Tuning a Circular p-n Junction in Graphene from Quantum Confinement to Optical Guiding

The motion of massless Dirac-electrons in graphene mimics the propagation of photons. This makes it possible to control the charge-carriers with components based on geometrical-optics and has led to proposals for an all-graphene electron-optics platform. An open question arising from the possibility of reducing the component-size to the nanometer-scale is how to access and understand the transition from optical-transport to quantum-confinement. Here we report on the realization of a circular p-n junction that can be continuously tuned from the nanometer-scale, where quantum effects are dominant, to the micrometer scale where optical-guiding takes over. We find that in the nanometer-scale junction electrons are trapped in states that resemble atomic-collapse at a supercritical charge. As the junction-size increases, the transition to optical-guiding is signaled by the emergence of whispering-gallery modes and Fabry-Perot interference. The creation of tunable junctions that straddle the crossover between quantum-confinement and optical-guiding, paves the way to novel design-architectures for controlling electronic transport.Comment: 16 pages, 4 figure

Global and decomposition evolutionary support vector machine approaches for time series forecasting

Multi-step ahead Time Series Forecasting (TSF) is a key tool for support- ing tactical decisions (e.g., planning resources). Recently, the support vector machine emerged as a natural solution for TSF due to its nonlinear learning capabilities. This paper presents two novel Evolutionary Support Vector Machine (ESVM) methods for multi-step TSF. Both methods are based on an Estimation Distribution Algorithm (EDA) search engine that automatically performs a simultaneous variable (number of inputs) and model (hyperparameters) selection. The Global ESVM (GESVM) uses all past patterns to fit the support vector machine, while the Decomposition ESVM (DESVM) separates the series into trended and stationary effects, using a distinct ESVM to forecast each effect and then summing both predictions into a sin- gle response. Several experiments were held, using six time series. The proposed approaches were analyzed under two criteria and compared against a recent Evolu- tionary Artificial Neural Network (EANN) and two classical forecasting methods, Holt-Winters and ARIMA. Overall, the DESVM and GESVM obtained competitive and high quality results. Furthermore, both ESVM approaches consume much less computational effort when compared with EANN.The authors wish to thank Ramon Sagarna for introducing the subject of EDA. The work of P. Cortez was supported by FEDER (program COMPETE and FCT) under project FCOMP-01-0124-FEDER-022674

Hedgehog pathway mutations drive oncogenic transformation in high-risk T-cell acute lymphoblastic leukemia.

The role of Hedgehog signaling in normal and malignant T-cell development is controversial. Recently, Hedgehog pathway mutations have been described in T-ALL, but whether mutational activation of Hedgehog signaling drives T-cell transformation is unknown, hindering the rationale for therapeutic intervention. Here, we show that Hedgehog pathway mutations predict chemotherapy resistance in human T-ALL, and drive oncogenic transformation in a zebrafish model of the disease. We found Hedgehog pathway mutations in 16% of 109 childhood T-ALL cases, most commonly affecting its negative regulator PTCH1. Hedgehog mutations were associated with resistance to induction chemotherapy (P = 0.009). Transduction of wild-type PTCH1 into PTCH1-mutant T-ALL cells induced apoptosis (P = 0.005), a phenotype that was reversed by downstream Hedgehog pathway activation (P = 0.007). Transduction of most mutant PTCH1, SUFU, and GLI alleles into mammalian cells induced aberrant regulation of Hedgehog signaling, indicating that these mutations are pathogenic. Using a CRISPR/Cas9 system for lineage-restricted gene disruption in transgenic zebrafish, we found that ptch1 mutations accelerated the onset of notch1-induced T-ALL (P = 0.0001), and pharmacologic Hedgehog pathway inhibition had therapeutic activity. Thus, Hedgehog-activating mutations are driver oncogenic alterations in high-risk T-ALL, providing a molecular rationale for targeted therapy in this disease

Evidence-Based African First Aid Guidelines and Training Materials

Stijn Van de Velde and colleagues describe the African First Aid Materials project, which developed evidence-based guidelines on administering first aid in the African context as well as training materials to support the implementation of the guidelines

Prognosis and serum creatinine levels in acute renal failure at the time of nephrology consultation: an observational cohort study

The aim of this study is to evaluate the association between acute serum creatinine changes in acute renal failure (ARF), before specialized treatment begins, and in-hospital mortality, recovery of renal function, and overall mortality at 6 months, on an equal degree of ARF severity, using the RIFLE criteria, and comorbid illnesses. METHODS: Prospective cohort study of 1008 consecutive patients who had been diagnosed as having ARF, and had been admitted in an university-affiliated hospital over 10 years. Demographic, clinical information and outcomes were measured. After that, 646 patients who had presented enough increment in serum creatinine to qualify for the RIFLE criteria were included for subsequent analysis. The population was divided into two groups using the median serum creatinine change (101%) as the cut-off value. Multivariate non-conditional logistic and linear regression models were used. RESULTS: A >or= 101% increment of creatinine respect to its baseline before nephrology consultation was associated with significant increase of in-hospital mortality (35.6% vs. 22.6%, p < 0.001), with an adjusted odds ratio of 1.81 (95% CI: 1.08-3.03). Patients who required continuous renal replacement therapy in the >or= 101% increment group presented a higher increase of in-hospital mortality (62.7% vs 46.4%, p = 0.048), with an adjusted odds ratio of 2.66 (95% CI: 1.00-7.21). Patients in the >or= 101% increment group had a higher mean serum creatinine level with respect to their baseline level (114.72% vs. 37.96%) at hospital discharge. This was an adjusted 48.92% (95% CI: 13.05-84.79) more serum creatinine than in the < 101% increment group. CONCLUSION: In this cohort, patients who had presented an increment in serum level of creatinine of >or= 101% with respect to basal values, at the time of nephrology consultation, had increased mortality rates and were discharged from hospital with a more deteriorated renal function than those with similar Liano scoring and the same RIFLE classes, but with a < 101% increment. This finding may provide more information about the factors involved in the prognosis of ARF. Furthermore, the calculation of relative serum creatinine increase could be used as a practical tool to identify those patients at risk, and that would benefit from an intensive therapy

