nils-herrmann/clean_scirepeval huggingface dataset:
Modulation of Habit Formation by Levodopa in Parkinson's Disease

Dopamine promotes the execution of positively reinforced actions, but its role for the formation of behaviour when feedback is unavailable remains open. To study this issue, the performance of treated/untreated patients with Parkinson's disease and controls was analysed in an implicit learning task, hypothesising dopamine-dependent adherence to hidden task rules. Sixteen patients on/off levodopa and fourteen healthy subjects engaged in a Go/NoGo paradigm comprising four equiprobable stimuli. One of the stimuli was defined as target which was first consistently preceded by one of the three non-target stimuli (conditioning), whereas this coupling was dissolved thereafter (deconditioning). Two task versions were presented: in a 'Go version', only the target cue required the execution of a button press, whereas non-target stimuli were not instructive of a response; in a 'NoGo version', only the target cue demanded the inhibition of the button press which was demanded upon any non-target stimulus. Levodopa influenced in which task version errors grew from conditioning to deconditioning: in unmedicated patients just as controls errors only rose in the NoGo version with an increase of incorrect responses to target cues. Contrarily, in medicated patients errors went up only in the Go version with an increase of response omissions to target cues. The error increases during deconditioning can be understood as a perpetuation of reaction tendencies acquired during conditioning. The levodopa-mediated modulation of this carry-over effect suggests that dopamine supports habit conditioning under the task demand of response execution, but dampens it when inhibition is required. However, other than in reinforcement learning, supporting dopaminergic actions referred to the most frequent, i. e., non-target behaviour. Since this is passive whenever selective actions are executed against an inactive background, dopaminergic treatment could in according scenarios contribute to passive behaviour in patients with Parkinson's disease.
An automated nanoliter dispenser for staining individual biopsies in tissue microarrays.

In the field of molecular analysis of cancer, there exists a need for a clinical device that can automate protocols for immunohistochemical and in situ hybridization diagnostic staining on tissue microarrays. The tissue microarray antibody spotter (TMAS) has been developed to provide fundamental improvements over current histological staining techniques by enabling precision application of reagents to individual biopsies within a tissue microarray. This allows for multiplexed reactions on a single slide and promises to significantly reduce costs associated with immunohistochemistry and in situ hybridization based assays. Additionally, because TMAS allows for testing of different biomarkers on each element of a tissue array, a complete cancer profile can be obtained from a single TMA slide. Ultimately this may lead to cost-effective, faster and more accurate diagnosis of the patient.
Hemodynamic and clinical effects of tezosentan, an intravenous dual endothelin receptor antagonist, in patients hospitalized for acute decompensated heart failure.

We sought to investigate the efficacy and safety of tezosentan, a dual endothelin receptor antagonist, in patients hospitalized for acute heart failure (HF).



Tezosentan has been previously shown to improve hemodynamics in patients with stable chronic HF.



In a double-blind fashion, 292 patients (cardiac index < or =2.5 l/min per m(2) and pulmonary capillary wedge pressure (PCWP) > or =15 mm Hg) who were admitted to the hospital and in need of intravenous treatment for acute HF and central hemodynamic monitoring were randomized to 24-h intravenous treatment with tezosentan (50 or 100 mg/h) or placebo. Central hemodynamic variables, the dyspnea score, and safety variables were measured.



After 6 h of treatment, significantly greater increases in the cardiac index and decreases in PCWP were observed with both tezosentan dosages than with placebo (mean treatment effects at 0.38 and 0.37 l/min per m(2) with 50 and 100 mg/h and -3.9 mm Hg for each dose, respectively; p < 0.0001). This effect was maintained during the remaining infusion and for > or =6 h after treatment cessation. A tendency for an improved dyspnea score and a decreased risk of clinical worsening was observed after 24 h of treatment with each tezosentan dose. Adverse events, more frequent with tezosentan than with placebo (headache, asymptomatic hypotension, early worsening of renal function, nausea, vomiting), were dose-related.



