Variations in clinical decision-making between cardiologists and cardiac surgeons; a case for management by multidisciplinary teams?

OBJECTIVE: To assess variations in decisions to revascularise patients with coronary heart disease between general cardiologists, interventional cardiologists and cardiac surgeons DESIGN: Six cases of coronary heart disease were presented at an open meeting in a standard format including clinical details which might influence the decision to revascularise. Clinicians (n = 53) were then asked to vote using an anonymous electronic system for one of 5 treatment options: medical, surgical (CABG), percutaneous coronary intervention (PCI) or initially medical proceeding to revascularisation if symptoms dictated. Each case was then discussed in an open forum following which clinicians were asked to revote. Differences in treatment preference were compared by chi squared test and agreement between groups and between voting rounds compared using Kappa. RESULTS: Surgeons were more likely to choose surgery as a form of treatment (p = 0.034) while interventional cardiologists were more likely to choose PCI (p = 0.056). There were no significant differences between non-interventional and interventional cardiologists (p = 0.13) in their choice of treatment. There was poor agreement between all clinicians in the first round of voting (Kappa 0.26) but this improved to a moderate level of agreement after open discussion for the second vote (Kappa 0.44). The level of agreement among surgeons (0.15) was less than that for cardiologists (0.34) in Round 1, but was similar in Round 2 (0.45 and 0.45 respectively) CONCLUSION: In this case series, there was poor agreement between cardiac clinical specialists in the choice of treatment offered to patients. Open discussion appeared to improve agreement. These results would support the need for decisions to revascularise to be made by a multidisciplinary panel

Impaired decisional impulsivity in pathological videogamers

Abstract Background Pathological gaming is an emerging and poorly understood problem. Impulsivity is commonly impaired in disorders of behavioural and substance addiction, hence we sought to systematically investigate the different subtypes of decisional and motor impulsivity in a well-defined pathological gaming cohort. Methods Fifty-two pathological gaming subjects and age-, gender- and IQ-matched healthy volunteers were tested on decisional impulsivity (Information Sampling Task testing reflection impulsivity and delay discounting questionnaire testing impulsive choice), and motor impulsivity (Stop Signal Task testing motor response inhibition, and the premature responding task). We used stringent diagnostic criteria highlighting functional impairment. Results In the Information Sampling Task, pathological gaming participants sampled less evidence prior to making a decision and scored fewer points compared with healthy volunteers. Gaming severity was also negatively correlated with evidence gathered and positively correlated with sampling error and points acquired. In the delay discounting task, pathological gamers made more impulsive choices, preferring smaller immediate over larger delayed rewards. Pathological gamers made more premature responses related to comorbid nicotine use. Greater number of hours played also correlated with a Motivational Index. Greater frequency of role playing games was associated with impaired motor response inhibition and strategy games with faster Go reaction time. Conclusions We show that pathological gaming is associated with impaired decisional impulsivity with negative consequences in task performance. Decisional impulsivity may be a potential target in therapeutic management

Electrically controlled long-distance spin transport through an antiferromagnetic insulator

Spintronics uses spins, the intrinsic angular momentum of electrons, as an alternative for the electron charge. Its long-term goal is in the development of beyond-Moore low dissipation technology devices. Recent progress demonstrated the long-distance transport of spin signals across ferromagnetic insulators. Antiferromagnetically ordered materials are however the most common class of magnetic materials with several crucial advantages over ferromagnetic systems. In contrast to the latter, antiferromagnets exhibit no net magnetic moment, which renders them stable and impervious to external fields. In addition, they can be operated at THz frequencies. While fundamentally their properties bode well for spin transport, previous indirect observations indicate that spin transmission through antiferromagnets is limited to short distances of a few nanometers. Here we demonstrate the long-distance, over tens of micrometers, propagation of spin currents through hematite (\alpha-Fe2O3), the most common antiferromagnetic iron oxide, exploiting the spin Hall effect for spin injection. We control the spin current flow by the interfacial spin-bias and by tuning the antiferromagnetic resonance frequency with an external magnetic field. This simple antiferromagnetic insulator is shown to convey spin information parallel to the compensated moment (N\'eel order) over distances exceeding tens of micrometers. This newly-discovered mechanism transports spin as efficiently as the net magnetic moments in the best-suited complex ferromagnets. Our results pave the way to ultra-fast, low-power antiferromagnet-insulator-based spin-logic devices that operate at room temperature and in the absence of magnetic fields

