Miracle-dz/UniFAR-FTUs huggingface dataset:
e-Learning in medical education: Guide supplement 32.5 – Viewpoint

e-Learning is now established as a fundamental component at all levels of contemporary healthcare education, from preregistration and undergraduate study, through to postgraduate training and continuing professional development (cpd). This viewpoint, which complements AMEE Guide No 32 (Ellaway & Masters 2008), will explore some critical aspects in harnessing e-learning to maximise its effectiveness in clinical and healthcare education. Many studies, guides and experts consider e-learning from a technical or technological perspective or are fashioned around teaching, or teachers, rather than learning. Whilst these are important, such a perspective often overlooks the learner, or the consequential impact of technical solutions upon learning. This viewpoint seeks to reassert the importance of the ‘student voice’ and of focusing upon the effectiveness of learning. Starting from the perspective of the learner it will consider the importance of context, the centrality of educational design and the roles and development
Modulation of phosphoinositide metabolism by pathogenic bacteria

Phosphoinositide metabolism plays a pivotal role in the regulation of receptor‐mediated signal transduction, actin remodelling and membrane dynamics. Phosphoinositides co‐ordinate these processes by recruiting protein effectors to distinct cellular membranes in a time‐ and organelle‐dependent manner. Intracellular bacterial pathogens interfere with phosphoinositide metabolism to direct their entry into eukaryotic cells, form replication‐permissive vacuoles, modulate apoptosis, or trigger fluid secretion. Gram‐negative pathogens such as Legionella pneumophila, Shigella flexneri, or Salmonella enterica employ secretion systems to invade host cells by ‘pathogen‐triggered phagocytosis’ and thereby bypass a requirement for phosphatidylinositol 3‐kinases [PI(3)Ks]. Contrarily, ‘receptor‐mediated phagocytosis’ of Yersinia spp. , Listeria monocytogenes and other pathogenic bacteria depends on PI(3)Ks. Secreted effector proteins have been found to directly bind to and modify host cell phosphoinositides, thus modulating phagocytosis and intracellular survival of the pathogens. These effectors include L. pneumophila proteins that specifically attach to phosphatidylinositol 4‐phosphate [PI(4)P] on the Legionella‐containing vacuole, and phosphoinositide phosphatases produced by S. flexneri, S. enterica or Mycobacterium tuberculosis. This review covers current knowledge about subversion of host cell phosphoinositide metabolism by intracellular bacterial pathogens with an emphasis on recently identified secreted effector proteins directly engaging phosphoinositides.
Use of assistive technology devices in mainstream schools: students' perspective.

OBJECTIVE The use and nonuse of assistive technology devices in school by students with physical disabilities was investigated, and the students' experiences in using these devices is described. METHOD We used a mixed-methods approach with predominantly qualitative methods to collect and analyze data, which included observations of and interviews with 20 students with physical disabilities and the number and type of assistive technology devices provided. RESULTS It is vital that devices be integrated into educational practice and that students experience immediate benefits for their function in everyday school activities without detrimental effects on their social participation. The latter was often more important than being able to perform activities independently. CONCLUSION The students adopted both a functional and a psychosocial perspective of their devices, and providers should neglect neither. Children and youth need both verbal information and practical experience using devices to be able to make informed decisions.
Server based QoS routing with implicit network state updates

We propose centralized server based QoS routing schemes, where a route server is responsible for determining QoS paths on behalf of all the routers in a routing domain. In the proposed server based schemes, the dynamic link QoS state information, which is required for a QoS path computation, is implicitly maintained at the route server as it assigns or gets back QoS paths. By maintaining the network state information this way, we may not only eliminate the overhead to exchange network state update messages but also achieve higher routing performance by utilizing accurate network state information in the path computation. We discuss path caching techniques for reducing the amount of path computation overhead at the route server, and evaluate the performance of the proposed schemes using simulation. The simulation results show that the path caching schemes may significantly reduce the route server load. The proposed schemes are also compared to the distributed QoS routing schemes proposed in the literature. It has been shown that the proposed server based schemes not only enhance the routing performance, but they are also competitive with respect to routing overheads.
Prognostic impact of serum calcitonin and carcinoembryonic antigen doubling-times in patients with medullary thyroid carcinoma.

