Dominant CST3 variants cause adult onset leukodystrophy without amyloid angiopathy.

Leukodystrophies are rare genetic white matter disorders that have been regarded as mainly occurring in childhood. Recent years altered this perception, as a growing number of leukodystrophies was described to have an onset at adult ages. Still, many adult patients presenting with white matter changes remain without a specific molecular diagnosis. We describe a novel adult onset leukodystrophy in 16 patients from eight families carrying one of four different stop-gain or frameshift dominant variants in the CST3 gene. Clinical and radiological features differ markedly from the previously described Icelandic Cerebral Amyloid Angiopathy that was found in patients carrying p.Leu68Asn substitution in CST3. The clinical phenotype consists of recurrent episodes of hemiplegic migraine associated with transient unilateral focal deficits and slowly progressing motor symptoms and cognitive decline in mid-old adult ages. In addition, in some cases acute onset clinical deterioration led to a prolonged episode with reduced consciousness and even early death. Radiologically, pathognomonic changes are found at typical predilection sites involving the deep cerebral white matter sparing a periventricular and directly subcortical rim, the middle blade of corpus callosum, posterior limb of the internal capsule, middle cerebellar peduncles, cerebral peduncles, and specifically the globus pallidus. Histopathologic characterization in two autopsy cases did not reveal angiopathy, but instead micro- to macrocystic degeneration of the white matter. Astrocytes were activated at early stages and later on displayed severe degeneration and loss. In addition, despite loss of myelin, elevated numbers of partly apoptotic oligodendrocytes were observed. A structural comparison of the variants in CST3 suggests that specific truncations of Cystatin C result in an abnormal function, possibly by rendering the protein more prone to aggregation. Future studies are required to confirm the assumed effect on the protein and to determine pathophysiologic downstream events at the cellular level.

Cognitive Functions in Adult-Onset Phenotypes of X-Linked Adrenoleukodystrophy.

OBJECTIVE: X-linked adrenoleukodystrophy (X-ALD) is a rare genetic disorder characterized by progressive demyelination ranging from mild myelopathic forms (adrenomyeloneuropathy [AMN]) to severe cerebral variants (adult cerebral adrenoleukodystrophy [ACALD]). The aim of this study was to compare cognitive function in adult-onset X-ALD phenotypes. METHODS: Cognitive function in various domains (intelligence, attention, memory, executive function, and processing speed) was assessed in 172 adults (117 with AMN, 30 with arrested ACALD, and 25 with acute ACALD) using comprehensive neuropsychological batteries. Phenotype differences were examined by analyses of variance. RESULTS: X-ALD phenotypes significantly differed in nonverbal intelligence, sustained attention, verbal encoding, nonverbal recognition, and processing speed (ps < 0.050). No group differences emerged regarding verbal intelligence, verbal retrieval and recognition, and executive function (ps > 0.050). Specifically, patients with acute ACALD showed severe cognitive deficits compared to AMN and normal data, with largest effects on processing speed. Contrary, cognition was overall intact in patients with AMN, independent of sex and corticospinal tract involvement, and those with arrested ACALD showed mild cognitive dysfunction, particularly in verbal encoding and processing speed. INTERPRETATION: Cerebral demyelination in patients with X-ALD causes white matter dementia, mainly characterized by an extreme slowdown in processing speed associated with deficits in attention and learning. Most patients with AMN show intact cognitive function. Future prospective, longitudinal studies with more sensitive imaging techniques are required to clarify whether early mild cognitive dysfunction found in some patients with AMN may be associated with subtle myelin abnormalities that do not yet appear as white matter lesions on cerebral MRI (cMRI) but have the potential to serve as early predictors of later cerebral progression. ANN NEUROL 2021;90:266-273.

Creatine supplementation improves performance above critical power but does not influence the magnitude of neuromuscular fatigue at task failure.

