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IntroductionTo establish clinical trial readiness for dystonia, a crucial step is to develop a Patient-Centered Outcome (PCO) measure to capture therapeutic response in focal dystonia such as in cervical dystonia (CD). Botulinum neurotoxin (BoNT) is the gold standard treatment for focal dystonia and yields improvement; yet the therapy may not meet all patient expectations as there is a high rate of discontinuation. A PCO that can measure therapeutic response, including the waxing and waning benefit of BoNT, across multiple domains and is easy to use on a frequent basis in the home environment is critical.MethodsA modified iterative Delphi process based on FDA (Food and Drug Administration) guidelines was used to develop and select items to document patient symptoms and response to treatment. Potential items then were improved using patient focus groups, validated for content with specialist panels, and confirmed items based on a patient survey. Using data from 200 CD patients in the Dystonia Coalition Natural History Database, initial PCO items were identified. Utilizing Random Forests, prospective items were analyzed for their contribution to the overall severity scores on the clinical and patient-centered outcome scales. Items that were repetitive were merged. Iterative meetings with a specialist panel consisting of neurologists, physical therapists, and Patient Advocacy Group (PAG) representatives as well as virtual focus groups of CD patients were held. An online survey was conducted with over 600 CD patients participating. Finally, specialist panel members provided input for a content validity ratio (CVR) with iterations until there was good agreement as to the relevance and clarity of the items.ResultsPCO measures tailored for CD were successfully developed. The PCO consists of 16 items covering three domains (motor, disability, and psychosocial) and reflects the input of international specialist panels, more than 800 CD patients, and PAGs (patient advocacy groups) following FDA guidance. The PCO is simple enough to be used in an app-based format compatible with smartphones and tablets.ConclusionThis comprehensive CD PCO measure was developed through the combination of using robust existing patient centered data (from previous Dystonia Coalition Projects); active engagement with PAGs to provide the patient voice; and use of virtual focus groups and online surveys. This PCO will be used in a prospective study to characterize the therapeutic response to BoNT over time. This will provide peak effect size as well as capturing the “yo-yo” effect during BoNT treatment; and will prepare for a future trials.

Instances of high-intensity wildfires which generate a fire-cloud chimney reaching all the way to the stratosphere have risen since 2013, signaling a need for closer monitoring and analysis, suggests a synthesis of confirmed occurrences.

Abstract Objective Deviated head posture is a defining characteristic of cervical dystonia (CD). Head posture severity is typically quantified with clinical rating scales such as the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Because clinical rating scales are inherently subjective, they are susceptible to variability that reduces their sensitivity as outcome measures. The variability could be circumvented with methods to measure CD head posture objectively. However, previously used objective methods require specialized equipment and have been limited to studies with a small number of cases. The objective of this study was to evaluate a novel software system—the Computational Motor Objective Rater (CMOR)—to quantify multi‐axis directionality and severity of head posture in CD using only conventional video camera recordings. Methods CMOR is based on computer vision and machine learning technology that captures 3D head angle from video. We used CMOR to quantify the axial patterns and severity of predominant head posture in a retrospective, cross‐sectional study of 185 patients with isolated CD recruited from 10 sites in the Dystonia Coalition. Results The predominant head posture involved more than one axis in 80.5% of patients and all three axes in 44.4%. CMOR's metrics for head posture severity correlated with severity ratings from movement disorders neurologists using both the TWSTRS‐2 and an adapted version of the Global Dystonia Rating Scale (rho = 0.59–0.68, all p

