The Impact of Resource Availability on Patterns of Discharge to Inpatient Rehabilitation after Stroke in Ontario, Canada

Stroke is a leading cause of death and disability in Canada. As patients, their families, and their friends adjust to life after stroke, organized rehabilitation can play an important role in functional recovery and improving quality of life. Best-practice recommendations suggest that moderately-to-severely impaired patients receive care in an inpatient rehabilitation unit and more mildly impaired patients in out-of-hospital settings (outpatient clinics or in-home). However, data from Ontario (Canada’s most populous province) suggest that post-stroke rehabilitation resources in both settings may be lacking. This has led to concern that some patients may be receiving rehabilitation that is not appropriate for their needs, while others receive none at all. The objective of this thesis was to formally test the hypotheses that access to rehabilitation varies across the province and that this variation is due, in part, to limited availability of rehabilitation resources. An integrated article approach was adopted consisting of two literature reviews and two original research papers. Literature reviews were performed to identify patient-level variables that can be used to 1) predict functional outcomes after inpatient rehabilitation and 2) infer suitability for early supported discharge to community-based rehabilitation. Findings from the first review were used to inform analyses testing variation in the proportion of patients discharged to inpatient rehabilitation across regions of Ontario, while adjusting for patient-level characteristics. Hierarchical logistic regression confirmed variability in referral patterns across the province, but mixed results in the association between resources and the adjusted probability of discharge to rehabilitation. Results from the second review were used to inform an ecological study of regional variation in the proportion of mild stroke patients unnecessarily admitted to inpatient rehabilitation after stroke across Ontario. This study also confirmed suspicions that variability exists across the province and suggested an association with the availability of in-home rehabilitation services. In combination, these articles offer Ontario’s policy makers confirmation of regional inequity in access to post-stroke rehabilitation and evidence to justify further exploration into the possibility that regional investment in rehabilitation may have a positive effect. The methods proposed here may also be useful in informing future health system evaluations

Thermodynamics of ligand binding to histone deacetylase like amidohydrolase from Bordetella/Alcaligenes

Thermodynamic studies on ligand–protein binding have become increasingly important in the process of drug design. In combination with structural data and molecular dynamics simulations, thermodynamic studies provide relevant information about the mode of interaction between compounds and their target proteins and therefore build a sound basis for further drug optimization. Using the example of histone deacetylases (HDACs), particularly the histone deacetylase like amidohydrolase (HDAH) from Bordetella/Alcaligenes, a novel sensitive competitive fluorescence resonance energy transfer-based binding assay was developed and the thermodynamics of interaction of both fluorescent ligands and inhibitors to histone deacetylase like amidohydrolase were investigated. The assay consumes only small amounts of valuable target proteins and is suitable for fast kinetic and mechanistic studies as well as high throughput screening applications. Binding affinity increased with increasing length of aliphatic spacers (n?=?4–7) between the hydroxamate moiety and the dansyl head group of ligand probes. Van't Hoff plots revealed an optimum in enthalpy contribution to the free energy of binding for the dansyl-ligand with hexyl spacer. The selectivity in the series of dansyl-ligands against human class I HDAC1 but not class II HDACs 4 and 6 increased with the ratio of deltaH0/deltaG0. The data clearly emphasize the importance of thermodynamic signatures as useful general guidance for the optimization of ligands or rational drug design

Gathering Perceptions to Strengthen Program Planning: A Citizen Science Project Highlighting Deer Impacts on Vegetation

White-tailed deer can significantly influence the composition and health of forests. University of Minnesota Extension implemented a citizen science project to help monitor the impact of deer populations on forests. Prior to design of the program, we administered a survey to potential volunteers to understand their perceptions of and knowledge about deer and their willingness to participate in our citizen science project. The survey responses helped us make informed decisions when developing our program, including decisions regarding not having a negative deer message, teaching more information about the impact of deer on vegetation, and providing both in-person and web-based resources for volunteers

