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Climate observations inform about the past and present state of the climate system. They underpin climate science, feed into policies for adaptation and mitigation, and increase awareness of the impacts of climate change. The Global Climate Observing System (GCOS), a body of the World Meteorological Organization (WMO), assesses the maturity of the required observing system and gives guidance for its development. The Essential Climate Variables (ECVs) are central to GCOS, and the global community must monitor them with the highest standards in the form of Climate Data Records (CDR). Today, a single ECV—the sea ice ECV—encapsulates all aspects of the sea ice environment. In the early 1990s it was a single variable (sea ice concentration) but is today an umbrella for four variables (adding thickness, edge/extent, and drift). In this contribution, we argue that GCOS should from now on consider a set of seven ECVs (sea ice concentration, thickness, snow depth, surface temperature, surface albedo, age, and drift). These seven ECVs are critical and cost effective to monitor with existing satellite Earth observation capability. We advise against placing these new variables under the umbrella of the single sea ice ECV. To start a set of distinct ECVs is indeed critical to avoid adding to the suboptimal situation we experience today and to reconcile the sea ice variables with the practice in other ECV domains.

Sea ice drift data at high spatial resolution and surface wind model output are used to explore atmosphere-sea ice interactions in the Western Ross Sea including the three main polynyas areas; McMurdo Sound polynya (MSP), Terra Nova Bay polynya (TNBP), and the Ross Sea polynya (RSP). This study quantifies the relationship between the winds and sea ice drift and observes the average and annual anomalies across the region. Sea ice drift velocities are based on high-resolution (150 m) Advanced Synthetic Aperture Radar (ASAR) images from Envisat for winters between 2002 and 2012. Sea ice motion vectors were first correlated with the corresponding Antarctic Mesoscale Prediction System (AMPS) surface wind velocities, and the sensitivity of the spatial correlations and residuals were examined. Four drift parameters were selected (mean drift, the correlation between drift and wind, drift to wind scaling factor, and the directional drift constancy) to perform an unsupervised k-means classification to automatically distinguish six zones of distinctive sea ice characteristics solely based on ice drift and wind information. Results indicate a heterogeneous pattern of sea ice movement at a rate ranging from 0.41 to 2.24% of the wind speed in different areas. We also find that the directional constancy of sea ice drift is closely related to the wind fields. Sea ice drift and wind velocities display the highest correlation in free-drift areas (R = 0.70), followed by deformational drift zones (R = 0.54), and more random drift areas (R = 0.28). The classification illustrates the significance of localized wind-driven sea ice drift in this coastal area resulting in zones of convergence, shear, and free drift. The results also indicate that the most persistent patterns of sea ice motion are near the RSP and TNBP areas, both being driven by strong localized winds. Our findings identify that large-scale sea ice motion is predominantly wind-driven over much of the study area while ocean currents play only a minor role.

Background: In total knee arthroplasty (TKA), inserts can have different levels of medial and lateral congruency determined by the acuteness of the upslopes of the anterior and posterior articular surfaces. The present study evaluated an insert with different levels of lateral congruency and a medial ball-in-socket congruency to test the hypothesis that a lateral flat (F) insert maximizes external tibial orientation at extension and internal orientation at 90° flexion and lowers the incidence of anterior lift-off relative to low-congruent (LC) and ultracongruent (UC) lateral inserts. Methods: Two surgeons treated 23 patients with unrestricted caliper-verified kinematic alignment (KA) and posterior cruciate ligament (PCL) retention. They randomly trialed inserts with a medial radial dial that functioned as a built-in goniometer by measuring the tibial orientation relative to a sagittal line on the femoral trial component. Anterior lift-off of the insert from the baseplate indicated PCL tightness. Results: The F insert’s mean of 9° of external tibial orientation was higher than that of the LC (5°, p < 0.0001) and UC inserts (2°, p < 0.0001). The −13° of internal tibial orientation at 90° flexion was higher than that of the LC (−9°, p < 0.0001) and UC inserts (−7°, p < 0.0001). The 0% incidence of anterior lift-off was less than that of the LC (26%) and UC inserts (57%) (p < 0.0001). Conclusions: Surgeons and implant manufacturers should know that adding congruency to the lateral articular surface limits external tibial orientation in extension and internal tibial orientation at 90° flexion and overtightens the PCL. These rotational limitations and flexion space tightness can adversely affect patellofemoral tracking and knee flexion.

