• e-GRASP: An integrated evolutionary and GRASP resource for exploring disease associations

      Karim, S; NourEldin, HF; Abusamra, H; Salem, N; Alhathli, E; Dudley, J; Sanderford, M; Scheinfeldt, LB; Kumar, S; Kumar, Sudhir|0000-0002-9918-8212 (2016-10-17)
      © 2016 The Author(s). Background: Genome-wide association studies (GWAS) have become a mainstay of biological research concerned with discovering genetic variation linked to phenotypic traits and diseases. Both discrete and continuous traits can be analyzed in GWAS to discover associations between single nucleotide polymorphisms (SNPs) and traits of interest. Associations are typically determined by estimating the significance of the statistical relationship between genetic loci and the given trait. However, the prioritization of bona fide, reproducible genetic associations from GWAS results remains a central challenge in identifying genomic loci underlying common complex diseases. Evolutionary-aware meta-analysis of the growing GWAS literature is one way to address this challenge and to advance from association to causation in the discovery of genotype-phenotype relationships. Description: We have created an evolutionary GWAS resource to enable in-depth query and exploration of published GWAS results. This resource uses the publically available GWAS results annotated in the GRASP2 database. The GRASP2 database includes results from 2082 studies, 177 broad phenotype categories, and ~8.87 million SNP-phenotype associations. For each SNP in e-GRASP, we present information from the GRASP2 database for convenience as well as evolutionary information (e.g., rate and timespan). Users can, therefore, identify not only SNPs with highly significant phenotype-association P-values, but also SNPs that are highly replicated and/or occur at evolutionarily conserved sites that are likely to be functionally important. Additionally, we provide an evolutionary-adjusted SNP association ranking (E-rank) that uses cross-species evolutionary conservation scores and population allele frequencies to transform P-values in an effort to enhance the discovery of SNPs with a greater probability of biologically meaningful disease associations. Conclusion: By adding an evolutionary dimension to the GWAS results available in the GRASP2 database, our e-GRASP resource will enable a more effective exploration of SNPs not only by the statistical significance of trait associations, but also by the number of studies in which associations have been replicated, and the evolutionary context of the associated mutations. Therefore, e-GRASP will be a valuable resource for aiding researchers in the identification of bona fide, reproducible genetic associations from GWAS results. This resource is freely available at http://www.mypeg.info/egrasp.
    • Early childhood cognitive development is affected by interactions among illness, diet, enteropathogens and the home environment: Findings from the MAL-ED birth cohort study

