Ciliopathy proteins regulate paracrine signaling by modulating proteasomal degradation of mediators

PubMed Central

Liu, Yangfan P.; Tsai, I-Chun; Morleo, Manuela; Oh, Edwin C.; Leitch, Carmen C.; Massa, Filomena; Lee, Byung-Hoon; Parker, David S.; Finley, Daniel; Zaghloul, Norann A.; Franco, Brunella; Katsanis, Nicholas

2014-01-01

Cilia are critical mediators of paracrine signaling; however, it is unknown whether proteins that contribute to ciliopathies converge on multiple paracrine pathways through a common mechanism. Here, we show that loss of cilopathy-associated proteins Bardet-Biedl syndrome 4 (BBS4) or oral-facial-digital syndrome 1 (OFD1) results in the accumulation of signaling mediators normally targeted for proteasomal degradation. In WT cells, several BBS proteins and OFD1 interacted with proteasomal subunits, and loss of either BBS4 or OFD1 led to depletion of multiple subunits from the centrosomal proteasome. Furthermore, overexpression of proteasomal regulatory components or treatment with proteasomal activators sulforaphane (SFN) and mevalonolactone (MVA) ameliorated signaling defects in cells lacking BBS1, BBS4, and OFD1, in morphant zebrafish embryos, and in induced neurons from Ofd1-deficient mice. Finally, we tested the hypothesis that other proteasome-dependent pathways not known to be associated with ciliopathies are defective in the absence of ciliopathy proteins. We found that loss of BBS1, BBS4, or OFD1 led to decreased NF-κB activity and concomitant IκBβ accumulation and that these defects were ameliorated with SFN treatment. Taken together, our data indicate that basal body proteasomal regulation governs paracrine signaling pathways and suggest that augmenting proteasomal function might benefit ciliopathy patients. PMID:24691443

Mutation analysis in 129 genes associated with other forms of retinal dystrophy in 157 families with retinitis pigmentosa based on exome sequencing.

PubMed

Xu, Yan; Guan, Liping; Xiao, Xueshan; Zhang, Jianguo; Li, Shiqiang; Jiang, Hui; Jia, Xiaoyun; Yang, Jianhua; Guo, Xiangming; Yin, Ye; Wang, Jun; Zhang, Qingjiong

2015-01-01

Mutations in 60 known genes were previously identified by exome sequencing in 79 of 157 families with retinitis pigmentosa (RP). This study analyzed variants in 129 genes associated with other forms of hereditary retinal dystrophy in the same cohort. Apart from the 73 genes previously analyzed, a further 129 genes responsible for other forms of hereditary retinal dystrophy were selected based on RetNet. Variants in the 129 genes determined by whole exome sequencing were selected and filtered by bioinformatics analysis. Candidate variants were confirmed by Sanger sequencing and validated by analysis of available family members and controls. A total of 90 candidate variants were present in the 129 genes. Sanger sequencing confirmed 83 of the 90 variants. Analysis of family members and controls excluded 76 of these 83 variants. The remaining seven variants were considered to be potential pathogenic mutations; these were c.899A>G, c.1814C>G, and c.2107C>T in BBS2; c.1073C>T and c.1669C>T in INPP5E; and c.3582C>G and c.5704-5C>G in CACNA1F. Six of these seven mutations were novel. The mutations were detected in five unrelated patients without a family history, including three patients with homozygous or compound heterozygous mutations in BBS2 and INPP5E, and two patients with hemizygous mutations in CACNA1F. None of the patients had mutations in the genes associated with autosome dominant retinal dystrophy. Only a small portion of patients with RP, about 3% (5/157), had causative mutations in the 129 genes associated with other forms of hereditary retinal dystrophy.

DisAp-dependent striated fiber elongation is required to organize ciliary arrays

PubMed Central

Galati, Domenico F.; Bonney, Stephanie; Kronenberg, Zev; Clarissa, Christina; Yandell, Mark; Elde, Nels C.; Jerka-Dziadosz, Maria; Giddings, Thomas H.; Frankel, Joseph

2014-01-01

Cilia-organizing basal bodies (BBs) are microtubule scaffolds that are visibly asymmetrical because they have attached auxiliary structures, such as striated fibers. In multiciliated cells, BB orientation aligns to ensure coherent ciliary beating, but the mechanisms that maintain BB orientation are unclear. For the first time in Tetrahymena thermophila, we use comparative whole-genome sequencing to identify the mutation in the BB disorientation mutant disA-1. disA-1 abolishes the localization of the novel protein DisAp to T. thermophila striated fibers (kinetodesmal fibers; KFs), which is consistent with DisAp’s similarity to the striated fiber protein SF-assemblin. We demonstrate that DisAp is required for KFs to elongate and to resist BB disorientation in response to ciliary forces. Newly formed BBs move along KFs as they approach their cortical attachment sites. However, because they contain short KFs that are rotated, BBs in disA-1 cells display aberrant spacing and disorientation. Therefore, DisAp is a novel KF component that is essential for force-dependent KF elongation and BB orientation in multiciliary arrays. PMID:25533842

Effects of single cycle binaural beat duration on auditory evoked potentials.

