Ground Motions from the Northridge Earthquake

The magnitude, duration and frequency content of ground motions from the Northridge Earthquake are analyzed and compared to predictive relationships typically used in engineering design and to the 1994 Uniform Building Code. The effect of geologic conditions on localized damage patterns is shown to be important for this earthquake, even though many of the sites within the affected region are stiff soil sites classified as UBC sites S1 or S2

Damage Patterns/Response of Deep Stiff Clay in Oakland

The 1985 Mexico City earthquake and the 1989 Loma Prieta earthquake provided well-documented evidence of the effect of local ground conditions on site response and damage patterns. Deep soft clay deposits, in particular, were often cited as the culprit of amplified ground motions. However, during the 1989 Loma Prieta earthquake, ground accelerations in the downtown Oakland area were amplified by a factor of two to four and a significant number of structures were heavily damaged, despite the fact that much of the area is underlain by deposits of deep stiff clay. A preliminary review of damage patterns in the Oakland area and preliminary site response analyses were performed to investigate the influence of deep stiff clay deposits on the observed ground motions

Gut microbiota in HIV-pneumonia patients is related to peripheral CD4 counts, lung microbiota, and in vitro macrophage dysfunction.

Pneumonia is common and frequently fatal in HIV-infected patients, due to rampant, systemic inflammation and failure to control microbial infection. While airway microbiota composition is related to local inflammatory response, gut microbiota has been shown to correlate with the degree of peripheral immune activation (IL6 and IP10 expression) in HIV-infected patients. We thus hypothesized that both airway and gut microbiota are perturbed in HIV-infected pneumonia patients, that the gut microbiota is related to peripheral CD4+ cell counts, and that its associated products differentially program immune cell populations necessary for controlling microbial infection in CD4-high and CD4-low patients. To assess these relationships, paired bronchoalveolar lavage and stool microbiota (bacterial and fungal) from a large cohort of Ugandan, HIV-infected patients with pneumonia were examined, and in vitro tests of the effect of gut microbiome products on macrophage effector phenotypes performed. While lower airway microbiota stratified into three compositionally distinct microbiota as previously described, these were not related to peripheral CD4 cell count. In contrast, variation in gut microbiota composition significantly related to CD4 cell count, lung microbiota composition, and patient mortality. Compared with patients with high CD4+ cell counts, those with low counts possessed more compositionally similar airway and gut microbiota, evidence of microbial translocation, and their associated gut microbiome products reduced macrophage activation and IL-10 expression and increased IL-1β expression in vitro. These findings suggest that the gut microbiome is related to CD4 status and plays a key role in modulating macrophage function, critical to microbial control in HIV-infected patients with pneumonia

Engaging the Dynamics of Pastoral Imagination for Field Education

The importance and the process of engaging pastoral imagination in field education

Regulation of Brown and White Adipocyte Transcriptome by the Transcriptional Coactivator NT-PGC-1α

The β3-adrenergic receptor (AR) signaling pathway is a major component of adaptive thermogenesis in brown and white adipose tissue during cold acclimation. The β3-AR signaling highly induces the expression of transcriptional coactivator PGC-1α and its splice variant N-terminal (NT)-PGC-1α, which in turn activate the transcription program of adaptive thermogenesis by co-activating a number of transcription factors. We previously reported that NT-PGC-1α is able to increase mitochondrial number and activity in cultured brown adipocytes by promoting the expression of mitochondrial and thermogenic genes. In the present study, we performed genome-wide profiling of NT-PGC-1α-responsive genes in brown adipocytes to identify genes potentially regulated by NT-PGC-1α. Canonical pathway analysis revealed that a number of genes upregulated by NT-PGC-1α are highly enriched in mitochondrial pathways including fatty acid transport and β-oxidation, TCA cycle and electron transport system, thus reinforcing the crucial role of NT-PGC-1α in the enhancement of mitochondrial function. Moreover, canonical pathway analysis of NT-PGC-1α-responsive genes identified several metabolic pathways including glycolysis and fatty acid synthesis. In order to validate the identified genes in vivo, we utilized the FL-PGC-1α-/- mouse that is deficient in full-length PGC-1α (FL-PGC-1α) but expresses a slightly shorter and functionally equivalent form of NT-PGC-1α (NT-PGC-1α254). The β3-AR-induced increase of NT-PGC-1α254 in FL-PGC-1α-/-brown and white adipose tissue was closely associated with elevated expression of genes involved in thermogenesis, mitochondrial oxidative metabolism, glycolysis and fatty acid synthesis. Increased adipose tissue thermogenesis by β3-AR activation resulted in attenuation of adipose tissue expansion in FL-PGC-1α-/- adipose tissue under the high-fat diet condition. Together, the data strengthen our previous findings that NT-PGC-1α regulates mitochondrial genes involved in thermogenesis and oxidative metabolism in brown and white adipocytes and further suggest that NT-PGC-1α regulates a broad spectrum of genes to meet cellular needs for adaptive thermogenesis

