Miracle-dz/UniFAR-FTUs huggingface dataset:
Measuring Use of Positive Thinking Skills

Positive thinking interventions improve adaptive functioning and quality of life in many populations. However, no direct measure of positive thinking skills taught during intervention exists. This psychometric study of a convenience sample of 109 autism spectrum disorder (ASD) caregivers examined a new eight-item Positive Thinking Skills Scale (PTSS), which measures the frequency of use of positive thinking skills. The PTSS was found to be internally consistent (α = .90). Construct validity was supported by significant correlations (p < .01) with positive cognitions (r = .53), resourcefulness (r = .63), depression (r = −.45), and general well-being (r = .40). The findings support use of the PTSS as a potential indicator of intervention fidelity among ASD caregivers. However, because it is not specific for ASD caregivers, the PTSS has the potential for wider usage in other populations for whom the identification of specific positive thinking skills could provide direction for future intervention.
Characterization of a novel, dominant negative KCNJ2 mutation associated with Andersen-Tawil syndrome

Andersen-Tawil syndrome is characterized by periodic paralysis, ventricular ectopy, and dysmorphic features. Approximately 60% of patients exhibit loss-of-function mutations in KCNJ2, which encodes the inwardly rectifying K+ channel pore forming subunit Kir2.1. Here, we report the identification of a novel KCNJ2 mutation (G211T), resulting in the amino acid substitution D71Y, in a patient presenting with signs and symptoms of Andersen-Tawil syndrome. The functional properties of the mutant subunit were characterized using voltage-clamp experiments on transiently transfected HEK-293 cells and neonatal mouse ventricular myocytes. Whole-cell current recordings of transfected HEK-293 cells demonstrated that the mutant protein Kir2.1-D71Y fails to form functional ion channels when expressed alone, but co-assembles with wild-type Kir2.1 subunits and suppresses wild-type subunit function. Further analysis revealed that current suppression requires at least two mutant subunits per channel. The D71Y mutation does not measurably affect the membrane trafficking of either the mutant or the wild-type subunit or alter the kinetic properties of the currents. Additional experiments revealed that expression of the mutant subunit suppresses native IK1 in neonatal mouse ventricular myocytes. Simulations predict that the D71Y mutation in human ventricular myocytes will result in a mild prolongation of the action potential and potentially increase cell excitability. These experiments indicate that the Kir2.1-D71Y mutant protein functions as a dominant negative subunit resulting in reduced inwardly rectifying K+ current amplitudes and altered cellular excitability in patients with Andersen-Tawil syndrome.
The End of the Welfare State

This paper attempts to assess the results of George W. Bush’s Administration in the social field. Paradoxically, during its first term, this conservative Administration displays a strong will to reform the education and the Social Security systems. Then, in 2005, the failure of Bush’s Social Security plan and the aftermath of Hurricane Katrinae led to a change of plan. During the second term, the non-intervention of the Federal Government was conceived as a form of intervention. Eventually, the "non-intervention" of the Federal Emergency Management Agency communicates a new definition of the links between the State and the civil society. Far from the concept of "Associative State," advocated by Herbert Hoover and his fellow Republicans, the Bush Administration has assigned a new mission and new goals for the Federal Government: in the field of domestic policy, non-intervention must become the rule.
Structural basis for the Golgi membrane recruitment of Sly1p by Sed5p

Cytosolic Sec1/munc18‐like proteins (SM proteins) are recruited to membrane fusion sites by interaction with syntaxin‐type SNARE proteins, constituting indispensable positive regulators of intracellular membrane fusion. Here we present the crystal structure of the yeast SM protein Sly1p in complex with a short N‐terminal peptide derived from the Golgi‐resident syntaxin Sed5p. Sly1p folds, similarly to neuronal Sec1, into a three‐domain arch‐shaped assembly, and Sed5p interacts in a helical conformation predominantly with domain I of Sly1p on the opposite site of the nSec1/syntaxin‐1‐binding site. Sequence conservation of the major interactions suggests that homologues of Sly1p as well as the paralogous Vps45p group bind their respective syntaxins in the same way. Furthermore, we present indirect evidence that nSec1 might be able to contact syntaxin 1 in a similar fashion. The observed Sly1p‐Sed5p interaction mode therefore indicates how SM proteins can stay associated with the assembling fusion machinery in order to participate in late fusion steps.
Genetic diversity and differentiation of Kermode bear populations