      Murray-Kolb, LE; Acosta, AM; De Burga, RR; Chavez, CB; Flores, JT; Olotegui, MP; Pinedo, SR; Salas, MS; Trigoso, DR; Vasquez, AO; Ahmed, I; Alam, D; Ali, A; Bhutta, ZA; Qureshi, S; Rasheed, M; Soofi, S; Turab, A; Zaidi, AKM; Bodhidatta, L; Mason, CJ; Babji, S; Bose, A; George, AT; Hariraju, D; Jennifer, MS; John, S; Kaki, S; Kang, G; Karunakaran, P; Koshy, B; Lazarus, RP; Muliyil, J; Raghava, MV; Raju, S; Ramachandran, A; Ramadas, R; Ramanujam, K; Bose, A; Roshan, R; Sharma, SL; Sundaram, SE; Thomas, RJ; Pan, WK; Ambikapathi, R; Carreon, JD; Charu, V; Doan, V; Graham, J; Hoest, C; Knobler, S; Lang, DR; McCormick, BJJ; McGrath, M; Miller, MA; Mohale, A; Nayyar, G; Psaki, S; Rasmussen, Z; Richard, SA; Seidman, JC; Wang, V; Blank, R; Gottlieb, M; Tountas, KH; Amour, C; Bayyo, E; Mduma, ER; Mvungi, R; Nshama, R; Pascal, J; Swema, BM; Yarrot, L; Ahmed, T; Ahmed, AMS; Haque, R; Hossain, I; Islam, M; Mahfuz, M; Mondal, D; Tofail, F; Chandyo, RK; Shrestha, PS; Shrestha, R; Ulak, M; Bauck, A; Black, RE; Caulfield, LE; Checkley, W; Kosek, MN; Lee, G; Schulze, K; Yori, PP; Murray-Kolb, LE; Catharine Ross, A; Schaefer, B; Simons, S; Pendergast, L; Abreu, CB; Costa, H (2018-07-01)
      © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. background Millions of children in low-income and middle-income countries (LMICs) are at risk of not reaching their full cognitive potential. Malnutrition and enteric infections in early life are implicated as risk factors; however, most studies on these risks and their associations with cognitive development have failed to adequately account for confounding factors or the accumulation of putative insults. Here, we examine the interaction between infections and illness on cognitive development in LMIC community settings. Methods As part of the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) longitudinal birth cohort study, children from eight LMICs were followed from birth to 24 months to understand the influence of repeated enteric infections on child growth and development. Here, data from six sites were employed to evaluate associations between infection, illness, the home environment, micronutrient intake and status, maternal reasoning, and cognitive development at 24 months. results Higher rates of enteropathogen detection and days with illness were associated with lower haemoglobin concentrations, which in turn were associated with lower cognitive scores at 24 months. Children with lower environmental health/safety scores and lower intakes of vitamin B 6 and folate had more enteropathogen detections and illness. Strength of associations varied by weight-for-age in the first 17 days of life; lower weight infants were more susceptible to the negative effects of enteropathogens and illness. Conclusions Enteropathogens were negatively related to child cognitive development. However, other factors were more strongly associated with child cognition. Targeting of interventions to improve cognitive development should include a focus on reducing frequency of illness, improving the safety and healthfulness of the child's environment, and improving dietary intake.
    • Early classification of multivariate temporal observations by extraction of interpretable shapelets

      Ghalwash, MF; Obradovic, Z (2012-08-08)
      Background: Early classification of time series is beneficial for biomedical informatics problems such including, but not limited to, disease change detection. Early classification can be of tremendous help by identifying the onset of a disease before it has time to fully take hold. In addition, extracting patterns from the original time series helps domain experts to gain insights into the classification results. This problem has been studied recently using time series segments called shapelets. In this paper, we present a method, which we call Multivariate Shapelets Detection (MSD), that allows for early and patient-specific classification of multivariate time series. The method extracts time series patterns, called multivariate shapelets, from all dimensions of the time series that distinctly manifest the target class locally. The time series were classified by searching for the earliest closest patterns.Results: The proposed early classification method for multivariate time series has been evaluated on eight gene expression datasets from viral infection and drug response studies in humans. In our experiments, the MSD method outperformed the baseline methods, achieving highly accurate classification by using as little as 40%-64% of the time series. The obtained results provide evidence that using conventional classification methods on short time series is not as accurate as using the proposed methods specialized for early classification.Conclusion: For the early classification task, we proposed a method called Multivariate Shapelets Detection (MSD), which extracts patterns from all dimensions of the time series. We showed that the MSD method can classify the time series early by using as little as 40%-64% of the time series' length. © 2012 Ghalwash and Obradovic; licensee BioMed Central Ltd.
    • Early Life Child Micronutrient Status, Maternal Reasoning, and a Nurturing Household Environment have Persistent Influences on Child Cognitive Development at Age 5 years: Results from MAL-ED