NEW FINDINGS: What is the central question of this study? Does the magnitude of neuromuscular fatigue depend on the amount of work done (W') at task failure when cycling above critical power (CP)? What is the main finding and its importance? Creatine supplementation increases W' and enhances supra-CP performance, but induces similar magnitudes of neuromuscular fatigue at task failure compared to placebo. Increased W' does not lead to higher levels of neuromuscular fatigue. This supports the notion of a critical level of neuromuscular fatigue at task failure and challenges a direct causative link between W' depletion and neuromuscular fatigue. ABSTRACT: The present study examined the effect of creatine supplementation on neuromuscular fatigue and exercise tolerance when cycling above critical power (CP). Eleven males performed an incremental cycling test with four to five constant-load trials to task failure (TTF) to obtain asymptote (CP) and curvature constant (W') of the power-duration relationship, followed by three constant-load supra-CP trials: (1) one TTF following placebo supplementation (PLA); (2) one TTF following creatine supplementation (CRE); and (3) one trial of equal duration to PLA following creatine supplementation (ISO). Neuromuscular assessment of the right knee extensors was performed pre- and post-exercise to measure maximal voluntary contraction (MVC), twitch forces evoked by single (Qpot ) and paired high- (PS100) and low- (PS10) frequency stimulations and voluntary activation. Creatine supplementation increased TTF in CRE vs. PLA by ∼11% (P = 0.017) and work done above CP by ∼10% (P = 0.015), with no difference (P > 0.05) in reductions in MVC (-24 ± 8% vs. -20 ± 9%), Qpot (-39 ± 13% vs. -32 ± 14%), PS10 (-42 ± 14% vs. -36 ± 13%), PS100 (-25 ± 10% vs. -18 ± 12%) and voluntary activation (-7 ± 8% vs. -5 ± 7%). No significant difference was found between ISO and either PLA or CRE (P > 0.05). These findings suggest similar levels of neuromuscular fatigue can be found following supra-CP cycling despite increases in performance time and amount of work done above CP, supporting the notion of a critical level of neuromuscular fatigue and challenging a direct causative link between W' depletion and neuromuscular fatigue.

The magnitude of neuromuscular fatigue is not intensity dependent when cycling above critical power but relates to aerobic and anaerobic capacities.

NEW FINDINGS: What is the central question of this study? Is the magnitude of neuromuscular fatigue dependent upon exercise intensity above critical power (CP) when W' (the curvature constant of the power-duration relationship) is depleted? What is the main finding and its importance? The magnitude of neuromuscular fatigue is the same after two bouts of supra-CP cycling (3 versus 12 min) when controlling for W' depletion but is larger for individuals of greater anaerobic capacity after the shorter bout and smaller for individuals of greater aerobic capacity after the longer exercise bout. These findings provide new insight into the mechanisms underpinning exercise above CP. ABSTRACT: The aim of the present study was to test whether the development of neuromuscular fatigue within the severe-intensity domain could be linked to the depletion of the curvature constant (W') of the power-duration relationship. Twelve recreationally active men completed tests to determine peak oxygen consumption, critical power (CP) and W', followed by two randomly assigned constant-load supra-CP trials set to deplete W' fully in 3 (P-3) and 12 min (P-12). Pre- to postexercise changes in maximal voluntary contraction, potentiated quadriceps twitch force evoked by single (Qpot ) and paired high- (PS100) and low-frequency (PS10) stimulations and voluntary activation were determined. Cycling above CP reduced maximal voluntary contraction (P-3, -20 ± 10% versus P-12, -15 ± 7%), measures associated with peripheral fatigue (Qpot , -35 ± 13 versus -31 ± 14%; PS10, -38 ± 13 versus -37 ± 17%; PS100, -18 ± 9 versus -13 ± 8% for P-3 and P-12, respectively) and voluntary activation (P-3, -12 ± 3% versus P-12, -13 ± 3%; P < 0.05), with no significant difference between trials (P > 0.05). Changes in maximal voluntary contraction and evoked twitch forces were inversely correlated with CP and peak oxygen consumption after P-12, whereas W' was significantly correlated with changes in Qpot and PS10 after P-3 (P < 0.05). Therefore, the magnitude of neuromuscular fatigue does not depend on exercise intensity when W' is fully exhausted during severe-intensity exercise; nonetheless, exploration of inter-individual variations suggests that mechanisms underpinning exercise tolerance within this domain differ between short- and long-duration exercise.

Identifying prebariatric subtypes based on temperament traits, emotion dysregulation, and disinhibited eating: A latent profile analysis.