The Kermode bear is a white phase of the North American black bear that occurs in low to moderate frequency on British Columbia’s mid‐coast. To investigate the genetic uniqueness of populations containing the white phase, and to ascertain levels of gene flow among populations, we surveyed 10 highly polymorphic microsatellite loci, assayed from trapped bear hairs. A total of 216 unique bear genotypes, 18 of which were white, was sampled among 12 localities. Island populations, where Kermodes are most frequent, show ≈ 4% less diversity than mainland populations, and the island richest in white bears (Gribbell) exhibited substantial genetic isolation, with a mean pairwise FST of 0.14 with other localities. Among all localities, FST for the molecular variant underlying the coat‐colour difference (A893G) was 0.223, which falls into the 95th percentile of the distribution of FST values among microsatellite alleles, suggestive of greater differentiation for coat colour than expected under neutrality. Control‐region sequences confirm that Kermode bears are part of a coastal or western lineage of black bears whose existence predates the Wisconsin glaciation, but microsatellite variation gave no evidence of past population expansion. We conclude that Kermodism was established and is maintained in populations by a combination of genetic isolation and somewhat reduced population sizes in insular habitat, with the possible contribution of selective pressure and/or nonrandom mating.
Balancing confidentiality and the information provided to families of patients in primary care

Background: Medical confidentiality underpins the doctor–patient relationship and ensures privacy so that intimate information can be exchanged to improve, preserve, and protect the health of the patient. The right to information applies to the patient alone, and, only if expressly desired, can it be extended to family members. However, it must be remembered that one of the primary tenets of family medicine is precisely that patient care occurs ideally within the context of the family. There may be, then, certain occasions when difficulties will arise as to the extent of the information provided to family members. Objectives: This study aimed to describe family doctors’ attitudes to confidentiality and providing patient information to relatives as well as their justifications for sharing information. Method: A descriptive postal questionnaire was self-administered by family doctors. Results: Of 227 doctors, 95.1% provided information to a patient’s family and over a third (35%) disclosed information to others without prior patient consent. Conclusions: The findings reveal that family doctors should pay more attention to their patients’ rights to information, privacy, and confidentiality, and reflect very carefully on the fine balance between this and the occasional need for the support and collaboration of family members in delivery of care. Emphasis should be placed on ethics and legal problems during undergraduate education and in-service training of doctors.
Leukocyte function in children with malignancies

Blood was obtained on 414 occasions from 106 children with acute lymphocytic leukemia (ALL) or solid tumors. Resting and stimulated hexose monophosphate shunt (HMPS) activity and unstimulated and stimulated nitroblue tetrazolium (NBT) dye reduction were assessed on each sample. The values obtained were compared to similar determinations made on blood obtained from 178 healthy children. Resting HMPS activity of all patients with malignant diseases was significantly (p < 0.01) greater, and ability to stimulate HMPS activity significantly (p < 0.01) less than that noted in healthy control patients. Unstimulated NBT dye reduction of leukocytes obtained from patients with malignant disorders was significantly (p < 0.01) less than that observed in nealthy control children. No significant differences were noted in HMPS activity or NBT dye reduction in patients with ALL, rhabdomyosarcoma, or other solid tumors who had bacterial infection when compared to uninfected patients, or when patients were categorized according to the type of chemotherapy provided. HMPS activity and NBT dye reduction of patients with ALL prior to treatment, in remission, and during episodes of relapse did not differ from each other. Thus, a functional impairment in leukocyte function was noted in patients with ALL even when their peripheral blood and bone marrow cells exhibited normal morphology.
Behavioural and physiological characterization of inbred mouse strains: prospects for elucidating the molecular mechanisms of mammalian learning and memory

