Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical Aspects of Type 3 Long-QT Syndrome: An International Multicenter Study.

BACKGROUND Risk stratification in patients with type 3 long-QT syndrome (LQT3) by clinical and genetic characteristics and effectiveness of β-blocker therapy has not been studied previously in a large LQT3 population. METHODS The study population included 406 LQT3 patients with 51 sodium channel mutations; 391 patients were known to be event free during the first year of life and were the focus of our study. Clinical, electrocardiographic, and genetic parameters were acquired for patients from 7 participating LQT3 registries. Cox regression analysis was used to evaluate the independent contribution of clinical, genetic, and therapeutic factors to the first occurrence of time-dependent cardiac events (CEs) from age 1 to 41 years. RESULTS Of the 391 patients, 118 (41 males, 77 females) patients (30%) experienced at least 1 CE (syncope, aborted cardiac arrest, or long-QT syndrome-related sudden death), and 24 (20%) suffered from LQT3-related aborted cardiac arrest/sudden death. The risk of a first CE was directly related to the degree of QTc prolongation. Cox regression analysis revealed that time-dependent β-blocker therapy was associated with an 83% reduction in CEs in females (P=0.015) but not in males (who had many fewer events), with a significant sex × β-blocker interaction (P=0.04). Each 10-ms increase in QTc duration up to 500 ms was associated with a 19% increase in CEs. Prior syncope doubled the risk for life-threatening events (P<0.02). CONCLUSIONS Prolonged QTc and syncope predispose patients with LQT3 to life-threatening CEs. However, β-blocker therapy reduces this risk in females; efficacy in males could not be determined conclusively because of the low number of events.
Towards efficient motion planning for manipulators with complex geometry

Considers the issues involved in writing path planners that can work well with complex geometric models of robots and workspaces, and outline the authors' work in implementing a solution. The authors' claim that many path planning problems can be solved by a mixture of global and local planning. In turn, local planning can be usefully supported by the provision of efficient distance computations, and the authors describe a variation on the algorithm of Gilbert, Johnson and Keerthi (1988), that they have packaged together with a hierarchical decomposition of objects for added efficiency. Global planning requires more domain-dependent techniques, but the authors have been experimenting with approximations to the generalised Voronoi diagram, and results for this system are shown using a path planner based on the authors' method of virtual springs.
Characterization of coronary plaques with combined use of intravascular ultrasound, virtual histology and optical coherence tomography

According to post-mortem studies, luminal thrombosis occurs from plaque rupture, erosion and calcified nodules. In vivo studies have found thin cap fibroatheroma (TCFA) as the main vulnerable lesion, prone to rupture. Few data about other post-mortem lesions have been reported in vivo. Our main objective is to characterize in vivo the coronary plaques with intravascular ultrasound-virtual histology (IVUS-VH) and optical coherence tomography (OCT), in order to detect not only thin cap fibroatheroma (TCFA), but also other possible vulnerable lesions. The secondary objective is to correlate these findings with clinical and analytical data. Twenty-five patients (18 stable) submitted to coronary angiography were included in this pilot study. After angiography, the three vessels were studied (when possible) with IVUS-VH and OCT. Plaque characteristics were correlated with clinical and analytical data. Forty-six lesions were analyzed. IVUS-VH detected significant necrotic core in 15 (3 were definite TCFA). OCT detected TCFA in 10 lesions, erosion in 6, thrombus in 5 and calcified nodule in 8. Possible vulnerable lesion was found in 61% of stable and 57% of unstable patients. Erosions and calcified nodules were only found in stable patients. Those with significant necrotic core had higher body mass index (P=0.016), higher levels of hs-CRP (P=0.019) and triglycerides (P=0.040). The higher the levels of hs-CRP, the larger the size of the necrotic core (r=0.69, P=0.003). Lesions with characteristics of vulnerability were detected by IVUS-VH and OCT in more than 50% of stable and unstable coronary patients. A significant necrotic core was mainly correlated with higher hs-CRP.
A 255 MHz Programmable Gain Amplifier and Low-Pass Filter for Ultra Low Power Impulse-Radio UWB Receivers