      McCormick, BJJ; Richard, SA; Caulfield, LE; Pendergast, LL; Seidman, JC; Koshy, B; Roshan, R; Shrestha, R; Svensen, E; Blacy, L; Rasmussen, Z; Maphula, A; Scharf, R; Nahar, B; Haque, S; Rasheed, M; Oria, R; Rogawski, ET; Murray-Kolb, LE; Acosta, AM; De Burga, RR; Chavez, CB; Flores, JT; Olotegui, MP; Pinedo, SR; Salas, MS; Trigoso, DR; Vasquez, AO; Ahmed, I; Alam, D; Ali, A; Bhutta, ZA; Qureshi, S; Soofi, S; Turab, A; Zaidi, AKM; Bodhidatta, L; Mason, CJ; Babji, S; Bose, A; George, AT; Hariraju, D; Jennifer, MS; John, S; Kaki, S; Kang, G; Karunakaran, P; Lazarus, RP; Muliyil, J; Raghava, MV; Raju, S; Ramachandran, A; Ramadas, R; Ramanujam, K; Sharma, SL; Sundaram, SE; Thomas, RJ; Pan, WK; Ambikapathi, R; Carreon, JD; Charu, V; Doan, V; Graham, J; Hoest, C; Knobler, S; Lang, DR; McGrath, M; Miller, MA; Mohale, A; Nayyar, G; Psaki, S; Wang, V; Blank, R; Gottlieb, M; Tountas, KH; Amour, C; Bayyo, E; Mduma, ER; Mvungi, R; Nshama, R; Pascal, J; Swema, BM; Yarrot, L; Ahmed, T; Ahmed, AMS; Haque, R; Hossain, I; Islam, M; Mahfuz, M; Mondal, D; Tofail, F; Chandyo, RK; Shrestha, PS; Ulak, M; Bauck, A; Black, RE; Checkley, W; Kosek, MN; Lee, G; Schulze, K (2019-08-01)
      © Copyright American Society for Nutrition 2019. Background: Child cognitive development is influenced by early-life insults and protective factors. To what extent these factors have a long-term legacy on child development and hence fulfillment of cognitive potential is unknown. Objective: The aim of this study was to examine the relation between early-life factors (birth to 2 y) and cognitive development at 5 y. Methods: Observational follow-up visits were made of children at 5 y, previously enrolled in the community-based MAL-ED longitudinal cohort. The burden of enteropathogens, prevalence of illness, complementary diet intake, micronutrient status, and household and maternal factors from birth to 2 y were extensively measured and their relation with the Wechsler Preschool Primary Scales of Intelligence at 5 y was examined through use of linear regression. Results: Cognitive T-scores from 813 of 1198 (68%) children were examined and 5 variables had significant associations in multivariable models: mean child plasma transferrin receptor concentration (β: -1.81, 95% CI: -2.75, -0.86), number of years of maternal education (β: 0.27, 95% CI: 0.08, 0.45), maternal cognitive reasoning score (β: 0.09, 95% CI: 0.03, 0.15), household assets score (β: 0.64, 95% CI: 0.24, 1.04), and HOME child cleanliness factor (β: 0.60, 95% CI: 0.05, 1.15). In multivariable models, the mean rate of enteropathogen detections, burden of illness, and complementary food intakes between birth and 2 y were not significantly related to 5-y cognition. Conclusions: A nurturing home context in terms of a healthy/clean environment and household wealth, provision of adequate micronutrients, maternal education, and cognitive reasoning have a strong and persistent influence on child cognitive development. Efforts addressing aspects of poverty around micronutrient status, nurturing caregiving, and enabling home environments are likely to have lasting positive impacts on child cognitive development.
    • Earth system data cubes unravel global multivariate dynamics

      Mahecha, Miguel D.; Gans, Fabian; Brandt, Gunnar; Christiansen, Rune; Cornell, Sarah E.; Fomferra, Normann; Kraemer, Guido; Peters, Jonas; Bodesheim, Paul; Camps-Valls, Gustau; Donges, Jonathan F.; Dorigo, Wouter; Estupinan-Suarez, Lina M.; Gutiérrez-Vélez, Víctor Hugo; Gutwin, Martin; Jung, Martin; Londoño, Maria C.; Miralles, Diego G.; Papastefanou, Phillip; Reichstein, Markus (2020-02-25)
      Understanding Earth system dynamics in light of ongoing human intervention and dependency remains a major scientific challenge. The unprecedented availability of data streams describing different facets of the Earth now offers fundamentally new avenues to address this quest. However, several practical hurdles, especially the lack of data interoperability, limit the joint potential of these data streams. Today, many initiatives within and beyond the Earth system sciences are exploring new approaches to overcome these hurdles and meet the growing interdisciplinary need for data-intensive research; using data cubes is one promising avenue. Here, we introduce the concept of Earth system data cubes and how to operate on them in a formal way. The idea is that treating multiple data dimensions, such as spatial, temporal, variable, frequency, and other grids alike, allows effective application of user-defined functions to co-interpret Earth observations and/or model–data integration. An implementation of this concept combines analysis-ready data cubes with a suitable analytic interface. In three case studies, we demonstrate how the concept and its implementation facilitate the execution of complex workflows for research across multiple variables, and spatial and temporal scales: (1) summary statistics for ecosystem and climate dynamics; (2) intrinsic dimensionality analysis on multiple timescales; and (3) model–data integration. We discuss the emerging perspectives for investigating global interacting and coupled phenomena in observed or simulated data. In particular, we see many emerging perspectives of this approach for interpreting large-scale model ensembles. The latest developments in machine learning, causal inference, and model–data integration can be seamlessly implemented in the proposed framework, supporting rapid progress in data-intensive research across disciplinary boundaries.
    • Economic Paradigms and Latin American Development Theory: The Search for Nirvana