OBJECTIVE: The efficacy of bariatric surgery has been proven; however, a subset of patients fails to achieve expected long-term weight loss postoperatively. As differences in surgery outcome may be influenced by heterogeneous psychological profiles in prebariatric patients, previous subtyping models differentiated patients based on temperament traits. The objective of this study was to expand these models by additionally considering emotion dysregulation and disinhibited eating behaviors for subtyping, as these factors were associated with maladaptive eating behaviors and poor postbariatric weight loss outcome. METHOD: Within a prospective multicenter registry, N = 370 prebariatric patients were examined using interview and self-report questionnaires. A latent profile analysis was performed to identify subtypes based on temperament traits, emotion dysregulation, and disinhibited eating behaviors. RESULTS: Five prebariatric subtypes were identified with specific profiles regarding self-control, emotion dysregulation, and disinhibited eating behaviors. Subtypes were associated with different levels of eating disorder psychopathology, depression, and quality of life. The expanded model increased variance explanation compared to temperament-based models. CONCLUSION: By adding emotion dysregulation and disinhibited eating behaviors to previous subtyping models, specific prebariatric subtypes emerged with distinct psychological deficit patterns. Future investigations should test the predictive value of these subtypes for postbariatric weight loss and health-related outcomes.

New perspectives on patient expectations of treatment outcomes: results from qualitative interviews with patients seeking complementary and alternative medicine treatments for chronic low back pain.

BACKGROUND: Positive patient expectations are often believed to be associated with greater benefits from complementary and alternative medicine (CAM) treatments. However, clinical studies of CAM treatments for chronic pain have not consistently supported this assumption, possibly because of differences in definitions and measures of expectations. The goal of this qualitative paper is to provide new perspectives on the outcome expectations of patients prior to receiving CAM therapies for chronic low back pain. METHODS: We conducted semi-structured interviews with 64 individuals receiving massage, chiropractic, acupuncture or yoga for chronic low back pain. Interviews were recorded and transcribed. Transcripts were analyzed by a team of experienced qualitative researchers using an immersion/crystallization approach to coding and analysis. RESULTS: Overall, participants' expectations of treatment outcomes tended to cluster in four key domains: pain relief, improved function (including an increase in ability to engage in meaningful activities), improved physical fitness, and improved overall well-being (including mental well-being). Typically, patients had modest expectations for outcomes from treatment. Furthermore, outcome expectations were complex on several levels. First, the concept of expectations overlapped with several related concepts; in particular, hopes. Participants sometimes used expectations and hopes interchangeably and at other times made clear distinctions between these two terms depending on context. A related finding was that participants were cautious about stating that they expected positive outcomes. Finally, participants articulated strong interrelationships among the four key domains and often discussed how changes in one domain might affect other domains. CONCLUSIONS: Overall, these findings contribute to a growing body of literature exploring the role of expectations in patient outcomes. This paper provides important guidance that may help refine the way treatment expectations are studied in the future. In particular, participants' statements indicate that standardized measures of patient expectations should include items that capture hesitancy to articulate overly optimistic outcomes as well as interrelationships among different outcomes.

Development and Validation of a Prediction Model of Outcome After B-Cell Maturation Antigen-Directed Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory Multiple Myeloma.

PURPOSE: Although chimeric antigen receptor T therapy (CAR-T) cells are an established therapy for relapsed/refractory multiple myeloma (RRMM), there are no established models predicting outcome to identify patients who may benefit the most from CAR-T. PATIENTS AND METHODS: This is an international retrospective observational study including patients with RRMM infused with currently available commercial or academically produced anti-B-cell maturation antigen (BCMA) CAR-T. We describe characteristics and outcomes in Europe (n = 136) and the United States (n = 133). Independent predictors of relapse/progression built a simple prediction model (Myeloma CAR-T Relapse [MyCARe] model) in the training cohort (Europe), which was externally validated (US cohort) and tested within patient- and treatment-specific subgroups. RESULTS: The overall response rate was 87% and comparable between both cohorts, and complete responses were seen in 48% (Europe) and 49% (the United States). The median time to relapse was 5 months, and early relapse <5 months from infusion showed poor survival across cohorts, with the 12-month overall survival of 30% (Europe) and 14% (the United States). The presence of extramedullary disease or plasma cell leukemia, lenalidomide-refractoriness, high-risk cytogenetics, and increased ferritin at the time of lymphodepletion were independent predictors of early relapse or progression. Each factor received one point, forming the three-tiered MyCARe model: scores 0-1 (low risk), scores 2-3 (intermediate risk), and a score of 4 (high risk). The MyCARe model was significantly associated with distinct 5-month incidence of relapse/progression (P < .001): 7% for low-risk, 27% for intermediate-risk, and 53% for high-risk groups. The model was validated in the US cohort and maintained prognostic utility for response, survival, and outcomes across subgroups. CONCLUSION: Outcomes of patients with RRMM after CAR-T are comparable between Europe and the United States. The MyCARe model may facilitate optimal timing of CAR-T cells in patient-specific subgroups.