Background Individuals with intellectual disabilities (ID) may have difficulties in performing daily living tasks. Among other daily living tasks, independent oral hygiene is an essential life skill for people with ID. Materials and methods Four children with intellectual disabilities (two males and two females, ages 7-11) participated in the experiment. We employed the KinectTM V2 sensor to gamify oral hygiene skill training. Specifically, a non-concurrent multiple baseline design was adopted to demonstrate the relation between game-based intervention and independent oral hygiene skills. Results All students learned how to brush their teeth independently and maintained the skill 4 weeks later with the introduction of the game-based training. Social validity results showed the teachers and parents considered the video game was useful. Conclusions The proposed Kinect-based video game might be used for effective training of elementary students with ID to improve oral hygiene independently.

Purpose On 24/04/2018, the United Kingdom (UK) Medicines and Healthcare Products Regulatory Agency (MHRA) clarified previous policies by issuing a statement, that the use of sodium valproate is contraindicated in women of childbearing potential unless the conditions of a pregnancy prevention programme are met, and only if other treatments are ineffective or not tolerated. We evaluated the impact of this over the first year of implementation in a tertiary epilepsy centre. Methods Cross-sectional study of all women under active follow up, or newly referred, of childbearing age (16–55 years), taking valproate for the treatment of epilepsy, over 12 months from 01/05/2018. Results We identified 125 cases, with 31 newly referred in response to MHRA regulations. 9.6% of patients did not attend their appointment, 35.2% had a learning disability (LD), which in 19.2% was sufficiently severe that they could not consent to a sexual relationship. Patients with LD prescribed valproate were significantly younger, and more likely to have a focal or uncharacterised epilepsy than patients without LD. In 46.4% of patients, MHRA regulations were followed: women were already using highly active contraception (HAC), HAC was started, or valproate withdrawn. In 24.8% of cases, women elected to continue valproate, and were not willing to use HAC. Conclusions In 53.6% of cases, MHRA regulations contraindicating the use valproate in women of childbearing potential could not be followed fully, due to lack of patient attendance, lack of applicability in severe LD, or ethical concerns relating to patient choice.

Objective This retrospective study explores to what extent additional information from event witnesses provided using the novel 31-item Paroxysmal Event Observer (PEO) Questionnaire improves the differentiation among epilepsy, syncope, and psychogenic nonepileptic seizures (PNES) achievable with information provided by patients alone. Methods Patients with transient loss of consciousness caused by proven epilepsy (n = 86), syncope (n = 79), or PNES (n = 84) attending specialist neurology/syncope services in the United Kingdom and event observers provided Paroxysmal Event Profile (PEP), PEO, and personal information (PI) (e.g., sex, age, medical history) data. PEO data were subjected to exploratory factor analysis (EFA) followed by confirmatory factor analysis (CFA). PEO, PEP, and PI data were used separately and in combination to differentiate diagnoses by pairwise and multinomial logistic regressions. Predicted diagnoses were compared with gold standard medical diagnoses. Results EFA/CFA identified a 4-factor structure of the PEO based on 26/31 questionnaire items with loadings ≥0.4. Observer-reported factors alone differentiated better between syncope and epilepsy than patient-reported factors (accuracy: 96% vs 85%, p = 0.0004). Observer-reported data improved accuracy over differentiation based on patient-reported data alone from 90% to 100% between syncope and epilepsy ( p = 0.005), 76% to 83% between epilepsy and PNES ( p = 0.006), and 93% to 95% between syncope and PNES ( p = 0.098). Conclusions Information from observers can make an important contribution to the differentiation of epilepsy from syncope or PNES but adds less to that of syncope from PNES.