Prevalence of Posterior Shoulder Subluxation in Children With Neonatal Brachial Plexus Palsy After Early Full Passive Range of Motion Exercises

BackgroundChildren with neonatal brachial plexus palsy (NBPP) are often prescribed shoulder range of motion (ROM) exercises; however, the extent and timing of exercise implementation remains controversial in the context of shoulder joint integrity. The association of ROM exercises to delayed posterior shoulder subluxation (PSS) is unknown.ObjectiveTo determine prevalence of PSS in children with NBPP who began full passive ROM exercises before 6 months of age, and characteristics associated with development or absence of PSS in children.DesignCrossâ sectional study.SettingTertiary care NBPP referral center.ParticipantsFortyâ six children with NBPP, aged 24â 57 months, who began full ROM exercises before 6 months of age.MethodsOne radiologist conducted bilateral shoulder ultrasound (US) on each child to evaluate for PSS. One occupational therapist evaluated each child clinically for PSS using defined parameters without knowledge of US results.Main Outcome MeasuresBy US, 20% of children had PSS; 46% had PSS by clinical examination. Shoulder active ROM limitations and history of shoulder surgery were associated with presence of PSS. Extent of NBPP was not associated with PSS.ResultsNine of 46 children (20%) met US criteria for PSS; α angle was 58° ± 21° (mean ± standard deviation [SD]). Twentyâ one children (46%) met clinical criteria. Mean age at examination was 35 ± 10 months. Shoulder active ROM (P â ¤ .004) was associated with PSS, whereas passive ROM was not (P â ¥ .08). History of secondary shoulder surgery and primary nerve graft repair were associated with PSS (P = .04). Extent of NBPP by Narakas classification was not associated with PSS (P = .48).ConclusionsEarly use of fullâ arc passive ROM home exercise program is not associated with increased prevalence of PSS in children with NBPP compared to prevalence of PSS in published literature. We suggest careful clinical examination, based on defined criteria, provides a reasonable screening examination for evaluating PSS that can be confirmed by noninvasive US.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147125/1/pmr21235.pd

Pharmacogenomic Variants May Influence the Urinary Excretion of Novel Kidney Injury Biomarkers in Patients Receiving Cisplatin

Nephrotoxicity is a dose limiting side effect associated with the use of cisplatin in the treatment of solid tumors. The degree of nephrotoxicity is dictated by the selective accumulation of cisplatin in renal tubule cells due to: (1) uptake by organic cation transporter 2 (OCT2) and copper transporter 1 (CTR1); (2) metabolism by glutathione S-transferases (GSTs) and γ-glutamyltransferase 1 (GGT1); and (3) efflux by multidrug resistance-associated protein 2 (MRP2) and multidrug and toxin extrusion protein 1 (MATE1). The purpose of this study was to determine the significance of single nucleotide polymorphisms that regulate the expression and function of transporters and metabolism genes implicated in development of acute kidney injury (AKI) in cisplatin treated patients. Changes in the kidney function were assessed using novel urinary protein biomarkers and traditional markers. Genotyping was conducted by the QuantStudio 12K Flex Real-Time PCR System using a custom open array chip with metabolism, transport, and transcription factor polymorphisms of interest to cisplatin disposition and toxicity. Traditional and novel biomarker assays for kidney toxicity were assessed for differences according to genotype by ANOVA. Allele and genotype frequencies were determined based on Caucasian population frequencies. The polymorphisms rs596881 (SLC22A2/OCT2), and rs12686377 and rs7851395 (SLC31A1/CTR1) were associated with renoprotection and maintenance of estimated glomerular filtration rate (eGFR). Polymorphisms in SLC22A2/OCT2, SLC31A1/CTRI, SLC47A1/MATE1, ABCC2/MRP2, and GSTP1 were significantly associated with increases in the urinary excretion of novel AKI biomarkers: KIM-1, TFF3, MCP1, NGAL, clusterin, cystatin C, and calbindin. Knowledge concerning which genotypes in drug transporters are associated with cisplatin-induced nephrotoxicity may help to identify at-risk patients and initiate strategies, such as using lower or fractionated cisplatin doses or avoiding cisplatin altogether, in order to prevent AKI

