Doctor of Philosophy

dissertationFunctional vitamin B12 (cobalamin) deficiency is a subtle, progressive clinical disorder affecting 6-23% of elderly adults. Its symptoms, including fatigue, mood disturbances, and decreased strength, are vague and erroneously attributed to aging. Detection of cobalamin deficiency in elderly adults is confounded by clinical heterogeneity and lack of standardization in metabolic tests. Whereas some patients are asymptomatic with slightly altered metabolite profiles, others develop severe clinical outcomes. Better understanding of biologic factors contributing to cobalamin deficiency heterogeneity in older adults is needed. This is a candidate gene association study evaluating the relationship between genetic variation in the cobalamin-transport molecules (transcobalamin II and its receptor) with cobalamin-related outcome parameters in 795 research participants of the Women's Health and Aging 1 and 2 Studies. Research participant DNA was whole genome amplified and genotyped using the iPLEX Sequenom mass spectroscopy platform. Relationships between genotypes and clinical parameters were assessed using two-way analysis of variance and two-way analysis of covariance, on the fixed factors, race and Single Nucleotide Polymorphism genotype. Results of the dissertation research generated several genetic associations that are useful for further hypothesis testing and clinical validation research. In the transcobalamin II gene, two missense variants were associated with homocysteine and methylmalonic acid levels (rs9621049, rs35838082), two intronic variants were associated with serum cobalamin and homocysteine levels (rs4820888, rs4820887), and one missense variant was associated with mean corpuscular volume (rs11801198). A cluster of SNPs in the promoter region of the transcobalamin II gene was associated with the physical performance parameters, hand grip strength, and walking speed. In the transcobalamin II-receptor gene, a missense coding SNP (rs2336573) was associated with mean serum cobalamin concentrations. Scientific advances responsible for the technology used in this dissertation are being incorporated into healthcare. The tailoring of treatment to an individual's genetic make-up is termed Personalized Medicine. To assist nursing professionals in understanding and preparing for use of these technologies, four elements of Personalized Medicine are reviewed, including 1) discovery of novel biology that guides clinical translation mechanisms, 2) genetic risk assessment, 3) molecular diagnostic technology, and 4) pharmacogenetics and pharmacogenomics. Opportunities for nursing profession engagement are addressed

Early Gait Biomechanics Linked to Daily Steps Following Anterior Cruciate Ligament Reconstruction.

CONTEXT: Gait biomechanics and daily steps are important aspects of knee joint loading that change following anterior cruciate ligament reconstruction (ACLR). Understanding their relationship during the first 6 months post-ACLR could help develop comprehensive rehabilitation interventions that promote optimal joint loading following injury, thereby improving long-term knee joint health. OBJECTIVE: Our primary objective was to compare biomechanical gait waveforms throughout stance at early timepoints post-ACLR in individuals with different daily step behaviors at 6 months post-ACLR. The secondary aim was to examine how these gait waveforms compare to those of uninjured controls. DESIGN: Case-Control Study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Individuals with primary ACLR assigned to a low (LSG) (n=13) or high step group (HSG) (n=19) based on their average daily steps at 6 months post- ACLR, and uninjured matched controls (n=32). MAIN OUTCOME MEASURE(S): Gait biomechanics were collected at 2, 4, and 6 months post-ACLR in ACLR individuals and at a single session for controls. Knee adduction moment (KAM), knee extension moment (KEM), and knee flexion angle (KFA) waveforms were calculated during gait stance and then compared via functional waveform analyses. Mean differences and corresponding 95% confident intervals between groups were reported. RESULTS: Primary results demonstrated lesser KFA (1-45%, 79-92% of stance) and greater KEM (65-93% of stance) at 2 months and greater KAM (14-20%, 68-92% of stance) at 4 months post-ACLR for the HSG compared to the LSG. KEM, KAM, and KFA waveforms differed across various proportions of stance at all timepoints between step groups and controls. CONCLUSION: Differences in gait biomechanics are present at 2 and 4 months post-ACLR between step groups, with the LSG demonstrating an overall more flexed knee and more profound stepwise underloading throughout stance than the HSG. The results indicate a relation between early gait biomechanics and later daily steps behaviors following ACLR