Intravenous tezosentan rapidly and effectively improved hemodynamics in these patients. The similar beneficial effects of the two dosages and the increased dose-related adverse events with the higher dosage suggest that the optimal dosing regimen is <50 mg/h.
Evaluation of a peer-led hypertension intervention for veterans: impact on peer leaders.

Volunteer peer leaders (PLs) benefit from their involvement in health interventions but we know little about how they compare with other non-PL volunteers or with the intervention recipients themselves. We randomized 58 veterans' service organizations' posts (e.g. VFW) to peer- versus professionally led self-management support interventions. Our primary research questions were whether hypertensive PLs changed over the course of the project, whether they changed more than hypertensive volunteers who were not randomized to such a role [i.e. post representatives (PRs)] and whether they changed more than the intervention recipients with respect to health knowledge, health beliefs and health outcomes from baseline to 12 months. After the intervention, PLs provided open-ended feedback and participated in focus groups designed to explore intervention impact. Hypertensive PLs improved their systolic blood pressure and hypertension knowledge and increased their fruit/vegetable intake and pedometer use. We found no differences between PLs and PRs. PLs improved knowledge and increased fruit/vegetable intake more than intervention recipients did; they provided specific examples of personal health behavior change and knowledge acquisition. Individuals who volunteer to be peer health leaders are likely to receive important benefits even if they do not actually take on such a role.
An analytical flow control scheme for real-time traffic in wireless mesh network: from theoretic model to practical mechanism

The link interference and multi-hop characters make Wireless Mesh Network (WMN) performance can not be tuned well by local information. We propose an analytical flow control scheme (AFCS) based on the optimal bandwidth allocation model that is specifically designed for the unique characteristics of WMN. The original contribution incorporated in a flow contention model of WMN based on maximal link interference region. With the contention constraint, the optimality of bandwidth allocation can be achieved by maximizing the aggregated utility across all flows. We then deduce a practical equation for adjusting sending rate from the bandwidth allocation model. Based on the simplified analytical equation and the congestion notification message mechanism, we propose an equation-based flow control framework for real-time traffic in WMN. Simulation results have shown the AFCS can improve the capacity of the WMN by 40% and alleviate the unfairness and delay jitter greatly. The fast response, fairness and steadiness characters of the AFCS are helpful for rigorous real-time traffic and dynamic wireless network.
Service Use and Costs for People with Long-Term Neurological Conditions in the First Year following Discharge from In-Patient Neuro-Rehabilitation: A Longitudinal Cohort Study

Knowledge of the configuration and costs of community rehabilitation and support for people with long-term neurological conditions (LTNCs) is needed to inform future service development and resource allocation. In a multicentre prospective cohort study evaluating community service delivery during the year post-discharge from in-patient neuro-rehabilitation, a key objective was to determine service use, costs, and predictors of these costs.



Patients consecutively admitted over one year to all nine London specialised (Level 1) in-patient neuro-rehabilitation units were recruited on discharge. They or their carers completed postal/web-based questionnaires at discharge and six and twelve months later, providing demographic data and measures of impairment, disability, service needs and provision. This paper describes health and social care service use, informal care and associated costs. Regression models using non-parametric boot-strapping identified predictors of costs over time.



Overall, 152 patients provided consistent data. Mean formal service costs fell significantly from £13,290 (sd £19,369) during the first six months to £9,335 (sd £19,036) from six-twelve months, (t = 2.35, P<0.05), mainly due to declining health service use. At six months, informal care was received on average for 8.2 hours/day, mean cost £14,615 (sd 23,305), comprising 52% of overall care costs. By twelve months, it had increased to 8.8 hours per day, mean cost £15,468 (sd £25,534), accounting for 62% of overall care costs. Being younger and more disabled predicted higher formal care costs, explaining 32% and 30% of the variation in costs respectively at six and twelve months.