PubMed

Mihajloski, Todor; Bohorquez, Jorge; Özdamar, Özcan

2014-01-01

Binaural beat (BB) illusions are experienced as continuous central pulsations when two sounds with slightly different frequencies are delivered to each ear. It has been shown that steady-state auditory evoked potentials (AEPs) to BBs can be captured and investigated. The authors recently developed a new method of evoking transient AEPs to binaural beats using frequency modulated stimuli. This methodology was able to create single BBs in predetermined intervals with varying carrier frequencies. This study examines the effects of the BB duration and the frequency modulating component of the stimulus on the binaural beats and their evoked potentials. Normal hearing subjects were tested with a set of four durations (25, 50, 100, and 200 ms) with two stimulation configurations, binaural dichotic (binaural beats) and diotic (frequency modulation). The results obtained from the study showed that out of the given durations, the 100 ms beat, was capable of evoking the largest amplitude responses. The frequency modulation effect showed a decrease in peak amplitudes with increasing beat duration until their complete disappearance at 200 ms. Even though, at 200 ms, the frequency modulation effects were not present, the binaural beats were still perceived and captured as evoked potentials.

A truncating mutation of Alms1 reduces the number of hypothalamic neuronal cilia in obese mice.

PubMed

Heydet, Déborah; Chen, Lesley X; Larter, Claire Z; Inglis, Chrystal; Silverman, Michael A; Farrell, Geoffrey C; Leroux, Michel R

2013-01-01

Primary cilia are ubiquitous cellular antennae whose dysfunction collectively causes various disorders, including vision and hearing impairment, as well as renal, skeletal, and central nervous system anomalies. One ciliopathy, Alström syndrome, is closely related to Bardet-Biedl syndrome (BBS), sharing amongst other phenotypic features morbid obesity. As the cellular and molecular links between weight regulation and cilia are poorly understood, we used the obese mouse strain foz/foz, bearing a truncating mutation in the Alström syndrome protein (Alms1), to help elucidate why it develops hyperphagia, leading to early onset obesity and metabolic anomalies. Our in vivo studies reveal that Alms1 localizes at the base of cilia in hypothalamic neurons, which are implicated in the control of satiety. Alms1 is lost from this location in foz/foz mice, coinciding with a strong postnatal reduction (∼70%) in neurons displaying cilia marked with adenylyl cyclase 3 (AC3), a signaling protein implicated in obesity. Notably, the reduction in AC3-bearing cilia parallels the decrease in cilia containing two appetite-regulating proteins, Mchr1 and Sstr3, as well as another established Arl13b ciliary marker, consistent with progressive loss of cilia during development. Together, our results suggest that Alms1 maintains the function of neuronal cilia implicated in weight regulation by influencing the maintenance and/or stability of the organelle. Given that Mchr1 and Sstr3 localization to remaining cilia is maintained in foz/foz animals but known to be lost from BBS knockout mice, our findings suggest different molecular etiologies for the satiety defects associated with the Alström syndrome and BBS ciliopathies. Copyright © 2012 Wiley Periodicals, Inc.

Calcitonin gene-related peptide enhances substance P-induced behaviors via metabolic inhibition: in vivo evidence for a new mechanism of neuromodulation.

PubMed

Mao, J; Coghill, R C; Kellstein, D E; Frenk, H; Mayer, D J

1992-03-06

The present study examined the effects of intrathecal (i.t.) injection of calcitonin gene-related peptide (CGRP) on caudally directed biting and scratching induced by i.t. substance P (SP), bombesin (BBS), strychnine (STR), and kainic acid (KA). CGRP alone (5.25, 10.5 and 21 nmol) had no effect on these behaviors, but CGRP pretreatment produced a dose-related enhancement of behaviors induced by SP or BBS, but not by KA or STR. 2-Amino-5-phosphonovaleric acid (APV, 25 nmol), a selective N-methyl-D-aspartate (NMDA) receptor antagonist, did not block the CGRP potentiation of SP and BBS induced behaviors. CGRP, however, failed to enhance scratching and biting induced by a SP analogue [pGlu5-Mephe8-MeGly9]SP(5-11) (Dime-C7) that is resistant to enzymatic degradation by SP endopeptidase. These findings demonstrate that CGRP potentiates SP induced behavioral responses via inhibition of neuropeptide degradation and that this mechanism may serve as a physiological mechanism of SP modulation.

