Miracle-dz/UniFAR-FTUs huggingface dataset:
Preliminary definition of improvement in juvenile arthritis.

OBJECTIVE To identify a core set of outcome variables for the assessment of children with juvenile arthritis (JA), to use the core set to develop a definition of improvement to determine whether individual patients demonstrate clinically important improvement, and to promote this definition as a single efficacy measure in JA clinical trials. METHODS A core set of outcome variables was established using a combination of statistical and consensus formation techniques. Variables in the core set consisted of 1) physician global assessment of disease activity; 2) parent/patient assessment of overall well-being; 3) functional ability; 4) number of joints with active arthritis; 5) number of joints with limited range of motion; and 6) erythrocyte sedimentation rate. To establish a definition of improvement using this core set, 21 pediatric rheumatologists from 14 countries met, and, using consensus formation techniques, scored each of 72 patient profiles as improved or not improved. Using the physicians' consensus as the gold standard, the chi-square, sensitivity, and specificity were calculated for each of 240 possible definitions of improvement. Definitions with sensitivity or specificity of <80% were eliminated. The ability of the remaining definitions to discriminate between the effects of active agent and those of placebo, using actual trial data, was then observed. Each definition was also ranked for face validity, and the sum of the ranks was then multiplied by the kappa statistic. RESULTS The definition of improvement with the highest final score was as follows: at least 30% improvement from baseline in 3 of any 6 variables in the core set, with no more than 1 of the remaining variables worsening by >30%. The second highest scoring definition was closely related to the first; the third highest was similar to the Paulus criteria used in adult rheumatoid arthritis trials, except with different variables. This indicates convergent validity of the process used. CONCLUSION We propose a definition of improvement for JA. Use of a uniform definition will help standardize the conduct and reporting of clinical trials, and should help practitioners decide if a child with JA has responded adequately to therapy. We are in the process of prospectively validating this definition and several others that scored highly.
Full bridge MMC converter optimal design to HVDC operational requirements

Summary form only given. Design and operation of FB (full bridge) MMC that meets HVDC specifications are studied in this paper. Three new design parameters: the over-modulation index (kMMC), the DC modulation index (Mdc), the minimal DC voltage (Vminpu) are introduced to specify the operation of a FB MMC. Power increase and semiconductor count increase with the increase of kMMC is analyzed to understand benefits of over-modulation. The required number of submodules and the number of more-costly FB submodules for specified rated dc voltage, Vminpu and kMMC are calculated. The relationship of the submodule inserting logic and dynamics of an arm is analyzed. The submodule voltage balancing is studied and the constraints on the required number of FB submodules are deduced. The capability of over-modulation and the operation under low DC voltage with optimal submodule count are verified using EMTP simulation.
Combined use of electroencephalogram and magnetic resonance imaging in full-term neonates with acute encephalopathy.

OBJECTIVE The electroencephalogram (EEG) is widely used in full-term infants with acute neonatal encephalopathy, and its prognostic value has been confirmed by several studies. Magnetic resonance imaging (MRI) of the brain has also been applied in these patients, and increasing numbers of reports affirm its prognostic reliability. The aim of this study has been to investigate the correlation between an early EEG and MRI findings in infants with acute neonatal encephalopathy and to assess the prognostic value of a combination of EEG and MRI findings. PARTICIPANTS AND METHODS Twenty-five full-term infants had an EEG recorded within the first 72 hours after birth and a neonatal brain MRI scan after the end of the first week. RESULTS Both EEG and MRI were predictive of outcome. A normal MRI was always associated with normal EEG background activity and normal outcome and severe abnormalities on MRI with marked EEG abnormalities and an abnormal outcome. When the MRI showed moderate abnormalities, the EEG in all cases but one identified patients with normal and abnormal outcome.EEG, MRI, HIE, neurodevelopment.
A Literature Review of Quetiapine for Generalized Anxiety Disorder