CONTEXT After unsuccessful surgery, medullary thyroid carcinoma (MTC) may be fatal or remain stable for decades, and precise survival predictors are needed. OBJECTIVE This study assesses the prognostic value of calcitonin and carcinoembryonic antigen (CEA) doubling-times (DT). DESIGN This is a retrospective study on 65 MTC patients from 2.9-29.5 yr after surgery. SETTING Data registered in the database of the French Neuroendocrine Tumor Group were analyzed anonymously. PATIENTS All patients had abnormal calcitonin levels after total thyroidectomy and bilateral lymph node dissection. INTERVENTION Calcitonin and CEA serum levels were measured during routine disease follow-up. MAIN OUTCOME MEASURE To assess DT as prognostic factors, a patient population was extracted from the database. RESULTS When calcitonin DT was less than 6 months, 5- and 10-yr survivals were three of 12 (25%) and one of 12 (8%), respectively; when between 6 months and 2 yr, 5- and 10-yr survivals were 11 of 12 (92%) and three of eight (37%), whereas all 41 patients with calcitonin DT greater than 2 yr were alive at the end of the study. Tumor-Node-Metastasis (TNM) stage, European Organization for Research and Treatment of Cancer (EORTC) score, and calcitonin DT were significant predictors of survival by univariate analysis, but only calcitonin DT remained an independent predictor of survival by multivariate analysis (P = 0.002) with a proportion of variance explained (PVE) of 37.4%. Calcitonin DT was a better predictor than CEA (PVE 63.3% and 47.0%, respectively). Calcitonin DT calculated using only the first four measurements was also an independent predictor of survival (P < 0.000001; PVE 40.4%). CONCLUSION Calcitonin DT may be superior to initial clinical staging and among the most powerful prognostic indicators in MTC.
Autonomic Blockade Unmasks Maturational Differences in Rate‐Dependent Atrioventricular Nodal Conduction and Facilitation in the Mouse

Maturational Differences in Murine AVN Conduction. Introduction: In large animals, rate‐dependent AV nodal (AVN) properties of conduction are modulated by autonomic inputs. In this study, we investigated whether the properties of AVN conduction and facilitation are altered by autonomic blockade in the mouse and whether this effect is age dependent.
Anaerobiosis and symbiosis with bacteria in free-living ciliates.

Marine, sediment-dwelling ciliates were examined for cytochrome oxidase activity by a cytochemical method and for fine structural details. Species of Plagiopylidae (Trichostomatida), i.e. Plagiopyla frontata, Sonderia vorax and Sonderia sp. , and of Heterotrichda, i.e., Parablepharisma pellitum, Parablepharisma sp. , Metopus contortus, Metopus vestitus and Caenomorpha capucina; previously considered to be obligate anaerobes because of their sulfide-containing habitat, do not have cytochrome oxidase activity or mitochondria with cristae or tubuli. The evolutionary origin and significance of anaerobic ciliates is discussed. Most of the anaerobic ciliates harbor a flora of ecto- and endosymbiotic bacteria as demonstrated by transmission and scanning electron micrographs. It is speculated that the bacteria may utilize the metabolic end products of the protozoa for growth and energy yielding processes. These associations are also compared with other, previously described cases of symbiosis involving prokaryotes and protozoa.
Fasting respiratory exchange ratio and resting metabolic rate as predictors of weight gain: the Baltimore Longitudinal Study on Aging.

