Fast and flexible selection with a single switch

Selection methods that require only a single-switch input, such as a button click or blink, are potentially useful for individuals with motor impairments, mobile technology users, and individuals wishing to transmit information securely. We present a single-switch selection method, "Nomon," that is general and efficient. Existing single-switch selection methods require selectable options to be arranged in ways that limit potential applications. By contrast, traditional operating systems, web browsers, and free-form applications (such as drawing) place options at arbitrary points on the screen. Nomon, however, has the flexibility to select any point on a screen. Nomon adapts automatically to an individual's clicking ability; it allows a person who clicks precisely to make a selection quickly and allows a person who clicks imprecisely more time to make a selection without error. Nomon reaps gains in information rate by allowing the specification of beliefs (priors) about option selection probabilities and by avoiding tree-based selection schemes in favor of direct (posterior) inference. We have developed both a Nomon-based writing application and a drawing application. To evaluate Nomon's performance, we compared the writing application with a popular existing method for single-switch writing (row-column scanning). Novice users wrote 35% faster with the Nomon interface than with the scanning interface. An experienced user (author TB, with > 10 hours practice) wrote at speeds of 9.3 words per minute with Nomon, using 1.2 clicks per character and making no errors in the final text.Comment: 14 pages, 5 figures, 1 table, presented at NIPS 2009 Mini-symposi

Contrasting signals from multiple markers illuminate population connectivity in a marine fish

Recent advances in molecular biology and bioinformatics have helped to unveil striking and previously unrecognized patterns of geographic genetic structure in marine populations. Largely driven by the pressing needs of fisheries management and conservation, studies on marine fish populations have played a pivotal role in testing the efficiency of a range of approaches to explore connectivity and dispersal at sea. Here, we employed nuclear and mitochondrial DNA markers and parasitic infestations to examine the nature and patterns of population structure in a warm-temperate coastal marine teleost across major putative biogeographic barriers in the Mediterranean Sea and Eastern Atlantic Ocean. We detected deep genetic divergence between mitochondrial lineages, likely caused by dramatic climatic and geological transformations before and during the Pleistocene. Such long-diverged lineages later came into secondary contact and can now be found in sympatry. More importantly, microsatellite data revealed that these lineages, after millions of years of independent evolution, now interbreed extensively. By combining genetic and parasite data, we were able to identify at least five independent demographic units. While the different genetic and parasite-based methods produce notably contrasting signals and may complicate the reconstruction of connectivity dynamics, we show that by tailoring the correct interpretation to each of the descriptors used, it is possible to achieve a deeper understanding of the micro-evolutionary process and, consequently, resolve population structure

The association between renal function and structural parameters: a pig study

<p>Abstract</p> <p>Background</p> <p>The objective was to investigate the association between renal structural parameters and renal function. The structural parameters were renal cortical volume, total renal volume, number of glomeruli, and total glomerular volume, and renal function was expressed by the single kidney GFR (skGFR). Investigations were performed using both healthy and chronically diseased kidneys. We investigated which of the structural parameters showed the best correlation to renal function and evaluated the possibility of predicting the renal function from structural parameters.</p> <p>Methods</p> <p>Twenty-four pigs, twelve with healthy kidneys and twelve with diseased kidneys, underwent skGFR measurements. Nephrectomies were performed and structural parameters were estimated using stereological procedures. The correlation between the structural parameters and skGFR was analysed by Pearson's correlation test. The prediction of skGFR from structural parameters was analysed by a linear regression test.</p> <p>Results</p> <p>In general, we demonstrated a good correlation between structural parameters and skGFR. When all kidneys were evaluated together Pearson's correlation coefficient between skGFR and any stereological parameter was above 0.60 and highly significant (p < 0.001), and with r-values ranging from 0.62 regarding number of glomeruli, to 0.78 regarding cortical volume. The best correlation was found between cortical volume and skGFR. Prediction of single kidney GFR from any structural parameter showed to be quite imprecise.</p> <p>Conclusion</p> <p>The observed correlations between structural parameters and renal function suggest that these parameters may potentially be useful as surrogate markers of the renal function. At present, however, precise prediction of renal function based on a single structural parameter seems hard to obtain.</p

Design, conduct, analysis and reporting of a multi-national placebo-controlled trial of activated protein C for persistent septic shock