Self-reported quality of life in symptomatic and asymptomatic women with X-linked adrenoleukodystrophy.

BACKGROUND: Up to 80% of women with X-linked adrenoleukodystrophy (X-ALD) develop symptoms of myelopathy and peripheral neuropathy during their lifetime. The study's objective was to compare symptomatic versus asymptomatic women with X-ALD regarding their physical and mental well-being and quality of life. METHODS: Data were obtained from a prospective, international, cross-sectional cohort study of women with X-ALD recruited both clinically and population based. Symptoms, quality of life, and physical and mental co-morbidities were assessed by questionnaires. Women were considered symptomatic if they reported any sign of myelopathy or peripheral neuropathy. Group differences between symptomatic versus asymptomatic women and between age groups were examined using χ2 tests for categorical and independent sample t tests or analysis of variance for continuous variables. RESULTS: Complete data were available from N = 180 women (mean age: 51.2 ± 13.6 years, range: 18-85), of whom 71.7% were classified as symptomatic, with prevalence increasing with age. Symptomatic versus asymptomatic women reported poorer physical and mental health, with 26.4% meeting the criteria for a clinical depression, 73.6% reporting chronic pain, 80.6% sleeping disturbances, 38.2% sexual dysfunction, and 47.3% restless legs syndrome. Large group differences were found on the physical health, but not on the mental health component of quality of life, where symptomatic women only differed when controlling for having a boy affected by X-ALD (small effect) and treatment frequency (medium effect). CONCLUSIONS: Symptomatic women with X-ALD present with physical and psychological co-morbidities significantly reducing individuals' quality of life. The findings emphasize the need to develop new multi-disciplinary treatment options tailored to women's specific needs.

Case report: Treatment of advanced CSF1-receptor associated leukoencephalopathy with hematopoietic stem cell transplant.

CSF1 receptor-related leukoencephalopathy is a rare genetic disorder presenting with severe, adult-onset white matter dementia as one of the leading symptoms. Within the central nervous system, the affected CSF1-receptor is expressed exclusively in microglia cells. Growing evidence implicates that replacing the defective microglia with healthy donor cells through hematopoietic stem cell transplant might halt disease progression. Early initiation of that treatment is crucial to limit persistent disability. However, which patients are suitable for this treatment is not clear, and imaging biomarkers that specifically depict lasting structural damage are lacking. In this study, we report on two patients with CSF1R-related leukoencephalopathy in whom allogenic hematopoietic stem cell transplant at advanced disease stages led to clinical stabilization. We compare their disease course with that of two patients admitted in the same timeframe to our hospital, considered too late for treatment, and place our cases in context with the respective literature. We propose that the rate of clinical progression might be a suitable stratification measure for treatment amenability in patients. Furthermore, for the first time we evaluate [18F] florbetaben, a PET tracer known to bind to intact myelin, as a novel MRI-adjunct tool to image white matter damage in CSF1R-related leukoencephalopathy. In conclusion, our data add evidence for allogenic hematopoietic stem cell transplant as a promising treatment in CSF1R-related leukoencephalopathy patients with slow to moderate disease progression.

Survival benefit with checkpoint inhibitors versus chemotherapy is modified by brain metastases in patients with recurrent small cell lung cancer.