Abstract The Black Summer fire season of 2019–2020 in southeastern Australia contributed to an intense ‘super outbreak’ of fire-induced and smoke-infused thunderstorms, known as pyrocumulonimbus (pyroCb). More than half of the 38 observed pyroCbs injected smoke particles directly into the stratosphere, producing two of the three largest smoke plumes observed at such altitudes to date. Over the course of 3 months, these plumes encircled a large swath of the Southern Hemisphere while continuing to rise, in a manner consistent with existing nuclear winter theory. We connect cause and effect of this event by quantifying the fire characteristics, fuel consumption, and meteorology contributing to the pyroCb spatiotemporal evolution. Emphasis is placed on the unusually long duration of sustained pyroCb activity and anomalous persistence during nighttime hours. The ensuing stratospheric smoke plumes are compared with plumes injected by significant volcanic eruptions over the last decade. As the second record-setting stratospheric pyroCb event in the last 4 years, the Australian super outbreak offers new clues on the potential scale and intensity of this increasingly extreme fire-weather phenomenon in a warming climate.

The increasing use of endovascular aneurysm repair to treat abdominal aortic aneurysms has mandated solutions to the limitations of this operation, including the requirement for additional procedures. A 64-year-old man had presented with symptomatic thrombosis of the left iliac limb after endovascular aneurysm repair. We have reported the use of an innovative endovascular repair for our patient.

Background: Although abnormal head and neck postures are defining features of cervical dystonia (CD), head tremor (HT) is also common. However, little is known about the relationship between abnormal postures and HT in CD. Methods: We analyzed clinical data and video recordings from 185 patients enrolled by the Dystonia Coalition. We calculated the likelihood of their HT and HT type (“regular” vs. “jerky”) given directionality of abnormal head postures, disease duration, sex, and age. Results: Patients with retrocollis were more likely to have HT than patients with anterocollis (X2 (1, N = 121) = 7.98, p = 0.005). There was no difference in HT likelihood given left or right turning in laterocollis and rotation. Patients with HT had longer disease duration (t(183) = 2.27, p = 0.024). There was no difference in age between patients with and without HT. In a logistic regression model, anterocollis/retrocollis direction (X2 (1, N = 121) = 6.04, p = 0.014), disease duration (X2 (1, N = 121) = 7.28, p = 0.007), and the interaction term between age and disease duration (X2 (1, N = 121) = 7.77, p = 0.005) collectively contributed to HT likelihood. None of the postural directionality or demographic variables were associated with differential likelihood of having regular versus jerky HT. Discussion: We found that HT is more likely for CD patients with a specific directionality in their predominant posture. Our finding that CD patients with longer disease duration have a higher likelihood of HT also raises the question of whether HT becomes more likely over time in individual patients.

Background: Sensory tricks are compensatory gestures that cervical dystonia (CD) patients use to reduce abnormal neck posture and movements. Although sensory tricks are common in CD, little is known about whether trick efficacy changes over time or has effect on quality of life. Methods: We analyzed clinical data and video recordings from 188 patients with isolated CD. We calculated the duration of CD and assessed the Toronto Western Spasmodic Torticollis Rating Scales and the Cervical Dystonia Impact Profile (CDIP-58). Results: A longer duration of CD corresponded to a less effective sensory trick (r(187) = 0.1901, p = 0.009). Patients who demonstrated more effective sensory tricks reported higher sleep-related quality of life than patients with less effective sensory tricks (r(187) = 0.1680, p = 0.0212). There were no significant relationships between the effectiveness of a sensory trick and the other aspects of quality of life as measured by the CDIP-58. Discussion: Patients who have had CD longer had less effective sensory tricks consistent with patients’ verbal reports of previously having a trick that no longer works. Patients should be apprised of a wide variety of sensory tricks because their previous tricks may lose efficacy over time and because more effective tricks are associated with higher sleep-related quality of life.