A donor-chromophore-catalyst assembly for solar CO2 reduction

We describe here the preparation and characterization of a photocathode assembly for CO2 reduction to CO in 0.1 M LiClO4 acetonitrile. The assembly was formed on 1.0 μm thick mesoporous films of NiO using a layer-by-layer procedure based on Zr(IV)–phosphonate bridging units. The structure of the Zr(IV) bridged assembly, abbreviated as NiO|-DA-RuCP22+-Re(I), where DA is the dianiline-based electron donor (N,N,N′,N′-((CH2)3PO3H2)4-4,4′-dianiline), RuCP2+ is the light absorber [Ru((4,4′-(PO3H2CH2)2-2,2′-bipyridine)(2,2′-bipyridine))2]2+, and Re(I) is the CO2 reduction catalyst, ReI((4,4′-PO3H2CH2)2-2,2′-bipyridine)(CO)3Cl. Visible light excitation of the assembly in CO2 saturated solution resulted in CO2 reduction to CO. A steady-state photocurrent density of 65 μA cm−2 was achieved under one sun illumination and an IPCE value of 1.9% was obtained with 450 nm illumination. The importance of the DA aniline donor in the assembly as an initial site for reduction of the RuCP2+ excited state was demonstrated by an 8 times higher photocurrent generated with DA present in the surface film compared to a control without DA. Nanosecond transient absorption measurements showed that the expected reduced one-electron intermediate, RuCP+, was formed on a sub-nanosecond time scale with back electron transfer to the electrode on the microsecond timescale which competes with forward electron transfer to the Re(I) catalyst at t1/2 = 2.6 μs (kET = 2.7 × 105 s−1)

Identifying Structural Variation in Haploid Microbial Genomes from Short-Read Resequencing Data Using Breseq

Mutations that alter chromosomal structure play critical roles in evolution and disease, including in the origin of new lifestyles and pathogenic traits in microbes. Large-scale rearrangements in genomes are often mediated by recombination events involving new or existing copies of mobile genetic elements, recently duplicated genes, or other repetitive sequences. Most current software programs for predicting structural variation from short-read DNA resequencing data are intended primarily for use on human genomes. They typically disregard information in reads mapping to repeat sequences, and significant post-processing and manual examination of their output is often required to rule out false-positive predictions and precisely describe mutational events. Results: We have implemented an algorithm for identifying structural variation from DNA resequencing data as part of the breseq computational pipeline for predicting mutations in haploid microbial genomes. Our method evaluates the support for new sequence junctions present in a clonal sample from split-read alignments to a reference genome, including matches to repeat sequences. Then, it uses a statistical model of read coverage evenness to accept or reject these predictions. Finally, breseq combines predictions of new junctions and deleted chromosomal regions to output biologically relevant descriptions of mutations and their effects on genes. We demonstrate the performance of breseq on simulated Escherichia coli genomes with deletions generating unique breakpoint sequences, new insertions of mobile genetic elements, and deletions mediated by mobile elements. Then, we reanalyze data from an E. coli K-12 mutation accumulation evolution experiment in which structural variation was not previously identified. Transposon insertions and large-scale chromosomal changes detected by breseq account for similar to 25% of spontaneous mutations in this strain. In all cases, we find that breseq is able to reliably predict structural variation with modest read-depth coverage of the reference genome (>40-fold). Conclusions: Using breseq to predict structural variation should be useful for studies of microbial epidemiology, experimental evolution, synthetic biology, and genetics when a reference genome for a closely related strain is available. In these cases, breseq can discover mutations that may be responsible for important or unintended changes in genomes that might otherwise go undetected.U.S. National Institutes of Health R00-GM087550U.S. National Science Foundation (NSF) DEB-0515729NSF BEACON Center for the Study of Evolution in Action DBI-0939454Cancer Prevention & Research Institute of Texas (CPRIT) RP130124University of Texas at Austin startup fundsUniversity of Texas at AustinCPRIT Cancer Research TraineeshipMolecular Bioscience