MSH3 polymorphisms and protein levels affect CAG repeat instability in huntington's disease mice

Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)~100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of DNA repair genes may have prognostic implications for various repeat-associated diseases

The osteoporosis care gap in Canada

BACKGROUND: The presence of a fragility fracture is a major risk factor for osteoporosis, and should be an indicator for osteoporosis diagnosis and therapy. However, the extent to which patients who fracture are assessed and treated for osteoporosis is not clear. METHODS: We performed a review of the literature to identify the practice patterns in the diagnosis and treatment of osteoporosis in adults over the age of 40 who experience a fragility fracture in Canada. Searches were performed in MEDLINE (1966 to January 2, 2003) and CINAHL (1982 to February 1, 2003) databases. RESULTS: There is evidence of a care gap between the occurrence of a fragility fracture and the diagnosis and treatment of osteoporosis in Canada. The proportion of individuals with a fragility fracture who received an osteoporosis diagnostic test or physician diagnosis ranged from 1.7% to 50%. Therapies such as hormone replacement therapy, bisphosphonates or calcitonin were being prescribed to 5.2% to 37.5% of patients. Calcium and vitamin D supplement intake was variable, and ranged between 2.8% to 61.6% of patients. CONCLUSION: Many Canadians who experience fragility fracture are not receiving osteoporosis management for the prevention of future fractures

Human Cell Chips: Adapting DNA Microarray Spotting Technology to Cell-Based Imaging Assays

Here we describe human spotted cell chips, a technology for determining cellular state across arrays of cells subjected to chemical or genetic perturbation. Cells are grown and treated under standard tissue culture conditions before being fixed and printed onto replicate glass slides, effectively decoupling the experimental conditions from the assay technique. Each slide is then probed using immunofluorescence or other optical reporter and assayed by automated microscopy. We show potential applications of the cell chip by assaying HeLa and A549 samples for changes in target protein abundance (of the dsRNA-activated protein kinase PKR), subcellular localization (nuclear translocation of NFκB) and activation state (phosphorylation of STAT1 and of the p38 and JNK stress kinases) in response to treatment by several chemical effectors (anisomycin, TNFα, and interferon), and we demonstrate scalability by printing a chip with ∼4,700 discrete samples of HeLa cells. Coupling this technology to high-throughput methods for culturing and treating cell lines could enable researchers to examine the impact of exogenous effectors on the same population of experimentally treated cells across multiple reporter targets potentially representing a variety of molecular systems, thus producing a highly multiplexed dataset with minimized experimental variance and at reduced reagent cost compared to alternative techniques. The ability to prepare and store chips also allows researchers to follow up on observations gleaned from initial screens with maximal repeatability

Response of the photosynthetic apparatus to a flowering-inductive period by water stress in Citrus