The World Meteorological Organization has developed a set of headline indicators for global climate monitoring. These seven indicators are a subset of the existing set of essential climate variables (ECVs) established by the Global Climate Observing System and are intended to provide the most essential parameters representing the state of the climate system. These indicators include global mean surface temperature, global ocean heat content, state of ocean acidification, glacier mass balance, Arctic and Antarctic sea ice extent, global CO2 mole fraction, and global mean sea level. This paper describes how well each of these indicators are currently monitored, including the number and quality of the underlying datasets; the health of those datasets; observation systems used to estimate each indicator; the timeliness of information; and how well recent values can be linked to preindustrial conditions. These aspects vary widely between indicators. While global mean surface temperature is available in close to real time and changes from preindustrial levels can be determined with relatively low uncertainty, this is not the case for many other indicators. Some indicators (e.g., sea ice extent) are largely dependent on satellite data only available in the last 40 years, while some (e.g., ocean acidification) have limited underlying observational bases, and others (e.g., glacial mass balance) with data only available a year or more in arrears.

Clinical Features Which Predict Neuronal Surface Autoantibodies in New-Onset Focal Epilepsy: Implications for Immunotherapies McGinty RN, Handel A, Moloney T, et al. J Neurol Neurosurg Psychiatry. 2020;92(3):291-294. doi:10.1136/jnnp-2020-325011Objective:To generate a score which clinically identifies surface-directed autoantibodies in adults with new-onset focal epilepsy and evaluate the value of immunotherapy in this clinical setting.Methods:Prospective clinical and autoantibody evaluations in a cohort of 219 consecutive patients with new-onset focal epilepsy.Results:A total of 10.5% (23/219) of people with new-onset focal epilepsy had detectable serum autoantibodies to known or novel cell surface antigenic targets. Nine of 23 with autoantibodies were diagnosed with encephalitis, by contrast to 0/196 without autoantibodies (P < .0001). Multivariate analysis identified 6 features which predicted autoantibody positivity (area under the curve = 0.83): age ≥54 years, ictal piloerection, lowered self-reported mood, reduced attention, magnetic resonance imaging limbic system changes, and the absence of conventional epilepsy risk factors. Eleven (79%) of 14 patients with detectable autoantibodies, but without encephalitis, showed excellent long-term outcomes (modified Rankin Score = 0) despite no immunotherapy. These outcomes were superior to those of immunotherapy-treated patients with confirmed autoantibody-mediated encephalitis (P < .05).Conclusions:Seizure semiology, cognitive and mood phenotypes, alongside inflammatory investigation findings, aid the identification of surface autoantibodies among unselected people with new-onset focal epilepsy. The excellent immunotherapy-independent outcomes of autoantibody-positive patients without encephalitis suggest immunotherapy administration should be guided by clinical features of encephalitis, rather than autoantibody positivity. Our findings suggest that, in this cohort, immunotherapy-responsive seizure syndromes with autoantibodies largely fall under the umbrella of autoimmune encephalitis. Antibodies Contributing to Focal Epilepsy Signs and Symptoms Score. de Bruijn M, Bastiaansen AEM, Mojzisova H, et al. Ann Neurol. 2021;89(4):698-710. doi:https://doi.org/10.1002/ana.26013.Objective:Diagnosing autoimmune encephalitis (AIE) is difficult in patients with less fulminant diseases such as epilepsy. However, recognition is important, as patients require immunotherapy. This study aims to identify antibodies in patients with focal epilepsy of unknown etiology and to create a score to preselect patients requiring testing.Methods:In this prospective, multicenter cohort study, adults with focal epilepsy of unknown etiology, without recognized AIE, were included, between December 2014 and December 2017, and followed for 1 year. Serum, and if available cerebrospinal fluid, were analyzed using different laboratory techniques. The ACES score was created using factors favoring an autoimmune etiology of seizures (AES), as determined by multivariate logistic regression. The model was externally validated and evaluated using the Concordance (C) statistic.Results:We included 582 patients, with median epilepsy duration of 8 years (interquartile range = 2-18). Twenty (3.4%) patients had AES, of whom 3 had anti-leucine-rich glioma inactivated 1, 3 had anti-contactin-associated protein-like 2, 1 had anti-N-methyl-d-aspartate receptor, and 13 had antiglutamic acid decarboxylase 65 (enzyme-linked immunosorbent assay concentrations >10 000 IU/mL). Risk factors for AES were temporal magnetic resonance imaging hyperintensities (odds ratio [OR] = 255.3, 95% CI = 19.6-3332.2, P < .0001), autoimmune diseases (OR = 13.31, 95% CI = 3.1-56.6, P = .0005), behavioral changes (OR = 12.3, 95% CI = 3.2-49.9, P = .0003), autonomic symptoms (OR = 13.3, 95% CI = 3.1-56.6, P = .0005), cognitive symptoms (OR = 30.6, 95% CI = 2.4-382.7, P = .009), and speech problems (OR = 9.6, 95% CI = 2.0-46.7, P = .005). The internally validated C-statistic was 0.95 and 0.92 in the validation cohort (n = 128). Assigning each factor 1 point, an antibodies contributing to focal epilepsy signs and symptoms (ACES) score ≥2 had a sensitivity of 100% to detect AES, and a specificity of 84.9%.Interpretation:Specific signs point toward AES in focal epilepsy of unknown etiology. The ACES score (cutoff ≥ 2) is useful to select patients requiring antibody testing.