      Porrata-Doria, Rafael A., Jr. (2006)
      The pursuit of the optimal, economic development paradigm in Latin America has proved to be as elusive as the search for nirvana. This paper will describe and put into context the major theories of economic development that have served as the basis for Latin American trade policy, both in the United States and Latin America. I will do so by first analyzing the modem theory of economic andpolitical development articulated by Walt Rostow and others. I will then examinethe theory of import substitution principally put forth by Ratil Prebisch and the United Nations Economic Commission for Latin America. Thirdly, I will consider the neo-liberal economic development theory first articulated by the University of Chicago-trained economists who served in the Chilean government led by General Augusto Pinochet. I will then conclude with a number of observations regarding the analysis and applicability of these paradigms to the Latin American context.
    • Edge-terminated molybdenum disulfide with a 9.4-Å interlayer spacing for electrochemical hydrogen production

      Gao, MR; Chan, MKY; Sun, Y; Sun, Yugang|0000-0001-6351-6977 (2015-07-03)
      Layered molybdenum disulfide has demonstrated great promise as a low-cost alternative to platinum-based catalysts for electrochemical hydrogen production from water. Research effort on this material has focused mainly on synthesizing highly nanostructured molybdenum disulfide that allows the exposure of a large fraction of active edge sites. Here we report a promising microwave-assisted strategy for the synthesis of narrow molybdenum disulfide nanosheets with edge-terminated structure and a significantly expanded interlayer spacing, which exhibit striking kinetic metrics with onset potential of 103mV, Tafel slope of 49 mV per decade and exchange current density of 9.62 × 10<sup>-3</sup> mA cm<sup>-2</sup>, performing among the best of current molybdenum disulfide catalysts. Besides benefits from the edge-terminated structure, the expanded interlayer distance with modified electronic structure is also responsible for the observed catalytic improvement, which suggests a potential way to design newly advanced molybdenum disulfide catalysts through modulating the interlayer distance.
    • Editorial: Global Education of Health Management

      Evashwick, CJ; Aaronson, WE (2019-01-01)
    • Editorial: Modeling Play in Early Infant Development

      Shaw, P; Lee, M; Shen, Q; Hirsh-Pasek, K; Adolph, KE; Oudeyer, PY; Popp, J (2020-08-06)
    • Editorial: Music and Disorders of Consciousness: Emerging Research, Practice and Theory

      Magee, Wendy L.; Tillmann, Barbara; Perrin, Fabien; Schnakers, Caroline; Magee|0000-0003-4350-1289 (2016-08-31)
    • Editorial: Obesity Science and Practice (Dec 2015)

      Sarwer, David B; Sarwer, David B|0000-0003-1033-5528 (2015-12)
    • Editorial: Obesity Science and Practice (Dec 2016)

      Sarwer, David; 0000-0003-1033-5528 (2016-12-28)
    • Editorial: Obesity Science and Practice (Feb 2018)

      Sarwer, DB; Sarwer, David B|0000-0003-1033-5528 (2018-02-01)
    • Editorial: Obesity Science and Practice (Sep 2016)