Concepts émergents dans le référentiel de compétences CanMEDS pour les médecins

Background: The CanMEDS physician competency framework will be updated in 2025. The revision occurs during a time of disruption and transformation to society, healthcare, and medical education caused by the COVID-19 pandemic and growing acknowledgement of the impacts of colonialism, systemic discrimination, climate change, and emerging technologies on healthcare and training. To inform this revision, we sought to identify emerging concepts in the literature related to physician competencies. Methods: Emerging concepts were defined as ideas discussed in the literature related to the roles and competencies of physicians that are absent or underrepresented in the 2015 CanMEDS framework. We conducted a literature scan, title and abstract review, and thematic analysis to identify emerging concepts. Metadata for all articles published in five medical education journals between October 1, 2018 and October 1, 2021 were extracted. Fifteen authors performed a title and abstract review to identify and label underrepresented concepts. Two authors thematically analyzed the results to identify emerging concepts. A member check was conducted. Results: 1017 of 4973 (20.5%) of the included articles discussed an emerging concept. The thematic analysis identified ten themes: Equity, Diversity, Inclusion, and Social Justice; Anti-racism; Physician Humanism; Data-Informed Medicine; Complex Adaptive Systems; Clinical Learning Environment; Virtual Care; Clinical Reasoning; Adaptive Expertise; and Planetary Health. All themes were endorsed by the authorship team as emerging concepts. Conclusion: This literature scan identified ten emerging concepts to inform the 2025 revision of the CanMEDS physician competency framework. Open publication of this work will promote greater transparency in the revision process and support an ongoing dialogue on physician competence. Writing groups have been recruited to elaborate on each of the emerging concepts and how they could be further incorporated into CanMEDS 2025.Contexte : Le référentiel de compétences CanMEDS pour les médecins sera mis à jour en 2025. Cette révision intervient à un moment où la société, les soins de santé et l’enseignement médical sont bouleversés et en pleine mutation à cause de la pandémie de la COVID-19; on est aussi à l’heure où l’on reconnaît de plus en plus les effets du colonialisme, de la discrimination systémique, des changements climatiques et des nouvelles technologies sur les soins de santé et la formation des médecins. Pour éclairer cette révision, nous avons tenté d’extraire de la littérature scientifique les concepts émergents se rapportant aux compétences des médecins. Méthodes : Les concepts émergents ont été définis comme des idées ayant trait aux rôles et aux compétences des médecins qui sont débattues dans la littérature, mais qui sont absentes ou sous-représentées dans le cadre CanMEDS 2015. Nous avons réalisé une recherche documentaire, un examen des titres et des résumés, et une analyse thématique pour repérer les concepts émergents. Les métadonnées de tous les articles publiés dans cinq revues d’éducation médicale entre le 1er octobre 2018 et le 1er octobre 2021 ont été extraites. Quinze auteurs ont effectué un examen des titres et des résumés pour relever et étiqueter les concepts sous-représentés. Deux auteurs ont procédé à une analyse thématique des résultats pour dégager les concepts émergents. Une vérification a été faite par les membres de l’équipe. Résultats : Parmi les 4973 articles dépouillés, 1017 (20,5 %) abordaient un concept émergent. Les dix thèmes suivants sont ressortis de l’analyse thématique : l’équité, la diversité, l’inclusion et la justice sociale; l’antiracisme; humanisme des médecin; la médecine fondée sur les données; les systèmes adaptatifs complexes; l’environnement de l’apprentissage clinique; les soins virtuels; le raisonnement clinique; l’expertise adaptative; et la santé planétaire. L’ensemble de ces thèmes ont été approuvés comme concepts émergents par l’équipe de rédaction. Conclusion : Cet examen de la littérature a permis de relever dix concepts émergents qui peuvent servir à éclairer la révision du référentiel de compétences CanMEDS pour les médecins qui aura lieu en 2025. La publication en libre accès de ce travail favorisera la transparence du processus de révision et le dialogue continu sur les compétences des médecins. Des groupes de rédaction ont été recrutés pour développer chacun des concepts émergents et pour examiner la façon dont ils pourraient être intégrés dans la version du référentiel CanMEDS de 2025

