Charter Rights & Health Care Funding: A Typology of Canadian Health Rights Litigation

Canadian health consumers have increasingly relied on the Charter of Rights and Freedoms to demand certain therapies and reasonably timely access to care. Organizing these cases into a 5-part typology, we examine how a rights-based discourse affects allocation of health care resources. First, successful Charter challenges can, in theory, lead to courts granting and enforcing positive rights to therapies or to timely care. Second, courts may grant a right to certain health services; however, subsequently government fails to deliver on this right. Third, successful litigation may create negative rights, i.e. rights to access care or private health insurance without government interference. Fourth, consumers can fail in their legal pursuit of a right but galvanize public support in the process, ultimately effecting the desired policy changes. Lastly, a failed lawsuit can stifle an entire advocacy campaign for the sought-after therapies. The typology illustrates the need to examine both legal and policy outcomes of health right litigation. This broader analysis reveals that the pursuit of health rights seems to have caused largely a regressive rather than progressive impact on Canadian Medicare

Long-term carbon and nitrogen dynamics at SPRUCE revealed through stable isotopes in peat profiles

Peatlands encode information about past vegetation dynamics, climate, and microbial processes. Here, we used δ15N and δ13C patterns from 16 peat profiles to deduce how the biogeochemistry of the Marcell S1 forested bog in northern Minnesota responded to environmental and vegetation change over the past  ∼ 10000 years. In multiple regression analyses, δ15N and δ13C correlated strongly with depth, plot location, C∕N, %N, and each other. Correlations with %N, %C, C∕N, and the other isotope accounted for 80% of variance for δ15N and 38% of variance for δ13C, reflecting N and C losses. In contrast, correlations with depth and topography (hummock or hollow) reflected peatland successional history and climate. Higher δ15N in plots closer to uplands may reflect upland-derived DON inputs and accompanying shifts in N dynamics in the lagg drainage area surrounding the bog. The Suess effect (declining δ13CO2 since the Industrial Revolution) lowered δ13C in recent surficial samples. High δ15N from −35 to −55cm probably indicated the depth of ectomycorrhizal activity after tree colonization of the peatland over the last 400 years, as confirmed by the occasional presence of wood down to −35cm depth. High δ13C at  ∼ 4000 years BP (−65 to −105cm) could reflect a transition at that time to slower rates of peat accumulation, when 13C discrimination during peat decomposition may increase in importance. Low δ13C and high δ15N at −213 and −225cm ( ∼ 8500 years BP) corresponded to a warm period during a sedge-dominated rich fen stage. The above processes appear to be the primary drivers of the observed isotopic patterns, whereas there was no clear evidence for methane dynamics influencing δ13C patterns

Detection of Protein Structure of Frozen Ancient Human Remains Recovered from a Glacier in Canada Using Synchrotron Fourier Transform Infrared Microspectroscopy

We previously used synchrotron infrared microspectroscopy to describe the biochemical signature of skeletal muscle (biceps brachii) from the frozen ancient remains of a young man. In this current paper, we use light microscopy to assess the state of preservation of cellular components in the trapezius muscle from these same ancient remains and then use mid-infrared analysis at the Canadian Light Source synchrotron facility to further analyze the tissue. We compare spectra between the trapezius samples from the ancient remains and a recently deceased cadaver (control). Infrared spectra indicate preservation of secondary structure, with the α-helix being the principal component, along with triple helical portions of the protein backbone. Our mid-infrared analysis indicates an energy reserve in the skeletal muscle in the ancient remain

A Randomized Clinical Trial of an Identity Intervention Programme for Women with Eating Disorders

Objective Findings of a randomized trial of an identity intervention programme (IIP) designed to build new positive self‐schemas that are separate from other conceptions of the self in memory as the means to promote improved health in women diagnosed with eating disorders are reported. Method After baseline data collection, women with anorexia nervosa or bulimia nervosa were randomly assigned to IIP ( n  = 34) or supportive psychotherapy (SPI) ( n  = 35) and followed at 1, 6, and 12 months post‐intervention. Results The IIP and supportive psychotherapy were equally effective in reducing eating disorder symptoms at 1 month post‐intervention, and changes were stable through the 12‐month follow‐up period. The IIP tended to be more effective in fostering development of positive self‐schemas, and the increase was stable over time. Regardless of baseline level, an increase in the number of positive self‐schemas between pre‐intervention and 1‐month post‐intervention predicted a decrease in desire for thinness and an increase in psychological well‐being and functional health over the same period. Discussion A cognitive behavioural intervention that focuses on increasing the number of positive self‐schemas may be central to improving emotional health in women with anorexia nervosa and bulimia nervosa. Copyright © 2012 John Wiley & Sons, Ltd and Eating Disorders Association.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96416/1/erv2195.pd