The authors followed 775 men (aged 18-98 years) participating in the Baltimore Longitudinal Study in Aging for an average of ten years. Resting metabolic rate and fasting respiratory exchange ratio (RER) were measured by indirect calorimetry on their first visit and related to subsequent weight change. Deviations from the predicted value of resting metabolic rates (predicted from their estimated fat-free mass) were calculated. Average weight change was 0.07 kg (s.d. 6.4 kg); 122 men (15.3%) gained more than 5 kg and 40 (5.2%) more than 10 kg during the follow-up. After adjustment for initial age, body mass index, fat-free mass, and duration of follow-up, RER, but not RMR or deviations from predicted RMR, was positively related to weight change (P less than 0.001). Major weight gain (from at least 5 kg to at least 15 kg) was related to initial RER in non-obese men only (initial body mass index less than 25 kg/m2). From Cox proportional hazard regression analyses the adjusted relative risk of gaining 5 kg or more in initially non-obese men with a fasting RER of 0.85 or more was calculated to be 2.42 (95% confidence interval: 1.10-5.32) compared to men with a fasting RER less than 0.76. It was concluded that a relatively high fasting RER is a weak but significant predictor of substantial weight gain in non-obese white men.
Lipoprotein(a) Concentrations in Cord and Capillary Blood from Newborns and in Serum from In-Patient Children, Adolescents and Adults

Investigations have been made upon the distribution of lipoprotein(a) concentrations in cord and capillary blood from newborns and in serum from in-patient children and adults. Full-term neonates (n = 123), children aged 1 month to 16 years (n = 331) and adults aged between 17 and 88 years (n = 252) of age were included in the study. Lipoprotein(a) was determined using an immunoluminometric assay and a single lot of reagents. The assay had an effective measuring range of 1-800 mg/l. Lipoprotein(a) could be measured either in cord or capillary blood in the majority of cases. Problems arose in isolated cases, in each of which there was a large concentration difference in lipoprotein(a) between mother and child. The correlation data was: r = 0.897, n = 37, log (capillary blood) = 0.874 log (cord blood) + 0.165. The median lipoprotein(a) concentrations in cord and capillary blood were 13.9 and 10.2 mg/l respectively. Median lipoprotein(a) concentrations increased from birth up until the 6th decade (159 mg/l), decreasing to 95 mg/l during the 9th decade of life. In mature newborns, the median lipoprotein(a) concentrations correlated with gestational age. The distribution of lipoprotein(a) concentrations in serum is skewed throughout life, the ratio mean/median being 2.07 at birth, 2.71 in children and 2.72 in adults. The percentage of children with lipoprotein(a) concentrations above 250 mg/l was 23.0 (male) and 23.8 (female). The corresponding figures for adults was 38.2 for males and 28.2 for females respectively. In the group of newborns 27.7 percent had concentrations above 25 mg/l. (ABSTRACT TRUNCATED AT 250 WORDS)
Design of a guaranteed throughput router for on-chip networks

The complexity of system-on-chip (SoC) designs continues to increase, and traditional bus-based interconnects will not be sufficient to manage the communication requirements of future billion transistor chips. On-chip networks (OCNs) provide a scalable alternative to existing on-chip interconnects. The key element of the OCN is the router We present a prototype design of a 5-input, 5-output, scalable guaranteed throughput (GT) router The router is constructed from a collection of parameterizable and reusable hardware blocks and is a basic building block of the OCN. The router supports wormhole routing, and is characterized by an area of 0.1 mm/sup 2/ in 0.18 micron CMOS technology.
Calorie restriction mimetics: an emerging research field

When considering all possible aging interventions evaluated to date, it is clear that calorie restriction (CR) remains the most robust. Studies in numerous species have demonstrated that reduction of calories 30–50% below ad libitum levels of a nutritious diet can increase lifespan, reduce the incidence and delay the onset of age‐related diseases, improve stress resistance, and decelerate functional decline. A current major focus of this research area is whether this nutritional intervention is relevant to human aging. Evidence emerging from studies in rhesus monkeys suggests that their response to CR parallels that observed in rodents. To assess CR effects in humans, clinical trials have been initiated. However, even if results from these studies could eventually substantiate CR as an effective pro‐longevity strategy for humans, the utility of this intervention would be hampered because of the degree and length of restriction required. As an alternative strategy, new research has focused on the development of ‘CR mimetics’. The objective of this strategy is to identify compounds that mimic CR effects by targeting metabolic and stress response pathways affected by CR, but without actually restricting caloric intake. For example, drugs that inhibit glycolysis (2‐deoxyglucose), enhance insulin action (metformin), or affect stress signaling pathways (resveratrol), are being assessed as CR mimetics (CRM). Promising results have emerged from initial studies regarding physiological responses which resemble those observed in CR (e.g. reduced body temperature and plasma insulin) as well as protection against neurotoxicity (e.g. enhanced dopamine action and up‐regulated neurotrophic factors). Ultimately, lifespan analyses in addition to expanded toxicity studies must be accomplished to fully assess the potential of any CRM. Nonetheless, this strategy clearly offers a very promising and expanding research endeavor.
Functional Analysis of the Tsh Autotransporter from an Avian Pathogenic Escherichia coli Strain