BackgroundTransient loss of consciousness (TLOC) is a common reason for presentation to primary/emergency care; over 90% are because of epilepsy, syncope, or psychogenic non-epileptic seizures (PNES). Misdiagnoses are common, and there are currently no validated decision rules to aid diagnosis and management. We seek to explore the utility of machine-learning techniques to develop a short diagnostic instrument by extracting features with optimal discriminatory values from responses to detailed questionnaires about TLOC manifestations and comorbidities (86 questions to patients, 31 to TLOC witnesses).MethodsMulti-center retrospective self- and witness-report questionnaire study in secondary care settings. Feature selection was performed by an iterative algorithm based on random forest analysis. Data were randomly divided in a 2:1 ratio into training and validation sets (163:86 for all data; 208:92 for analysis excluding witness reports).ResultsThree hundred patients with proven diagnoses (100 each: epilepsy, syncope and PNES) were recruited from epilepsy and syncope services. Two hundred forty-nine completed patient and witness questionnaires: 86 epilepsy (64 female), 84 PNES (61 female), and 79 syncope (59 female). Responses to 36 questions optimally predicted diagnoses. A classifier trained on these features classified 74/86 (86.0% [95% confidence interval 76.9%–92.6%]) of patients correctly in validation (100 [86.7%–100%] syncope, 85.7 [67.3%–96.0%] epilepsy, 75.0 [56.6%–88.5%] PNES). Excluding witness reports, 34 features provided optimal prediction (classifier accuracy of 72/92 [78.3 (68.4%–86.2%)] in validation, 83.8 [68.0%–93.8%] syncope, 81.5 [61.9%–93.7%] epilepsy, 67.9 [47.7%–84.1%] PNES).ConclusionsA tool based on patient symptoms/comorbidities and witness reports separates well between syncope and other common causes of TLOC. It can help to differentiate epilepsy and PNES. Validated decision rules may improve diagnostic processes and reduce misdiagnosis rates.Classification of evidenceThis study provides Class III evidence that for patients with TLOC, patient and witness questionnaires discriminate between syncope, epilepsy and PNES.

Clan CA cysteine proteases, also known as papain-like proteases, play important roles throughout the malaria parasite life cycle and are therefore potential drug targets to treat this disease and prevent its transmission. In order to study the biological function of these proteases and to chemically validate some of them as viable drug targets, highly specific inhibitors need to be developed. This is especially challenging given the large number of clan CA proteases present in Plasmodium species (ten in Plasmodium falciparum), and the difficulty of designing selective inhibitors that do not cross-react with other members of the same family. Additionally, any efforts to develop antimalarial drugs targeting these proteases will also have to take into account potential off-target effects against the 11 human cysteine cathepsins. Activity-based protein profiling has been a very useful tool to determine the specificity of inhibitors against all members of an enzyme family. However, current clan CA proteases broad-spectrum activity-based probes either target endopeptidases or dipeptidyl aminopeptidases, but not both subfamilies efficiently. In this study, we present a new series of dipeptydic vinyl sulfone probes containing a free N-terminal tryptophan and a fluorophore at the P1 position that are able to label both subfamilies efficiently, both in Plasmodium falciparum and in mammalian cells, thus making them better broad-spectrum activity-based probes. We also show that some of these probes are cell permeable and can therefore be used to determine the specificity of inhibitors in living cells. Interestingly, we show that the choice of fluorophore greatly influences the specificity of the probes as well as their cell permeability.