The photosynthetic responses to a flowering-inductive water-stress period and recovery were studied and compared in two Citrus species. Under greenhouse conditions, Fino lemon and Owari satsuma trees were subjected to moderate (-2 MPa at predawn) and severe (-3 MPa) water stress levels and were re-watered after 60 days. Vegetative growth was inhibited during the stress assays, and strong defoliation levels were reported, especially in Fino lemon. In both species, bud sprouting was induced after re-watering. Flowers and vegetative shoots developed in Owari satsuma after a drought period, and the development was independent of the stress level. In Fino lemon, vegetative shoots and flowers were primarily formed after moderate and severe stress, respectively. The photosynthetic rate and stomatal conductance were reduced by water stress, and a marked increase in water-use efficiency at the moderate water deficit level was observed. Nevertheless, the photosynthetic apparatus was not damaged, since the maximum quantum yield, photosynthetic pigment concentrations and Rubisco level and activity did not change. Furthermore, the measured malonyldialdehyde (MDA) and peroxidase activity indicated that oxidative stress was not specifically triggered by water stress in our study. Therefore, the gas exchange, fluorescence and biochemical parameters suggested that diffusional limitations to photosynthesis predominated in both of the studied Citrus species, and explained the rapid recovery of the photosynthetic parameters after rehydration. The net CO 2 fixation rate and stomatal conductance were recovered within 24 h in Fino lemon, whereas 3 days were required in Owari satsuma. This suggests the presence of some metabolic limitations in the latter species. 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Productive restructuring and the reallocation of work and employment: a survey of the “new” forms of social inequality

O propósito do presente artigo consiste em questionar a inevitabilidade dos processos de segmentação e precarização das relações de trabalho e emprego, responsáveis pela inscrição de “novas” formas de desigualdade social que alicerçam o actual modelo de desenvolvimento das economias e sociedades. Visa-se criticar os limites da lógica econômica e financeira, de contornos globais, que configuram um “novo espírito do capitalismo”, ou seja, uma espécie de divinização da ordem natural das coisas. Impõe-se fazer, por isso, um périplo analítico pelas transformações em curso no mercado de trabalho, acompanhado pela vigilância epistemológica que permita enquadrar e relativizar as (di)visões neoliberais e teses tecnodeterministas dominantes. A perspectivação de cenários sobre o futuro do trabalho encerrará este périplo, permitindo-nos alertar para os condicionalismos histórico-temporais, para a urgência de se desocultar o que de ideológico e político existe nas actuais lógicas de racionalização e para os processos de ressimbolização do trabalho e emprego enquanto “experiência social central” na contemporaneidade.The scope of this paper is to question the inevitability of the processes of segmentation and increased precariousness of the relations of labor and employment, which are responsible for the introduction of “new” forms of social inequality that underpin the current model of development of economies and societies. It seeks to criticize the limits of global financial and economic logic, which constitute a “new spirit of capitalism,” namely a kind of reverence for the natural order of things. It is therefore necessary to conduct an analytical survey of the ongoing changes in the labor market, accompanied by epistemological vigilance which makes it possible to see neoliberal (di)visions and dominant technodeterministic theses in context. The enunciation of scenarios on the future of work will conclude this survey and will make it possible to draw attention to both the historical and temporal constraints and to the urgent need to unveil what is ideological and political in the prevailing logic of rationalization and processes to reinstate work and employment as a “central social experience” in contemporary times

Molecular, clinical, and muscle studies in myotonic dystrophy type 1 (DM1) associated with novel variant CCG expansions

We assessed clinical, molecular and muscle histopathological features in five unrelated Italian DM1 patients carrying novel variant pathological expansions containing CCG interruptions within the 3'-end of the CTG array at the DMPK locus, detected by bidirectional triplet primed PCR (TP-PCR) and sequencing. Three patients had a negative DM1 testing by routine long-range PCR; the other two patients were identified among 100 unrelated DM1 cases and re-evaluated to estimate the prevalence of variant expansions. The overall prevalence was 4.8 % in our study cohort. There were no major clinical differences between variant and non-variant DM1 patients, except for cognitive involvement. Muscle RNA-FISH, immunofluorescence for MBNL1 and RT-PCR analysis documented the presence of ribonuclear inclusions, their co-localization with MBNL1, and an aberrant splicing pattern involved in DM1 pathogenesis, without any obvious differences between variant and non-variant DM1 patients. Therefore, this study shows that the CCG interruptions at the 3'-end of expanded DMPK alleles do not produce qualitative effects on the RNA-mediated toxic gain-of-function in DM1 muscle tissues. Finally, our results support the conclusion that different patterns of CCG interruptions within the CTG array could modulate the DM1 clinical phenotype, variably affecting the mutational dynamics of the variant repeat