Role of educational level in the relationship between Body Mass Index (BMI) and health-related quality of life (HRQL) among rural Spanish women

BACKGROUND: The impact of obesity on health-related quality of life (HRQL) has been little explored in rural areas. The goal of this study is to ascertain the association between obesity and HRQL among Spanish women living in a rural area, and the influence of their educational level. METHODS: Cross-sectional study with personal interview of 1298 women (aged 18 to 60) randomly selected from the electoral rolls of 14 towns in Galicia, a region in the north-west of Spain. HRQL was assessed using the SF-36 questionnaire. The association between body mass index (BMI) and suboptimal scores in the different HRQL dimensions was summarised using odds ratios (ORs), obtained from multivariate logistic regression models. Separate analyses were conducted for women who had finished their education younger than 16 years old and women with secondary education to assess differences in the relationship between BMI and HRQL according to educational level. RESULTS: Among women with primary or lower education, obesity was associated with a higher prevalence of suboptimal values in the following dimensions: Physical functioning (OR: 1.97; 95%CI: 1.22-3.18); Role-physical (OR: 1.81; 95%CI: 1.04-3.14); General health (OR: 1.76; 95%CI: 1.10-2.81); and Role-emotional (OR: 2.52; 95%CI: 1.27-5.03). In women with higher education, physical functioning was the only dimension associated with obesity (OR: 2.02: 95%CI 0.83-4.97). CONCLUSION: The impact of obesity on women's HRQL is greater among those with a lower educational level. This group registered higher prevalence of obesity and poorer self-perceived health.This study was funded by the Instituto de Salud Carlos III (grant 001/05).S

Functional diversification of the nematode mbd2/3 gene between Pristionchus pacificus and Caenorhabditis elegans

Abstract Background Several members of the Methyl-Binding Domain protein family link DNA methylation with chromatin remodeling complexes in vertebrates. Amongst the four classes of MBD proteins, MBD2/3 is the most highly conserved and widespread in metazoans. We have previously reported that an mbd2/3 like gene (mbd-2) is encoded in the genomes of the nematodes Pristionchus pacificus, Caenorhabditis elegans and Caenorhabditis briggsae. RNAi knock-down of mbd-2 in the two Caenorhabditis species results in varying percentages of lethality. Results Here, we report that a general feature of nematode MBD2/3 proteins seems to be the lack of a bona fide methyl-binding domain. We isolated a null allele of mbd-2 in P. pacificus and show that Ppa-mbd-2 mutants are viable, fertile and display a fully penetrant egg laying defect. This egg laying defect is partially rescued by treatment with acetylcholine or nicotine suggesting a specific function of this protein in vulval neurons. Using Yeast-two-hybrid screens, Ppa-MBD-2 was found to associate with microtubule interacting and vesicle transfer proteins. Conclusion These results imply that MBD2/3 proteins in nematodes are more variable than their relatives in insects and vertebrates both in structure and function. Moreover, nematode MBD2/3 proteins assume functions independent of DNA methylation ranging from the indispensable to the non-essential.</p

Anion gap, anion gap corrected for albumin, base deficit and unmeasured anions in critically ill patients: implications on the assessment of metabolic acidosis and the diagnosis of hyperlactatemia

Abstract Background Base deficit (BD), anion gap (AG), and albumin corrected anion gap (ACAG) are used by clinicians to assess the presence or absence of hyperlactatemia (HL). We set out to determine if these tools can diagnose the presence of HL using cotemporaneous samples. Methods We conducted a chart review of ICU patients who had cotemporaneous arterial blood gas, serum chemistry, serum albumin (Alb) and lactate(Lac) levels measured from the same sample. We assessed the capacity of AG, BD, and ACAG to diagnose HL and severe hyperlactatemia (SHL). HL was defined as Lac > 2.5 mmol/L. SHL was defined as a Lac of > 4.0 mmol/L. Results From 143 patients we identified 497 series of lab values that met our study criteria. Mean age was 62.2 ± 15.7 years. Mean Lac was 2.11 ± 2.6 mmol/L, mean AG was 9.0 ± 5.1, mean ACAG was 14.1 ± 3.8, mean BD was 1.50 ± 5.4. The area under the curve for the ROC for BD, AG, and ACAG to diagnose HL were 0.79, 0.70, and 0.72, respectively. Conclusion AG and BD failed to reliably detect the presence of clinically significant hyperlactatemia. Under idealized conditions, ACAG has the capacity to rule out the presence of hyperlactatemia. Lac levels should be obtained routinely in all patients admitted to the ICU in whom the possibility of shock/hypoperfusion is being considered. If an AG assessment is required in the ICU, it must be corrected for albumin for there to be sufficient diagnostic utility.</p