To evaluate the efficacy and tolerability of quetiapine for the treatment of generalized anxiety disorder (GAD), a literature search of the Medline database was conducted from inception to May 2014. The search was not restricted by language. Keywords used in the search were quetiapine and generalized anxiety disorder or anxiety. All studies assessing the use of quetiapine as monotherapy or adjunct therapy for the primary management of GAD in adults 18–65 years of age were included in this review. The nine studies included in this review were three studies evaluating the use of quetiapine extended release (XR) as monotherapy for acute GAD treatment, one study evaluating quetiapine XR monotherapy for maintenance treatment of GAD, and five studies evaluating quetiapine (2 XR, 3 immediate release) as adjunct therapy for acute GAD treatment. Quetiapine displayed both efficacy and tolerability in all monotherapy trials evaluating its use for acute and long‐term treatment of GAD. Despite some limitations to and heterogeneity among the five adjunct therapy studies, three studies showed that quetiapine resulted in statistically significant changes in the Hamilton Anxiety Rating Scale or Clinical Global Impressions‐Severity of Illness Scale scores. Although future studies of longer duration with broader inclusion criteria are needed to further evaluate the benefits and risks of quetiapine for GAD, in patients failing to respond to conventional antidepressant therapy, quetiapine may be a potential treatment option. With appropriate monitoring and management of adverse effects, the potential benefits of quetiapine in patients with treatment‐refractory GAD may outweigh the risks associated with its use.
Green tea polyphenols induce cell death in breast cancer MCF-7 cells through induction of cell cycle arrest and mitochondrial-mediated apoptosis

In order to study the molecular mechanisms of green tea polyphenols (GTPs) in treatment or prevention of breast cancer, the cytotoxic effects of GTPs on five human cell lines (MCF-7, A549, Hela, PC3, and HepG2 cells) were determined and the antitumor mechanisms of GTPs in MCF-7 cells were analyzed. The results showed that GTPs exhibited a broad spectrum of inhibition against the detected cancer cell lines, particularly the MCF-7 cells. Studies on the mechanisms revealed that the main modes of cell death induced by GTPs were cell cycle arrest and mitochondrialmediated apoptosis. Flow cytometric analysis showed that GTPs mediated cell cycle arrest at both G1/M and G2/M transitions. GTP dose dependently led to apoptosis of MCF-7 cells via the mitochondrial pathways, as evidenced by induction of chromatin condensation, reduction of mitochondrial membrane potential (ΔΨm), improvement in the generation of reactive oxygen species (ROS), induction of DNA fragmentation, and activations of caspase-3 and caspase-9 in the present paper.
Multivariate analysis of donor risk factors for graft survival in kidney transplantation

Background. The results of the transplantation of marginal donor kidneys remain controversial. This study aimed to investigate the impact of donor risk factors as predictors of kidney-graft outcome. Methods. Allograft failure risk factors were studied in 7,209 cadaveric kidney-transplant recipients reporting to the Etablissement français des Greffes (EfG) from 1996 to 2000, of which 544 (7.6%) were from donors aged over 60. Both univariate and multivariate analysis were used to assess the effect of donor risk factors and were stratified according to recipient age. Results. Overall graft survival was 91.1% (95% confidence interval [CI] 90.5–91.8) at 1 year, 88.6% (95% CI 87.8–89.4) at 2 years, and 85.6% (95% CI 84.6–86.6) at 3 years posttransplant. Univariate analysis of risk factors showed a significant reduction of graft survival in recipients transplanted with kidneys coming from donors older than 60 years, donors with a history of hypertension, a cerebrovascular cause of death, and a preharvesting serum creatinine greater than 150 &mgr;mol/L. Multivariate analysis revealed significantly higher failure rate associated with cerebrovascular cause of death (RR=1.2, P =0.02), history of hypertension (RR=1.2, P =0.04), and elevated serum creatinine (RR=1.3, P =0.03), whereas donor age greater than 60 years was not found as an independent risk factor. Conclusions. Our results suggest that cerebrovascular cause of death, history of hypertension, and elevated creatinine are significant independent donor risk factors for graft survival, whereas donor age is a statistically significant, but dependent, risk factor. This result is important for the design of allocation and transplantation strategies for kidneys procured in elderly donors.
Platelet procoagulant complex assembly in a tissue factor‐initiated system