With the advent of recombinant DNA methodology, it has become possible to dissect the molecular mechanisms of complex traits, including brain function and behaviour. The increasing amount of available information on the genomes of mammalian organisms, including our own, has facilitated this research. The present review focuses on a somewhat neglected area of genetics, one that involves the study of inbred mouse strains. It is argued that the use of inbred mice is complementary to transgenic approaches in the analysis of molecular mechanisms of complex traits. Whereas transgenic technology allows one to manipulate a single gene and investigate the in vivo effects of highly specific, artificially induced mutations, the study of inbred mouse strains should shed light on the roles of naturally occurring allelic variants in brain function and behaviour. Systematic characterization of the behavioural, electrophysiological, neurochemical, and neuroanatomical properties of a large number of inbred strains is required to elucidate mechanisms of mammalian brain function and behaviour. In essence, a ‘mouse phenome’ project is needed, entailing the construction of databases to investigate possible causal relationships amongst the phenotypical characteristics. This review focuses on electrophysiological and behavioural characterization of mouse strains. Nevertheless, it is emphasized that the full potential of the analysis of inbred mouse strains may be attained if techniques of numerous disciplines, including gene expression profiling, biochemical analysis, and quantitative trait loci (QTL) mapping, to name but a few, are also included.
Synthesis and biological evaluation of 2-fluoro and 3-trifluoromethyl-phenyl-piperazinylalkyl derivatives of 1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione as potential antidepressant agents

Abstract A series of 2-fluoro and 3-trifluoromethylphenylpiperazinylalkyl derivatives of 1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione (4–21) were synthesized and evaluated for their serotonin (5-HT1A/5-HT7) receptor affinity and phosphodiesterase (PDE4B and PDE10A) inhibitor activity. The study enabled the identification of potent 5-HT1A, 5-HT7 and mixed 5-HT1A/5-HT7 receptor ligands with weak inhibitory potencies for PDE4B and PDE10A. The tests have been completed with the determination of lipophilicity and metabolic stability using micellar electrokinetic chromatography (MEKC) system and human liver microsomes (HLM) model. In preliminary pharmacological in vivo studies, selected compound 8-(5-(4-(2-fluorophenyl)piperazin-1-yl)pentyl)-1,3,7-trimethyl-1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione (9) behaved as a potential antidepressant in forced swim test (FST) in mice. Moreover, potency of antianxiety effects evoked by 9 (2.5 mg/kg) is greater than that of the reference anxiolytic drug, diazepam. Molecular modeling revealed that fluorinated arylpiperazinylalkyl derivatives of 1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione have major significance for the provision of lead compounds for antidepressant and/or anxiolytic application.
Phosphorylated K-Ras limits cell survival by blocking Bcl-xL sensitization of inositol trisphosphate receptors

Significance K-Ras is mutated more often than any other oncogene, making the protein and the pathways it regulates attractive targets for anticancer drug discovery. We have shown that phosphorylation of serine 181 in the membrane-targeting region of K-Ras causes the protein to translocate from plasma membrane to intracellular membranes. Translocation is associated with toxicity but the mechanism has remained undefined. Here we show that phospho–K-Ras associates with inositol trisphosphate receptors (IP3Rs) on the endoplasmic reticulum (ER) and thereby blocks one of the prosurvival activities of Bcl-xL, which is to sensitize IP3Rs and thereby allow constitutive transfer of calcium from ER to mitochondria where it is required for efficient respiration. This pathway could be exploited to limit the oncogenic activity of mutant K-Ras. K-Ras4B is targeted to the plasma membrane by a farnesyl modification that operates in conjunction with a polybasic domain. We characterized a farnesyl-electrostatic switch whereby protein kinase C phosphorylates K-Ras4B on serine 181 in the polybasic region and thereby induces translocation from the plasma membrane to internal membranes that include the endoplasmic reticulum (ER) and outer mitochondrial membrane. This translocation is associated with cell death. Here we have explored the mechanism of phospho–K-Ras4B toxicity and found that GTP-bound, phosphorylated K-Ras4B associates with inositol trisphosphate receptors on the ER in a Bcl-xL–dependent fashion and, in so doing, blocks the ability of Bcl-xL to potentiate the InsP3 regulated flux of calcium from ER to mitochondria that is required for efficient respiration, inhibition of autophagy, and cell survival. Thus, we have identified inositol trisphosphate receptors as unique effectors of K-Ras4B that antagonize the prosurvival signals of other K-Ras effectors.
CEO Turnover and Firm Performance In Indonesia

