Models for Partnership: IUPUI's Collaborative Digital Projects in Content DM

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Fractionation of human red blood cells based on intrinsic magnetization

Red blood cell (RBC) transfusion is clinically used to treat hemodynamic instability and O2 carrying deficits in patients with acute blood loss, and patients with chronic anemia caused by bone marrow failure/suppression. Currently, cold storage of human RBCs (hRBCs) can preserve hRBCs for a maximum of six weeks (i.e. 42 days), set by the United States Food and Drug Administration (US FDA). However, as stored RBCs age, they undergo biochemical and biophysical changes that are often referred to as the storage lesion, which decreases the efficacy of transfusion while increasing the risk for transfusion-associated adverse effects. It is well known that upon transfusion of stored RBCs, there is a population of RBCs (i.e. healthy RBCs) that circulate for more than 24 hours, and another smaller population (i.e. damaged RBCs) that are cleared within 24 hours post transfusion. This population of cells destined to be cleared quickly can be higher than 25% in units stored for a mean of 30 days. The objective of our current project is to remove aged RBCs based on hemoglobin content. Under the influence of ultra-high magnetic fields and gradients, we have demonstrated that it is possible to fractionate RBCs into multiple factions based solely on difference in the intrinsic magnetization of the deoxygenated form of hemoglobin inside the RBCs (i.e. labeless separation). We hypothesize for our currently funded National Institute of Heart Lung and Blood project that healthy RBCs with higher Hb content correlate with longer half lives in transfused animal models than unhealthy RBCs which have lost some of their hemoglobin. In addition, material balances are being performed to track the hemoglobin molecules that are lost during the extended periods of storage. This work will reveal the mechanism behind the lost hemoglobin during RBC storage, deepen the knowledge about aged RBCs and RBC-associated exosomes, and facilitate bulk separation of RBCs without labeling the cells. Therefore, it could be clinically beneficial if the damaged RBCs in any unit of RBCs could be separated leaving a population of only healthy RBCs behind for transfusion. When a recipient is transfused with a dose of RBCs that overwhelms their circulatory system’s ability to compensate for the increased intravascular volume, heart failure can ensue. This condition is known as Transfusion Associated Circulatory Overload (TACO). It is the second leading cause of death related to transfusion reported to the FDA

Are Employment Protection Laws for Disabled People Effective in a Developing Country Evidence from Cambodia

This paper investigates the impact of a law protecting and promoting the employment rights of disabled people in a developing country setting. Using data from the Cambodian Socioeconomic Survey and a difference-in-difference design, we find that employment of the disabled fell by around 9 percentage points in the four years following the introduction of the disability law. The reduction in employment is greater for women than men and is concentrated amongst employees, with the self-employment rate unaffected by the policy change. Several mechanisms via which the introduction of the law reduced employment of the disabled are explored. We find that the most plausible mechanism is that employers reduce their demand for disabled labor in order to avoid the cost of workplace accommodations for disabled workers. We also find that families respond to the reduced employment of their disabled members by providing unpaid work and roles within the family home, and by providing income transfers to non-resident disabled family members

Are Employment Protection Laws for Disabled People Effective in a Developing Country Evidence from Cambodia

This paper investigates the impact of a law protecting and promoting the employment rights of disabled people in a developing country setting. Using data from the Cambodian Socioeconomic Survey and a difference-in-difference design, we find that employment of the disabled fell by around 9 percentage points in the four years following the introduction of the disability law. The reduction in employment is greater for women than men and is concentrated amongst employees, with the self-employment rate unaffected by the policy change. Several mechanisms via which the introduction of the law reduced employment of the disabled are explored. We find that the most plausible mechanism is that employers reduce their demand for disabled labor in order to avoid the cost of workplace accommodations for disabled workers. We also find that families respond to the reduced employment of their disabled members by providing unpaid work and roles within the family home, and by providing income transfers to non-resident disabled family members

A trait-based approach for predicting species responses to environmental change from sparse data : how well might terrestrial mammals track climate change?