Aim: The Scratch programming language allows learner developers to write games. The Kinect2Scratch extension makes Scratch games with bodily motion control possible by connecting to Microsoft's Kinect sensor. This study examined the feasibility and possible efficacy of a suite of motion-controlled games designed for upper extremity (UE) training in children with cerebral palsy (CP) using Kinect2Scratch. Materials and Methods: This is a proof-of-concept study. We developed three games, requiring three UE movement patterns (shoulder holding, reaching, and handclap), for use in children with CP. The primary outcome was feasibility, addressed by adherence, engagement, satisfaction, and safety. The secondary outcome was efficacy, which was evaluated by Quality of Upper Extremities Skills Test (QUEST), Box and Block Test (BBT), Melbourne Assessment 2 (MA2) test, and ABILHAND-kids score. Results: Thirteen children with CP (mean age 6.9 years) received 24 sessions of training (30 minutes per session). The adherence rate was 100%. During the first 2 weeks of training, children had a significantly higher level of participation in Kinect2Scratch training than in conventional rehabilitation [Pittsburgh Participation Scale, median (interquartile range [IQR]), 6 (3–6) vs. 4 (3–6) P = 0.04]. However, during the last 2 weeks of training, there was no significant difference in participation between the Kinect2Scratch and conventional training [Pittsburgh Rehabilitation Participation Scale, median (IQR), 4 (3–5) vs. 4 (3–6) P = 0.55]. Most children enjoyed playing the games. The mean score of enjoyment was 4.54 ± 0.66. There were no adverse events during the training periods. The children had significant improvement in total score of QUEST and MA2. There were no significant improvements in BBT and ABILHAND-kids score. Conclusion: Using Kinect2Scratch games for UE training is a feasible adjunctive program for children with CP.

Background\ud Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency.\ud \ud Methods\ud In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544.\ud \ud Findings\ud Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0–20] in the CBT plus standardised medical care group vs 7 seizures [1–35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56–1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference −0·53 [95% CI −0·97 to −0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference −4·12 [95% CI −6·35 to −1·89]; p

In an era of dynamically priced tickets, sport marketers benefit from a greater understanding of factors impacting the price consumers are willing to pay. Past research has investigated external factors affecting ticket price on the secondary market, but little work has investigated internal factors and no prior research has utilized actual price paid as a dependent variable. The current study found age, income, prior attendance, timing of purchase, and seat location influenced secondary ticket price paid, explaining 44.9% of the variance, while fan identification and alumni status did not impact the amount patrons paid for tickets to a major college men’s basketball tournament. Subscribe to JASM

Objective: To examine a rural-serving HBPC program's 12-year experience and historical trends to inform future program direction and expansion. Background: There is limited information about longitudinal trends in mature hospital-based palliative care (HBPC) programs serving racially diverse rural populations. Methods: This is a retrospective cross-sectional study of operational and patient-reported outcomes from the University of Alabama at Birmingham (UAB) Center for Palliative and Supportive Care (CPSC) inpatient (n=11,786) and outpatient (n=315) databases from October 2004 to March 2016. Results: Inpatients were a mean age of 63.7 years, male (50.1%), white (62.3%), general medicine referred (19.5%), primarily for goals of care (84.4%); 47.1% had "do not resuscitate/do not intubate" status and 46.9% were transferred to the Palliative Care and Comfort Unit (PCCU) after consultation. Median time from admission to consultation was three days, median PCCU length of stay (LOS) was four days, and median hospital LOS was nine days. Increased emergency department and cardiology referrals were notable in later years. Outpatients' mean age was 53.02 years, 63.5% were female, 76.8% were white, and 75.6% had a cancer diagnosis. Fatigue, pain, and disturbed sleep were the most common symptoms at the time of the visit; 34.6% reported mild-to-moderate depressive symptoms. Of patients reporting pain (64.8%), one-third had 50% or less relief from pain treatment. Discussion: The CPSC, which serves a racially diverse rural population, has demonstrated robust growth. We are poised to scale and spread our lessons learned to underserved communities.