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal postures, repetitive movements, or both. Research in dystonia has been challenged by several factors. First, dystonia is uncommon. Dystonia is not a single disorder but a family of heterogenous disorders with varied clinical manifestations and different causes. The different subtypes may be seen by providers in different clinical specialties including neurology, ophthalmology, otolaryngology, and others. These issues have made it difficult for any single center to recruit large numbers of subjects with specific types of dystonia for research studies in a timely manner. The Dystonia Coalition is a consortium of investigators that was established to address these challenges. Since 2009, the Dystonia Coalition has encouraged collaboration by engaging 56 sites across North America, Europe, Asia, and Australia. Its emphasis on collaboration has facilitated establishment of international consensus for the definition and classification of all dystonias, diagnostic criteria for specific subtypes of dystonia, standardized evaluation strategies, development of clinimetrically sound measurement tools, and large multicenter studies that document the phenotypic heterogeneity and evolution of specific types of dystonia.

The Korea-United States Air Quality Study (KORUS-AQ) took place in spring 2016 to better understand air pollution in Korea. In support of KORUS-AQ, 2554 whole air samples (WAS) were collected aboard the NASA DC-8 research aircraft and analyzed for 82 C1–C10 volatile organic compounds (VOCs) using multi-column gas chromatography. Together with fast-response measurements from other groups, the air samples were used to characterize the VOC composition in Seoul and surrounding regions, determine which VOCs are major ozone precursors in Seoul, and identify the sources of these reactive VOCs. (1) The WAS VOCs showed distinct signatures depending on their source origins. Air collected over Seoul had abundant ethane, propane, toluene and 'n'-butane while plumes from the Daesan petrochemical complex were rich in ethene, C2–C6 alkanes and benzene. Carbonyl sulfide (COS), CFC-113, CFC-114, carbon tetrachloride (CCl4) and 1,2-dichloroethane were good tracers of air originating from China. CFC-11 was also elevated in air from China but was surprisingly more elevated in air over Seoul. (2) Methanol, isoprene, toluene, xylenes and ethene were strong individual contributors to OH reactivity in Seoul. However methanol contributed less to ozone formation based on photochemical box modeling, which better accounts for radical chemistry. (3) Positive Matrix Factorization (PMF) and other techniques indicated a mix of VOC source influences in Seoul, including solvents, traffic, biogenic, and long-range transport. The solvent and traffic sources were roughly equal using PMF, and the solvents source was stronger in the KORUS-AQ emission inventory. Based on PMF, ethene and propene were primarily associated with traffic, and toluene, ethylbenzene and xylenes with solvents, especially non-paint solvents for toluene and paint solvents for ethylbenzene and xylenes. This suggests that VOC control strategies in Seoul could continue to target vehicle exhaust and paint solvents, with additional regulations to limit the VOC content in a variety of non-paint solvents.

The Korea – United States Air Quality Study (May – June 2016) deployed instrumented aircraft and ground-based measurements to elucidate causes of poor air quality related to high ozone and aerosol concentrations in South Korea. This work synthesizes data pertaining to aerosols (specifically, particulate matter with aerodynamic diameters

In an environment with many local, remote, persistent, and episodic sources of pollution, meteorology is the primary factor that drives periods of unhealthy air quality and reduced visibility. The 2016 Korea-United States Air Quality (KORUS-AQ) field study provides a unique opportunity to examine the impact of meteorology on the relative influence of local and transboundary pollution. Much of the KORUS-AQ campaign can be grouped into four distinct research periods based on observed synoptic meteorology, including a period of complex aerosol vertical profiles driven by dynamic meteorology, stagnation under a persistent anticyclone, low-level transport and haze development, and a blocking pattern. These episodes are examined using a diverse archive of ground, airborne, and satellite data. While frontal boundaries are recognized as the primary mechanism driving pollution transport in eastern Asia, results show that they are not always related to sustained periods of hazardous air quality and reduced visibility at the surface. Significant long-range transport of pollution and dust was constrained to a few short events, suggesting that the majority of pollutants sampled during KORUS-AQ originated from local sources. A severe regional pollution episode is examined in detail, featuring dense haze and significant secondary particle formation within a shallow moist boundary layer. Observations during KORUS-AQ also highlight a rapid, 40 ppbv increase in ozone pollution as a strong sea breeze front traversed the Seoul Metropolitan Area. Representativeness of meteorology and pollution conditions measured by KORUS-AQ is considered by comparison with climatology. This analysis is an essential step toward improved local and regional forecasting of air quality and visibility.