Community services for people with LTNCs carry substantial costs that shift from health to social care over time, increasing the burden on families. Prioritising rehabilitation services towards those in greatest need could limit access to others needing on-going support to promote their independence and reduce their reliance on families. This argues for greater investment in future rehabilitation services.
The effect of glibenclamide on insulin secretion at normal glucose concentrations

The aim of this study was to investigate the incremental and proportional effect of a sulfonylurea on insulin secretion rates at low, elevated and high blood glucose, using parallel groups with ascending or descending glucose steps to minimise potential biases of a single stepped clamp order. Following 14 days on placebo or glibenclamide (2.5 mg) tablets twice daily, separated by 14 days washout, 19 type 2 diabetic patients had ascending or descending three-step hyperinsulinaemic glucose clamps at 4, 8 and 12 mmol/l. C-peptide secretion was estimated by two-compartment C-peptide deconvolution. Patients in the ascending glucose steps group (n = 10) had mean (SD) age of 60.3 (6.5) years, BMI of 29.8 (4.9) kg/m2 and fasting glucose on diet alone of 10.6 (2.9) mmol/l; while those in the descending glucose steps group (n = 9) had mean age of 58.2 (8.0) years, BMI of 30.5 (5.4) kg/m2 and fasting glucose on diet alone of 9.8 (2.2) mmol/l. The geometric means (95% CI) of C-peptide secretion rates on placebo for glucose at 4.0, 8.0 and 12.0 mmol/l were 63 (46, 86), 143 (105, 195) and 205 (149, 281) pmol/min, respectively. On glibenclamide, this increased by 140 (99, 181), 126 (85, 167) and 158 (117, 199) pmol/min, respectively (p < 0.001 vs placebo). The absolute increment was significant (p < 0.001) and independent of clamp glucose concentration (p = 0.54). The proportional increase was greater at 4 mmol/l: 2.8-fold (2.4, 3.2), compared with 1.8-fold (1.5, 2.0) and 1.7-fold (1.4, 1.9) at 8 and 12 mmol/l, respectively (p < 0.001). At low-normal glucose, glibenclamide exerted a disproportionate effect on insulin secretion. This study highlights the risks of hypoglycaemia when aiming for tight glucose control on this agent.
Impact of cancer-related fatigue on chemotherapy-induced nausea and vomiting in Asian cancer patients.

Cancer-related fatigue (CRF) has been suggested to be associated with the occurrence of chemotherapy-induced nausea and vomiting (CINV). This study aims to evaluate the potential of CRF in predicting the occurrence of CINV.



This is a prospective, observational study. Recruited patients received moderately to highly emetogenic single-day chemotherapy regimens. On the day of chemotherapy, patients were instructed to provide a score (Likert scale of 0-10) to describe how CRF interfered with his or her ability to engage in daily activities and a score for how severe it was. Patients were then given a standardized 5-day diary to document their CINV events.



A total of 473 eligible patients (median age: 55 years, interquartile range (IQR): 48-61 years) were recruited, with most of the patients diagnosed with gastrointestinal (45%) and breast (37%) cancers. The median score of fatigue interference was 3 (IQR: 0-5). After confounders were adjusted for, patients with low fatigue interference scores (≤3) were more likely to achieve complete protection (no nausea, no vomiting, and no breakthrough antiemetics) of CINV (adjusted odds ratio = 1.57, 95%CI [1.05, 2.35], p = 0.027).



This is the largest study to date to evaluate the association between CRF and CINV. Patients experiencing CRF possessed a higher risk of poor control for CINV.
Steroid-sparing properties of sargramostim in patients with corticosteroid-dependent Crohn's disease: a randomised, double-blind, placebo-controlled, phase 2 study.

Although treatment with corticosteroids induces remission in Crohn's disease, prolonged exposure to corticosteroids is undesirable. This randomised clinical trial evaluated the efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (sargramostim), an activator of innate immunity, in corticosteroid-dependent patients with Crohn's disease.



Patients were randomised in a 2:1 ratio, to sargramostim 6 microg/kg subcutaneously once daily or placebo for up to 22 weeks. The study consisted of (1) an adjunctive phase (weeks 1-4) in which patients received study drug plus corticosteroid therapy; (2) a forced corticosteroid tapering phase (weeks 4-14); and (3) an observation phase (4 weeks) in which patients received study drug plus prednisone < or =7.5 mg. The primary endpoint was corticosteroid-free remission (Crohn's Disease Activity Index (CDAI) < or =150) 4 weeks after corticosteroid elimination. Secondary endpoints were corticosteroid-free response (CDAI decreased by > or =100) and induction of remission in patients who reduced the dose of corticosteroid to 2.5-7.5 mg.