The gastrin-releasing peptide analog bombesin preserves exocrine and endocrine pancreas morphology and function during parenteral nutrition

PubMed Central

Pierre, Joseph F.; Neuman, Joshua C.; Brill, Allison L.; Brar, Harpreet K.; Thompson, Mary F.; Cadena, Mark T.; Connors, Kelsey M.; Busch, Rebecca A.; Heneghan, Aaron F.; Cham, Candace M.; Jones, Elaina K.; Kibbe, Carly R.; Davis, Dawn B.; Groblewski, Guy E.; Kudsk, Kenneth A.

2015-01-01

Stimulation of digestive organs by enteric peptides is lost during total parental nutrition (PN). Here we examine the role of the enteric peptide bombesin (BBS) in stimulation of the exocrine and endocrine pancreas during PN. BBS protects against exocrine pancreas atrophy and dysfunction caused by PN. BBS also augments circulating insulin levels, suggesting an endocrine pancreas phenotype. While no significant changes in gross endocrine pancreas morphology were observed, pancreatic islets isolated from BBS-treated PN mice showed a significantly enhanced insulin secretion response to the glucagon-like peptide-1 (GLP-1) agonist exendin-4, correlating with enhanced GLP-1 receptor expression. BBS itself had no effect on islet function, as reflected in low expression of BBS receptors in islet samples. Intestinal BBS receptor expression was enhanced in PN with BBS, and circulating active GLP-1 levels were significantly enhanced in BBS-treated PN mice. We hypothesized that BBS preserved islet function indirectly, through the enteroendocrine cell-pancreas axis. We confirmed the ability of BBS to directly stimulate intestinal enteroid cells to express the GLP-1 precursor preproglucagon. In conclusion, BBS preserves the exocrine and endocrine pancreas functions during PN; however, the endocrine stimulation is likely indirect, through the enteroendocrine cell-pancreas axis. PMID:26185331

Prenatal administration of neuropeptide bombesin promotes lung development in a rat model of nitrofen-induced congenital diaphragmatic hernia.

PubMed

Sakai, Kohei; Kimura, Osamu; Furukawa, Taizo; Fumino, Shigehisa; Higuchi, Koji; Wakao, Junko; Kimura, Koseki; Aoi, Shigeyoshi; Masumoto, Kouji; Tajiri, Tatsuro

2014-12-01

Fetal medical treatment to improve lung hypoplasia in congenital diaphragmatic hernia (CDH) has yet to be established. The neuropeptide bombesin (BBS) might play an important role in lung development. The present study aims to determine whether prenatally administered BBS could be useful to promote fetal lung development in a rat model of nitrofen-induced CDH. Pregnant rats were administered with nitrofen (100mg) on gestation day 9.5 (E9.5). BBS (50mg/kg/day) was then daily infused intraperitoneally from E14, and fetal lungs were harvested on E21. The expression of PCNA was assessed by both immunohistochemical staining and RT-PCR to determine the amount of cell proliferation. Lung maturity was assessed as the expression of TTF-1, a marker of alveolar epithelial cell type II. The lung-body-weight ratio was significantly increased in CDH/BBS(+) compared with CDH/BBS(-) (p<0.05). The number of cells stained positive for PCNA and TTF-1 was significantly decreased in CDH/BBS(+) compared with CDH/BBS(-) (p<0.01). The TTF-1 mRNA expression levels were significantly decreased in CDH/BBS(+) compared with CDH/BBS(-) (p<0.05). Prenatally administered BBS promotes lung development in a rat model of nitrofen-induced CDH. Neuropeptide BBS could help to rescue lung hypoplasia in fetal CDH. Copyright © 2014 Elsevier Inc. All rights reserved.

Bardet-Biedl Syndrome

PubMed Central

Suspitsin, Evgeny N.; Imyanitov, Evgeny N.

2016-01-01

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive genetic disorder. It is characterized by heterogeneous clinical manifestations including primary features of the disease (rod-cone dystrophy, polydactyly, obesity, genital abnormalities, renal defects, and learning difficulties) and secondary BBS characteristics (developmental delay, speech deficit, brachydactyly or syndactyly, dental defects, ataxia or poor coordination, olfactory deficit, diabetes mellitus, congenital heart disease, etc.); most of these symptoms may not be present at birth but appear and progressively worsen during the first and second decades of life. At least 20 BBS genes have already been identified, and all of them are involved in primary cilia functioning. Genetic diagnosis of BBS is complicated due to lack of gene-specific disease symptoms; however, it is gradually becoming more accessible with the invention of multigene sequencing technologies. Clinical management of BBS is largely limited to a symptomatic treatment. Mouse experiments demonstrate that the most debilitating complication of BBS, blindness, can be rescued by topical gene therapy. There is a published case report describing the delay of BBS symptoms by nutritional compensation of the disease-related biochemical deficiencies. Progress in DNA testing technologies is likely to rapidly resolve all limitations in BBS diagnosis; however, much slower improvement is expected with regard to BBS treatment. PMID:27385962

The Endocrine and Metabolic Characteristics of a Large Bardet-Biedl Syndrome Clinic Population.