The Dual Pathway to Creativity Model theorizes that creative performance arises from cognitive flexibility, persistence, or a combination of the two. Existing research has only examined these pathways independently, limiting our understanding of the model and of how people generate ideas. We extend the DPCM model by predicting that creative output arises from the generation of response sets containing both highly related (persistence pathway) and unrelated (flexibility) ideas, an idea generation strategy we call Dual Pathway Divergent Thinking (DPDT). In a study of 147 subjects, we propose a serial mediation model: people higher in Openness to Ideas use DPDT as an idea generation strategy which leads to higher nascent creativity which, in turn, leads to higher final creativity. The results provide initial evidence that the two pathways may operate simultaneously as a single idea generation strategy. Theoretical and practical implications are discussed.

Dystonia is a functionally disabling movement disorder characterized by abnormal movements and postures. Although substantial recent progress has been made in identifying genetic factors, the pathophysiology of the disease remains a mystery. A provocative suggestion gaining broader acceptance is that some aspect of neural plasticity may be abnormal. There is also evidence that, at least in some forms of dystonia, sensorimotor “use” may be a contributing factor. Most empirical evidence of abnormal plasticity in dystonia comes from measures of sensorimotor cortical organization and physiology. However, the basal ganglia also play a critical role in sensorimotor function. Furthermore, the basal ganglia are prominently implicated in traditional models of dystonia, are the primary targets of stereotactic neurosurgical interventions, and provide a neural substrate for sensorimotor learning influenced by neuromodulators. Our working hypothesis is that abnormal plasticity in the basal ganglia is a critical link between the etiology and pathophysiology of dystonia. In this review we set up the background for this hypothesis by integrating a large body of disparate indirect evidence that dystonia may involve abnormalities in synaptic plasticity in the striatum. After reviewing evidence implicating the striatum in dystonia, we focus on the influence of two neuromodulatory systems: dopamine and acetylcholine. For both of these neuromodulators, we first describe the evidence for abnormalities in dystonia and then the means by which it may influence striatal synaptic plasticity. Collectively, the evidence suggests that many different forms of dystonia may involve abnormal plasticity in the striatum. An improved understanding of these altered plastic processes would help inform our understanding of the pathophysiology of dystonia, and, given the role of the striatum in sensorimotor learning, provide a principled basis for designing therapies aimed at the dynamic processes linking etiology to pathophysiology of the disease.

Most EEG-based BCI systems make use of well-studied patterns of brain activity. However, those systems involve tasks that indirectly map to simple binary commands such as “yes†or “no†or require many weeks of biofeedback training. We hypothesized that signal processing and machine learning methods can be used to discriminate EEG in a direct “yesâ€Â/“no†BCI from a single session. Blind source separation (BSS) and spectral transformations of the EEG produced a 180-dimensional feature space. We used a modified genetic algorithm (GA) wrapped around a support vector machine (SVM) classifier to search the space of feature subsets. The GA-based search found feature subsets that outperform full feature sets and random feature subsets. Also, BSS transformations of the EEG outperformed the original time series, particularly in conjunction with a subset search of both spaces. The results suggest that BSS and feature selection can be used to improve the performance of even a “direct,†single-session BCI.