      Sarwer, David; 0000-0003-1033-5528 (2016-09-19)
    • Effect of deinstitutionalisation for adults with intellectual disabilities on costs: A systematic review

      May, P; Lombard Vance, R; Murphy, E; O'Donovan, MA; Webb, N; Sheaf, G; McCallion, P; Stancliffe, R; Normand, C; Smith, V; McCarron, M; Mccallion, Philip|0000-0001-5129-6399 (2019-01-01)
      © 2019 Author(s). Objective To review systematically the evidence on the costs and cost-effectiveness of deinstitutionalisation for adults with intellectual disabilities. Design Systematic review. Population Adults (aged 18 years and over) with intellectual disabilities. Intervention Deinstitutionalisation, that is, the move from institutional to community settings. Primary and secondary outcome measures Studies were eligible if evaluating within any cost-consequence framework (eg, cost-effectiveness analysis, cost-utility analysis) or resource use typically considered to fall within the societal viewpoint (eg, cost to payers, service-users, families and informal care costs). Search We searched MEDLINE, PsycINFO, CENTRAL, CINAHL, EconLit, Embase and Scopus to September 2017 and supplemented this with grey literature searches and handsearching of the references of the eligible studies. We assessed study quality using the Critical Appraisals Skills Programme suite of tools, excluding those judged to be of poor methodological quality. Results Two studies were included; both were cohort studies from the payer perspective of people leaving long-stay National Health Service hospitals in the UK between 1984 and 1992. One study found that deinstitutionalisation reduced costs, one study found an increase in costs. Conclusion A wide-ranging literature review found limited evidence on costs associated with deinstitutionalisation for people with intellectual disabilities. From two studies included in the review, the results were conflicting. Significant gaps in the evidence base were observable, particularly with respect to priority populations in contemporary policy: older people with intellectual disabilities and serious medical illness, and younger people with very complex needs and challenging behaviours. PROSPERO registration number CRD42018077406
    • Effect of deinstitutionalisation on quality of life for adults with intellectual disabilities: A systematic review

      McCarron, M; Lombard-Vance, R; Murphy, E; May, P; Webb, N; Sheaf, G; McCallion, P; Stancliffe, R; Normand, C; Smith, V; O'Donovan, MA; Mccallion, Philip|0000-0001-5129-6399 (2019-04-01)
      © 2019 Author(s). Objective To review systematically the evidence on how deinstitutionalisation affects quality of life (QoL) for adults with intellectual disabilities. Design Systematic review. Population Adults (aged 18 years and over) with intellectual disabilities. Interventions A move from residential to community setting. Primary and secondary outcome measures Studies were eligible if evaluating effect on QoL or life quality, as defined by study authors. Search We searched MEDLINE, PsycINFO, CENTRAL, CINAHL, EconLit, Embase and Scopus to September 2017 and supplemented this with grey literature searches. We assessed study quality using the Critical Appraisal Skills Programme suite of tools, excluding those judged to be of poor methodological quality. Results Thirteen studies were included; eight quantitative studies, two qualitative, two mixed methods studies and one case study. There was substantial agreement across quantitative and qualitative studies that a move to community living was associated with improved QoL. QoL for people with any level of intellectual disabilities who move from any type of institutional setting to any type of community setting was increased at up to 1 year postmove (standardised mean difference [SMD] 2.03; 95% CI [1.21 to 2.85], five studies, 246 participants) and beyond 1 year postmove (SMD 2.34. 95% CI [0.49 to 4.20], three studies, 160 participants), with total QoL change scores higher at 24 months comparative to 12 months, regardless of QoL measure used. Conclusion Our systematic review demonstrated a consistent pattern that moving to the community was associated with improved QoL compared with the institution. It is recommended that gaps in the evidence base, for example, with regard to growing populations of older people with intellectual disability and complex needs are addressed.
    • Effect of event selection on jetlike correlation measurement in d + Au collisions at √sNN = 200 GeV