Introduction: Small cell lung cancer (SCLC) is a rapidly growing malignancy with early distant metastases. Up to 70% will develop brain metastases, and the poor prognosis of these patients has not changed considerably. The potential of checkpoint inhibitors (CPI) in treating recurrent (r/r) SCLC and their effect on brain metastases remain unclear. Methods: In this retrospective multicenter study, we analyzed r/r SCLC patients receiving second or further-line CPI versus chemotherapy between 2010 and 2020. We applied multivariable-adjusted Cox regression analysis to test for differences in 1-year mortality and real-world progression. We then used interaction analysis to evaluate whether brain metastases (BM) and/or cranial radiotherapy (CRT) modified the effect of CPI versus chemotherapy on overall survival. Results: Among 285 patients, 99 (35%) received CPI and 186 (65%) patients received chemotherapy. Most patients (93%) in the CPI group received nivolumab/ipilimumab. Chemotherapy patients were entirely CPI-naïve and only one CPI patient had received atezolizumab for first-line treatment. CPI was associated with a lower risk of 1-year mortality (adjusted Hazard Ratio [HRadj] 0.59, 95% CI 0.42 to 0.82, p=0.002). This benefit was modified by BM and CRT, indicating a pronounced effect in patients without BM (with CRT: HRadj 0.34, p=0.003; no CRT: HRadj 0.50, p=0.05), while there was no effect in patients with BM who received CRT (HRadj 0.85, p=0.59). Conclusion: CPI was associated with a lower risk of 1-year mortality compared to chemotherapy. However, the effect on OS was significantly modified by intracranial disease and radiotherapy, suggesting the benefit was driven by patients without BM.

Complementary and alternative medicine (CAM) providers' views of chronic low back pain patients' expectations of CAM therapies: a qualitative study.

BACKGROUND: Some researchers think that patients with higher expectations for CAM therapies experience better outcomes and that enthusiastic providers can enhance treatment outcomes. This is in contrast to evidence suggesting conventional medical providers often reorient patient expectations to better match what providers believe to be realistic. However, there is a paucity of research on CAM providers' views of their patients' expectations regarding CAM therapy and the role of these expectations in patient outcomes. METHODS: To better understand how CAM providers view and respond to their patients' expectations of a particular therapy, we conducted 32 semi-structured, qualitative interviews with acupuncturists, chiropractors, massage therapists and yoga instructors identified through convenience sampling. Interviews were recorded, transcribed and analyzed thematically using Atlas ti version 6.1. RESULTS: CAM providers reported that they attempt to ensure that their patients' expectations are realistic. Providers indicated they manage their patients' expectations in a number of domains- roles and responsibilities of providers and patients, treatment outcomes, timeframe for improvement, and treatment experience. Providers reported that patients' expectations change over time and that they need to continually manage these expectations to enhance patient engagement and satisfaction with treatment. CONCLUSIONS: Providers of four types of CAM therapies viewed patients' expectations as an important component of their experiences with CAM therapy and indicated that they try to align patient expectations with reality. These findings suggest that CAM providers are similar in this respect to conventional medical providers.

Thermally Controlled Charge-Carrier Transitions in Disordered PbSbTe Chalcogenides.

Binary and ternary chalcogenides have recently attracted much attention due to their wide range of applications including phase-change memory materials, topological insulators, photonic switches, and thermoelectrics. These applications require a precise control of the number and mobility of charge carriers. Here, an unexpected charge-carrier transition in ternary compounds from the PbTe-Sb2 Te3 pseudo-binary line is reported. Upon thermal annealing, sputtered thin films of PbSb2 Te4 and Pb2 Sb2 Te5 undergo a transition in the temperature coefficient of resistance and in the type of the majority charge carriers from n-type to p-type. These transitions are observed upon increasing structural order within one crystallographic phase. To account for this striking observation, it is proposed that the Fermi energy shifts from the tail of the conduction band to the valence band because different levels of overall structural disorder lead to different predominant types of native point defects. This view is confirmed by an extensive computational study, revealing a transition from excess cations and SbPb for high levels of disorder to PbSb prevailing for low disorder. The findings will help fine-tune transport properties in certain chalcogenides via proper thermal treatment, with potential benefits for memories, thermoelectric material optimization, and neuromorphic devices.

Food-Induced Brain Activity in Children with Overweight or Obesity versus Normal Weight: An Electroencephalographic Pilot Study.