Acknowledgements LS was supported by two STSMs by the COST Action ES1101 ”Harmonising Global Biodiversity Modelling“ (Harmbio), supported by COST (European Cooperation in Science and Technology). JMB and SMW were funded by CEH projects NEC05264 and NEC05100. JMJT and SCFP are grateful for the support of the Natural Environment Research Council UK (NE/J008001/1). LS, JAH and JMJT conceived the original idea. LS, JAH, JMB, TC & JMJT designed the study; LS collected the data; LS and TC performed the statistical analyses; LS conducted the integrodifference modelling assisted by JMB and SMW. LS conducted the individual-based modelling assisted by SCFP. LS led the writing supported by JMJT, JMB, SCFP, SMW, TC, JAH and GB.Peer reviewedPublisher PD

Gene-Environment Interaction in the Onset of Eczema in Infancy: Filaggrin Loss-of-Function Mutations Enhanced by Neonatal Cat Exposure

Background Loss-of-function variants in the gene encoding filaggrin (FLG) are major determinants of eczema. We hypothesized that weakening of the physical barrier in FLG-deficient individuals may potentiate the effect of environmental exposures. Therefore, we investigated whether there is an interaction between FLG loss-of-function mutations with environmental exposures (pets and dust mites) in relation to the development of eczema. Methods and Findings We used data obtained in early life in a high-risk birth cohort in Denmark and replicated the findings in an unselected birth cohort in the United Kingdom. Primary outcome was age of onset of eczema; environmental exposures included pet ownership and mite and pet allergen levels. In Copenhagen(n = 379), FLG mutation increased the risk of eczema during the first year of life (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.27–4.00, p = 0.005), with a further increase in risk related to cat exposure at birth amongst children with FLG mutation (HR 11.11, 95% CI 3.79–32.60, p < 0.0001); dog exposure was moderately protective (HR 0.49, 95% CI 0.24–1.01, p = 0.05), but not related to FLG genotype. In Manchester (n = 503) an independent and significant association of the development of eczema by age 12 mo with FLG genotype was confirmed (HR 1.95, 95% CI 1.13–3.36, p = 0.02). In addition, the risk increased because of the interaction of cat ownership at birth and FLG genotype (HR 3.82, 95% CI 1.35–10.81, p = 0.01), with no significant effect of the interaction with dog ownership (HR 0.59, 95% CI 0.16–2.20, p = 0.43). Mite-allergen had no effects in either cohort. The observed effects were independent of sensitisation. Conclusions We have demonstrated a significant interaction between FLG loss-of-function main mutations (501x and 2282del4) and cat ownership at birth on the development of early-life eczema in two independent birth cohorts. Our data suggest that cat but not dog ownership substantially increases the risk of eczema within the first year of life in children with FLG loss-of-function variants, but not amongst those without. FLG-deficient individuals may need to avoid cats but not dogs in early life

Wave-tide interaction modulates nearshore wave height

The combined hazard of large waves occurring at an extreme high water could increase the risk of coastal flooding. Wave-tide interaction processes are known to modulate the wave climate in regions of strong tidal dynamics, yet this process is typically omitted in flood risk assessments. Here, we investigate the role of tidal dynamics in the nearshore wave climate (i.e. water depths > 10 m), with the hypothesis that larger waves occur during high water, when the risk of flooding is greater, because tidal dynamics alter the wave climate propagating into the coast. A dynamically coupled wave-tide model “COAWST” was applied to the Irish Sea for a 2-month period (January–February 2014). High water wave heights were simulated to be 20% larger in some regions, compared with an uncoupled approach, with clear implications for coastal hazards. Three model spatial resolutions were applied (1/60°, 1/120°, 1/240°), and, although all models displayed similar validation statistics, differences in the simulated tidal modulation of wave height were found (up to a 10% difference in high water wave height); therefore, sub-kilometre-scale model resolution is necessary to capture tidal flow variability and wave-tide interactions around the coast. Additionally, the effects of predicted mean sea-level rise were investigated (0.44–2.00 m to reflect likely and extreme sea-level rise by the end of the twenty-first century), showing a 5% increase in high water wave height in some areas. Therefore, some regions may experience a future increase in the combined hazard of large waves occurring at an extreme high water

Evaluation of a prototype tool for communicating body perception disturbances in complex regional pain syndrome

Patients with Complex Regional Pain Syndrome (CRPS) experience distressing changes in body perception. However representing body perception is a challenge. A digital media tool for communicating body perception disturbances was developed. A proof of concept study evaluating the acceptability of the application for patients to communicate their body perception is reported in this methods paper. Thirteen CRPS participants admitted to a 2-week inpatient rehabilitation program used the application in a consultation with a research nurse. Audio recordings were made of the process and a structured questionnaire was administered to capture experiences of using the tool. Participants produced powerful images of disturbances in their body perception. All reported the tool acceptable for communicating their body perception. Participants described the positive impact of now seeing an image they had previously only imagined and could now convey to others. The application has provided a novel way for communicating perceptions that are otherwise difficult to convey