Expression of ISG15, UBE1L and MX2 in white blood cells of early pregnant and bred-nonpregnant dairy cows

Abstract only availableIdentifying pregnant and nonpregnant cows shortly after insemination can improve reproductive efficiency in dairy cows if resynchronization is practiced on nonpregnant cows. Bovine Interferon Stimulated Gene Product 15 (ISG15), Bovine Ubiquitin-Activating E1-Like (UBE1L) Enzyme and MX2 are produced in response to conceptus-dervied interferon-τ. The objective was to determine the level of these mRNA in pregnant and bred-nonpregnant Holstein cows (n=14). We hypothesized that the amount of ISG15, UBE1L and MX2 mRNA would increase between d 14 to 20 in pregnant cows but not increase in bred-nonpregnant cows. Cows were synchronized to estrus and inseminated (d 0). Blood samples were collected on d 14, 16, 18 and 20 following insemination. Pregnancy status was determined at approximately 30 and 60 d after insemination. RNA was isolated, reverse transcribed into cDNA and amplified using quantitative RTPCR. Six cows were nonpregnant (open) and eight cows were pregnant on d 30. On d 60, four of the pregnant cows remained pregnant (pregnant-pregnant) and four were found open (aborted; pregnant-open). mRNA data were expressed as fold increase above control and relative to cyclophilin. A status by day interaction was detected for ISG15 (P<.001) and MX2 (P<.02). The interaction was not significant for UBE1L. Mean ISG15 and mean MX2 remained low for open cows, but increased markedly on d 18 and 20 in pregnant-pregnant cows. Pregnant-open cows either had low levels of ISG15 and MX2 or underwent an increase in ISG15 and MX2 on d 18 and 20. We conclude that ISG15, UBE1L and MX2 are differentially regulated in dairy cows during pregnancy recognition. ISG15 and MX2 mRNA expression could be used as an indicator of early pregnancy. Cows that abort their pregnancy after d 28 (pregnant-open) have abnormal ISG15 and MX2 mRNA expression between d 14 to 20.F.B. Miller Undergraduate Research Program in Animal Science

Investigation of the middle corona with SWAP and a data-driven non-potential coronal magnetic field model

The large field-of-view of the Sun Watcher using Active Pixel System detector and Image Processing (SWAP) instrument onboard the PRoject for Onboard Autonomy 2 (PROBA2) spacecraft provides a unique opportunity to study extended coronal structures observed in the EUV in conjunction with global coronal magnetic field simulations. A global non-potential magnetic field model is used to simulate the evolution of the global corona from 1 September 2014 to 31 March 2015, driven by newly emerging bipolar active regions determined from Helioseismic and Magnetic Imager (HMI) magnetograms. We compare the large-scale structure of the simulated magnetic field with structures seen off-limb in SWAP EUV observations. In particular, we investigate how successful the model is in reproducing regions of closed and open structures, the scale of structures, and compare the evolution of a coronal fan observed over several rotations. The model is found to accurately reproduce observed large-scale, off-limb structures. When discrepancies do arise they mainly occur off the east solar limb due to active regions emerging on the far side of the Sun, which cannot be incorporated into the model until they are observed on the Earth-facing side. When such “late” active region emergences are incorporated into the model, we find that the simulated corona self-corrects within a few days, so that simulated structures off the west limb more closely match what is observed. Where the model is less successful, we consider how this may be addressed, through model developments or additional observational products

Current state of pediatric neuro-oncology imaging, challenges and future directions

Imaging plays a central role in neuro-oncology including primary diagnosis, treatment planning, and surveillance of tumors. The emergence of quantitative imaging and radiomics provided an uprecedented opportunity to compile mineable databases that can be utilized in a variety of applications. In this review, we aim to summarize the current state of conventional and advanced imaging techniques, standardization efforts, fast protocols, contrast and sedation in pediatric neuro-oncologic imaging, radiomics-radiogenomics, multi-omics and molecular imaging approaches. We will also address the existing challenges and discuss future directions