Summary. The aim of this study was to examine the assembly of the factor IXa/VIIIa (Xase) and factor Xa/Va (IIase) complexes on the platelet surface in a system designed to mimic tissue factor‐initiated coagulation. The experimental system contained tissue factor‐bearing monocytes, unactivated platelets, and plasma concentrations of factors V, VIII, IX, X, prothrombin, tissue factor pathway inhibitor (TFPI), antithrombin III (ATIII), and small amounts of factor VIIa. The time courses of platelet activation, coagulation factor binding and thrombin generation were compared. In this system, thrombin generation by the combination of monocytes and platelets was synergistic compared to each cell type alone. Platelet activation and thrombin generation were minimal in the absence of prothrombin or factor X. After a lag period, platelet activation began, followed by progressive binding of factors Va and VIIIa. This was followed by factor IXa and Xa binding and the onset of thrombin generation. Unexpectedly, a transient early increase in platelet‐associated factor IX and X was also seen, that was due to release from platelets. The amount of factor IX bound to isolated activated platelets was increased by addition of factor VIIIa, or by activation of factor IX to IXa. In contrast, factor VIIIa binding was not altered by the presence of factor IX or IXa. We conclude that in a tissue factor‐initiated system, assembly of the procoagulant complexes on the platelet surface begins after platelet activation occurs. Platelet activation requires thrombin generation in the vicinity of the tissue factor bearing cells. The cofactors Va and VIIIa bind to the platelets and facilitate subsequent binding of factors IXa and Xa to form functional procoagulant complexes.
Subcomplexes of PA700, the 19 S Regulator of the 26 S Proteasome, Reveal Relative Roles of AAA Subunits in 26 S Proteasome Assembly and Activation and ATPase Activity*

We have identified, purified, and characterized three subcomplexes of PA700, the 19 S regulatory complex of the 26 S proteasome. These subcomplexes (denoted PS-1, PS-2, and PS-3) collectively account for all subunits present in purified PA700 but contain no overlapping components or significant levels of non-PA700 proteins. Each subcomplex contained two of the six AAA subunits (Rpt1–6) that form the binding interface of PA700 with the 20 S proteasome, the protease component of the 26 S proteasome. Unlike intact PA700, no individual PA700 subcomplex displayed ATPase activity or proteasome activating activity. However, both activities were manifested by ATP-dependent in vitro reconstitution of PA700 from the subcomplexes. We exploited functional reconstitution to define and distinguish roles of different PA700 subunits in PA700 function by selective alteration of subunits within individual subcomplexes prior to reconstitution. Carboxypeptidase treatment of either PS-2 or PS-3, subcomplexes containing specific Rpt subunits previously shown to have important roles in 26 S proteasome assembly and activation, inhibited these processes but did not affect PA700 reconstitution or ATPase activity. Thus, the intact C termini of both subunits are required for 26 S proteasome assembly and activation but not for PA700 reconstitution. Surprisingly, carboxypeptidase treatment of PS-1 also inhibited 26 S proteasome assembly and activation upon reconstitution with untreated PS-2 and PS-3. These results suggest a previously unidentified role for other PA700 subunits in 26 S proteasome assembly and activation. Our results reveal relative structural and functional relationships among the AAA subunits of PA700 and new insights about mechanisms of 26 S proteasome assembly and activation.
Microsatellite analyses reveal fine‐scale genetic structure in grey mouse lemurs (Microcebus murinus)

