Deep Brain Stimulation of the Subthalamic Nucleus Improves Reward-Based Decision-Learning in Parkinson's Disease

Recently, the subthalamic nucleus (STN) has been shown to be critically involved in decision-making, action selection, and motor control. Here we investigate the effect of deep brain stimulation (DBS) of the STN on reward-based decision-learning in patients diagnosed with Parkinson's disease (PD). We determined computational measures of outcome evaluation and reward prediction from PD patients who performed a probabilistic reward-based decision-learning task. In previous work, these measures covaried with activation in the nucleus caudatus (outcome evaluation during the early phases of learning) and the putamen (reward prediction during later phases of learning). We observed that stimulation of the STN motor regions in PD patients served to improve reward-based decision-learning, probably through its effect on activity in frontostriatal motor loops (prominently involving the putamen and, hence, reward prediction). In a subset of relatively younger patients with relatively shorter disease duration, the effects of DBS appeared to spread to more cognitive regions of the STN, benefiting loops that connect the caudate to various prefrontal areas importantfor outcome evaluation. These results highlight positive effects of STN stimulation on cognitive functions that may benefit PD patients in daily-life association-learning situations

A Note on Monotonically Metacompact Spaces

We show that any metacompact Moore space is monotonically metacompact and use that result to characterize monotone metacompactness in certain generalized ordered (GO)spaces. We show, for example, that a generalized ordered space with a sigma-closed-discrete dense subset is metrizable if and only if it is monotonically (countably) metacompact, that a monotonically (countably) metacompact GO-space is hereditarily paracompact, and that a locally countably compact GO-space is metrizable if and only if it is monotonically (countably) metacompact. We give an example of a non-metrizable LOTS that is monotonically metacompact, thereby answering a question posed by S. G. Popvassilev. We also give consistent examples showing that if there is a Souslin line, then there is one Souslin line that is monotonically countable metacompact, and another Souslin line that is not monotonically countably metacompact

Scalable software framework for real-time data processing in the railway environment

B

Predictive factors for severe toxicity of sunitinib in unselected patients with advanced renal cell cancer

Sunitinib has been registered for the treatment of advanced renal cell cancer (RCC). As patient inclusion was highly selective in previous studies, experience with sunitinib in general oncological practice remains to be reported. We determined the efficacy and safety of sunitinib in patients with advanced RCC included in an expanded access programme. ECOG performance status >1, histology other than clear cell and presence of brain metastases were no exclusion criteria. Eighty-two patients were treated: 23% reached a partial response, 50% had stable disease, 20% progressed and six patients were not evaluable. Median progression-free survival (PFS) was 9 months and median overall survival (OS) was 15 months. Importantly, 47 patients (57%) needed a dose reduction, 35 (43%) because of treatment-related adverse events, 10 (12%) because of continuous dosing, and two because of both. Stomatitis, fatigue, hand–foot syndrome and a combination of grade 1–2 adverse events were the most frequent reasons for dose reduction. In 40 patients (49%), there was severe toxicity, defined as dose reduction or permanent discontinuation, which was highly correlated with low body surface area, high age and female gender. On the basis of age and gender, a model was developed that could predict the probability of severe toxicity

Development, Problem Behavior, and Quality of Life in a Population Based Sample of Eight-Year-Old Children with Down Syndrome

OBJECTIVE: Children with Down syndrome (DS) have delayed psychomotor development. We investigated levels of development, problem behavior, and Health-Related Quality of Life (HRQoL) in a population sample of Dutch eight-year-old children with DS. Developmental outcomes were compared with normative data of eight-year-old children from the general population. METHOD: Over a three-year-period all parents with an eight-year-old child with DS were approached by the national parent organization. Developmental skills were assessed by means of the McCarthy Scales of Children's Ability. To measure emotional and behavioral problems we used the Child Behavior Checklist. HRQoL was assessed with the TNO-AZL Children's Quality of Life questionnaire. Analyses of variance were applied to compare groups. RESULTS: A total of 337 children participated. Mean developmental age was substantially lower than mean calendar age (3.9 years, SD 0.87 and 8.1 years, SD 0.15 respectively). Mean developmental age was significantly lower among boys than girls (3.6 (SD 0.85) and 4.2 years (SD 0.82) respectively; p<0.001). Compared with the general population, children with DS had more emotional and behavioral problems (p<0.001). However on the anxious/depressed scale, they scored significantly more favorably (p<0.001). Significantly lower HRQoL scores for the scales gross motor skills, autonomy, social functioning and cognitive functioning were found (p-values<0.001). Hardly any differences were observed for the scales physical complaints, positive and negative emotions. CONCLUSION: Eight-year-old children with DS have an average developmental delay of four years, more often have emotional and behavioral problems, and have a less favorable HRQoL compared with children from the general population

Effectiveness of a training program for police officers who come into contact with people with mental health problems : A pragmatic randomised controlled trial