A 90 nm-CMOS power-optimized analog baseband chain for ultra-low-power impulse-radio ultra-wideband (IR-UWB) receivers is presented. The proposed device merges the functions of a programmable gain amplifier (PGA) and a low-pass filter (LPF). It consists of the cascade of three biquadratic cells made up by opamps in a series-shunt configuration, which features high input impedance, low load effects in the cascade blocks, and better frequency response. The opamp parameters are included in the overall biquad transfer function. This allows getting very low power performance, since the opamp bandwidth is not required to be much larger than the filter cutoff frequency. Moreover, the current consumption is optimized according to the selected gain level (1.3 mA at 0 dB-gain up to 1.9 mA at 40 dB-gain). The PGA features a 0-40 dB programmable gain range with a 5 dB gain-step. The LPF performs a sixth-order 255 MHz low-pass frequency response. For the overall chain the IIP3 is 14 dBm at 0 dB gain, while the input referred noise is 12.5 nV/√Hz at 40 dB gain.
Learning Distances for Arbitrary Visual Features

This paper presents a method for learning distance functions of arbitrary feature representations that is based on the concept of wormholes. We introduce wormholes and describe how it provides a method for warping the topology of visual representation spaces such that a meaningful distance between examples is available. Additionally, we show how a more general distance function can be learnt through the combination of many wormholes via an inter-wormhole network. We then demonstrate the application of the distance learning method on a variety of problems including nonlinear synthetic data, face illumination detection and the retrieval of images containing natural landscapes and man-made objects (e.g. cities).
Childhood Obesity and Self-Esteem

Background. Although childhood obesity may have detrimental consequences for childhood self-esteem, the prevalence and magnitude of this problem is controversial. In addition, the social and emotional effects of decreased self-esteem in obese children are unknown. Methods. A total of 1520 children, 9 to 10 years of age, born to mothers in the National Longitudinal Survey of Youth were studied. Comprehensive demographic data including race and family income were available in 97% of the cohort. Self-esteem was measured using Self-Perception Profile for Children. The 4-year follow-up Self-Perception Profile for Children scores were available in 79% of the children. Obesity was defined as a body mass index greater than the 95th percentile for age and gender. Additional data include a self-administered questionnaire at 13 to 14 years of age concerning emotional well being, smoking, and alcohol consumption. Data were stratified by race and gender. The data were weighted to reflect a nationally representative sample of children born to mothers 17 to 28 years of age. Results. Scholastic and global self-esteem scores were not significantly different among 9- to 10-year-old obese and nonobese children. However, over the 4-year period, obese Hispanic females and obese white females showed significantly decreased levels of global self-esteem compared with nonobese Hispanic females and nonobese white females, respectively. Mild decreases in self-esteem also were observed in obese boys compared with nonobese boys. As a result, by 13 to 14 years of age, significantly lower levels of self-esteem were observed in obese boys, obese Hispanic girls, and obese white girls compared with their nonobese counterparts. Decreasing levels of self-esteem in obese children were associated with significantly increased rates of sadness, loneliness, and nervousness compared with obese children whose self-esteem increased or remained unchanged. In addition, obese children with decreasing levels of self-esteem over the 4-year period were more likely to smoke and drink alcohol compared with obese children whose self-esteem increased or remained unchanged. Conclusion. Obese Hispanic and white females demonstrate significantly lower levels of self-esteem by early adolescence. In addition, obese children with decreasing levels of self-esteem demonstrate significantly higher rates of sadness, loneliness, and nervousness and are more likely to engage in high-risk behaviors such as smoking or consuming alcohol.
DMA-damaging Activity in Vivo and Bacterial Mutagenicity of Sixteen Hydrazine Derivatives as Related Quantitatively to their Carcinogenicity1