PubMed

Mujahid, Safa; Hunt, Katharine F; Cheah, Yee S; Forsythe, Elizabeth; Hazlehurst, Jonathan M; Sparks, Kathryn; Mohammed, Shehla; Tomlinson, Jeremy W; Amiel, Stephanie A; Carroll, Paul V; Beales, Phillip L; Huda, Mohammed S B; McGowan, Barbara M

2018-05-01

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder in which previous reports have described obesity and a metabolic syndrome. We describe the endocrine and metabolic characteristics of a large BBS population compared with matched control subjects. We performed a case-control study. This study was performed at a hospital clinic. Study patients had a clinical or genetic diagnosis of BBS. Our study determined the prevalence of a metabolic syndrome in our cohort. A total of 152 subjects were studied. Eighty-four (55.3%) were male. Mean (± standard deviation) age was 33.2 ± 1.0 years. Compared with age-, sex-, and body mass index-matched control subjects, fasting glucose and insulin levels were significantly higher in subjects with BBS (glucose: BBS, 5.2 ± 1.2 mmol/L vs control, 4.9 ± 0.9 mmol/L, P = 0.04; insulin: BBS, 24.2 ± 17.0 pmol/L vs control, 14.2 ± 14.8 pmol/L, P < 0.001). Serum triglycerides were significantly higher in subjects with BBS (2.0 ± 1.2 mmol/L) compared with control subjects (1.3 ± 0.8 mmol/L; P < 0.001), but total cholesterol, high-density lipoprotein, and low-density lipoprotein were similar in both groups. Systolic blood pressure was higher in the BBS group (BBS, 135 ± 18 mm Hg vs control subjects, 129 ± 16 mm Hg; P = 0.02). Alanine transaminase was raised in 34 (26.8%) subjects with BBS, compared with five (8.9%) control subjects (P = 0.01). The rate of metabolic syndrome, determined using International Diabetes Federation criteria, was significantly higher in the BBS group (54.3%) compared with control subjects (26% P < 0.001). Twenty-six (19.5%) of male subjects with BBS were hypogonadal (serum testosterone, 9.9 ± 5.3 mmol/L), but significant pituitary abnormalities were uncommon. Subclinical hypothyroidism was present in 24 of 125 (19.4%) patients with BBS, compared with 3 of 65 (4.6%) control subjects (P = 0.01). Insulin resistance and the metabolic syndrome are increased in adult patients with BBS compared with matched control subjects. Increased subclinical hypothyroidism in the BBS cohort needs further investigation.

A Retrospective Analysis of Post-Stroke Berg Balance Scale Scores: How Should Normal and At-Risk Scores Be Interpreted?

PubMed Central

Inness, Elizabeth; McIlroy, William E.; Mansfield, Avril

2017-01-01

Purpose: The Berg Balance Scale (BBS) is a performance-based measure of standing balance commonly used by clinicians working with individuals post-stroke. Performance on the BBS can be influenced by compensatory strategies, but measures derived from two force plates can isolate compensatory strategies and thus better indicate balance impairment. This study examined BBS scores that reflect “normal” and disordered balance with respect to dual force-plate measures of standing balance in individuals post-stroke. Methods: BBS and force-plate measures were extracted from 75 patient charts. Individuals were classified by BBS score with respect to (1) age-matched normative values and (2) values that suggested increased risk of falls. Multiple analysis of variance was used to examine the effect of group assignment on force-plate measures of standing balance. Results: Individuals with BBS scores within and below normative values did not differ in force-plate measures. Individuals with BBS scores below the falls risk cutoff loaded their affected leg less than individuals with BBS scores above the cutoff. There were no other differences in force-plate measures between these two groups. Conclusions: BBS scores indicating either normal or disordered balance function are not necessarily associated with normal or disordered quiet standing-balance control measured by two force plates. This finding suggests that the BBS may reflect a capacity for compensation rather than any underlying impairments. PMID:28539694

Improving the breeding bird survey

Treesearch

Jonathan Bart; Joseph B. Buchanan; Bob Altman

2005-01-01

We investigated increasing the number of Breeding Bird Survey (BBS) routes and reducing potential bias as ways to increase the number of species adequately monitored by the BBS in the Pacific Northwest. Estimates of place-to-place variance in trends were used to assess the effects of increasing the number of additional BBS routes. Increasing the number of BBS routes...