INTRODUCTION: Police officers frequently come into contact with individuals with mental health problems. Specialist training in this area for police officers may improve how they respond to individuals with mental health problems; however, evidence to support this is sparse. This study evaluated the effectiveness of one bespoke mental health training package for frontline police officers relative to routine training. DESIGN: Pragmatic, two-armed cluster randomised controlled trial in one police force in England. Police stations in North Yorkshire were randomised with frontline police officers receiving either a bespoke mental health training package or routine training. The primary outcome was the number of incidents which resulted in a police response reported to the North Yorkshire Police control room up to six months after delivery of training. Secondary outcomes included: likelihood of incidents using Section 136 of the Mental Health Act; likelihood of incidents having a mental health tag applied; and number of individuals with a mental health warning marker involved in incidents. The appropriateness of mental health tags applied to a random sample of incidents was checked by an independent mental health professional. Routinely collected data were used. RESULTS: Twelve police stations were recruited and randomised (Intervention group n = 6; Control group n = 6), and 249 officers received the bespoke mental health training intervention. At follow-up, a median of 397 incidents were assigned to trial stations in the intervention group, and 498 in the control group. There was no evidence of a difference in the number of incidents with a police response (adjusted incidence rate ratio (IRR) 0.92, 95% CI 0.61 to 1.38, p = 0.69), or in the number of people with mental health warning markers involved in incidents (adjusted IRR 1.39, 95% CI 0.91 to 2.10, p = 0.13) between the intervention and control groups up to six months following the intervention; however, incidents assigned to stations in the intervention group were more likely to have a mental health tag applied to them than incidents assigned to control stations (adjusted odds ratio 1.41, 95% CI 1.16 to 1.71, p = 0.001). The review of 100 incidents suggests that there may be incidents involving individuals with mental health issues that are not being recorded as such (Kappa coefficient 0.65). There was no statistically significant difference in the likelihood of Section 136 of the Mental Health Act being applied to an incident. CONCLUSIONS: The bespoke one day mental health training delivered to frontline officers by mental health professionals did not reduce the number of incidents reported to the police control room up to six months after its delivery; however training may have a positive effect on how the police record incidents involving individuals with mental health problems. Our trial has shown that conducting pragmatic trials within the police setting is feasible and acceptable. There is a wealth of routinely collected police data that can be utilised for research and further collaboration between police forces and academia is encouraged. TRIAL REGISTRATION: ISRCTN (ISRCTN11685602). The authors confirm that all ongoing and related trials for this drug/intervention are registered

Multidisciplinaire Richtlijn Probleemgedrag bij volwassenen met een verstandelijke beperking

Probleemgedrag komt regelmatig voor bij mensen met een verstandelijke beperking (VB). Het kan een grote impact hebben op de persoon zelf, diens familie en op anderen in de omgeving. Zo kan probleemgedrag leiden tot een verminderde kwaliteit van leven en (mogelijk vermijdbaar) hoog zorggebruik. De richtlijn ‘Probleemgedrag bij volwassenen met een verstandelijke beperking’ is ontwikkeld om de kwaliteit van leven bij volwassenen met een VB en probleemgedrag te verbeteren en last en lijden bij deze groep én naastbetrokkenen te verminderen. Belangrijke bijkomende doelen zijn het beter signaleren, vaststellen en behandelen van psychiatrische stoornissen, het verbeteren van de inzet van niet-medicamenteuze behandelingen en de effectieve inzet van psychofarmaca

Clinical practice: The care of children with Down syndrome

Down syndrome (DS) is one of the most common chromosomal abnormalities. Because of medical advances and improvements in overall medical care, the median survival of individuals with DS has increased considerably. This longer life expectancy requires giving the necessary care to the individual with DS over their total longer lifespan. DS medical guidelines are designed for the optimal care of the child in whom a diagnosis of DS has been confirmed. We present an overview of the most important issues related to children with DS based on the most relevant literature currently available

Facility type and primary care performance in sub-district health promotion hospitals in Northern Thailand

This paper examines primary care performance in three types of community health facilities in five provinces in northern Thailand. Tambon (sub-district) health promotion hospitals (THPHs) were introduced in 2009 to upgrade the services offered by the previous health centres, but were hampered by shortages of trained doctors and nurses. The Ministry of Public Health (MoPH) designated three categories of THPH, defined according to whether they were regularly staffed by a medical practitioner, a qualified nurse or non-clinical public health officers. While the plan is to move over time to doctor-staffed THPHs, many rural areas rely on facilities staffed by public health officers or nurses. The study used structured interviews to measure patient views on performance, defined in terms of accessibility, continuity, comprehensiveness, co-ordination and community orientation, in 23 THPHs divided across the three types. Counter-intuitively it was the THPHs staffed by public health officers which achieved the highest scores, followed by nurse-staffed facilities and then doctor-staffed facilities. The sharpest differences found were in the scores for accessibility, continuity, and comprehensiveness of care. The authors argue that these are associated with local services, which rural patients in particular value more than services offered by doctors on rotation in larger outpatient department-like centres. Patients value these aspects of care more than professional skill-mix per se. This is not an argument for delaying an increase in use of qualified staff, but an indication of the need to do this in a way that preserves the features of local services that patients value