      Adamczyk, L; Adkins, JK; Agakishiev, G; Aggarwal, MM; Ahammed, Z; Alekseev, I; Alford, J; Aparin, A; Arkhipkin, D; Aschenauer, EC; Averichev, GS; Banerjee, A; Bellwied, R; Bhasin, A; Bhati, AK; Bhattarai, P; Bielcik, J; Bielcikova, J; Bland, LC; Bordyuzhin, IG; Bouchet, J; Brandin, AV; Bunzarov, I; Burton, TP; Butterworth, J; Caines, H; Calder'on de la Barca S'anchez, M; Campbell, JM; Cebra, D; Cervantes, MC; Chakaberia, I; Chaloupka, P; Chang, Z; Chattopadhyay, S; Chen, JH; Cheng, J; Cherney, M; Christie, W; Codrington, MJM; Contin, G; Crawford, HJ; Das, S; De Silva, LC; Debbe, RR; Dedovich, TG; Deng, J; Derevschikov, AA; Derradi De Souza, R; Di Ruzza, B; Didenko, L; Dilks, C; Dong, X; Drachenberg, JL; Draper, JE; Du, CM; Dunkelberger, LE; Dunlop, JC; Efimov, LG; Engelage, J; Eppley, G; Esha, R; Evdokimov, O; Eyser, O; Fatemi, R; Fazio, S; Federic, P; Fedorisin, J; Feng; Filip, P; Fisyak, Y; Flores, CE; Gagliardi, CA; Garand, D; Geurts, F; Gibson, A; Girard, M; Greiner, L; Grosnick, D; Gunarathne, DS; Guo, Y; Gupta, S; Gupta, A; Guryn, W; Hamad, A; Hamed, A; Haque, R; Harris, JW; He, L; Heppelmann, S; Hirsch, A; Hoffmann, GW; Hofman, DJ; Horvat, S; Huang, HZ; Huang, X; Huang, B; Huck, P; Humanic, TJ; Igo, G; Jacobs, WW (2015-04-09)
      © 2015 The Authors. Dihadron correlations are analyzed in √sNN = 200 GeV d + Au collisions classified by forward charged particle multiplicity and zero-degree neutral energy in the Au-beam direction. It is found that the jetlike correlated yield increases with the event multiplicity. After taking into account this dependence, the non-jet contribution on the away side is minimal, leaving little room for a back-to-back ridge in these collisions.
    • Effect of Zephyr Endobronchial Valves on Dyspnea, Activity Levels, and Quality of Life at One Year. Results from a Randomized Clinical Trial

      LIBERATE Study Group (2020-03-30)
      Rationale: Bronchoscopic lung volume reduction with Zephyr Valves improves lung function, exercise tolerance, and quality of life of patients with hyperinflated emphysema and little to no collateral ventilation. Objectives: Post hoc analysis of patient-reported outcomes (PROs), including multidimensional measures of dyspnea, activity, and quality of life, in the LIBERATE (Lung Function Improvement after Bronchoscopic Lung Volume Reduction with Pulmonx Endobronchial Valves used in Treatment of Emphysema) study are reported. Methods: A total of 190 patients with severe heterogeneous emphysema and little to no collateral ventilation in the target lobe were randomized 2:1 to the Zephyr Valve or standard of care. Changes in PROs at 12 months in the two groups were compared: dyspnea with the Transitional Dyspnea Index (TDI), focal score; the Chronic Obstructive Pulmonary Disease Assessment Test (CAT; breathlessness on hill/stairs); Borg; the EXAcerbations of Chronic pulmonary disease Tool–PRO, dyspnea domain; activity with the TDI, magnitude of task/effort/functional impairment, CAT (limited activities), and the St. George’s Respiratory Questionnaire (SGRQ), activity domain; and psychosocial status with the SGRQ, impacts domain, and CAT (confidence and energy). Results: At 12 months, patients using the Zephyr Valve achieved statistically significant and clinically meaningful improvements in the SGRQ; CAT; and the TDI, focal score, compared with standard of care. Improvements in the SGRQ were driven by the impacts and activity domains (P < 0.05 and P < 0.001, respectively). Reduction in CAT was through improvements in breathlessness (P < 0.05), energy level (P < 0.05), activities (P < 0.001), and increased confidence when leaving home (P < 0.05). The TDI measures of effort, task, and functional impairment were uniformly improved (P < 0.001). The EXAcerbations of Chronic Pulmonary Disease Tool (EXACT)–PRO, dyspnea domain, was significantly improved in the Zephyr Valve group. Improvements correlated with changes in residual volume and residual volume/TLC ratio. Conclusions: Patients with severe hyperinflated emphysema achieving lung volume reductions with Zephyr Valves experience improvements in multidimensional scores for breathlessness, activity, and psychosocial parameters out to at least 12 months. Clinical trial registered with www.clinicaltrials.gov (NCT01796392).
    • Effectiveness of multiple blood-cleansing interventions in sepsis, characterized in rats

