Identifying Bedrest Using Waist-worn Triaxial Accelerometers in Preschool Children

Purpose To adapt and validate a previously developed decision tree for youth to identify bedrest for use in preschool children. Methods Parents of healthy preschool (3-6-year-old) children (n = 610; 294 males) were asked to help them to wear an accelerometer for 7 to 10 days and 24 hours/day on their waist. Children with ≥3 nights of valid recordings were randomly allocated to the development (n = 200) and validation (n = 200) groups. Wear periods from accelerometer recordings were identified minute-by-minute as bedrest or wake using visual identification by two independent raters. To automate visual identification, chosen decision tree (DT) parameters (block length, threshold, bedrest-start trigger, and bedrest-end trigger) were optimized in the development group using a Nelder-Mead simplex optimization method, which maximized the accuracy of DT-identified bedrest in 1-min epochs against synchronized visually identified bedrest (n = 4,730,734). DT\u27s performance with optimized parameters was compared with the visual identification, commonly used Sadeh’s sleep detection algorithm, DT for youth (10-18-years-old), and parental survey of sleep duration in the validation group. Results On average, children wore an accelerometer for 8.3 days and 20.8 hours/day. Comparing the DT-identified bedrest with visual identification in the validation group yielded sensitivity = 0.941, specificity = 0.974, and accuracy = 0.956. The optimal block length was 36 min, the threshold 230 counts/min, the bedrest-start trigger 305 counts/min, and the bedrest-end trigger 1,129 counts/min. In the validation group, DT identified bedrest with greater accuracy than Sadeh’s algorithm (0.956 and 0.902) and DT for youth (0.956 and 0.861) (both P\u3c0.001). Both DT (564±77 min/day) and Sadeh’s algorithm (604±80 min/day) identified significantly less bedrest/sleep than parental survey (650±81 min/day) (both P\u3c0.001). Conclusions The DT-based algorithm initially developed for youth was adapted for preschool children to identify time spent in bedrest with high accuracy. The DT is available as a package for the R open-source software environment (“PhysActBedRest”)

Contrasting histopathology and crystal deposits in kidneys of idiopathic stone formers who produce hydroxy apatite, brushite, or calcium oxalate stones

Our previous work has shown that stone formers who form calcium phosphate (CaP) stones that contain any brushite (BRSF) have a distinctive renal histopathology and surgical anatomy when compared with idiopathic calcium oxalate stone formers (ICSF). Here we report on another group of idiopathic CaP stone formers, those forming stone containing primarily hydroxyapatite, in order to clarify in what ways their pathology differs from BRSF and ICSF. Eleven hydroxyapatite stone formers (HASF) (2 males, 9 females) were studied using intra-operative digital photography and biopsy of papillary and cortical regions to measure tissue changes associated with stone formation. Our main finding is that HASF and BRSF differ significantly from each other and that both differ greatly from ICSF. Both BRSF and ICSF patients have significant levels of Randall's plaque compared with HASF. Intra-tubular deposit number is greater in HASF than BRSF and nonexistent in ICSF while deposit size is smaller in HASF than BRSF. Cortical pathology is distinctly greater in BRSF than HASF. Four attached stones were observed in HASF, three in 25 BRSF and 5-10 per ICSF patient. HASF and BRSF differ clinically in that both have higher average urine pH, supersaturation of CaP, and calcium excretion than ICSF. Our work suggests that HASF and BRSF are two distinct and separate diseases and both differ greatly from ICSF

Biopsy proven medullary sponge kidney: clinical findings, histopathology, and role of osteogenesis in stone and plaque formation

Medullary sponge kidney (MSK) is associated with recurrent stone formation, but the clinical phenotype is unclear because patients with other disorders may be incorrectly labeled MSK. We studied 12 patients with histologic findings pathognomonic of MSK. All patients had an endoscopically recognizable pattern of papillary malformation, which may be segmental or diffuse. Affected papillae are enlarged and billowy, due to markedly enlarged inner medullary collecting ducts (IMCD), which contain small, mobile ductal stones. Patients had frequent dilation of Bellini ducts, with occasional mineral plugs. Stones may form over white (Randall's) plaque, but most renal pelvic stones are not attached, and have a similar morphology as ductal stones, which are a mixture of calcium oxalate and apatite. Patients had no abnormalities of urinary acidification or acid excretion; the most frequent metabolic abnormality was idiopathic hypercalciuria. Although both Runx2 and Osterix are expressed in papillae of MSK patients, no mineral deposition was seen at the sites of gene expression, arguing against a role of these genes in this process. Similar studies in idiopathic calcium stone formers showed no expression of these genes at sites of Randall's plaque. The most likely mechanism for stone formation in MSK appears to be crystallization due to urinary stasis in dilated IMCD with subsequent passage of ductal stones into the renal pelvis where they may serve as nuclei for stone formation

A characterization of the molecular phenotype and inflammatory response of schizophrenia patient-derived microglia-like cells

Different lines of evidence support a causal role for microglia in the pathogenesis of schizophrenia. However, how schizophrenia patient-derived microglia are affected at the phenotypic and functional level is still largely unknown. We used a recently described model to induce patient-derived microglia-like cells and used this to analyze changes in the molecular phenotype and function of myeloid cells in schizophrenia. We isolated monocytes from twenty recent-onset schizophrenia patients and twenty non-psychiatric controls. We cultured the cells towards an induced microglia-like phenotype (iMG), analyzed the phenotype of the cells by RNA sequencing and mass cytometry, and their response to LPS. Mass cytometry showed a high heterogeneity of iMG in cells derived from patients as well as controls. The prevalence of two iMG clusters was significantly higher in schizophrenia patients (adjusted p-value <0.001). These subsets are characterized by expression of ApoE, Ccr2, CD18, CD44, and CD95, as well as IRF8, P2Y(12), Cx3cr1 and HLA-DR. In addition, we found that patient derived iMG show an enhanced response to LPS, with increased secretion of TNF-alpha. Further studies are needed to replicate these findings, to determine whether similar subclusters are present in schizophrenia patients in vivo, and to address how these subclusters are related to the increased response to LPS, as well as other microglial functions