Identifying Early Changes in Myocardial Microstructure in Hypertensive Heart Disease

The transition from healthy myocardium to hypertensive heart disease is characterized by a series of poorly understood changes in myocardial tissue microstructure. Incremental alterations in the orientation and integrity of myocardial fibers can be assessed using advanced ultrasonic image analysis. We used a modified algorithm to investigate left ventricular myocardial microstructure based on analysis of the reflection intensity at the myocardial-pericardial interface on B-mode echocardiographic images. We evaluated the extent to which the novel algorithm can differentiate between normal myocardium and hypertensive heart disease in humans as well as in a mouse model of afterload resistance. The algorithm significantly differentiated between individuals with uncomplicated essential hypertension (N = 30) and healthy controls (N = 28), even after adjusting for age and sex (P = 0.025). There was a trend in higher relative wall thickness in hypertensive individuals compared to controls (P = 0.08), but no difference between groups in left ventricular mass (P = 0.98) or total wall thickness (P = 0.37). In mice, algorithm measurements (P = 0.026) compared with left ventricular mass (P = 0.053) more clearly differentiated between animal groups that underwent fixed aortic banding, temporary aortic banding, or sham procedure, on echocardiography at 7 weeks after surgery. Based on sonographic signal intensity analysis, a novel imaging algorithm provides an accessible, non-invasive measure that appears to differentiate normal left ventricular microstructure from myocardium exposed to chronic afterload stress. The algorithm may represent a particularly sensitive measure of the myocardial changes that occur early in the course of disease progression

Budget impact analysis of robotic exoskeleton use for locomotor training following spinal cord injury in four SCI Model Systems

Background We know little about the budget impact of integrating robotic exoskeleton over-ground training into therapy services for locomotor training. The purpose of this study was to estimate the budget impact of adding robotic exoskeleton over-ground training to existing locomotor training strategies in the rehabilitation of people with spinal cord injury. Methods A Budget Impact Analysis (BIA) was conducted using data provided by four Spinal Cord Injury (SCI) Model Systems rehabilitation hospitals. Hospitals provided estimates of therapy utilization and costs about people with spinal cord injury who participated in locomotor training in the calendar year 2017. Interventions were standard of care walking training including body-weight supported treadmill training, overground training, stationary robotic systems (i.e., treadmill-based robotic gait orthoses), and overground robotic exoskeleton training. The main outcome measures included device costs, training costs for personnel to use the device, human capital costs of locomotor training, device demand, and the number of training sessions per person with SCI. Results Robotic exoskeletons for over-ground training decreased hospital costs associated with delivering locomotor training in the base case analysis. This analysis assumed no difference in intervention effectiveness across locomotor training strategies. Providing robotic exoskeleton overground training for 10% of locomotor training sessions over the course of the year (range 226–397 sessions) results in decreased annual locomotor training costs (i.e., net savings) between $1114 to$4784 per annum. The base case shows small savings that are sensitive to parameters of the BIA model which were tested in one-way sensitivity analyses, scenarios analyses, and probability sensitivity analyses. The base case scenario was more sensitive to clinical utilization parameters (e.g., how often devices sit idle and the substitution of high cost training) than device-specific parameters (e.g., robotic exoskeleton device cost or device life). Probabilistic sensitivity analysis simultaneously considered human capital cost, device cost, and locomotor device substitution. With probabilistic sensitivity analysis, the introduction of a robotic exoskeleton only remained cost saving for one facility. Conclusions Providing robotic exoskeleton for over-ground training was associated with lower costs for the locomotor training of people with SCI in the base case analyses. The analysis was sensitive to parameter assumptions