      Stojkovic, I; Ghalwash, M; Cao, XH; Obradovic, Z (2016-04-21)
      Sepsis is a serious, life-threatening condition that presents a growing problem in medicine, but there is still no satisfying solution for treating it. Several blood cleansing approaches recently gained attention as promising interventions that target the main site of problem development-the blood. The focus of this study is an evaluation of the theoretical effectiveness of hemoadsorption therapy and pathogen reduction therapy. This is evaluated using the mathematical model of Murine sepsis, and the results of over 2,200 configurations of single and multiple intervention therapies simulated on 5,000 virtual subjects suggest the advantage of pathogen reduction over hemoadsorption therapy. However, a combination of two approaches is found to take advantage of their complementary effects and outperform either therapy alone. The conducted computational experiments provide unprecedented evidence that the combination of two therapies synergistically enhances the positive effects beyond the simple superposition of the benefits of two approaches. Such a characteristic could have a profound influence on the way sepsis treatment is conducted.
    • Effectiveness of Noise-Attenuating Headphones on Physiological Responses for Children With Autism Spectrum Disorders

      Pfeiffer, B; Stein Duker, L; Murphy, AM; Shui, C (2019-11-12)
      © Copyright © 2019 Pfeiffer, Stein Duker, Murphy and Shui. Objective: The purpose of this study was to evaluate the proof of concept of an intervention to decrease sympathetic activation as measured by skin conductivity (electrodermal activity, EDA) in children with an autism spectrum disorder (ASD) and auditory hypersensitivity (hyperacusis). In addition, researchers examined if the intervention provided protection against the negative effects of decibel level of environmental noises on electrodermal measures between interventions. The feasibility of implementation and outcome measures within natural environments were evaluated. Method: A single-subject multi-treatment design was used with six children, aged 8–16 years, with a form of Autism (i.e., Autism, PDD-NOS). Participants used in-ear (IE) and over-ear (OE) headphones for two randomly sequenced treatment phases. Each child completed four phases: (1) a week of baseline data collection; (2) a week of an intervention; (3) a week of no intervention; and (4) a week of the other intervention. Empatica E4 wristbands collected EDA data. Data was collected on 16–20 occasions per participant, with five measurements per phase. Results: Separated tests for paired study phases suggested that regardless of intervention type, noise attenuating headphones led to a significance difference in both skin conductance levels (SCL) and frequency of non-specific conductance responses (NS-SCRs) between the baseline measurement and subsequent phases. Overall, SCL and NS-SCR frequency significantly decreased between baseline and the first intervention phase. A protective effect of the intervention was tested by collapsing intervention results into three phases. Slope correlation suggested constant SCL and NS-SCR frequency after initial use of the headphones regardless of the increase in environmental noises. A subsequent analysis of the quality of EDA data identified that later phases of data collection were associated with better data quality. Conclusion: Many children with ASD have hypersensitivities to sound resulting in high levels of sympathetic nervous system reactivity, which is associated with problematic behaviors and distress. The findings of this study suggest that the use of noise attenuating headphones for individuals with ASD and hyperacusis may reduce sympathetic activation. Additionally, results suggest that the use of wearable sensors to collect physiological data in natural environments is feasible with established protocols and training procedures.