Characterization of bombesin receptors in peripheral contractile organs.

PubMed Central

Rouissi, N.; Rhaleb, N. E.; Nantel, F.; Dion, S.; Drapeau, G.; Regoli, D.

1991-01-01

1 Guinea-pig and rat urinary bladders, rat stomach and the guinea-pig gall bladder, four isolated organs that show high sensitivity to bombesin, were used to characterize bombesin receptors in peripheral organs. 2 The order of potency of agonists was determined with several naturally occurring peptides of the bombesin series, namely bombesin (BBS), litorin (Lit), neuromedin B (NMB), the gastrin-releasing peptide (GRP 18-27), neuromedin C (NMC) and with some bombesin fragments. It was found that bombesin, neuromedin C, litorin and two bombesin fragments, BBS (6-14) and AcBBS (6-14) had similar activities in the four preparations, while neuromedin B and [Phe6]-neuromedin C were more active on the rat urinary bladder than on the other tissues. 3 The order of potency of agonists determined in the rat urinary bladder was as follows: BBS = NMB greater than Lit greater than NMC greater than [Phe6]NMC = GRP and it was found to be different from that observed in the other preparations: BBS greater than GRP = Lit greater than or equal to NMC much greater than NMB greater than [Phe6]NMC, suggesting the existence of two different bombesin receptors, BBS1 and BBS2. 4 This interpretation was convalidated by the finding that bombesin antagonists, namely Ac.GRP(20-26)OCH3 and Ac.GRP(20-26)OC2H5 reduced or blocked the effects of bombesin-related peptides on BBS2 receptor systems while being completely inactive on the rat urinary bladder (BBS1 system). PMID:1652341

Oral and Craniofacial Anomalies of Bardet-Biedl Syndrome: Dental Management in the Context of a Rare Disease.

PubMed

Panny, A; Glurich, I; Haws, R M; Acharya, A

2017-11-01

Standardized guidelines for the oral health management of patients with rare diseases exhibiting morphologic anomalies are currently lacking. This review considers Bardet-Biedl syndrome (BBS), a monogenic autosomal recessive nonmotile ciliopathy, as an archetypal condition. Dental anomalies are present in a majority of individuals affected by BBS due to abnormal embryonic orofacial and tooth development. Genetically encoded intrinsic oral structural anomalies and heterogeneous BBS clinical phenotypes and consequent oral comorbidities confound oral health management. Since the comorbid spectrum of BBS phenotypes spans diabetes, renal disease, obesity, sleep apnea, cardiovascular disease, and cognitive disorders, a broad spectrum of collateral oral disease may be encountered. The genetic impact of BBS on the anatomic development of oral components and oral pathology encountered in the context of various BBS phenotypes and their associated comorbidities are reviewed herein. Challenges encountered in managing patients with BBS are highlighted, emphasizing the spectrum of oral pathology associated with heterogeneous clinical phenotypic expression. Guidelines for provision of care across the spectrum of BBS clinical phenotypes are considered. Establishment of integrated medical-dental delivery models of oral care in the context of rare diseases is emphasized, including involvement of caregivers in the context of managing these patients with special needs.

Classification of walking ability of household walkers versus community walkers based on K-BBS, gait velocity and upright motor control.

PubMed

Joa, K L; Kwon, S Y; Choi, J W; Hong, S E; Kim, C H; Jung, H Y

2015-10-01

Few guidelines are available to assist clinicians with assessment of whether a patient is a household or community walker. To assess the Korean Berg balance scale (K-BBS) and gait velocity cut-off points of a household walker versus a community walker and evaluate which combinations of the three scales (K-BBS, upright motor control test (UMCT), and gait velocity) best assessed walking ability. Cross-sectional study. Outpatient. A total of 124 stroke patients with walking difficulty. Participants were classified into one of six walking classifications (three household walkers and three community walkers) and K-BBS, UMCT, and gait velocity were evaluated. The optimal cut-off scores for walking classification were determined based on received operator characteristic (ROC) analyses. The cut-off value of K-BBS for dividing the household walker versus the community walker was 42 points. The cut-off value of gait velocity was 48 m/s for the community walker. The area under the ROC curve of the combined K-BBS and gait velocity values was larger than that of each individual scale and those of the other combined scales. The results suggest that K-BBS, gait velocity, and UMCT are useful instruments for classifying household ambulation and community ambulation. The authors recommend K-BBS as single scale and K-BBS and gait velocity as combined scales for evaluating community ambulation in stroke patients In this report, we have some clinical implication. We recommend 3 outcome measures to assess walking ability about home or community; K-BBS (>42 points), gait speed (>48 m/min), UMCT (strong grade in either knee flexion of extension). Suggesting cut-off points of Korean Berg balance scale, gait velocity, and level of upright motor control test for community ambulation could be used as outcome measures to evaluate patient's actual performance level. It is also important to combine several scales for determining walking classification. We suggest to evaluate walking ability by combining K-BBS and UMCT to best predict community ambulation.

