Prediction of Nephropathy in Type 2 Diabetes: An Analysis of the ACCORD Trial Applying Machine Learning Techniques

Applying data mining and machine learning (ML) techniques to clinical data might identify predictive biomarkers for diabetic nephropathy (DN), a common complication of type 2 diabetes mellitus (T2DM). A retrospective analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was intended to identify such factors using ML. The longitudinal data were stratified by time after patient enrollment to differentiate early and late predictors. Our results showed that Random Forest and Simple Logistic Regression methods exhibited the best performance among the evaluated algorithms. Baseline values for glomerular filtration rate (GFR), urinary creatinine, urinary albumin, potassium, cholesterol, low-density lipoprotein, and urinary albumin to creatinine ratio were identified as DN predictors. Early predictors were the baseline values of GFR, systolic blood pressure, as well as fasting plasma glucose (FPG) and potassium at month 4. Changes per year in GFR, FPG, and triglycerides were recognized as predictors of late development. In conclusion, ML-based methods successfully identified predictive factors for DN among patients with T2DM

1-Alpha, 25-dihydroxyvitamin D3 alters the pharmacokinetics of mycophenolic acid in renal transplant recipients by regulating two extrahepatic UDP-glucuronosyltransferases 1A8 and 1A10

Mycophenolic acid (MPA) is an important immunosuppressant broadly used in renal transplantation. However, the large inter-patient variability in mycophenolic acid (MPA) pharmacokinetics (PK) limits its use. We hypothesize that extrahepatic metabolism of MPA may have significant impact on MPA PK variability. Two intestinal UDP-glucuronosyltransferases 1A8 and 1A10 plays critical role in MPA metabolism. Both in silico and previous genome-wide analyses suggested that vitamin D (VD) may regulate intestinal UGT1A expression. We validated the VD response elements (VDREs) across the UGT1A locus with chromatin immunoprecipitation (ChIP) and luciferase reporter assays. The impact of 1-alpha,25-dihydroxyvitamin D3 (D3) on UGT1A8 and UGT1A10 transcription and on MPA glucuronidation was tested in human intestinal cell lines LS180, Caco-2 and HCT-116. The correlation between transcription levels of VD receptor (VDR) and the two UGT genes were examined in human normal colorectal tissue samples (n = 73). PK alterations of MPA following the parent drug, mycophenolate mofetil (MMF), and D3 treatment was assessed among renal transplant recipients (n = 10). Our ChIP assay validate three VDREs which were further demonstrated as transcriptional enhancers with the luciferase assays. D3 treatment significantly increased transcription of both UGT genes as well as MPA glucuronidation in cells. The VDR mRNA level was highly correlated with that of both UGT1A8 and UGT1A10 in human colorectal tissue. D3 treatment in patients led to about 40% reduction in both AUC0-12 and Cmax while over 70% elevation of total clearance of MPA. Our study suggested a significant regulatory role of VD on MPA metabolism and PK via modulating extrahepatic UGT activity

Perception versus polysomnographic assessment of sleep in CFS and non-fatigued control subjects: results from a population-based study

<p>Abstract</p> <p>Background</p> <p>Complaints of unrefreshing sleep are a prominent component of chronic fatigue syndrome (CFS); yet, polysomnographic studies have not consistently documented sleep abnormalities in CFS patients. We conducted this study to determine whether alterations in objective sleep characteristics are associated with subjective measures of poor sleep quality in persons with CFS.</p> <p>Methods</p> <p>We examined the relationship between perceived sleep quality and polysomnographic measures of nighttime and daytime sleep in 35 people with CFS and 40 non-fatigued control subjects, identified from the general population of Wichita, Kansas and defined by empiric criteria. Perceived sleep quality and daytime sleepiness were assessed using clinical sleep questionnaires. Objective sleep characteristics were assessed by nocturnal polysomnography and daytime multiple sleep latency testing.</p> <p>Results</p> <p>Participants with CFS reported unrefreshing sleep and problems sleeping during the preceding month significantly more often than did non-fatigued controls. Participants with CFS also rated their quality of sleep during the overnight sleep study as significantly worse than did control subjects. Control subjects reported significantly longer sleep onset latency than latency to fall asleep as measured by PSG and MSLT. There were no significant differences in sleep pathology or architecture between subjects with CFS and control subjects.</p> <p>Conclusion</p> <p>People with CFS reported sleep problems significantly more often than control subjects. Yet, when measured these parameters and sleep architecture did not differ between the two subject groups. A unique finding requiring further study is that control, but not CFS subjects, significantly over reported sleep latency suggesting CFS subjects may have an increased appreciation of sleep behaviour that may contribute to their perception of sleep problems.</p