Novel patterns of physical activity in a large sample of preschool-aged children

Abstract Background Moderate-to-vigorous physical activity (MVPA), shown to be associated with health benefits, is not well-characterized in preschool-aged children. MVPA is commonly described as a threshold amount to achieve. We examined a novel way to characterize MVPA patterns in preschool-aged children by gender and age. Methods Preschool-aged children from Nashville, TN and Minneapolis, MN wore triaxial accelerometers. Four distinct MVPA patterns were identified: isolated spurt (IS), isolated sustained activity (ISA), clustered spurt (CS), and clustered sustained activity (CSA). Multivariable linear regression models were used to test associations of gender and age with each pattern. Results One thousand one hundred thirty-one children (3.9 years old, 51% girls, 30% overweight, 11% obese, and 76% Hispanic) wore accelerometers for 12.9 (SD = 1.4) hours/day for 6.7 (SD = 0.7) days. Children spent 53% of wear time in sedentary behavior and 13% in MVPA. On average, boys and girls achieved > 90 min/day of MVPA (98.2 min, SD = 32.3). Most MVPA (80%) was obtained in spurt-like (IS and CS) MVPA; however, girls spent a higher proportion of MVPA in IS and CS, and lower proportion of time in CSA (all p < 0.001). Controlling for gender, an increase of 1-year in age corresponded to a 1.5% increase in CSA (p < 0.05). Conclusions How MVPA was obtained varied depending on the gender and age of the child. On average, boys spent more time in sustained MVPA than girls and MVPA was more sustained in older children. Utilizing these patterns could inform PA practice and policy guidelines. Trial registration NCT01316653 , date of registration: March 3, 2011; NCT01606891, date of registration: May 23, 2012

Nondestructive analysis of urinary calculi using micro computed tomography

BACKGROUND: Micro computed tomography (micro CT) has been shown to provide exceptionally high quality imaging of the fine structural detail within urinary calculi. We tested the idea that micro CT might also be used to identify the mineral composition of urinary stones non-destructively. METHODS: Micro CT x-ray attenuation values were measured for mineral that was positively identified by infrared microspectroscopy (FT-IR). To do this, human urinary stones were sectioned with a diamond wire saw. The cut surface was explored by FT-IR and regions of pure mineral were evaluated by micro CT to correlate x-ray attenuation values with mineral content. Additionally, intact stones were imaged with micro CT to visualize internal morphology and map the distribution of specific mineral components in 3-D. RESULTS: Micro CT images taken just beneath the cut surface of urinary stones showed excellent resolution of structural detail that could be correlated with structure visible in the optical image mode of FT-IR. Regions of pure mineral were not difficult to find by FT-IR for most stones and such regions could be localized on micro CT images of the cut surface. This was not true, however, for two brushite stones tested; in these, brushite was closely intermixed with calcium oxalate. Micro CT x-ray attenuation values were collected for six minerals that could be found in regions that appeared to be pure, including uric acid (3515 – 4995 micro CT attenuation units, AU), struvite (7242 – 7969 AU), cystine (8619 – 9921 AU), calcium oxalate dihydrate (13815 – 15797 AU), calcium oxalate monohydrate (16297 – 18449 AU), and hydroxyapatite (21144 – 23121 AU). These AU values did not overlap. Analysis of intact stones showed excellent resolution of structural detail and could discriminate multiple mineral types within heterogeneous stones. CONCLUSIONS: Micro CT gives excellent structural detail of urinary stones, and these results demonstrate the feasibility of identifying and localizing most of the common mineral types found in urinary calculi using laboratory CT

Identifying Contributions to the Stellar Halo from Accreted, Kicked-Out, and In Situ Populations

[Abridged] We present a medium-resolution spectroscopic survey of late-type giant stars at mid-Galactic latitudes of (30$^{\circ}<|b|<60^{\circ}$), designed to probe the properties of this population to distances of $\sim$9 kpc. Because M giants are generally metal-rich and we have limited contamination from thin disk stars by the latitude selection, most of the stars in the survey are expected to be members of the thick disk ($\sim$-0.6) with some contribution from the metal-rich component of the nearby halo. Here we report first results for 1799 stars. The distribution of radial velocity (RV) as a function of l for these stars shows (1) the expected thick disk population and (2) local metal-rich halo stars moving at high speeds relative to the disk, that in some cases form distinct sequences in RV-$l$ space. High-resolution echelle spectra taken for 34 of these "RV outliers" reveal the following patterns across the [Ti/Fe]-[Fe/H] plane: seventeen of the stars have abundances reminiscent of the populations present in dwarf satellites of the Milky Way; eight have abundances coincident with those of the Galactic disk and more metal-rich halo; and nine of the stars fall on the locus defined by the majority of stars in the halo. The chemical abundance trends of the RV outliers suggest that this sample consists predominantly of stars accreted from infalling dwarf galaxies. A smaller fraction of stars in the RV outlier sample may have been formed in the inner Galaxy and subsequently kicked to higher eccentricity orbits, but the sample is not large enough to distinguish conclusively between this interpretation and the alternative that these stars represent the tail of the velocity distribution of the thick disk. Our data do not rule out the possibility that a minority of the sample could have formed from gas {\it in situ} on their current orbits.Comment: 43 pages, 9 figures, 4 tables, published in the Astrophysical Journa