Human Computation and Convergence

Humans are the most effective integrators and producers of information, directly and through the use of information-processing inventions. As these inventions become increasingly sophisticated, the substantive role of humans in processing information will tend toward capabilities that derive from our most complex cognitive processes, e.g., abstraction, creativity, and applied world knowledge. Through the advancement of human computation - methods that leverage the respective strengths of humans and machines in distributed information-processing systems - formerly discrete processes will combine synergistically into increasingly integrated and complex information processing systems. These new, collective systems will exhibit an unprecedented degree of predictive accuracy in modeling physical and techno-social processes, and may ultimately coalesce into a single unified predictive organism, with the capacity to address societies most wicked problems and achieve planetary homeostasis.Comment: Pre-publication draft of chapter. 24 pages, 3 figures; added references to page 1 and 3, and corrected typ

Risk factors for wound infection in surgery for spinal metastasis

Wound infection rates are generally higher in patients undergoing surgery for spinal metastasis. Risk factors of wound infection in these patients are poorly understood. Purpose To identify demographic and clinical variables that may be associated with patients experiencing a higher wound infection rate. Study design Retrospective study with prospectively collected data of spinal metastasis patients operated consecutively at a University Teaching Hospital, adult spine division which is a tertiary referral centre for complex spinal surgery. Patient sample Ninety-eight patients were all surgically treated, consecutively from January 2009 to September 2011. Three patients had to be excluded due to inadequate data. Outcome measures Physiological measures, with presence or absence of microbiologically proven infection. Methods Various demographic and clinical data were recorded, including age, serum albumin level, blood total lymphocyte count, corticosteroid intake, Malnutrition Universal Screening Tool (MUST) score, neurological disability, skin closure material used, levels of surgery and administration of peri-operative corticosteroids. No funding was received from any sources for this study and as far as we are aware, there are no potential conflict of interest-associated biases in this study. Results Higher probabilities of infection were associated with low albumin level, seven or more levels of surgery, use of delayed/non-absorbable skin closure material and presence of neurological disability. Of these factors, levels of surgery were found to be statistically significant at the 5 % significance level. Conclusion Risk of infection is high (17.9 %) in patients undergoing surgery for spinal metastasis. Seven or more vertebral levels of surgery increase the risk of infection significantly (p < 0.05). Low albumin level and presence of neurological disability appear to show a trend towards increased risk of infection. Use of absorbable skin closure material, age, low lymphocyte count, peri-operative administration of corticosteroids and MUST score do not appear to influence the risk of infection

Information-Derived Mechanistic Hypotheses for Structural Cardiotoxicity

Adverse events resulting from drug therapy can be a cause of drug withdrawal, reduced and or restricted clinical use, as well as a major economic burden for society. To increase the safety of new drugs, there is a need to better understand the mechanisms causing the adverse events. One way to derive new mechanistic hypotheses is by linking data on drug adverse events with the drugs’ biological targets. In this study, we have used data mining techniques and mutual information statistical approaches to find associations between reported adverse events collected from the FDA Adverse Event Reporting System and assay outcomes from ToxCast, with the aim to generate mechanistic hypotheses related to structural cardiotoxicity (morphological damage to cardiomyocytes and/or loss of viability). Our workflow identified 22 adverse event-assay outcome associations. From these associations, 10 implicated targets could be substantiated with evidence from previous studies reported in the literature. For two of the identified targets, we also describe a more detailed mechanism, forming putative adverse outcome pathways associated with structural cardiotoxicity. Our study also highlights the difficulties deriving these type of associations from the very limited amount of data available

Chromosome 1p13 genetic variants antagonize the risk of myocardial infarction associated with high ApoB serum levels

PMCID: PMC3480949This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

The GATA1s isoform is normally down-regulated during terminal haematopoietic differentiation and over-expression leads to failure to repress MYB, CCND2 and SKI during erythroid differentiation of K562 cells