Test-retest reliability and minimal detectable change of two simplified 3-point balance measures in patients with stroke.

PubMed

Chen, Yi-Miau; Huang, Yi-Jing; Huang, Chien-Yu; Lin, Gong-Hong; Liaw, Lih-Jiun; Lee, Shih-Chieh; Hsieh, Ching-Lin

2017-10-01

The 3-point Berg Balance Scale (BBS-3P) and 3-point Postural Assessment Scale for Stroke Patients (PASS-3P) were simplified from the BBS and PASS to overcome the complex scoring systems. The BBS-3P and PASS-3P were more feasible in busy clinical practice and showed similarly sound validity and responsiveness to the original measures. However, the reliability of the BBS-3P and PASS-3P is unknown limiting their utility and the interpretability of scores. We aimed to examine the test-retest reliability and minimal detectable change (MDC) of the BBS-3P and PASS-3P in patients with stroke. Cross-sectional study. The rehabilitation departments of a medical center and a community hospital. A total of 51 chronic stroke patients (64.7% male). Both balance measures were administered twice 7 days apart. The test-retest reliability of both the BBS-3P and PASS-3P were examined by intraclass correlation coefficients (ICC). The MDC and its percentage over the total score (MDC%) of each measure was calculated for examining the random measurement errors. The ICC values of the BBS-3P and PASS-3P were 0.99 and 0.97, respectively. The MDC% (MDC) of the BBS-3P and PASS-3P were 9.1% (5.1 points) and 8.4% (3.0 points), respectively, indicating that both measures had small and acceptable random measurement errors. Our results showed that both the BBS-3P and the PASS-3P had good test-retest reliability, with small and acceptable random measurement error. These two simplified 3-level balance measures can provide reliable results over time. Our findings support the repeated administration of the BBS-3P and PASS-3P to monitor the balance of patients with stroke. The MDC values can help clinicians and researchers interpret the change scores more precisely.

Group- and Individual-Level Responsiveness of the 3-Point Berg Balance Scale and 3-Point Postural Assessment Scale for Stroke Patients.

PubMed

Huang, Yi-Jing; Lin, Gong-Hong; Lee, Shih-Chieh; Chen, Yi-Miau; Huang, Sheau-Ling; Hsieh, Ching-Lin

2018-03-01

To examine both group- and individual-level responsiveness of the 3-point Berg Balance Scale (BBS-3P) and 3-point Postural Assessment Scale for Stroke Patients (PASS-3P) in patients with stroke, and to compare the responsiveness of both 3-point measures versus their original measures (Berg Balance Scale [BBS] and Postural Assessment Scale for Stroke Patients [PASS]) and their short forms (short-form Berg Balance Scale [SFBBS] and short-form Postural Assessment Scale for Stroke Patients [SFPASS]) and between the BBS-3P and PASS-3P. Data were retrieved from a previous study wherein 212 patients were assessed at 14 and 30 days after stroke with the BBS and PASS. Medical center. Patients (N=212) with first onset of stroke within 14 days before hospitalization. Not applicable. Group-level responsiveness was examined by the standardized response mean (SRM), and individual-level responsiveness was examined by the proportion of patients whose change scores exceeded the minimal detectable change of each measure. The responsiveness was compared using the bootstrap approach. The BBS-3P and PASS-3P had good group-level (SRM, .60 and SRM, .56, respectively) and individual-level (48.1% and 44.8% of the patients with significant improvement, respectively) responsiveness. Bootstrap analyses showed that the BBS-3P generally had superior responsiveness to the BBS and SFBBS, and the PASS-3P had similar responsiveness to the PASS and SFPASS. The BBS-3P and PASS-3P were equally responsive to both group and individual change. The responsiveness of the BBS-3P and PASS-3P was comparable or superior to those of the original and short-form measures. We recommend the BBS-3P and PASS-3P as responsive outcome measures of balance for individuals with stroke. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Waste heat recovery from adiabatic diesel engines by exhaust-driven Brayton cycles

NASA Technical Reports Server (NTRS)

Khalifa, H. E.