Background Virtual reality and interactive video games could decrease the demands on the time of the therapists. However, the cost of a virtual reality system and the requirement for technical support limits the availability of these systems. Commercial exergames are not specifically designed for therapeutic use, most patients with hemiplegic stroke are either too weak to play the games or develop undesirable compensatory movements. Aim To develop Kinect2Scratch games and compare the effects of training with therapist-based training on upper extremity (UE) function of patients with chronic stroke. Design A randomized controlled single-blinded trial. Setting An outpatient rehabilitation clinic of a tertiary hospital. Population Thirty-three patients with chronic hemiplegic stroke. Methods We developed 8 Kinect2Scratch games. The participants were randomly assigned to either a Kinect2Scratch game group or a therapist-based training group. The training comprised 24 sessions of 30 minutes over 12 weeks. The primary outcome measure was the Fugl-Meyer UE scale and the secondary outcome measures were the Wolf Motor Function Test and Motor Activity Log. Patients were assessed at baseline, after intervention, and at the 3-month follow-up. We used the Pittsburgh participation scale (PPS) to assess the participation level of patients at each training session and an accelerometer to assess the activity counts of the affected UE of patients was used at the 12th and 24th training sessions. Results Seventeen patients were assigned to the Kinect2Scratch group and 16 were assigned to the therapist-based training group. There were no differences between the two groups for any of the outcome measures postintervention and at the 3-month follow-up (all P>0.05). The level of participation was higher in the Kinect2Scratch group than in the therapist-based training group (PPS 5.25 vs. 5.00, P=0.112). The total activity counts of the affected UE was significantly higher in the Kinect2Scratch group than in the therapist-based training group (P Conclusions Kinect2Scratch game training was feasible, with effects similar to those of therapist-based training on UE function of patients with chronic stroke. Clinical rehabilitation impact Kinect2Scratch games are low-cost and easily set-up games, which may serve as a complementary strategy to conventional therapy to decrease therapists' work load.

Studies have been completed which attempt to detect players' sentiment, and intensify game-play immersion. Emotions, while an indicator of experience, have been proposed to be 'reactive predictions' by the player, during interactions in game-play. Designers arrange core game-play mechanics, visuals and audio atmosphere to create mood. This arrangement of content and mechanics is crucial to ensuring the majority of players correctly choose an emotional context and feel the intended emotion based on stimuli. The proposed work is to identify classifications for players and contexts that improve player sensation thereby deepening game-play immersion, both vicarious and visceral immersion. A player's personality type influences their engagement with game genres and gameplay. The goal of proposed work is to assist designers in understanding the player personality type and design principals that address the preferences of these types. The game experience and user interface can be adapted to better suit a particular type. Players can also adopt a persona differing from their personality traits and this can also have positive outcomes in terms of immersion and engagement with the game and other players.

Purpose\ud \ud \ud Phenytoin is an effective anticonvulsant for focal epilepsy. Its use can be associated with long-term adverse effects including cerebellar ataxia. Whilst phenytoin is toxic to Purkinje cells in vitro; the clinical and radiological phenotype and mechanism of cerebellar degeneration in vivo remain unclear. We describe the prevalence, clinical and radiological characteristics of phenytoin-related ataxia.\ud \ud \ud \ud Methods\ud \ud \ud Patients with epilepsy receiving treatment with phenytoin were recruited from the Epilepsy clinics at Royal Hallamshire Hospital, Sheffield, UK. Neurological examination was performed on all patients after recruitment. Patients were categorised into those with and without ataxia. We determined the severity of ataxia clinically (SARA score) and the pattern of cerebellar involvement by neuroimaging (MRI volumetry and MR spectroscopy).\ud \ud \ud \ud Results\ud \ud \ud Forty-seven patients were recruited. Median duration of epilepsy was 24 years, median duration of phenytoin treatment was 15 years and current median phenytoin daily dose was 325 mg. Fifty-five percent of patients complained of poor balance. Clinical evidence of ataxia was seen in 40% patients. Gait, stance and heel-shin slide were the predominant features of cerebellar dysfunction. MRI demonstrated structural, volumetric and functional deficits of the cerebellum. Only one patient with ataxia had phenytoin levels above the normal range.\ud \ud \ud \ud Conclusions\ud \ud \ud Cerebellar ataxia is present in 40% of patients with epilepsy and chronic exposure to phenytoin. Patients on long-term phenytoin have reduced cerebellar volume even if they have no clinical evidence of ataxia. Evidence of structural deficits on imaging suggests a predilection for vermian involvement.