Background: Although GATA1 is one of the most extensively studied haematopoietic transcription factors little is currently known about the physiological functions of its naturally occurring isoforms GATA1s and GATA1FL in humans—particularly whether the isoforms have distinct roles in different lineages and whether they have non-redundant roles in haematopoietic differentiation. As well as being of general interest to understanding of haematopoiesis, GATA1 isoform biology is important for children with Down syndrome associated acute megakaryoblastic leukaemia (DS-AMKL) where GATA1FL mutations are an essential driver for disease pathogenesis. &lt;p/&gt;Methods: Human primary cells and cell lines were analyzed using GATA1 isoform specific PCR. K562 cells expressing GATA1s or GATA1FL transgenes were used to model the effects of the two isoforms on in vitro haematopoietic differentiation. &lt;p/&gt;Results: We found no evidence for lineage specific use of GATA1 isoforms; however GATA1s transcripts, but not GATA1FL transcripts, are down-regulated during in vitro induction of terminal megakaryocytic and erythroid differentiation in the cell line K562. In addition, transgenic K562-GATA1s and K562-GATA1FL cells have distinct gene expression profiles both in steady state and during terminal erythroid differentiation, with GATA1s expression characterised by lack of repression of MYB, CCND2 and SKI. &lt;p/&gt;Conclusions: These findings support the theory that the GATA1s isoform plays a role in the maintenance of proliferative multipotent megakaryocyte-erythroid precursor cells and must be down-regulated prior to terminal differentiation. In addition our data suggest that SKI may be a potential therapeutic target for the treatment of children with DS-AMKL

Linear Sigma Models with Torsion

Gauged linear sigma models with (0,2) supersymmetry allow a larger choice of couplings than models with (2,2) supersymmetry. We use this freedom to find a fully linear construction of torsional heterotic compactifications, including models with branes. As a non-compact example, we describe a family of metrics which correspond to deformations of the heterotic conifold by turning on H-flux. We then describe compact models which are gauge-invariant only at the quantum level. Our construction gives a generalization of symplectic reduction. The resulting spaces are non-Kahler analogues of familiar toric spaces like complex projective space. Perturbatively conformal models can be constructed by considering intersections.Comment: 40 pages, LaTeX, 1 figure; references added; a new section on supersymmetry added; quantization condition revisite

Prenatal hypoxia induces increased cardiac contractility on a background of decreased capillary density.

Background: Chronic hypoxia in utero (CHU) is one of the most common insults to fetal development and may be associated with poor cardiac recovery from ischaemia-reperfusion injury,yet the effects on normal cardiac mechanical performance are poorly understood. Methods: Pregnant female wistar rats were exposed to hypoxia (12% oxygen, balance nitrogen)for days 10–20 of pregnancy. Pups were born into normal room air and weaned normally. At 10 weeks of age, hearts were excised under anaesthesia and underwent retrograde 'Langendorff' perfusion. Mechanical performance was measured at constant filling pressure (100 cm H2O) with intraventricular balloon. Left ventricular free wall was dissected away and capillary density estimated following alkaline phosphatase staining. Expression of SERCA2a and Nitric Oxide Synthases (NOS) proteins were estimated by immunoblotting. Results: CHU significantly increased body mass (P < 0.001) compared with age-matched control rats but was without effect on relative cardiac mass. For incremental increases in left ventricular balloon volume, diastolic pressure was preserved. However, systolic pressure was significantly greater following CHU for balloon volume = 50 μl (P < 0.01) and up to 200 μl (P < 0.05). For higher balloon volumes systolic pressure was not significantly different from control. Developed pressures were correspondingly increased relative to controls for balloon volumes up to 250 μl (P < 0.05).Left ventricular free wall capillary density was significantly decreased in both epicardium (18%; P <0.05) and endocardium (11%; P < 0.05) despite preserved coronary flow. Western blot analysis revealed no change to the expression of SERCA2a or nNOS but immuno-detectable eNOS protein was significantly decreased (P < 0.001) in cardiac tissue following chronic hypoxia in utero. Conclusion: These data offer potential mechanisms for poor recovery following ischaemia, including decreased coronary flow reserve and impaired angiogenesis with subsequent detrimental effects of post-natal cardiac performance

Family Planning Decisions, Perceptions and Gender Dynamics among Couples in Mwanza, Tanzania: A Qualitative Study.