1983-01-01

An evaluation of Bryton Bottoming Systems (BBS) as waste heat recovery devices for future adiabatic diesel engines in heavy duty trucks is presented. Parametric studies were performed to evaluate the influence of external and internal design parameters on BBS performance. Conceptual design and trade-off studies were undertaken to estimate the optimum configuration, size, and cost of major hardware components. The potential annual fuel savings of long-haul trucks equipped with BBS were estimated. The addition of a BBS to a turbocharged, nonaftercooled adiabatic engine would improve fuel economy by as much as 12%. In comparison with an aftercooled, turbocompound engine, the BBS-equipped turbocharged engine would offer a 4.4% fuel economy advantage. If installed in tandem with an aftercooled turbocompound engine, the BBS could effect a 7.2% fuel economy improvement. The cost of a mass-produced 38 Bhp BBS is estimated at about $6460 or 170/Bhp. Technical and economic barriers that hinder the commercial introduction of bottoming systems were identified. Related studies in the area of waste heat recovery from adiabatic diesel engines and NASA-CR-168255 (Steam Rankine) and CR-168256 (Organic Rankine).

SHORT COMMUNICATION: Hyperphagia among patients with Bardet-Biedl syndrome

PubMed Central

Sherafat-Kazemzadeh, Roya; Ivey, Lauren; Kahn, Stephanie R.; Sapp, Julie C.; Hicks, Melanie D.; Kim, Rachel C.; Krause, Amanda J.; Shomaker, Lauren B.; Biesecker, Leslie G.; Han, Joan C.; Yanovski, Jack A.

2014-01-01

Summary Background The importance of hyperphagia as a cause for energy imbalance in humans with Bardet-Biedl syndrome (BBS) has not been established. We therefore compared hyperphagic symptoms in patients with BBS versus controls. Methods We studied 13 patients with BBS and 23 nonsyndromic controls with similar age, sex, and BMI z-score. A 13-item hyperphagia questionnaire was completed by patients’ parents/guardians. Results Total hyperphagia questionnaire score was higher in BBS than controls (27.6±9.0 vs. 19.1±7.9, p=0.005). Behavior and drive sub-scales were higher for BBS than controls (12.5±4.1 vs. 7.8±3.2, p=0.001, and 11.2±4.1 vs. 8.3±3.8, p=0.04, respectively); severity was not significantly different between groups (3.8±1.5 vs. 3.0±1.3, p=0.072). After adjustment for demographic variables and BMI-Z score, total and behavior subscale scores remained significantly different between groups, suggesting food-seeking activity, rather than preoccupation with food may be the main hyperphagic feature among patients with BBS. Conclusion Appetite dysregulation may contribute to obesity in BBS. PMID:23776152

Correlations between Berg balance scale and gait speed in individuals with stroke wearing ankle-foot orthoses - a pilot study.

PubMed

Kobayashi, Toshiki; Leung, Aaron K L; Akazawa, Yasushi; Hutchins, Stephen W

2016-01-01

The Berg balance scale (BBS) is commonly used to assess balancing ability in patients with stroke. The BBS may be a good candidate for clinical assessment prior to orthotic intervention, if it correlates well with outcome measures such as gait speed. The purpose of this study was to investigate the correlation between the BBS measured prior to walking with an ankle-foot orthosis (AFO) and specific temporal-spatial parameters of gait when walking with an AFO donned. Eight individuals with chronic stroke participated in this study. Balancing ability was assessed using the BBS, while temporal-spatial parameters of gait (gait speed, bilateral step length, stride length and step width) were measured using a three-dimensional motion analysis system. The correlations between the BBS and gait parameters were investigated using a non-parametric Kendall's Tau (τ) correlation analysis. The BBS showed correlations with gait speed (τ = 0.64, p < 0.05), the step length of the affected side (τ = 0.74, p < 0.05), and the stride length (τ = 0.64, p < 0.05). Assessment of the BBS prior to AFO prescription may potentially help clinicians to estimate the gait speed achievable following orthotic intervention in patients with stroke. Implications for Rehabilitation Assessment of the BBS prior to AFO prescription may help orthotists to estimate the gait speed following an orthotic intervention in patients with stroke. Assessment of the BBS prior to AFO prescription may help orthotists to understand overall balance and postural control abilities in patients with stroke. A larger scale multifactorial analysis is warranted to confirm the results of this pilot study.

A guanine insert in OsBBS1 leads to early leaf senescence and salt stress sensitivity in rice (Oryza sativa L.).