Eighty-seven patients were randomised to sargramostim and 42 to placebo. Significantly more sargramostim-treated patients than placebo patients achieved corticosteroid-free remission (18.6% vs 4.9%; p = 0.03). Similar differences were seen for corticosteroid-free response and in patients who tapered corticosteroids to 2.5-7.5 mg/day. Sargramostim treatment was also associated with significant improvements in health-related quality of life. Patients who received sargramostim were more likely to experience musculoskeletal pain, injection site reactions and dyspnoea.



Sargramostim was more effective than placebo for inducing corticosteroid-free remission in patients with Crohn's disease with corticosteroid dependence. Sargramostim may provide significant benefit in this population if these findings are confirmed.
Emergency centre investigation of first-onset seizures in adults in the Western Cape, South Africa.

Patients with first-onset seizures commonly present to emergency centres (ECs). The differential diagnosis is broad, potentially life-threatening conditions need to be excluded, and these patients need to be correctly diagnosed and appropriately referred. There are currently no data on adults presenting with first-onset seizures to ECs in South Africa.



To review which investigations were performed on adults presenting with first-onset seizures to six ECs in the Western Cape Province.



A prospective, cross-sectional study was conducted from 1 July 2011 to 31 December 2011. All adults with first-onset seizures were included; children and trauma patients were excluded. Subgroup analyses were conducted regarding HIV status and inter-facility variation.



A total of 309 patients were included. Computed tomography (CT) scans were planned in 218 (70.6%) patients, but only performed in 169; 96 (56.8%) showed abnormalities judged to be causative (infarction, intracerebral haemorrhage and atrophy being the most common). At least 80% of patients (n=247) received a full renal and electrolyte screen, blood glucose testing and a full haematological screen. Lumbar puncture (LP) was performed in 67 (21.7%) patients, with normal cerebrospinal fluid findings in 51 (76.1%). Only 27 (8%) patients had an electroencephalogram, of which 5 (18%) were abnormal. There was a statistically significant difference in the number of CT scans (p=0.002) and LPs (p<0.001) performed in the HIV-positive group (n=49).



This study demonstrated inconsistency and wide local variance for all types of investigations done. It emphasises the need for a local guideline to direct doctors to appropriate investigations, ensuring better quality patient care and potential cost-saving.
High dose heparin as pretreatment for primary angioplasty in acute myocardial infarction: the Heparin in Early Patency (HEAP) randomized trial.

In the Heparin in Early Patency (HEAP) pilot study a beneficial effect of high-dose heparin on early patency in acute myocardial infarction (MI) was observed in a matched-control study.



High dose bolus intravenous injection of heparin may achieve lysis of coronary thrombi and could enhance early patency of the infarct related vessel in patients with MI scheduled for primary angioplasty.



Before primary angioplasty, 584 patients with MI entered an open randomized trial of high dose (300 IU/kg) or low dose (0 or 5,000 IU) heparin. Of the 584 patients, 299 were randomized to high dose and 285 patients to low dose heparin.



Thrombolysis In Myocardial Infarction (TIMI) flow grade 2 or 3 was observed before primary angioplasty in 65 patients (22%) in the high dose group and 60 patients (21%) in the low dose heparin group (p > 0.1), whereas TIMI flow grade 3 was observed in 38 (13%) and 24 patients (9%), respectively (p = 0.11). There were no differences in the clinical end points between the two groups. There were no hemorrhagic strokes, while 10% of the patients in the high dose group required blood transfusion versus 6% in the low dose/no heparin group (p = 0.07). No subsets of patients showed beneficial effects of high dose heparin, such as patients with longer delay between heparin administration and diagnostic angiogram or patients with short delay between symptom onset and admission.



There is no benefit of high dose bolus heparin on early patency compared with no or low dose heparin.
Lone atrial fibrillation as a positive predictor of left atrial volume reduction following ablation of atrial fibrillation.

We investigated predictors of left atrial volume reduction (LAVR) in patients with atrial fibrillation (AF) undergoing AF ablation.



Sixty patients with AF underwent pulmonary vein isolation (PVI) using a pulmonary vein ablation catheter (PVAC). All patients underwent cardiac imaging by computed tomography or magnetic resonance imaging to determine LAV 1 day before and 140 ± 9.5 days after PVI. Clinical follow-up and 72 h electrocardiogram Holter monitoring were performed 1, 3, and 6 months after ablation, and every 6 months thereafter. Significant LAVR (n = 60, 89.3 ± 3.9 vs. 79.5 ± 3.6 mL, P < 0.0001) was shown for the study group as a whole, caused particularly by the subgroup of patients with ablation success (n = 45, 85.2 ± 4.6 vs. 72.5 ± 3.7 mL, P < 0.0001). In addition, significant LAVR was shown for patients with lone AF (n = 25, 88.8 ± 6.8 vs. 72.7 ± 5.3 mL, P < 0.0001), but not for patients with AF and concomitant arterial hypertension (n = 32, 89 ± 4.8 vs. 86.7 ± 5 mL, P = 0.3), coronary artery disease (n = 12, 91.6 ± 7.8 vs. 89.1 ± 7.8 mL, P = 0.26), or left ventricular hypertrophy (n = 10, 86.3 ± 5.5 vs. 83.1 ± 5.3 mL, P = 0.27). Multivariate analysis revealed absence of arterial hypertension, lone AF, ablation success, and initial LA enlargement as independent predictors for significant LAVR following ablation (each P < 0.05).



Based on the subgroup of patients with lone AF, PVI leads to a significant LAVR 4 months after the procedure, especially in patients with clinical success in terms of AF freedom. Comorbidities such as arterial hypertension may prevent this reverse atrial remodelling, despite AF freedom. Clinical implications need to be further elucidated.
Metabolism and pharmacokinetics of oral and intravenous ifosfamide

The initial metabolism of ifosfamide (IF) consists of two different pathways: enzymatic hydroxylation at carbon-4 forms the cytostatically active metabolite 4-OH-IF (“activated ifosfamide”) whereas side-chain oxidation results in the liberation of chloroacetaldehyde, a compound with possible neurotoxic properties. The pharmacokinetics of ifosfamide and its activated form were investigated in 12 cancer patients, who received both oral and i.v. treatment in a randomized sequence on days 1 and 3 at a dose of 1 g/m2 (n=7) or 1.5 g/m2 (n=5). In 3 patients the pharmacokinetics of chloroacetaldehyde were also investigated. After oral application, ifosfamide absorption proceeded rapidly, the oral bioavailability was 0.92. Independent of the route of ifosfamide application on day 1, the terminal half-life on day 3 (when the drug was given by the alternative route) was decreased in 6 out of the 12 patients, thus indicating self-induction of hepatic metabolism. 4-OH-IF was already present 20 min after ifosfamide administration. In the individual patient the concentrations of 4-OH-IF were always higher after oral than after i.v. IF application: the mean p.o.:i.v. ratios forc max and the area under the concentration/time curve were 2.3 and 1.7 respectively (P<0.05). In a first series of 3 patients the chloroacetaldehyde concentrations measured after oral ifosfamide application were about twice as high as those when the drug was given intravenously. These results indicate that (in comparison to the i.v. route) orally administered ifosfamide may be more cancerotoxic but also leads to higher levels of chloroacetaldehyde. This would explain the neurotoxic sideeffects previously seen after oral administration of comparatively low ifosfamide doses.
Dynamic Memory Allocation in Computer Simulation

e of 35 dynamic memory allocation algorithms when used to service simulation programs as represented by 18 test cases. Algorithm performance was measured in terms of processing time, memory usage, and external memory fragmentation. Algorithms maintaining separate free space lists for each size of memory block used tended to perform quite well compared with other algorithms. Simple algorithms operating on memory ordered lists (without any free list) performed surprisingly well. Algorithms employing power-of-two block sizes had favorable processing requirements but generally unfavorable memory usage. Algorithms employing LIFO, FIFO, or memory ordered free lists generally performed poorly compared with others.