Caught between ongoing habitat destruction and funding shortfalls, conservation organizations are using systematic planning approaches to identify places that offer the highest biodiversity return per dollar invested. However, available tools do not account for the landscape of funding for conservation or quantify the constraints this landscape imposes on conservation outcomes. Using state-level data on philanthropic giving to and investments in land conservation by a large nonprofit organization, we applied linear regression to evaluate whether the spatial distribution of conservation philanthropy better explained expenditures on conservation than maps of biodiversity priorities, which were derived from a planning process internal to the organization and return on investment (ROI) analyses based on data on species richness, land costs, and existing protected areas. Philanthropic fund raising accounted for considerably more spatial variation in conservation spending (r(2) = 0.64) than either of the 2 systematic conservation planning approaches (r(2) = 0.08-0.21). We used results of one of the ROI analyses to evaluate whether increases in flexibility to reallocate funding across space provides conservation gains. Small but plausible "tax" increments of 1-10% on states redistributed to the optimal funding allocation from the ROI analysis could result in gains in endemic species protected of 8.5-80.2%. When such increases in spatial flexibility are not possible, conservation organizations should seek to cultivate increased support for conservation in priority locations. We used lagged correlations of giving to and spending by the organization to evaluate whether investments in habitat protection stimulate future giving to conservation. The most common outcome at the state level was that conservation spending quarters correlated significantly and positively with lagged fund raising quarters. In effect, periods of high fund raising for biodiversity followed (rather than preceded) periods of high expenditure on land conservation projects, identifying one mechanism conservation organizations could explore to seed greater activity in priority locations. Our results demonstrate how limitations on the ability of conservation organizations to reallocate their funding across space can impede organizational effectiveness and elucidate ways conservation planning tools could be more useful if they quantified and incorporated these constraints.

Coal measures (coal bearing rock strata) can contain large reserves of methane. These reserves are being exploited at a rapidly increasing rate in many parts of the world. To extract coal seam gas, thousands of wells are drilled at relatively small spacing to depressurize coal seams to induce desorption and allow subsequent capture of the gas. To manage this process effectively, the effect of coal bed methane (CBM) extraction on regional aquifer systems must be properly understood and managed. Groundwater modeling is an integral part of this management process. However, modeling of CBM impacts presents some unique challenges, as processes that are operative at two very different scales must be adequately represented in the models. The impacts of large-scale gas extraction may be felt over a large area, yet despite the significant upscaling that accompanies construction of a regional model, near-well conditions and processes cannot be ignored. These include the highly heterogeneous nature of many coal measures, and the dual-phase flow of water and gas that is induced by coal seam depressurization. To understand these challenges, a fine-scale model was constructed incorporating a detailed representation of lithological heterogeneity to ensure that near-well processes and conditions could be examined. The detail of this heterogeneity was at a level not previously employed in models built to assess groundwater impacts arising from CBM extraction. A dual-phase reservoir simulator was used to examine depressurization and water desaturation processes in the vicinity of an extractive wellfield within this fine-scale model. A single-phase simulator was then employed so that depressurization errors incurred by neglecting near-well, dual-phase flow could be explored. Two models with fewer lithological details were then constructed in order to examine the nature of depressurization errors incurred by upscaling and to assess the interaction of the upscaling process with the requirement for adequate representation of near-source, dual-phase processes.

We present the analysis of a prospective multicentre study to investigate genetic effects on the prognosis of newly treated epilepsy. Patients with a new clinical diagnosis of epilepsy requiring medication were recruited and followed up prospectively. The clinical outcome was defined as freedom from seizures for a minimum of 12 months in accordance with the consensus statement from the International League Against Epilepsy (ILAE). Genetic effects on remission of seizures after starting treatment were analysed with and without adjustment for significant clinical prognostic factors, and the results from each cohort were combined using a fixed-effects meta-analysis. After quality control (QC), we analysed 889 newly treated epilepsy patients using 472 450 genotyped and 6.9 × 10(6) imputed single-nucleotide polymorphisms. Suggestive evidence for association (defined as Pmeta5.0 × 10(-7)) with remission of seizures after starting treatment was observed at three loci: 6p12.2 (rs492146, Pmeta = 2.1 × 10(-7), OR[G] = 0.57), 9p23 (rs72700966, Pmeta = 3.1 × 10(-7), OR[C] = 2.70) and 15q13.2 (rs143536437, Pmeta = 3.2 × 10(-7), OR[C] = 1.92). Genes of biological interest at these loci include PTPRD and ARHGAP11B (encoding functions implicated in neuronal development) and GSTA4 (a phase II biotransformation enzyme). Pathway analysis using two independent methods implicated a number of pathways in the prognosis of epilepsy, including KEGG categories 'calcium signaling pathway' and 'phosphatidylinositol signaling pathway'. Through a series of power curves, we conclude that it is unlikely any single common variant explains4.4% of the variation in the outcome of newly treated epilepsy.

