (UL) participated. Differences in stroke frequency, mean paddling force, and joint angles and correlation of the joint angles with paddling force were examined. Able-bodied demonstrated significantly greater paddling force as well as knee and ankle flexion ranges of movement (ROM) on the top hand paddling side compared to TL, BL and UL. Able-bodied, BL and UL demonstrated greater paddling force and trunk flexion compared to TL, and UL demonstrated larger bottom hand paddling side knee and ankle flexion ROM compared to BL. Significant positive correlations were observed for both male and female athletes between paddling force and all trunk flexion angles and ROM in the trunk and pelvis rotation and bottom hand paddling side hip, knee and ankle flexion. The results of this study are important for creating an evidence-based classification system for Para Va'a.

Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis.

Importance: Within 2 decades of onset, 80% of untreated patients with relapsing-remitting multiple sclerosis (MS) convert to a phase of irreversible disability accrual termed secondary progressive MS. The association between disease-modifying treatments (DMTs), and this conversion has rarely been studied and never using a validated definition. Objective: To determine the association between the use, the type of, and the timing of DMTs with the risk of conversion to secondary progressive MS diagnosed with a validated definition. Design, Setting, and Participants: Cohort study with prospective data from 68 neurology centers in 21 countries examining patients with relapsing-remitting MS commencing DMTs (or clinical monitoring) between 1988-2012 with minimum 4 years' follow-up. Exposures: The use, type, and timing of the following DMTs: interferon beta, glatiramer acetate, fingolimod, natalizumab, or alemtuzumab. After propensity-score matching, 1555 patients were included (last follow-up, February 14, 2017). Main Outcome and Measure: Conversion to objectively defined secondary progressive MS. Results: Of the 1555 patients, 1123 were female (mean baseline age, 35 years [SD, 10]). Patients initially treated with glatiramer acetate or interferon beta had a lower hazard of conversion to secondary progressive MS than matched untreated patients (HR, 0.71; 95% CI, 0.61-0.81; P < .001; 5-year absolute risk, 12% [49 of 407] vs 27% [58 of 213]; median follow-up, 7.6 years [IQR, 5.8-9.6]), as did fingolimod (HR, 0.37; 95% CI, 0.22-0.62; P < .001; 5-year absolute risk, 7% [6 of 85] vs 32% [56 of 174]; median follow-up, 4.5 years [IQR, 4.3-5.1]); natalizumab (HR, 0.61; 95% CI, 0.43-0.86; P = .005; 5-year absolute risk, 19% [16 of 82] vs 38% [62 of 164]; median follow-up, 4.9 years [IQR, 4.4-5.8]); and alemtuzumab (HR, 0.52; 95% CI, 0.32-0.85; P = .009; 5-year absolute risk, 10% [4 of 44] vs 25% [23 of 92]; median follow-up, 7.4 years [IQR, 6.0-8.6]). Initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a lower risk of conversion than initial treatment with glatiramer acetate or interferon beta (HR, 0.66; 95% CI, 0.44-0.99; P = .046); 5-year absolute risk, 7% [16 of 235] vs 12% [46 of 380]; median follow-up, 5.8 years [IQR, 4.7-8.0]). The probability of conversion was lower when glatiramer acetate or interferon beta was started within 5 years of disease onset vs later (HR, 0.77; 95% CI, 0.61-0.98; P = .03; 5-year absolute risk, 3% [4 of 120] vs 6% [2 of 38]; median follow-up, 13.4 years [IQR, 11-18.1]). When glatiramer acetate or interferon beta were escalated to fingolimod, alemtuzumab, or natalizumab within 5 years vs later, the HR was 0.76 (95% CI, 0.66-0.88; P < .001; 5-year absolute risk, 8% [25 of 307] vs 14% [46 of 331], median follow-up, 5.3 years [IQR], 4.6-6.1). Conclusions and Relevance: Among patients with relapsing-remitting MS, initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a lower risk of conversion to secondary progressive MS vs initial treatment with glatiramer acetate or interferon beta. These findings, considered along with these therapies' risks, may help inform decisions about DMT selection.

Machine Learning EEG to Predict Cognitive Functioning and Processing Speed Over a 2-Year Period in Multiple Sclerosis Patients and Controls.

Event-related potentials (ERPs) show promise to be objective indicators of cognitive functioning. The aim of the study was to examine if ERPs recorded during an oddball task would predict cognitive functioning and information processing speed in Multiple Sclerosis (MS) patients and controls at the individual level. Seventy-eight participants (35 MS patients, 43 healthy age-matched controls) completed visual and auditory 2- and 3-stimulus oddball tasks with 128-channel EEG, and a neuropsychological battery, at baseline (month 0) and at Months 13 and 26. ERPs from 0 to 700 ms and across the whole scalp were transformed into 1728 individual spatio-temporal datapoints per participant. A machine learning method that included penalized linear regression used the entire spatio-temporal ERP to predict composite scores of both cognitive functioning and processing speed at baseline (month 0), and months 13 and 26. The results showed ERPs during the visual oddball tasks could predict cognitive functioning and information processing speed at baseline and a year later in a sample of MS patients and healthy controls. In contrast, ERPs during auditory tasks were not predictive of cognitive performance. These objective neurophysiological indicators of cognitive functioning and processing speed, and machine learning methods that can interrogate high-dimensional data, show promise in outcome prediction.