Glacial meltwater identification in the Amundsen Sea

Pine Island Ice Shelf, in the Amundsen Sea, is losing mass because of warm ocean waters melting the ice from below. Tracing meltwater pathways from ice shelves is important for identifying the regions most affected by the increased input of this water type. Here, optimum multiparameter analysis is used to deduce glacial meltwater fractions from water mass characteristics (temperature, salinity, and dissolved oxygen concentrations), collected during a ship-based campaign in the eastern Amundsen Sea in February–March 2014. Using a one-dimensional ocean model, processes such as variability in the characteristics of the source water masses on shelf and biological productivity/respiration are shown to affect the calculated apparent meltwater fractions. These processes can result in a false meltwater signature, creating misleading apparent glacial meltwater pathways. An alternative glacial meltwater calculation is suggested, using a pseudo–Circumpolar Deep Water endpoint and using an artificial increase in uncertainty of the dissolved oxygen measurements. The pseudo–Circumpolar Deep Water characteristics are affected by the under ice shelf bathymetry. The glacial meltwater fractions reveal a pathway for 2014 meltwater leading to the west of Pine Island Ice Shelf, along the coastline

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153772/1/acr24131.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153772/2/acr24131_am.pd

Dissociation between exercise-induced reduction in liver fat and changes in hepatic and peripheral glucose homoeostasis in obese patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is associated with multi-organ (hepatic, skeletal muscle, adipose tissue) insulin resistance (IR). Exercise is an effective treatment for lowering liver fat but its effect on IR in NAFLD is unknown. We aimed to determine whether supervised exercise in NAFLD would reduce liver fat and improve hepatic and peripheral (skeletal muscle and adipose tissue) insulin sensitivity. Sixty nine NAFLD patients were randomized to 16 weeks exercise supervision (n=38) or counselling (n=31) without dietary modification. All participants underwent MRI/spectroscopy to assess changes in body fat and in liver and skeletal muscle triglyceride, before and following exercise/counselling. To quantify changes in hepatic and peripheral insulin sensitivity, a pre-determined subset (n=12 per group) underwent a two-stage hyperinsulinaemic euglycaemic clamp pre- and post-intervention. Results are shown as mean [95% confidence interval (CI)]. Fifty participants (30 exercise, 20 counselling), 51 years (IQR 40, 56), body mass index (BMI) 31 kg/m(2) (IQR 29, 35) with baseline liver fat/water % of 18.8% (IQR 10.7, 34.6) completed the study (12/12 exercise and 7/12 counselling completed the clamp studies). Supervised exercise mediated a greater reduction in liver fat/water percentage than counselling [Δ mean change 4.7% (0.01, 9.4); P<0.05], which correlated with the change in cardiorespiratory fitness (r=-0.34, P=0.0173). With exercise, peripheral insulin sensitivity significantly increased (following high-dose insulin) despite no significant change in hepatic glucose production (HGP; following low-dose insulin); no changes were observed in the control group. Although supervised exercise effectively reduced liver fat, improving peripheral IR in NAFLD, the reduction in liver fat was insufficient to improve hepatic IR

Vigorous lateral export of the meltwater outflow from beneath an Antarctic ice shelf

The instability and accelerated melting of the Antarctic Ice Sheet are among the foremost elements of contemporary global climate change1, 2. The increased freshwater output from Antarctica is important in determining sea level rise1, the fate of Antarctic sea ice and its effect on the Earth’s albedo4, 5, ongoing changes in global deep-ocean ventilation6, and the evolution of Southern Ocean ecosystems and carbon cycling7, 8. A key uncertainty in assessing and predicting the impacts of Antarctic Ice Sheet melting concerns the vertical distribution of the exported meltwater. This is usually represented by climate-scale models3–5, 9 as a near-surface freshwater input to the ocean, yet measurements around Antarctica reveal the meltwater to be concentrated at deeper levels10, 11, 12, 13, 14. Here we use observations of the turbulent properties of the meltwater outflows from beneath a rapidly melting Antarctic ice shelf to identify the mechanism responsible for the depth of the meltwater. We show that the initial ascent of the meltwater outflow from the ice shelf cavity triggers a centrifugal overturning instability that grows by extracting kinetic energy from the lateral shear of the background oceanic flow. The instability promotes vigorous lateral export, rapid dilution by turbulent mixing, and finally settling of meltwater at depth. We use an idealized ocean circulation model to show that this mechanism is relevant to a broad spectrum of Antarctic ice shelves. Our findings demonstrate that the mechanism producing meltwater at depth is a dynamically robust feature of Antarctic melting that should be incorporated into climate-scale models

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat