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In clinical and translational research, data science is often and fortuitously integrated with data collection. This contrasts to the typical position of data scientists in other settings, where they are isolated from data collectors. Because of this, effective use of data science techniques to resolve translational questions requires innovation in the organization and management of these data.
We propose an operational framework that respects this important difference in how research teams are organized. To maximize the accuracy and speed of the clinical and translational data science enterprise under this framework, we define a set of eight best practices for data management.
In our own work at the University of Rochester, we have strived to utilize these practices in a customized version of the open source LabKey platform for integrated data management and collaboration. We have applied this platform to cohorts that longitudinally track multidomain data from over 3000 subjects.
We argue that this has made analytical datasets more readily available and lowered the bar to interdisciplinary collaboration, enabling a team-based data science that is unique to the clinical and translational setting.
Most basic science research has focused on overt stroke caused by blockage of major blood vessels. Less attention has been paid to small vessel disease giving rise to covert stroke that often leads to vascular cognitive impairment (VCI). One reason for this may be the relative lack of relevant animal models. This talk will describe a model of VCI induced in middle-aged Sprague-Dawley rats exposed to a diet high in saturated fats, salt and refined sugar (HFSS). In Experiment 1, rats fed HFSS and subjected to a small mediodorsal (MD) thalamic stroke with or without concomitant cerebral hypoperfusion experienced significant executive dysfunction. In Experiment 2, dietary influences on functional, physiological and anatomical parameters were assessed. We found significant hypertension, blockage of brain microvessels (2-photon microscopy) and white matter atrophy in HFSS diet animals. As in Experiment 1, profound, specific set-shifting executive dysfunction was noted following both small MD infarcts (0.332 mm3) and the HFSS diet. In summary, these data describe a middle-aged animal model of VCI that includes clinically-relevant metabolic disturbances and small vessel disease and as such may be helpful in developing new cognitive therapies.
Obesity is undoubtedly caused by a chronic positive energy balance. However, the early metabolic and hormonal responses to overeating are poorly described. This study determined glycaemic control and selected gut hormone responses to nutrient intake before and after 7 d of high-fat overfeeding. Nine healthy individuals (five males, four females) performed a mixed meal tolerance test (MTT) before and after consuming a high-fat (65 %), high-energy (+50 %) diet for 7 d. Measurements of plasma glucose, NEFA, acylated ghrelin, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP) and serum insulin were taken before (fasting) and at 30-min intervals throughout the 180-min MTT (postprandial). Body mass increased by 0·79 (sem 0·14) kg after high-fat overfeeding (P<0·0001), and BMI increased by 0·27 (sem 0·05) kg/m2 (P=0·002). High-fat overfeeding also resulted in an 11·6 % increase in postprandial glucose AUC (P=0·007) and a 25·9 % increase in postprandial insulin AUC (P=0·005). Acylated ghrelin, GLP-1 and GIP responses to the MTT were all unaffected by the high-fat, high-energy diet. These findings demonstrate that even brief periods of overeating are sufficient to disrupt glycaemic control. However, as the postprandial orexigenic (ghrelin) and anorexigenic/insulintropic (GLP-1 and GIP) hormone responses were unaffected by the diet intervention, it appears that these hormones are resistant to short-term changes in energy balance, and that they do not play a role in the rapid reduction in glycaemic control.
Traditional solar power applications largely avoid using the infrared spectrum. Nevertheless, this region makes up about 45% of the solar power spectrum and therefore represents an untapped resource. Temperature control of buildings represents a significant cost for both businesses and private consumers. We are interested in developing thermochromic materials for building coatings to help moderate solar infrared absorption and thereby offset temperature control costs for buildings. Our initial effort in this study has been to characterize materials which might represent starting points for our research. We previously designed and 3D-printed an optical test platform to perform reflectance measurements with an ultraviolet-visible-near infrared spectrometer over a spectral range from 200-1000nm. The test platform temperature can be adjusted in real time using Peltier modules. In this study, a sample of microencapsulated 7-anilino-3-diethylamino-6-methyl fluoran was studied by diffuse reflectance spectroscopy from 15-40 degrees Celsius. Scanning electron microscopy was used to characterize the dye particles. Temperature and spectral data were monitored while the sample temperature was adjusted. The visible diffuse reflectance from the sample increased from around 15% below the transition to more than 40% above the transition. A modification of this fluoran which extends the switching behavior into the infrared may be viable for passive thermo-optical switching in building coatings.