We investigated the effect of changes in CEO position on subsequent firm performance by studying 91 CEO turnovers in Indonesia. Our results show that firm performance decreases during the turnover year. Moreover, the incoming CEO does not increase firm performance in subsequent years. Indeed, there is evidence that firm performance decreases after such turnovers. We ultimately conclude that CEO turnovers in Indonesia do not have a positive effect on firm performance. Going further, we divided CEO turnovers into routine and non-routine turnovers on the basis of the turnover process. Both routine and non-routine CEO turnovers show similar results with all samples, in which the incoming CEO in a routine or non-routine turnover does not have a positive effect upon firm performance. Further evidence suggests that the incoming CEO tends to upsize firm assets rather than downsize them.
Prediction of response to antiestrogen therapy in advanced breast cancer patients by pretreatment circulating levels of extracellular domain of the HER-2/c-neu protein.

PURPOSE Overexpression of the HER-2/c-neu/c-erbB2 proto-oncogene is associated with a worse prognosis in patients with breast cancer, perhaps due to an association of the HER-2 proto-oncogene protein with resistance to hormone and/or chemotherapy. Circulating levels of the extracellular domain (ECD) of the HER-2/c-neu-related protein (NRP) are elevated in 20% to 40% of patients with metastatic breast cancer. We investigated whether pretreatment levels of NRP predict response to hormone therapy (HT). MATERIALS AND METHODS Circulating NRP levels were determined in 94 patients who participated in a randomized trial of three different doses of the antiestrogen, droloxifene (DRO), as first-line HT for metastatic breast cancer. RESULTS NRP levels were elevated (> or = 5,000 U/mL) in 32 of 94 patients (34%). Only three of 32 patients (9%) with elevated NRP levels responded to DRO, compared with 35 of 62 (56%) with nonelevated NRP levels (P = .00001). Low pretreatment NRP level was the most powerful predictor of response to DRO (odds ratio of response, 22.4; P = .0001). Elevated pretreatment NRP levels were also associated with a shorter time to progression (TTP) and survival duration. CONCLUSION Pretreatment circulating NRP levels predict a low likelihood of benefit from HT, specifically DRO, in patients with estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive or receptor-unknown metastatic breast cancer, even when adjusted for other known predictive factors, such as ER and/or PgR levels, site of disease, disease-free interval from primary treatment to recurrence, and prior adjuvant chemotherapy. These data suggest that pretreatment NRP levels may be useful in deciding whether to treat a patient who otherwise appears to be likely to respond to HT.
Minimalist video-assisted thoracic surgery biopsy of mediastinal tumors.