The role of drotrecogin alfa (activated) (DAA) in severe sepsis remains controversial and clinicians are unsure whether or not to treat their patients with DAA. In response to a request from the European Medicines Agency, Eli Lilly will sponsor a new placebo-controlled trial and history suggests the results will be subject to great scrutiny. An academic steering committee will oversee the conduct of the study and will write the study manuscripts. The steering committee intends that the study will be conducted with the maximum possible transparency; this includes publication of the study protocol and a memorandum of understanding which delineates the role of the sponsor. The trial has the potential to provide clinicians with valuable data but patients will only benefit if clinicians have confidence in the conduct, analysis and reporting of the trial. This special article describes the process by which the trial was developed, major decisions regarding trial design, and plans for independent analysis, interpretation and reporting of the data

Multi-photon ionisation spectroscopy for rotational state preparation of N+2

In this paper we investigate the 2 + 1′ resonance enhanced multi-photon ionisation (REMPI) of molecular nitrogen via the a1Πg(v = 6) intermediate state and analyse its feasibility to generate molecular nitrogen ions in a well defined ro-vibrational state. This is an important tool for high precision experiments based on trapped molecular ions, and is crucial for studying the time variation of the fundamental constant mp/me using N+2. The transition is not reported in the literature and detailed spectral analysis has been conducted to extract the molecular constants of the intermediate state. By carefully choosing the intermediate ro-vibrational state, the ionisation laser wavelength and controlling the excitation laser pulse energy, unwanted formation of rotationally excited molecular ions can be suppressed and ro-vibrational ground state ions can be generated with high purity

Early growth patterns and cardiometabolic function at the age of 5 in a multiethnic birth cohort: the ABCD study

<p>Abstract</p> <p>Background</p> <p>The relation between fetal growth retardation and cardiovascular and metabolic diseases in later life has been demonstrated in many studies. However, debate exists around the potential independent role of postnatal growth acceleration. Furthermore, it is unknown whether a potential effect of growth acceleration on cardiovascular and metabolic function is confined to certain timeframes.</p> <p>The present study assesses the (predictive) role of prenatal and postnatal growth on 5 components of cardiovascular and metabolic function in children aged 5. The potential association of timing of postnatal growth acceleration with these outcomes will be explored.</p> <p>Methods and design</p> <p>Prospective multiethnic community-based cohort study of 8266 pregnancies (Amsterdam Born Children and their Development, ABCD study). Up till now, anthropometry of 5104 children from the original cohort was followed during the first 5 years of life, with additional information about birth weight, pregnancy duration, and various potential confounding variables.</p> <p>At age 5, various components of cardiovascular and metabolic function are being measured. Outcome variables are body size, body composition and fat distribution, insulin sensitivity, lipid profile, blood pressure and autonomic regulation of cardiovascular function.</p> <p>Discussion</p> <p>This study will be one of the first population-based prospective cohort studies to address the association between measures of both prenatal and postnatal growth and various components of cardiovascular and metabolic function. Specific attention is paid to the timing of acceleration in growth and its potential association with the outcome variables. Importantly, the longitudinal design of this study gives us the opportunity to gain more insight into growth trajectories associated with adverse outcomes in later life. If identified as an independent risk factor, this provides further basis for the hypothesis that accelerated growth during the first years of life is a modifiable factor for the prevention of cardiovascular and metabolic disorders in later life. Moreover, identification of specific vulnerable periods during development may reveal suitable timeframes for early interventions.</p

Presence of Avian Influenza Viruses in Waterfowl and Wetlands during Summer 2010 in California: Are Resident Birds a Potential Reservoir?

Although wild waterfowl are the main reservoir for low pathogenic avian influenza viruses (LPAIv), the environment plays a critical role for the circulation and persistence of AIv. LPAIv may persist for extended periods in cold environments, suggesting that waterfowl breeding areas in the northern hemisphere may be an important reservoir for AIv in contrast to the warmer southern wintering areas. We evaluated whether southern wetlands, with relatively small populations (thousands) of resident waterfowl, maintain AIv in the summer, prior to the arrival of millions of migratory birds. We collected water and fecal samples at ten wetlands in two regions (Yolo Bypass and Sacramento Valley) of the California Central Valley during three bi-weekly intervals beginning in late July, 2010. We detected AIv in 29/367 fecal samples (7.9%) and 12/597 water samples (2.0%) by matrix real time Reverse Transcription Polymerase Chain Reaction (rRT-PCR). We isolated two H3N8, two H2N3, and one H4N8 among rRT-PCR positive fecal samples but no live virus from water samples. Detection of AIv RNA in fecal samples was higher from wetlands in the Sacramento Valley (11.9%) than in the Yolo Bypass (0.0%), but no difference was found for water samples (2.7 vs. 1.7%, respectively). Our study showed that low densities of hosts and unfavorable environmental conditions did not prevent LPAIv circulation during summer in California wetlands. Our findings justify further investigations to understand AIv dynamics in resident waterfowl populations, compare AIv subtypes between migratory and resident waterfowl, and assess the importance of local AIv as a source of infection for migratory birds