Contraceptive use is low in developing countries which are still largely driven by male dominated culture and patriarchal values. This study explored family planning (FP) decisions, perceptions and gender dynamics among couples in Mwanza region of Tanzania. Twelve focus group discussions and six in-depth interviews were used to collect information from married or cohabiting males and females aged 18-49. The participants were purposively selected. Qualitative methods were used to explore family planning decisions, perceptions and gender dynamics among couples. A guide with questions related to family planning perceptions, decisions and gender dynamics was used. The discussions and interviews were tape-recorded, transcribed verbatim and analyzed manually and subjected to content analysis. Four themes emerged during the study. First, "risks and costs" which refer to the side effects of FP methods and the treatment of side -effects as well as the costs inherit in being labeled as an unfaithful spouse. Second, "male involvement" as men showed little interest in participating in family planning issues. However, the same men were mentioned as key decision-makers even on the number of children a couple should have and the child spacing of these children. Third, "gender relations and communication" as participants indicated that few women participated in decision-making on family planning and the number of children to have. Fourth, "urban-rural differences", life in rural favoring having more children than urban areas therefore, the value of children depended on the place of residence. Family Planning programs should adapt the promotion of communication as well as joint decision-making on FP among couples as a strategy aimed at enhancing FP use

Preschool Behavioral and Social-Cognitive Problems as Predictors of (Pre)adolescent Disruptive Behavior

This article describes preschool social understanding and difficult behaviors (hot temper, disobedience, bossiness and bullying) as predictors of oppositional defiant disorder (ODD) and aggressive conduct disorder (ACD) in a Dutch population sample of (pre)adolescents (N = 1943), measured at age 10–12 and at age 13–15. ODD and ACD were assessed by the Child Behavior Checklist and the Youth Self-Report, preschool behavior was evaluated by the parental questionnaire ‹How was your child as a preschooler? (age 4–5)’. Adjusted for each other, all difficult preschool behaviors except bullying were associated with adolescent ODD, while only bullying significantly predicted adolescent ACD. Furthermore, the results suggest a qualitative difference between ODD and ACD in terms of the social component of the disorders: poor preschool social understanding was associated with the development of ACD but not of ODD; and poor social understanding interacted with difficult preschool behaviors to predict later ACD but not ODD. The associations did not differ between boys and girls, and were roughly similar for preadolescent (age 10–12) and early adolescent (age 13–15) outcomes. The finding that poor social understanding was implicated in the development of ACD but not in the development of ODD may help to demarcate the individuality of each disorder and offer leads for (differential) treatment strategies

A Terminal Velocity on the Landscape: Particle Production near Extra Species Loci in Higher Dimensions

We investigate particle production near extra species loci (ESL) in a higher dimensional field space and derive a speed limit in moduli space at weak coupling. This terminal velocity is set by the characteristic ESL-separation and the coupling of the extra degrees of freedom to the moduli, but it is independent of the moduli's potential if the dimensionality of the field space is considerably larger than the dimensionality of the loci, D >> d. Once the terminal velocity is approached, particles are produced at a plethora of nearby ESLs, preventing a further increase in speed via their backreaction. It is possible to drive inflation at the terminal velocity, providing a generalization of trapped inflation with attractive features: we find that more than sixty e-folds of inflation for sub-Planckian excursions in field space are possible if ESLs are ubiquitous, without fine tuning of initial conditions and less tuned potentials. We construct a simple, observationally viable model with a slightly red scalar power-spectrum and suppressed gravitational waves; we comment on the presence of additional observational signatures originating from IR-cascading and individual massive particles. We also show that moduli-trapping at an ESL is suppressed for D >> d, hindering dynamical selection of high-symmetry vacua on the landscape based on this mechanism.Comment: 46 pages, 6 figures. V3: typos corrected compared to JHEP version, conclusions unchange