Summary Purpose Autoantibodies to specific neurologic proteins are associated with subacute onset encephalopathies, which often present with seizures that are poorly controlled by conventional antiepileptic drugs (AEDs). Previous cross-sectional studies have found specific neurologic antibodies in a small proportion of people with established epilepsy, but these investigations have seldom included patients with recent diagnosis. Methods We screened two large epilepsy cohorts to investigate the prevalence of multiple autoantibodies in adult patients with either established or newly diagnosed, untreated epilepsy. Key Findings Eleven percent of patients had antibodies to one or more antigen: voltage-gated potassium channel (VGKC) complex proteins (5%), glycine receptors (3%), and glutamic acid decarboxylase (GAD) and N-methyl-d-aspartate (NMDA) receptors (1.7% each). There was no difference in the prevalence of antibodies, individually or collectively, between patients with established and newly diagnosed epilepsy or with generalized or focal epilepsy. There was, however, a significantly higher prevalence of positive antibody titers in patients with focal epilepsy of unknown cause than in those with structural/metabolic focal epilepsy (14.8% vs. 6.3%; p

Palliative medicine has shown demonstrated benefit for patients with serious illness, their families, and hospital systems. As such, the demand for palliative care services is growing at a fast pace, and health care facilities frequently struggle to develop and implement effective and sustainable methods of providing this care. As with any new system, challenges and barriers naturally exist to instituting palliative care. Undertaking careful assessment, planning, and resource allocation can provide the greatest likelihood of success when developing these novel yet much needed models of care. This summary paper offers a qualitative overview of the potential benefits and the rationale to implement robust palliative care systems. We briefly review the history of palliative medicine in the broadest sense and address several seminal works from the US palliative care literature. Core practices to establish and advance palliative medicine are suggested. Commentary is provided on some of the particular barriers to palliative system development that may need to be addressed in the context of Korean medical culture. Collectively, we hope this overview can contribute to a framework within which such research and development can occur, leading to increasingly effective and sustainable palliative medicine in Korea.

Previous studies suggest that ictal panic symptoms are common in patients with psychogenic nonepileptic seizures (PNES). This study investigates the frequency of panic symptoms in PNES and if panic symptoms, just before or during episodes, can help distinguish PNES from the other common causes of transient loss of consciousness (TLOC), syncope and epilepsy.Patients with secure diagnoses of PNES (n=98), epilepsy (n=95) and syncope (n=100) were identified using clinical databases from three United Kingdom hospitals. Patients self-reported the frequency with which they experienced seven symptoms of panic disorder in association with their episodes. A composite panic symptom score was calculated on the basis of the frequency of symptoms.8.2% of patients with PNES reported "never" experiencing any of the seven panic symptoms in their episodes of TLOC. Patients with PNES reported more frequent panic symptoms in their attacks than those with epilepsy (p0.001) or syncope (p0.001), however, patients with PNES were more likely "rarely" or "never" to report five of the seven-ictal panic symptoms than "frequently" or "always" (45-69% versus 13-29%). A receiver operating characteristic analysis demonstrated that the composite panic symptom score distinguished patients with PNES from the other groups (sensitivity 71.1%, specificity 71.2%), but not epilepsy from syncope.Patients with PNES report TLOC associated panic symptoms more commonly than those with epilepsy or syncope. Although panic symptoms are reported infrequently by most patients with PNES, a composite symptom score may contribute to the differentiation between PNES and the other two common causes of TLOC.