ABSTRACT The temperature-sensitive hemagglutinin (Tsh) is an autotransporter protein secreted by avian-pathogenic Escherichia coli strains that colonize the respiratory tract and lead to airsacculitis, pericarditis, and colisepticemia. It is synthesized as a 140-kDa precursor protein, whose processing results in a 106-kDa passenger domain (Tshs) and a 33-kDa β-domain (Tshβ). The presence of a conserved 7-amino-acid serine protease motif within Tshs classifies the protein in a subfamily of autotransporters, known as serine protease autotransporters of the Enterobacteriaceae. In this study, we report that purified Tshs is capable of adhering to red blood cells, hemoglobin, and the extracellular matrix proteins fibronectin and collagen IV. We also demonstrate that Tshs exerts proteolytic activity against casein, and we provide experimental evidence demonstrating that serine 259 is essential for the protease function. However, this residue is not required for adherence to substrates, and its replacement by an alanine does not abolish binding activity. In summary, our results demonstrate that Tsh is a bifunctional protein with both adhesive and proteolytic properties.
ℋ2 guaranteed cost computation of discretized uncertain continuous-time systems

This paper proposes a new discretization technique with constant sampling time for time-invariant systems with uncertain parameters belonging to a polytopic domain. The aim is to provide an equivalent discrete-time representation of the continuous-time system whose ℋ2 guaranteed cost is an upper bound for the ℋ2 worst case norm of the original system. The resulting discrete-time model is described in terms of homogeneous polynomial matrices obtained by Taylor series expansion of degree ℓ. The discretization residual error, associated to the chosen approximation degree, is represented by additive norm-bounded uncertain terms. As a second contribution, new linear matrix inequality (LMI) relaxations for the computation of ℋ2 guaranteed costs for discrete-time systems with polynomial dependence on the uncertain parameter and additive norm-bounded uncertainties are proposed. A numerical experiment shows that the ℋ2 costs of the discretized system become tighter to the continuous-time ones as the order in the Taylor series expansion, the degrees in the Lyapunov function and the Pólya's relaxation level increase.
A Business Case Framework for Group Support Technology

Abstract:As groupwork gains recognition, emerging group support technologies raise questions about the merits of these systems relative to group performance and return on investment. Business case variables of efficiency, quality, effectiveness, customer satisfaction and decision making are useful in measuring the potential contribution that group support technologies offer. This paper presents findings from a recent field study that used business case concepts as its design approach. The paper explores the infrastructure development requirements for building a business case study. Such a framework is useful to business decision makers and researchers interested in the deployment of these technologies in complex business environments.
Routine initial exercise stress testing for treatment stratification in comprehensive cardiac rehabilitation

There is evidence of substantial benefit of cardiac rehabilitation (CR) for patients with low exercise capacity at admission. Nevertheless, some patients are not able to perform an initial exercise stress test (EST). We aimed to describe this group using data of 1094 consecutive patients after a cardiac event (71±7 years, 78% men) enrolled in nine centres for inpatient CR. We analysed sociodemographic and clinical variables (e.g. cardiovascular risk factors, comorbidities, complications at admission), amount of therapy (e.g. exercise training, nursing care) and the results of the initial and the final 6-min walking test (6MWT) with respect to the application of an EST. Fifteen per cent of patients did not undergo an EST (non-EST group). In multivariable analysis, the probability of obtaining an EST was higher for men [odds ratio (OR) 1.89, P=0.01], a 6MWT (per 10 m, OR 1.07, P<0.01) and lower for patients with diabetes mellitus (OR 0.48, P<0.01), NYHA-class III/IV (OR 0.27, P<0.01), osteoarthritis (OR 0.39, P<0.01) and a longer hospital stay (per 5 days, OR 0.87, P=0.02). The non-EST group received fewer therapy units of exercise training, but more units of nursing care and physiotherapy than the EST group. However, there were no significant differences between both groups in the increase of the 6MWT during CR (123 vs. 108 m, P=0.122). The present study confirms the feasibility of an EST at the start of CR as an indicator of disease severity. Nevertheless, patients without EST benefit from CR even if exercising less. Thus, there is a justified need for individualized, comprehensive and interdisciplinary CR.
Calcineurin involvement in the regulation of high‐threshold Ca2+ channels in NG108–15 (rodent neuroblastoma × glioma hybrid) cells