Modeling Flow, Nutrient, and Sediment Delivery from a Large International Watershed Using a Fieldâ Scale SWAT Model

A large international watershed, the St. Clairâ Detroit River System, containing both extensive urban and agricultural areas, was modeled using the Soil and Water Assessment Tool (SWAT) model. The watershed, located in southeastern Michigan, United States, and southwestern Ontario, Canada, encompasses the St. Clair, Clinton, Detroit (DT), Sydenham (SY), Upper, and Lower Thames subwatersheds. The SWAT input data and model resolution (i.e., hydrologic response units, HRUs), were established to mimic farm boundaries, the first time this has been done for a watershed of this size. The model was calibrated (2007â 2015) and validated (2001â 2006) with a mix of manual and automatic methods at six locations for flow and water quality at various time scales. The model was evaluated using Nashâ Sutcliffe efficiency and percent bias and was used to explore major water quality issues. We showed the importance of allowing key parameters to vary among subwatersheds to improve goodness of fit, and the resulting parameters were consistent with subwatershed characteristics. Agricultural sources in the Thames and SY subwatersheds and point sources from DT subwatershed were major contributors of phosphorus. Spatial distribution of phosphorus yields at HRU and subbasin levels identified locations for potential management targeting for both point and nonpoint sources and revealed that in some subwatersheds nonpoint sources are dominated by urban sources.Research Impact Statement: A wellâ calibrated and validated fieldâ scale flow and water quality model was used to assess nutrient load, concentration, yield, and distribution for a large international watershed.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151890/1/jawr12779.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151890/2/jawr12779_am.pd

In silico and in vitro drug screening identifies new therapeutic approaches for Ewing sarcoma.

The long-term overall survival of Ewing sarcoma (EWS) patients remains poor; less than 30% of patients with metastatic or recurrent disease survive despite aggressive combinations of chemotherapy, radiation and surgery. To identify new therapeutic options, we employed a multi-pronged approach using in silico predictions of drug activity via an integrated bioinformatics approach in parallel with an in vitro screen of FDA-approved drugs. Twenty-seven drugs and forty-six drugs were identified, respectively, to have anti-proliferative effects for EWS, including several classes of drugs in both screening approaches. Among these drugs, 30 were extensively validated as mono-therapeutic agents and 9 in 14 various combinations in vitro. Two drugs, auranofin, a thioredoxin reductase inhibitor, and ganetespib, an HSP90 inhibitor, were predicted to have anti-cancer activities in silico and were confirmed active across a panel of genetically diverse EWS cells. When given in combination, the survival rate in vivo was superior compared to auranofin or ganetespib alone. Importantly, extensive formulations, dose tolerance, and pharmacokinetics studies demonstrated that auranofin requires alternative delivery routes to achieve therapeutically effective levels of the gold compound. These combined screening approaches provide a rapid means to identify new treatment options for patients with a rare and often-fatal disease

Reforming Physics Exams Using Openly Accessible Large Isomorphic Problem Banks created with the assistance of Generative AI: an Explorative Study

This paper explores using large isomorphic problem banks to overcome many challenges of traditional exams in large STEM classes, especially the threat of content sharing websites and generative AI to the security of exam items. We first introduce an efficient procedure for creating large numbers of isomorphic physics problems, assisted by the large language model GPT-3 and several other open-source tools. We then propose that if exam items are randomly drawn from large enough problem banks, then giving students open access to problem banks prior to the exam will not dramatically impact students' performance on the exam or lead to wide-spread rote-memorization of solutions. We tested this hypothesis on two mid-term physics exams, comparing students' performance on problems drawn from open isomorphic problem banks to similar transfer problems that were not accessible to students prior to the exam. We found that on both exams, both open bank and transfer problems had the highest difficulty. The differences in percent correct were between 5% to 10%, which is comparable to the differences between different isomorphic versions of the same problem type. Item response theory analysis found that both types of problem have high discrimination (>1.5) with no significant differences. Student performance on open-bank and transfer problems are highly correlated with each other, and the correlations are stronger than average correlations between problems on the exam. Exploratory factor analysis also found that open-bank and transfer problems load on the same factor, and even formed their own factor on the second exam. Those observations all suggest that giving students open access to large isomorphic problem banks only had a small impact on students' performance on the exam but could have significant potential in reforming traditional classroom exams