Information on genetic structure can be used to complement direct inferences on social systems and behaviour. We studied the genetic structure of the solitary grey mouse lemur (Microcebus murinus), a small, nocturnal primate endemic to western Madagascar, with the aim of getting further insight on its breeding structure. Tissue samples from 167 grey mouse lemurs in an area covering 12.3 km2 in Kirindy Forest were obtained from trapping. The capture data indicated a noncontinuous distribution of individuals in the study area. Using 10 microsatellite markers, significant genetic differentiation in the study area was demonstrated and dispersal was found to be significantly male biased. Furthermore, we observed an overall excess of homozygotes in the total population (FIT = 0.131), which we interpret as caused by fine‐scale structure with breeding occurring in small units. Evidence for a clumped distribution of identical homozygotes was found, supporting the notion that dispersal distance for breeding was shorter than that for foraging, i.e. the breeding neighbourhood size is smaller than the foraging neighbourhood size. In conclusion, we found a more complex population structure than what has been previously reported in studies performed on smaller spatial scales. The noncontinuous distribution of individuals and the effects of social variables on the genetic structure have implications for the interpretation of social organization and the planning of conservation activities that may apply to other solitary and endangered mammals as well.
Qualitative Research and Evaluation Methods (3rd ed.)

‘In Utilization-Focused Evaluation (Patton, 1978) I suggested that if one had to choose between implementation information and outcomes information because of limited evaluation resoures, there are many instances in which implementation information would be of greater value. A decision maker can use implementation information to make sure that a policy is being put into operation according to design – or to test the feasibility of the policy. Unless one knows that a program is operating according to design, there may be little reason to expect it to produce the desired outcomes. Furthermore, until the program is implemented and a ‘treatment’ is believed to be in operation, there may be little reason even to bother evaluating outcomes. Where outcomes are evaluated without knowledge of implementation, the resuts seldom provide a direction for action because the decision maker lacks information about what produced the observed outcomes (or lack of outcomes). It is important to study and evaluate program implementation in order to understand how and why programs deviate from initial plans and expectations. Such deviations are quite common and natural . ’ (Patton, 1980, p 69; 1990, p. 105; Patton, 2002, p. 161)
Revisiting yardstick competition and spillover effects in in the new era of spatial econometrics: evidence from Italian cities

This paper exploits political features of Italian local governments to identify the presence of spatial interactions in spending decisions over the period 2001-2011. In particular, I take advantage of the political cycle to isolate the effect of spending decisions of one municipality on neighbors’ municipalities. The results of this analysis point to the presence of strategic interaction between neighboring municipalities, and indicate that such a fiscal behavior is more pronounced during electoral years, that is municipalities are engaged in yardstick competition. Moreover, to isolate any other source of spatial interactions from yardstick competition, I rely on a sample of municipalities experiencing a council dismissal, for which the political process is expected to be less marked - as they are led by a commissioner, who does not have any political concern. In this case, I build a measure of intensity of commissioner to induce variation in the spending decisions, finding, however, no evidence of spatial dependencies. Taken together these results suggest that the observed spatial dependence in spending decisions is unlikely to be driven by spillover e? ects, rather, it seems to be consent with the yardstick competition hypothesis.
Theory of Reasoned Action as a Framework for Communicating Climate Risk: A Case Study of Schoolchildren in the Mekong Delta in Vietnam

Communicating climate risks to vulnerable groups motivating them to take adaptive actions remains a significant challenge in many populations, especially to children. The theory of reasoned action (TRA) suggests that attitude and subjective norms are important for persuasive communication. This study assesses how to apply TRA, its constructs and other relevant factors to predict behavior intention and beliefs and to change behavior tendency. The randomized field experiment method was applied to explore the differences between pre- and post-communication treatments (2 × 2 design). Can Tho city, located in the Mekong Delta of Vietnam, was selected as the research context because of its vulnerability to climate change. The results show that, first, TRA was found to be a significant predictor model of children’s climate change behavior intentions. Second, attitude has a significant effect on the children’s intention to act while videos with subjective norm treatment had not. The treatment interaction of both constructs also had a significant effect. Third, TRA theory-based treatments are positively associated with changes in children’ salient beliefs on attitude and normative belief on social norm toward climate change. In addition, past practices, knowledge and gender are further factors that influence children’s behavior intentions. A theory-inspired design of communication strategy allows the prediction and influencing of intentions. This finding has strong implications for both research and development in Vietnam.
Acceptability of Day Care Surgery