1 We examined the relationship between calcineurin (protein phosphatase 2B (PP2B)) and voltage‐operated Ca2+ channels (VOCCs) in NG108–15 cells. PP2B expression in NG108–15 cells was altered by transfection with plasmid constructs containing a full length cDNA of human PP2Bβ3 in sense (CN‐15) and antisense (CN‐21) orientation. 2 Confocal immunocytochemical localization showed that in wild‐type cells, PP2B immunoreactivity is uniformly distributed in undifferentiated cells and located at the inner surface of soma membrane and neurites in differentiated cells. 3 To test the Ca2+ dependence of the VOCC, we used high‐frequency stimulation (HFS). The L‐ and N‐type VOCCs decreased by 37 and 52 %, respectively, whereas the T‐type current was only marginally sensitive to this procedure. FK‐506 (2 μM), a specific blocker of PP2B, reduced the inhibition of L‐ and N‐type VOCCs induced by HFS by 30 and 33 %, respectively. 4 In CN‐15‐transfected cells overexpressing PP2B, total high‐voltage‐activated (HVA) VOCCs were suppressed by about 60 % at a test potential of +20 mV. Intracellular addition of EGTA or FK‐506 into CN‐15‐transfected cells induced an up to 5‐fold increase of HVA VOCCs. 5 These findings indicate that PP2B activity does not influence the expression of HVA Ca2+ channels, but modulates their function by Ca2+‐dependent dephosphorylation. Thus HVA VOCCs, in a phosphorylated state under control conditions, are downregulated by PP2B upon stimulation, with the major effect being on N‐type VOCCs.
Bell's inequality violations: relation with de Finetti's coherence principle and inferential analysis of experimental data

It is often believed that de Finetti’s coherence principle naturally leads, in the finite case, to the Kolmogorov’s probability theory of random phenomena, which then implies Bell’s inequality. Thus, not only a violation of Bell’s inequality looks paradoxical in the Kolmogorovian framework, but it should violate also de Finetti’s coherence principle. Firstly, we show that this is not the case: the typical theoretical violations of Bell’s inequality in quantum physics are in agreement with de Finetti’s coherence principle. Secondly, we look for statistical evidence of such violations: we consider the experimental data of measurements of polarization of photons, performed to verify empirically violations of Bell’s inequality, and, on the basis of the estimated violation, we test the null hypothesis of Kolmogorovianity for the observed phenomenon. By standard inferential techniques we compute the pvalue for the test and get a clear strong conclusion against the Kolmogorovian hypothesis.
Whole stimulated salivary flow in patients with chronic hepatitis C virus infection.

BACKGROUND Salivary gland disorders have been included among the extra-hepatic manifestations related to HCV infection. METHODS The whole stimulated salivary flow rate (spitting technique) was studied in 74 HCV infected patients to evaluate salivary gland dysfunction. RESULTS The salivary flow of the patients with chronic HCV infection was similar to that of the healthy controls. The association between subjective xerostomia salivary flow was seen to be very weak. No significant associations were found between salivary flow and age, sex, risk factor of acquired infection, ALT, AST, GGT, ALP values, time lapsed since the diagnosis or HCV-RNA detection in saliva. CONCLUSIONS Although the functional repercussion of hepatitis C related lymphocytic sialoadenitis remains unclear, we did not find a significant reduction in the whole stimulated salivary flow in HCV infected patients.