Sixteen hydrazine derivatives (hydrazine, 1,1-dimethylhydra-zine, 1,2-dimethylhydrazine, phenylhydrazine, procarbazine, isoniazid, isocarboxazid, nialamide, 2,4-dinitrophenylhydra-zine, phenelzine, hydralazine, dihydralazine, carbamylhydrazine, mebanazine, iproniazid, and 1-carbamyl-2-phenylhydra-zine) were tested for DNA-damaging activity by the alkaline elution technique and for mutagenic activity in the Salmonella-microsome (Ames) test. The first nine compounds listed (56%) were found to induce a significant DNA fragmentation in the liver and/or in the lung of i.p.-treated male Swiss mice. The DNA-damaging potency varied over an ~30-fold range. Thir teen of the first 14 compounds listed (81% of the total), isocarboxazid being inactive, were positive in the Ames test, with a broad range of activity towards the five bacterial strains of Salmonella typhimurium used (TA1535, TA100, TA1537, TA1538, and TA98) and of metabolic behavior in the presence of S-9 mix containing rat liver, mouse liver, or mouse lung postmitochondrial preparations from Aroclor-treated animals. The mutagenic potency varied over an almost 7000-fold range. For 11 of the 16 hydrazine derivatives tested, homogeneous carcinogenicity data (induction of pulmonary tumors in mice chronically treated p.o.) were available from literature. Elabo ration of these data showed that carcinogenic potency varied over an ~ 1900-fold range. The five most potent carcinogens were all positive in the DNA damage test. Their carcinogenic potency varied over a 130-fold range and their DNA-damaging potency varied over a 22-fold range. DNA-damaging potency seemed to vary on a more compressed scale, but regression analysis indicated the existence of a strong positive correlation between in vivo DNA-damaging and carcinogenic potencies, while a lack of correlation was found between mutagenic and carcinogenic potencies. There was no correlation between DNA-damaging and mutagenic potencies.
Establishment of Lysogeny in Bacteriophage 186

The CII protein of bacteriophage 186 is a transcriptional activator of the helix-turn helix family required for establishment of the lysogenic state. DNA binding by 186 CII is unusual in that the invertedly repeated half sites are separated by 20 base pairs, or two turns of the DNA helix, rather than the one turn usually associated with this class of proteins. Here, we investigate quantitatively the DNA binding properties of CII and its interaction with RNA polymerase at the establishment promoter,p E. The stoichiometry of CII binding was determined by sedimentation equilibrium experiments using a fluorescein-labeled oligonucleotide and purified CII. These experiments indicate that the CII species bound to DNA is a dimer, with additional weak binding of a tetrameric species at high concentrations. Examination of the thermodynamic linkages between CII self-association and DNA binding shows that CII binds to the DNA as a preformed dimer (binding free energy, 9.9 kcal/mol at 4 °C) rather than by association of monomers on the DNA. CII binding induces in the DNA a bend of 41 (± 5) degrees. The spacing between the binding half sites was shown to be important for CII binding, insertion or removal of just 1 base pair significantly reducing the affinity for CII. Removal of 5 or 10 base pairs between binding half sites eliminated binding, as did insertion of an additional 10 base pairs. CII binding atp E was improved marginally by the presence of RNA polymerase (ΔΔG = –0.5 (± 0.3) kcal/mol). In contrast, the binding of RNA polymerase at p Ewas undetectable in the absence of CII but was improved markedly by the presence of CII. Thus, CII appears to recruit RNA polymerase to the promoter. The nature of the base pair changes in mutant phage, selected by their inability to establish lysogeny, are consistent with this mechanism of CII action.
Women just want to have fun - a study of adult female players of digital games

In the past twenty-five years, the production of digital games has become a global media industry stretching from Japan, to the UK, France and the US. Despite this growth playing digital games, particularly computer games, is still seen by many as a boy’s pastime and part of boy’s bedroom culture. While these perceptions may serve to exclude, this paper set out to explore the experiences of women who game despite these perceptions. This paper addresses the topic of gender and games from two perspectives:the producer’s and the consumer’s. The first part of the paper explores how Sony represented the PS2 in advertisements in Ireland and how adult female game players interpreted these representations. The second part goes on to chart the gaming biographies of these women and how this leisure activity is incorporated into their adult everyday life. It also discuses their views about the gendered nature of game culture, public game spaces and game content; and how these influence their enjoyment of game playing and their views of themselves as women. These research findings are based on semi-structured interviews with two marketing professionals and ten female game players aged 18 and over. The paper concludes that the construction of both gender and digital games are highly contested and even when access is difficult, and representations in the media, in console design and in games are strongly masculine these interviewees were able to contest and appropriate the technology for their own means. Indeed ‘social networks’ were important in relation to their recruitment into, and sustained playing of, digital games. At the same time, the paper found that these interviewees were largely ‘invisible’ to the wider gaming community and producers, an issue raised by Bryce and Rutter (2002:244) in an earlier paper, which has important implications for the development of the games industry.
A cross-sectional study on risk factors and their interactions with suicidal ideation among the elderly in rural communities of Hunan, China