Factors affecting individual foraging specialization and temporal diet stability across the range of a large “generalist” apex predator

Individual niche specialization (INS) is increasingly recognized as an important component of ecological and evolutionary dynamics. However, most studies that have investigated INS have focused on the effects of niche width and inter- and intraspecific competition on INS in small-bodied species for short time periods, with less attention paid to INS in large-bodied reptilian predators and the effects of available prey types on INS. We investigated the prevalence, causes, and consequences of INS in foraging behaviors across different populations of American alligators (Alligator mississippiensis), the dominant aquatic apex predator across the southeast US, using stomach contents and stable isotopes. Gut contents revealed that, over the short term, although alligator populations occupied wide ranges of the INS spectrum, general patterns were apparent. Alligator populations inhabiting lakes exhibited lower INS than coastal populations, likely driven by variation in habitat type and available prey types. Stable isotopes revealed that over longer time spans alligators exhibited remarkably consistent use of variable mixtures of carbon pools (e.g., marine and freshwater food webs). We conclude that INS in large-bodied reptilian predator populations is likely affected by variation in available prey types and habitat heterogeneity, and that INS should be incorporated into management strategies to efficiently meet intended goals. Also, ecological models, which typically do not consider behavioral variability, should include INS to increase model realism and applicability

Focal Plane Alignment Utilizing Optical CMM

In many applications, an optical detector has to be located relative to mechanical reference points. One solution is to specify stringent requirements on (1) mounting the optical detector relative to the chip carrier, (2) soldering the chip carrier onto the printed circuit board (PCB), and (3) installing the PCB to the mechanical structure of the subsystem. Figure 1 shows a sketch of an optical detector mounted relative to mechanical reference with high positional accuracy. The optical detector is typically a fragile wafer that cannot be physically touched by any measurement tool. An optical coordinate measuring machine (CMM) can be used to position optical detectors relative to mechanical reference points. This approach will eliminate all requirements on positional tolerances. The only requirement is that the PCB is manufactured with oversized holes. An exaggerated sketch of this situation is shown in Figure 2. The sketch shows very loose tolerances on mounting the optical detector in the chip carrier, loose tolerance on soldering the chip carrier to the PCB, and finally large tolerance on where the mounting screws are located. The PCB is held with large screws and oversized holes. The PCB is mounted loosely so it can move freely around. The optical CMM measures the mechanical reference points. Based on these measurements, the required positions of the optical detector corners can be calculated. The optical CMM is commanded to go to the position where one detector corner is supposed to be. This is indicated with the cross-hairs in Figure 2(a). This figure is representative of the image of the optical CMM monitor. Using a suitable tapping tool, the PCB is manually tapped around until the corner of the optical detector is at the crosshairs of the optical CMM. The CMM is commanded to another corner, and the process is repeated a number of times until all corners of the optical detector are within a distance of 10 to 30 microns of the required position. The situation is sketched in Figure 2(b) (the figure also shows the tapping tool and where to tap). At this point the fasteners for the PCB are torqued slightly so the PCB can still move. The PCB location is adjusted again with the tapping tool. This process is repeated 3 to 4 times until the final torque is achieved. The oversized mounting holes are then filled with a liquid bonding agent to secure the board in position (not shown in the sketch). A 10- to 30-micron mounting accuracy has been achieved utilizing this method.

Emergence of Superlattice Dirac Points in Graphene on Hexagonal Boron Nitride

The Schr\"odinger equation dictates that the propagation of nearly free electrons through a weak periodic potential results in the opening of band gaps near points of the reciprocal lattice known as Brillouin zone boundaries. However, in the case of massless Dirac fermions, it has been predicted that the chirality of the charge carriers prevents the opening of a band gap and instead new Dirac points appear in the electronic structure of the material. Graphene on hexagonal boron nitride (hBN) exhibits a rotation dependent Moir\'e pattern. In this letter, we show experimentally and theoretically that this Moir\'e pattern acts as a weak periodic potential and thereby leads to the emergence of a new set of Dirac points at an energy determined by its wavelength. The new massless Dirac fermions generated at these superlattice Dirac points are characterized by a significantly reduced Fermi velocity. The local density of states near these Dirac cones exhibits hexagonal modulations indicating an anisotropic Fermi velocity.Comment: 16 pages, 6 figure