BACKGROUND: Although increased food cue reactivity is evidenced to be crucial to the development and maintenance of pediatric obesity, virtually nothing is known about the underlying neurophysiological aspects of food cue reactivity in children with obesity. Therefore, this study aimed at investigating neural characteristics in children with overweight or obesity using electroencephalography (EEG). METHODS: Electrophysiological brain activity was measured using EEG frequency band analysis in n = 9 children with overweight or obesity versus n = 16 children with normal weight (8-13 years) during the presentation of high- and low-calorie food pictures and images of appealing non-food stimuli. RESULTS: Children with overweight or obesity showed significantly increased relative central beta band activity induced by high-calorie foods and appealing non-food stimuli compared to children with normal weight. Beyond significant effects of the scalp region on EEG activity, non-significant effects of stimulus category or weight status were seen for theta and alpha frequency bands. CONCLUSIONS: This study demonstrated elevated beta band activity in children with overweight or obesity when viewing high-calorie food stimuli. Beta band activity may, thus, be a valuable target for neuromodulatory interventions in children with overweight or obesity.

The Role of UID for the Usage of Verb Phrase Ellipsis: Psycholinguistic Evidence From Length and Context Effects.

We investigate the underexplored question of when speakers make use of the omission phenomenon verb phrase ellipsis (VPE) in English given that the full form is also available to them. We base the interpretation of our results on the well-established information-theoretic Uniform Information Density (UID) hypothesis: Speakers tend to distribute processing effort uniformly across utterances and avoid regions of low information by omitting redundant material through, e.g., VPE. We investigate the length of the omittable VP and its predictability in context as sources of redundancy which lead to larger or deeper regions of low information and an increased pressure to use ellipsis. We use both naturalness rating and self-paced reading studies in order to link naturalness patterns to potential processing difficulties. For the length effects our rating and reading results support a UID account. Surprisingly, we do not find an effect of the context on the naturalness and the processing of VPE. We suggest that our manipulation might have been too weak or not effective to evidence such an effect.

Predictable Words Are More Likely to Be Omitted in Fragments-Evidence From Production Data.

Instead of a full sentence like Bring me to the university (uttered by the passenger to a taxi driver) speakers often use fragments like To the university to get their message across. So far there is no comprehensive and empirically supported account of why and under which circumstances speakers sometimes prefer a fragment over the corresponding full sentence. We propose an information-theoretic account to model this choice: A speaker chooses the encoding that distributes information most uniformly across the utterance in order to make the most efficient use of the hearer's processing resources (Uniform Information Density, Levy and Jaeger, 2007). Since processing effort is related to the predictability of words (Hale, 2001) our account predicts two effects of word probability on omissions: First, omitting predictable words (which are more easily processed), avoids underutilizing processing resources. Second, inserting words before very unpredictable words distributes otherwise excessively high processing effort more uniformly. We test these predictions with a production study that supports both of these predictions. Our study makes two main contributions: First we develop an empirically motivated and supported account of fragment usage. Second, we extend previous evidence for information-theoretic processing constraints on language in two ways: We find predictability effects on omissions driven by extralinguistic context, whereas previous research mostly focused on effects of local linguistic context. Furthermore, we show that omissions of content words are also subject to information-theoretic well-formedness considerations. Previously, this has been shown mostly for the omission of function words.

Modeling the predictive potential of extralinguistic context with script knowledge: The case of fragments.

We describe a novel approach to estimating the predictability of utterances given extralinguistic context in psycholinguistic research. Predictability effects on language production and comprehension are widely attested, but so far predictability has mostly been manipulated through local linguistic context, which is captured with n-gram language models. However, this method does not allow to investigate predictability effects driven by extralinguistic context. Modeling effects of extralinguistic context is particularly relevant to discourse-initial expressions, which can be predictable even if they lack linguistic context at all. We propose to use script knowledge as an approximation to extralinguistic context. Since the application of script knowledge involves the generation of prediction about upcoming events, we expect that scrips can be used to manipulate the likelihood of linguistic expressions referring to these events. Previous research has shown that script-based discourse expectations modulate the likelihood of linguistic expressions, but script knowledge has often been operationalized with stimuli which were based on researchers' intuitions and/or expensive production and norming studies. We propose to quantify the likelihood of an utterance based on the probability of the event to which it refers. This probability is calculated with event language models trained on a script knowledge corpus and modulated with probabilistic event chains extracted from the corpus. We use the DeScript corpus of script knowledge to obtain empirically founded estimates of the likelihood of an event to occur in context without having to resort to expensive pre-tests of the stimuli. We exemplify our method at a case study on the usage of nonsentential expressions (fragments), which shows that utterances that are predictable given script-based extralinguistic context are more likely to be reduced.