Objectives To identify risk factors, and their interactions, for suicidal ideation among the elderly in rural communities of Hunan and to provide some scientific basis for suicide prevention. Design, setting and participants A cross-sectional survey was conducted among the elderly in rural communities in China's Hunan Province. Thirteen areas were selected by multi-staged cluster random sampling, and 1887 rural elders were investigated via face-to-face interviews. Main outcome measures Measures included sociodemographic information, suicidal ideation, activities of daily living (ADL), major depression disorder (MDD), drinking, stressful life events and social support. Non-conditional logistic regression was preformed to explore the influencing factors for suicidal ideation, and additive interaction was used to analyse the interaction between risk factors. Results Incidence of suicidal ideation among the elderly was 14.5% (95% CI 12.9% to 16.1%) in rural communities of Hunan. The independent influencing factors for suicidal ideation were annual personal income (OR 3.14; 95% CI 2.15 to 4.59), MDD (OR 17.04; 95% CI 11.91 to 24.39), chronic diseases (OR 2.99; 95% CI 1.84 to 4.85) and ADL (OR 2.00; 95% CI 1.37 to 2.94). Additive interactions were detected between MDD and ADL with a relative excess risk of interaction (RERI) of 21.18 (95% CI 5.47 to 36.89), and between MDD and annual personal income with an RERI of 35.00 (95% CI 9.00 to 61.00). Conclusions The independent risk factors for suicidal ideation are annual personal income (≤2200 CNY), MDD, chronic diseases and disabled ADL status. MDD has additive interactions with ADL and annual personal income. These findings have significant implications for the prediction and prevention of suicidal behaviours.
Swelling-activated and isoprenaline-activated chloride currents in guinea pig cardiac myocytes have distinct electrophysiology and pharmacology

We have used the whole-cell patch clamp recording technique to characterize a swelling-activated chloride current in guinea pig atrial and ventricular myocytes and to compare the electrophysiological and pharmacological properties of this current with the isoprenaline- activated chloride current in the same cell types. Osmotic swelling of guinea pig cardiac myocytes caused activation of an outwardly rectifying, anion-selective current with a conductance and permeability sequence of I- approximately NO3- > Br- > Cl- > Asp-. This current was inhibited by tamoxifen, 4,4'-diisothiocyano-stilbene-2,2'-disulphonate and anthracene-9-carboxylic acid, in decreasing order of potency. The isoprenaline-activated anion current, like the swelling-activated current, had a higher permeability to I- relative to Cl-, but it had a markedly reduced conductance for I- compared to Cl-. The isoprenaline- activated current was insensitive to inhibition by tamoxifen, 4,4'- diisothiocyanostilbene-2,2'-disulphonate and anthracene-9-carboxylic acid. The swelling-activated current could be elicited in > 90% atrial myocytes studied but only 34% ventricular myocytes. Conversely, the isoprenaline-activated current was elicited in < 10% atrial myocytes and > 90% ventricular myocytes. In those ventricular myocytes where it was possible to elicit swelling-activated and isoprenaline-activated currents simultaneously, the currents retained the same distinguishing characteristics as when they were elicited in isolation. Thus, while guinea pig atrial cells appear to preferentially express swelling- activated chloride channels and guinea pig ventricular myocytes preferentially express isoprenaline-activated chloride channels, the presence of these two channel types are not necessarily mutually exclusive. This raises the possibility that there may be coordinated regulation of the expression of different Cl- channels within the heart.
Undulatory locomotion of polychaete annelids: mechanics, neural control and robotic prototypes †