The Plasmodium falciparum protein VAR2CSA allows infected erythrocytes to accumulate within the placenta, inducing pathology and poor birth outcomes. Multiple exposures to placental malaria (PM) induce partial immunity against VAR2CSA, making it a promising vaccine candidate. However, the extent to which VAR2CSA genetic diversity contributes to immune evasion and virulence remains poorly understood. The deep sequencing of the var2csa DBL3X domain in placental blood from forty-nine primigravid and multigravid women living in malaria-endemic western Kenya revealed numerous unique sequences within individuals in association with chronic PM but not gravidity. Additional analysis unveiled four distinct sequence types that were variably present in mixed proportions amongst the study population. An analysis of the abundance of each of these sequence types revealed that one was inversely related to infant gestational age, another was inversely related to placental parasitemia, and a third was associated with chronic PM. The categorization of women according to the type to which their dominant sequence belonged resulted in the segregation of types as a function of gravidity: two types predominated in multigravidae whereas the other two predominated in primigravidae. The univariate logistic regression analysis of sequence type dominance further revealed that gravidity, maternal age, placental parasitemia, and hemozoin burden (within maternal leukocytes), reported a lack of antimalarial drug use, and infant gestational age and birth weight influenced the odds of membership in one or more of these sequence predominance groups. Cumulatively, these results show that unique var2csa sequences differentially appear in women with different PM exposure histories and segregate to types independently associated with maternal factors, infection parameters, and birth outcomes. The association of some var2csa sequence types with indicators of pathogenesis should motivate vaccine efforts to further identify and target VAR2CSA epitopes associated with maternal morbidity and poor birth outcomes.

National forests in the Blue Mountains (USA) region have developed adaptation options that address effects identified in a recent climate change vulnerability assessment. Adaptation strategies (general, overarching) and adaptation tactics (specific, on-the-ground) were elicited from resource specialists and stakeholders through a workshop process. For water supply and infrastructure, primary adaptation strategies restore hydrologic function of watersheds, connect floodplains, support groundwater-dependent ecosystems, maximize valley storage, and reduce fire hazard. For fisheries, strategies maintain or restore natural flow regimes and thermal conditions, improve water conservation, decrease fragmentation of stream networks, and develop geospatial data on stream temperature and geologic hazards. For upland vegetation, disturbance-focused strategies reduce severity and patch size of disturbances, protect refugia, increase resilience of native vegetation by reducing non-climate stressors, protect genotypic and phenotypic diversity, and focus on functional systems (not just species). For special habitats (riparian areas, wetlands, groundwater-dependent ecosystems), strategies restore or maintain natural flow regimes, maintain appropriate plant densities, improve soil health and streambank stability, and reduce non-climate stressors. Prominent interactions of resource effects makes coordination critical for implementation and effectiveness of adaptation tactics and restoration projects in the Blue Mountains. Keywords: Adaptation strategies, Adaptation tactics, Climate change, Restoration, Stressors

The long-term effectiveness of dry-forest fuels treatments (restoration thinning and prescribed burning) depends, in part, on the pace at which trees regenerate and recruit into the overstory. Knowledge of the factors that shape post-treatment regeneration and growth is limited by the short timeframes and simple disturbance histories of past research. Here, we present results of a 15-year fuels-reduction experiment in central Washington, including responses to planned and unplanned disturbances. We explore the changing patterns of Douglas-fir regeneration in 72 permanent plots (0.1 ha) varying in overstory abundance (a function of density and basal area) and disturbance history—the latter including thinning, prescribed burning, and/or wildfire. Plots were measured before treatment (2000/2001), soon afterwards (2004/2005), and more than a decade later (2015). Thinning combined with burning enhanced sapling recruitment (ingrowth) into the overstory, although rates of ingrowth were consistently low and greatly exceeded by mortality. Relationships between seedling frequency (proportion of quadrats within a plot) and overstory abundance shifted from weakly negative before treatment to positive after thinning, to neutral in the longer term. However, these relationships were overshadowed by more recent, higher-severity prescribed fire and wildfire that stimulated seedling establishment while killing advanced regeneration and overstory trees. Our results highlight the dependence of regeneration responses on the history of, and time since, fuels treatment and subsequent disturbance. Managers must be aware of this spatial and temporal complexity and plan for future disturbances that are inevitable but unpredictable in timing and severity.