Because individuals develop dementia as a manifestation of neurodegenerative or neurovascular disorder, there is a need to develop reliable approaches to their identification. We are undertaking an observational study (Ontario Neurodegenerative Disease Research Initiative [ONDRI]) that includes genomics, neuroimaging, and assessments of cognition as well as language, speech, gait, retinal imaging, and eye tracking. Disorders studied include Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, and vascular cognitive impairment. Data from ONDRI will be collected into the Brain-CODE database to facilitate correlative analysis. ONDRI will provide a repertoire of endophenotyped individuals that will be a unique, publicly available resource.
The essay clarifies the relationship between Locke's political and his religious thought. To the extent that Locke's political thought is an outgrowth of a particular strand of Christianity, its claims to universality would be significantly diminished. Several plausible interpretations of his political thought rely on his religiosity. Others maintain that this religiosity was a façade. Close attention to Locke's analysis of the Hebrew text of Gen. 1:28 unambiguously points to a critique of the Bible on semantic grounds. Locke subtly argues that the wording of the Bible makes the interpretation of scripture by scripture alone impossible. The fact that Locke goes out of his way to critique the Bible refutes interpretations of Locke's thought that rely on his religiosity and reestablishes the universalist claims of his political thought.
Foraminiferal analyses of 404 contiguous samples, supported by diatom, lithologic, geochronologic and seismic data, reveal both rapid and gradual Holocene paleoenvironmental changes in an 8.21-m vibracore taken from southern Pamlico Sound, North Carolina. Data record initial flooding of a latest Pleistocene river drainage and the formation of an estuary 9000 yr ago. Estuarine conditions were punctuated by two intervals of marine influence from approximately 4100 to 3700 and 1150 to 500 cal yr BP. Foraminiferal assemblages in the muddy sand facies that accumulated during these intervals contain many well-preserved benthic foraminiferal species, which occur today in open marine settings as deep as the mid shelf, and significant numbers of well-preserved planktonic foraminifera, some typical of Gulf Stream waters. We postulate that these marine-influenced units resulted from temporary destruction of the southern Outer Banks barrier islands by hurricanes. The second increase in marine influence is coeval with increased rate of sea-level rise and a peak in Atlantic tropical cyclone activity during the Medieval Climate Anomaly. This high-resolution analysis demonstrates the range of environmental variability and the rapidity of coastal change that can result from the interplay of changing climate, sea level and geomorphology in an estuarine setting.
This article addresses Andrew Rehfeld's attempt to ensure a place for political theory within political science, which he does partly by showing how political theory fits into a defensible definition of political science and partly by excluding much political theory from the discipline in order to safeguard the rest. His account of what the discipline should comprehend is overly narrow, however, and does not serve the interests of the sorts of political theory he strongly believes are worth doing. I argue instead that political science must be defined by its subject matter alone, and that political theory's contribution to this subject matter must be defended.
Foraminifera and diatoms preserved in salt-marsh sediments have been used to produce high-resolution records of Holocene relative sea-level (RSL) change. To determine which of these microfossil groups is most appropriate for this purpose we investigated their relative utility from salt marshes in North Carolina, USA. Regional-scale transfer functions were developed using foraminifera, diatoms and a combination of both (multi-proxy) from three salt marshes (Oregon Inlet, Currituck Barrier Island and Pea Island). We evaluated each approach on the basis of transfer-function performance. Foraminifera, diatoms and multi-proxy-based transfer functions all demonstrated a strong relationship between observed and predicted elevations (r2jack > 0.74 and RMSEP < 0.05 m), suggesting that they have equal utility. Application of the transfer functions to a fossil core from Salvo to reconstruct former sea levels enabled us to consider relative utility in light of ‘paleo-performance’. Fossil foraminifera had strong modern analogues, whilst diatoms had poor modern analogues making them unreliable. This result reflects the high diversity and site-specific distribution of modern diatoms. Consequently, we used foraminifera to reconstruct RSL change for the period since ∼ AD 1800 using a 210Pb- and 14C-based chronology, and we were able to reconcile this with tide-gauge records.