Although day case surgery is recommended, its widespread feasibility in an urban environment is unclear. We studied 100 consecutive unselected patients admitted for surgical procedures considered to be suitable for day case surgery. Their age, fitness and social details were recorded and they were asked both before surgery and after discharge by a postal questionnaire, whether they would have preferred treatment as an outpatient. There were 47 men and 53 women with a mean age of 42.5 years. Ninety-six were considered to be medically fit for day case surgery but 10 patients lived alone, seven had no suitable companion, 22 had too many stairs to climb, 13 lived too far from the hospital and two could not provide a lift home. Thus 58 of the patients were unsuitable for day case surgery. Seventy-eight of the patients replied to the postal questionnaire. Before the operation 51 patients preferred the idea of day care but only 14 felt the same way afterwards. The single postoperative complication was one case of acute retention after a hernia repair. In our experience, over half the patients initially deemed suitable for day case surgery would be unsuitable.
Premorbid brain size as a determinant of reserve capacity against intellectual decline in Alzheimer's disease.

OBJECTIVE Both the magnitude of brain atrophy and premorbid brain size determine the volume of the brain affected by Alzheimer's disease. To examine the possibility that premorbid brain volume is a determinant of cognitive reserve in patients with Alzheimer's disease, the relation between diffuse brain atrophy and cognitive decline and the impact of premorbid brain size on cognitive decline were studied in patients with Alzheimer's disease. METHOD By measuring whole brain volume and intracranial volume in 60 patients with probable Alzheimer's disease, mild to moderate in severity, with the use of high-resolution magnetic resonance imaging and image processing, the authors studied the impact of premorbid brain volume and magnitude of diffuse brain atrophy on cognitive functions. On the basis of the normative brain-calvarium relationship derived from data an 28 healthy adults and the total intracranial volume measure of each patient, the magnitude of brain atrophy and premorbid brain volume were estimated. RESULTS After control for the effects of age, sex, and education as confounding factors, it was found that the Alzheimer's disease patients' intelligence was correlated both positively with premorbid brain volume and negatively with magnitude of brain atrophy, while impairments in language and memory were correlated with magnitude of brain atrophy but not with premorbid brain volume. CONCLUSIONS These findings partially support the hypothesis that premorbid brain volume is a determinant of reserves against intellectual decline in Alzheimer's disease.
Matrix metalloproteinases in isolated hypercholesterolemia.

AIM Levels of circulating matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are altered in subjects with atherosclerosis. We hypothesized that also otherwise healthy hypercholesterolemic subjects will have altered MMP/TIMP concentrations. To validate this hypothesis, we compared MMPs/TIMPs in patients with moderate isolated hypercholesterolemia before and after atorvastatin therapy and in healthy normolipidemic controls. METHODS Twenty-seven otherwise healthy subjects with isolated hypercholesterolemia (total cholesterol 8.3+/-0.3 mmol/L) and 29 healthy normolipidemic controls were included. Patients were treated by atorvastatin for 10 weeks. We studied plasma levels of MMPs (MMP)-2, -3, and -9 and of their TIMPs (TIMP)-1 and -2. RESULTS Patients differed from controls by significantly lower MMP-3 [11.6 (5.7-21) vs 18.4 (12-22) ng/mL, P<10-4 (median, range 25-75%)] and TIMP-2 [13.3 (8.8-30.5) vs 22.1 (10.8-39) ng/mL, P=0.02] and by higher TIMP-1 [496 (461-538) vs 483 (456-500) ng/mL, P=0.004]. Atorvastatin decreased significantly TIMP-1 [from 496 (461-538) to 476 (451-525) ng/mL]. CONCLUSIONS Isolated hypercholesterolemia per se is associated with similar alterations of circulating MMPs and TIMPs as developed symptomatic atherosclerosis. Most consistent link to serum lipids was observed in case of TIMP-1. MMP and TIMP levels probably reflect the atherogenic process in its early stages in these subjects.