12-h clock regulation of genetic information flow by XBP1s

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Pan, Y., Ballance, H., Meng, H., Gonzalez, N., Kim, S., Abdurehman, L., York, B., Chen, X., Schnytzer, Y., Levy, O., Dacso, C. C., McClung, C. A., O'Malley, B. W., Liu, S., & Zhu, B. 12-h clock regulation of genetic information flow by XBP1s. Plos Biology, 18(1), (2020): e3000580, doi:10.1371/journal.pbio.3000580.Our group recently characterized a cell-autonomous mammalian 12-h clock independent from the circadian clock, but its function and mechanism of regulation remain poorly understood. Here, we show that in mouse liver, transcriptional regulation significantly contributes to the establishment of 12-h rhythms of mRNA expression in a manner dependent on Spliced Form of X-box Binding Protein 1 (XBP1s). Mechanistically, the motif stringency of XBP1s promoter binding sites dictates XBP1s’s ability to drive 12-h rhythms of nascent mRNA transcription at dawn and dusk, which are enriched for basal transcription regulation, mRNA processing and export, ribosome biogenesis, translation initiation, and protein processing/sorting in the Endoplasmic Reticulum (ER)-Golgi in a temporal order consistent with the progressive molecular processing sequence described by the central dogma information flow (CEDIF). We further identified GA-binding proteins (GABPs) as putative novel transcriptional regulators driving 12-h rhythms of gene expression with more diverse phases. These 12-h rhythms of gene expression are cell autonomous and evolutionarily conserved in marine animals possessing a circatidal clock. Our results demonstrate an evolutionarily conserved, intricate network of transcriptional control of the mammalian 12-h clock that mediates diverse biological pathways. We speculate that the 12-h clock is coopted to accommodate elevated gene expression and processing in mammals at the two rush hours, with the particular genes processed at each rush hour regulated by the circadian and/or tissue-specific pathways.This study was supported by the American Diabetes Association junior faculty development award 1-18-JDF-025 to B.Z., by funding from National Institute of Health HD07879 and 1P01DK113954 to B.W.O, by funding from National Science Foundation award 1703170 to C.C.D. and B.Z., and by funding from Brockman Foundation to C.C.D and B.W.O. This work was further supported by the UPMC Genome Center with funding from UPMC’s Immunotherapy and Transplant Center. This research was supported in part by the University of Pittsburgh Center for Research Computing through the resources provided. Research reported in this publication was further supported by the National Institute of Diabetes And Digestive And Kidney Diseases of the National Institutes of Health under award number P30DK120531 to Pittsburgh Liver Research Center, in which both S.L. and B.Z. are members. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Age-related synaptic loss of the medial olivocochlear efferent innervation

Age-related functional decline of the nervous system is consistently observed, though cellular and molecular events responsible for this decline remain largely unknown. One of the most prevalent age-related functional declines is age-related hearing loss (presbycusis), a major cause of which is the loss of outer hair cells (OHCs) and spiral ganglion neurons. Previous studies have also identified an age-related functional decline in the medial olivocochlear (MOC) efferent system prior to age-related loss of OHCs. The present study evaluated the hypothesis that this functional decline of the MOC efferent system is due to age-related synaptic loss of the efferent innervation of the OHCs. To this end, we used a recently-identified transgenic mouse line in which the expression of yellow fluorescent protein (YFP), under the control of neuron-specific elements from the thy1 gene, permits the visualization of the synaptic connections between MOC efferent fibers and OHCs. In this model, there was a dramatic synaptic loss between the MOC efferent fibers and the OHCs in older mice. However, age-related loss of efferent synapses was independent of OHC status. These data demonstrate for the first time that age-related loss of efferent synapses may contribute to the functional decline of the MOC efferent system and that this synaptic loss is not necessary for age-related loss of OHCs