Coordination between motor and cognitive tasks in dual task gait.

BACKGROUND: Dual Task (DT) paradigms are frequently used by researchers and clinicians to examine the integrity of motor processes in many movement disorders. However, the mechanism of this interaction is not fully understood. Therefore, the aim of this study was to examine the within-stride interactions between cognitive and motor processes during dual task gait (DT). RESEARCH QUESTION: Do healthy young adults coordinate gait with secondary task processing? If so, is cognitive task processing capability associated with the coordination observed? METHODS: Nineteen healthy young adults walked for two minutes on a motorized treadmill whilst counting backwards in sevens from three-digit numbers. The coordination of calculation verbalizations with gait parameters were assessed across six phases of the gait cycle. Mid verbalization time points (VERMid) were used as points of high cognitive processing of the dual task and compared with the end of the verbalizations (VEREnd) as points of low cognitive processing. RESULTS: VERMid and VEREnd did not systematically occur in any phase of the gait cycle. However, 10/19 and 9/19 participants showed non-random distributions of verbalizations for VERMid and VEREnd time points respectively (p < 0.01), indicating that these walkers coordinated gait with the cognitive task. Analysis of subgroups of Verbalization Coordinators and Non-Coordinators showed slower verbalization response durations (VRD) for VERMid Coordinators compared to VERMid Non-Coordinators, indicating that VERMid Coordinators found the cognitive tasks more demanding. No differences were found in VRD for VEREnd Coordinators and VEREnd Non-Coordinators. SIGNIFICANCE: It was found that cognitive processing is coordinated with gait phases in some but not all healthy young adults during DT gait. When demands on cognitive processes are high, healthy young adults coordinate cognitive processing with phases of gait. Analysis of within-stride coordination may be of use for studying clinical conditions where gait and attentional cognition performance breaks down.

Reducing indoor particle exposure using mobile air purifiers-Experimental and numerical analysis.

Aerosol particles are one of the main routes of transmission of COVID-19. Mobile air purifiers are used to reduce the risk of infection indoors. We focus on an air purifier that generates a defined volumetric air flow through a highly efficient filter material. We investigate the transport of aerosol particles from an infected dummy equipped with an aerosol generator to receiving thermal dummies. For analysis, we use up to 12 particle sensors to monitor the particle concentration with high spatial resolution. Based on the measurement data, a computational fluid dynamics (CFD) model is set up and validated. The experimental and numerical methods are used to investigate how the risk of infection suggested by the particle exposure in an exemplary lecture hall can be reduced by a clever choice of orientation of the air purifier. It turns out that obstructing the outlet stream of the air purifier may be particularly advantageous. The particle concentration at the head height deviates by 13% for variations of the location and orientation. At an air change per hour of 5, the cumulated PM1 mass at the head level was reduced by 75%, independently of the location of the infected dummy, compared to the "natural decay" case, showing that filtration is an effective means of reducing aerosol particle concentrations. Finally, CFD simulation was used to monitor the particle fates. The steady simulation results fit quite well with the experimental findings and provide additional information about the particle path and for assessing the comfort level due to air flow.

Modeling the depletion and reconstitution of W': Effects of prior exercise on cycling tolerance.

Thirteen healthy male subjects (age 28 ±â€¯7 years) performed tests for critical power and W' determination and two square-wave high-intensity exercises until exhaustion either with prior very-heavy intensity cycling (EXP) or without (CON). Prior exercise bout induced a depletion of 60 % of W'. After 10 min of recovery, W' reconstitution was not fully achieved (∼ 92 %). Time to exhaustion and Δ blood lactate concentration were significantly lower in EXP compared to CON (595 ±â€¯118 s vs. 683 ±â€¯148 s; 3.5 ±â€¯1.2 mmol.L-1 vs. 8.8 ±â€¯2.3 mmol.L-1; p < 0.05, respectively). Oxygen uptake (VO2) and heart rate were significantly higher in EXP, during the first 150 s of exercise (p < 0.05). The carbon dioxide production kinetics was significantly slower in EXP (mean response time = 87.8 ±â€¯17.8 s vs. 73.7 ±â€¯16.6 s in CON; p < 0.05). Thus, prior exercise impairs high-intensity cycling performance which can partly be explained by physiological disturbances linked to W' depletion.