BACKGROUND Mediastinal tumors often require surgical biopsy to achieve a precise and rapid diagnosis. However, subjects with mediastinal tumors may be unfit for general anesthesia, particularly when compression of major vessels or airways does occur. We tested the applicability in this setting of a minimalist (M) uniportal, video-assisted thoracic surgery (VATS) strategy carried out under locoregional anesthesia in awake patients (MVATS). METHODS We analyzed in a comparative fashion including propensity score matching, data from a prospectively collected database of patients who were offered surgical biopsy for mediastinal tumors through either MVATS or standard VATS. Tested outcome measures included feasibility, diagnostic yield, and morbidity. RESULTS A total of 24 procedures were performed through MVATS. Diagnostic yield was 100%. Median hospital stay and time interval to oncologic treatment were 2 days (IQR, 2-3 days) and 7 days (IQR, 5.5-11.5 days), respectively. At overall comparison (MVATS, N=24 vs. VATS, N=23), there was a significant difference in both frequency and severity of postoperative complication as measured by Clavien-Dindo classification (P<0.006). In a propensity score matched comparison (8 patients per group), grade 3 or 4 complications requiring aggressive management were found only in the general anesthesia group. Global time spent in the operating room was shorter in the MVATS group (P=0.05). Time interval to oncological treatment was the same between groups. Other differences were also found in SIRS score (P=0.05) and PaO2/FiO2 (P=0.04) thus suggesting better adaption to perioperative stress. CONCLUSIONS MVATS biopsy appears to be a reliable tool to optimize diagnostic assessment in patients with mediastinal tumors. It can offer high diagnostic accuracy due to large tissue samples, while reducing morbidity rate compared to the same operation under general anesthesia. More robust evaluation is needed to define the appropriateness of MVATS in this specific clinical setting.
Gaps in Protection: Undocumented Zimbabwean migrants in South Africa

This series provides a forum for researchers to publish preliminary findings on themes related to migration and displacement in Africa. These papers may be cited (including the full URL and the date downloaded), but reproduced only with direct permission of the author. Submissions are welcome by email (MS Word format) sent to the series editor: landaul@migration.wits. ac.za. Authors whose work is included here are encouraged to resubmit papers for publication elsewhere. Introduction This paper sets out to explore the position of undocumented migrants in South Africa from the perspective of three areas or frameworks. First are the current debates in refugee and forced migration studies about whether refugee studies should remain a separate field of study or whether the more recent trend of merging refugee studies with forced migration studies is problematic due to its potential negative impact on the protection of refugees. Secondly, the paper is concerned about the ways in which undocumented migrants, though in theory protected by the human rights framework are in fact falling outside of any protection disempowering them and leaving them vulnerable. Finally, the paper will see how structural barriers within South Africa as a receiving country impact on undocumented migrants both in terms of their position within that country but also on their transnational capacities which will impact on the wellbeing of families in Zimbabwe subjecting them to greater poverty and fewer options for mobility. In order to explore the lives of undocumented Zimbabwean migrants in South Africa, the paper will draw on a sub-sample of 500 Zimbabwean migrants living in South Africa of which 156 (32 per cent) were undocumented migrants. The data is extrapolated from a larger survey of 1000 Zimbabweans living in South Africa and the UK. The survey data was collected using mixed data collection modes: self-completion paper; web based and interviewer administered surveys. Snowball sampling was used and respondents were located through a number of different networks 1. Refugee and forced migration studies There has been a greater recognition in recent years through the work of Stephen Castles and others on the migration-asylum nexus and migration-development nexus that the categorization of migrants which is bureaucratically useful for governments does not necessarily reflect the reality of people's lives, motivations and experiences (Castles, 2003). Refugee motives for flight relating to persecution and those in response to violations of human rights are not always clear cut (Grant, 2005). While violations of social …
Fiscal Consequences of Structural Reform Under Constrained Monetary Policy

Given the weak economic performance of many countries since the recent crisis, there is an increasing need for structural reforms aimed at promoting long-run economic growth. Structural reforms can entail short-run output costs unless offset by a demand expansion. When monetary policy is constrained and cannot carry out this short-run expansion, there is a potential role for fiscal policy. In this case, reforms can go against fiscal consolidation in the short run, although they are expected to improve public finances in the long run. The aim of this paper is to quantify the short-run fiscal costs and long-run fiscal benefits of reforms, and investigate how the design of reforms can affect this trade-off. The focus is on the euro area, which has been particularly affected by high unemployment. In the model, both the costs and benefits of reforms are generally small, although increasingly large reforms entail larger rises in deficit-to-GDP in the short run. Results suggest that reforms in labour markets have little effect on public finances in the long run, but their short-run costs can be ameliorated by combining them with product market reforms.