Analysis of ancestral and functionally relevant CD5 variants in systemic lupus erythematosus patients

OBJECTIVE: CD5 plays a crucial role in autoimmunity and is a well-established genetic risk factor of developing RA. Recently, evidence of positive selection has been provided for the CD5 Pro224-Val471 haplotype in East Asian populations. The aim of the present work was to further analyze the functional relevance of non-synonymous CD5 polymorphisms conforming the ancestral and the newly derived haplotypes (Pro224-Ala471 and Pro224-Val471, respectively) as well as to investigate the potential role of CD5 on the development of SLE and/or SLE nephritis. METHODS: The CD5 SNPs rs2241002 (C/T; Pro224Leu) and rs2229177 (C/T; Ala471Val) were genotyped using TaqMan allelic discrimination assays in a total of 1,324 controls and 681 SLE patients of Spanish origin. In vitro analysis of CD3-mediated T cell proliferative and cytokine response profiles of healthy volunteers homozygous for the above mentioned CD5 haplotypes were also analyzed. RESULTS: T-cell proliferation and cytokine release were significantly increased showing a bias towards to a Th2 profile after CD3 cross-linking of peripheral mononuclear cells from healthy individuals homozygous for the ancestral Pro224-Ala471 (CC) haplotype, compared to the more recently derived Pro224-Val471 (CT). The same allelic combination was statistically associated with Lupus nephritis. CONCLUSION: The ancestral Ala471 CD5 allele confers lymphocyte hyper-responsiveness to TCR/CD3 cross-linking and is associated with nephritis in SLE patients

The Association between Intrauterine Inflammation and Spontaneous Vaginal Delivery at Term: A Cross-Sectional Study

BACKGROUND:Different factors contribute to the onset of labor at term. In animal models onset of labor is characterized by an inflammatory response. The role of intrauterine inflammation, although implicated in preterm birth, is not yet established in human term labor. We hypothesized that intrauterine inflammation at term is associated with spontaneous onset of labor. METHODS/RESULTS:In two large urban hospitals in the Netherlands, a cross-sectional study of spontaneous onset term vaginal deliveries and elective caesarean sections (CS), without signs of labor, was carried out. Placentas and amniotic fluid samples were collected during labor and/or at delivery. Histological signs of placenta inflammation were determined. Amniotic fluid proinflammatory cytokine concentrations were measured using ELISA. A total of 375 women were included. In term vaginal deliveries, more signs of intrauterine inflammation were found than in elective CS: the prevalence of chorioamnionitis was higher (18 vs 4%, p = 0.02) and amniotic fluid concentration of IL-6 was higher (3.1 vs 0.37 ng/mL, p<0.001). Similar results were obtained for IL-8 (10.93 vs 0.96 ng/mL, p<0.001) and percentage of detectable TNF-alpha (50 vs 4%, p<0.001). CONCLUSIONS:This large cross-sectional study shows that spontaneous term delivery is characterized by histopathological signs of placenta inflammation and increased amniotic fluid proinflammatory cytokines

Accelerated apoptotic death and <i>in vivo</i> turnover of erythrocytes in mice lacking functional mitogen- and stress-activated kinase MSK1/2

The mitogen- and stress-activated kinase MSK1/2 plays a decisive role in apoptosis. In analogy to apoptosis of nucleated cells, suicidal erythrocyte death called eryptosis is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine (PS) externalization. Here, we explored whether MSK1/2 participates in the regulation of eryptosis. To this end, erythrocytes were isolated from mice lacking functional MSK1/2 (msk−/−) and corresponding wild-type mice (msk+/+). Blood count, hematocrit, hemoglobin concentration and mean erythrocyte volume were similar in both msk−/− and msk+/+ mice, but reticulocyte count was significantly increased in msk−/− mice. Cell membrane PS exposure was similar in untreated msk−/− and msk+/+ erythrocytes, but was enhanced by pathophysiological cell stressors ex vivo such as hyperosmotic shock or energy depletion to significantly higher levels in msk−/− erythrocytes than in msk+/+ erythrocytes. Cell shrinkage following hyperosmotic shock and energy depletion, as well as hemolysis following decrease of extracellular osmolarity was more pronounced in msk−/− erythrocytes. The in vivo clearance of autologously-infused CFSE-labeled erythrocytes from circulating blood was faster in msk−/− mice. The spleens from msk−/− mice contained a significantly greater number of PS-exposing erythrocytes than spleens from msk+/+ mice. The present observations point to accelerated eryptosis and subsequent clearance of erythrocytes leading to enhanced erythrocyte turnover in MSK1/2-deficient mice