The undulatory locomotion of polychaete annelid worms is studied as a biological paradigm of a versatile body morphology and effective motion control, adaptable to a large variety of unstructured and tortuous environmental conditions (water, sand, mud, sediment, etc.). Computational models of this type of locomotion have been developed, based on the Lagrangian dynamics of the system, on resistive models of its interaction with the environment and on neural control using central pattern generators. Simulation studies demonstrate the possibility to generate undulatory gaits, which are characterized by essential features of polychaete locomotion, based on these models. A lightweight robotic prototype has been developed, whose undulatory actuation achieves propulsion on sand.
Candidate gene/loci studies in cleft lip/palate and dental anomalies finds novel susceptibility genes for clefts

Purpose: We revisited 42 families with two or more cleft-affected siblings who participated in previous studies. Complete dental information was collected to test the hypothesis that dental anomalies are part of the cleft phenotype spectrum, and can provide new opportunities for identification of cleft susceptibility genes.Methods: Genotypes from 1489 single nucleotide polymorphism markers located in 150 candidate genes/loci were reanalyzed. Two sets of association analyses were carried out. First, we ran the analysis solely on the cleft status. Second, we assigned affection to any cleft or dental anomaly (tooth agenesis, supernumerary teeth, and microdontia) and repeated the analysis.Results: Significant over-transmission was seen for a single nucleotide polymorphism in ankyrin repeat and sterile alpha motif domain containing 6 (rs4742741, 9q22.33; P = 0.0004) when a dental anomaly phenotype was included in the analysis. Significant over-transmission was also seen for a single nucleotide polymorphism in ERBB2 (rs1810132, 17q21.1; P = 0.0006). In the clefts only data, the most significant result was also for ERBB2 (P = 0.0006). Other markers with suggestive P values included interferon regulatory factor 6 and 6q21–q23 loci. In contrast to the above results, suggestive over-transmission of markers in GART, DPF3, and neurexin 3 were seen only when the dental anomaly phenotype was included in the analysis.Conclusions: These findings support the hypothesis that some loci may contribute to both clefts and congenital dental anomalies. Thus, including dental anomalies information in the genetics analysis of cleft lip and palate will provide new opportunities to map susceptibility loci for clefts.
KRN8602 (MX2-hydrochloride): an active new agent for the treatment of recurrent high-grade glioma.

PURPOSE To assess the efficacy and toxicity of KRN8602 when administered as an intravenous bolus to patients with recurrent high-grade malignant glioma. PATIENTS AND METHODS Patients with recurrent or persistent anaplastic astrocytoma or glioblastoma multiforme who had not received recent chemotherapy or radiotherapy and were of good performance status (Eastern Cooperative Oncology Group score < or = 2) were treated with an intravenous bolus of 40 mg/m(2) KRN8602 every 28 days. Tumor responses were assessed radiologically and clinically after every second cycle of therapy. Treatment was continued until documented progression or a total of six cycles. RESULTS A median of three cycles (range, one to six cycles) of KRN8602 was administered to 55 patients, 49 of whom received at least two cycles and were, therefore, assessable for response. The overall response rate (disease stabilization or better) was 43% (95% confidence interval, 29% to 58%). There were three complete responses, one partial response, seven minor responses, and 10 patients with stable disease. The median time to progression was 2 months (range, 1.5 to 37 months) and overall survival was 11 months (range, 1.5 to 40 months). Neutropenia was the most common toxicity, although it was generally of brief duration, and there were only seven episodes of febrile neutropenia in 176 cycles delivered. Nonhematologic toxicity was mostly gastrointestinal (nausea and vomiting, diarrhea) and events were grade 2 or lower except for a single episode of grade 3 vomiting. CONCLUSION KRN8602 is an active new agent with minimal toxicity in the treatment of relapsed or refractory high-grade glioma. Further studies with KRN8602 in combination with other cytotoxics and in adjuvant treatment of gliomas are warranted.