PubMed

Zeng, Dong-Dong; Yang, Cheng-Cong; Qin, Ran; Alamin, Md; Yue, Er-Kui; Jin, Xiao-Li; Shi, Chun-Hai

2018-06-01

A rice receptor-like kinase gene OSBBS1/OsRLCK109 was identified; this gene played vital roles in leaf senescence and the salt stress response. Early leaf senescence can cause negative effects on rice yield, but the underlying molecular regulation is not fully understood. bilateral blade senescence 1 (bbs1), an early leaf senescence mutant with a premature senescence phenotype that occurs mainly performing at the leaf margins, was isolated from a rice mutant population generated by ethylmethane sulfonate (EMS) treatment. The mutant showed premature leaf senescence beginning at the tillering stage and exhibited severe symptoms at the late grain-filling stage. bbs1 showed accelerated dark-induced leaf senescence. The OsBBS1 gene was cloned by a map-based cloning strategy, and a guanine (G) insertion was found in the first exon of LOC_Os03g24930. This gene encodes a receptor-like cytoplasmic kinase and was named OsRLCK109 in a previous study. Transgenic LOC_Os03g24930 knockout plants generated by a CRISPR/Cas9 strategy exhibited similar early leaf senescence phenotypes as did the bbs1 mutant, which confirmed that LOC_Os03g24930 was the OsBBS1 gene. OsBBS1/OsRLCK109 was expressed in all detected tissues and was predominantly expressed in the main vein region of mature leaves. The expression of OsBBS1 could be greatly induced by salt stress, and the bbs1 mutant exhibited hypersensitivity to salt stress. In conclusion, this is the first identification of OsRLCKs participating in leaf senescence and playing critical roles in the salt stress response in rice (Oryza sativa L.).

Whole exome sequencing as a diagnostic tool for patients with ciliopathy-like phenotypes.

PubMed

Castro-Sánchez, Sheila; Álvarez-Satta, María; Tohamy, Mohamed A; Beltran, Sergi; Derdak, Sophia; Valverde, Diana

2017-01-01

Ciliopathies are a group of rare disorders characterized by a high genetic and phenotypic variability, which complicates their molecular diagnosis. Hence the need to use the latest powerful approaches to faster identify the genetic defect in these patients. We applied whole exome sequencing to six consanguineous families clinically diagnosed with ciliopathy-like disease, and for which mutations in predominant Bardet-Biedl syndrome (BBS) genes had previously been excluded. Our strategy, based on first applying several filters to ciliary variants and using many of the bioinformatics tools available, allowed us to identify causal mutations in BBS2, ALMS1 and CRB1 genes in four families, thus confirming the molecular diagnosis of ciliopathy. In the remaining two families, after first rejecting the presence of pathogenic variants in common cilia-related genes, we adopted a new filtering strategy combined with prioritisation tools to rank the final candidate genes for each case. Thus, we propose CORO2B, LMO7 and ZNF17 as novel candidate ciliary genes, but further functional studies will be needed to confirm their role. Our data show the usefulness of this strategy to diagnose patients with unclear phenotypes, and therefore the success of applying such technologies to achieve a rapid and reliable molecular diagnosis, improving genetic counselling for these patients. In addition, the described pipeline also highlights the common pitfalls associated to the large volume of data we have to face and the difficulty of assigning a functional role to these changes, hence the importance of designing the most appropriate strategy according to each case.

Y balance test has no correlation with the Stability Index of the Biodex Balance System.

PubMed

Almeida, Gabriel Peixoto Leão; Monteiro, Isabel Oliveira; Marizeiro, Débora Fortes; Maia, Laísa Braga; de Paula Lima, Pedro Olavo

2017-02-01

A cross-sectional study design. The Stability Index of the Biodex Balance System (SI-BBS) and Y Balance Test (YBT) has been used in studies assessing postural stability but no studies have verified the association of the YBT with the SI-BBS. To analyze the association of the Y Balance Test (YBT) with the Stability Index of the Biodex Balance System (SI-BBS) to evaluate postural stability. Forty participants who engaged in recreational physical activities, 12 of whom had a history of injury to the lower limbs. Was used the SI-BBS and the anterior, posterolateral, posteromedial, and composite measures of the YBT. The order of execution of the tests and of the lower limbs evaluated was randomized and blind tested by two evaluators. Pearson's correlation coefficient was used to check the strength of the relationship between the distances achieved on the YBT and the SI-BBS. The YBT showed excellent reliability in the anterior, posteromedial, and posterolateral directions. However, the YBT showed no statistically significant correlation with any variables in the SI-BBS, indicating poor validity between YBT and SI-BBS assessments of postural stability in people with and without history of lower limb injuries. The results of this study showed the YBT is not correlated with the SI-BBS as an assessment of postural stability. This finding has implications for researchers and clinicians using YBT results as the only measure of postural stability. Copyright © 2016 Elsevier Ltd. All rights reserved.

Internet Database Review: The FDA BBS.

ERIC Educational Resources Information Center

Tomaiuolo, Nicholas G.

1993-01-01

Describes the electronic bulletin board system (BBS) of the Food and Drug Administration (FDA) that is accessible through the Internet. Highlights include how to gain access; the menu-driven software; other electronic sources of FDA information; and adding value. Examples of the FDA BBS menu and the help screen are included. (LRW)

Some considerations on the use of ecological models to predict species' geographic distributions

USGS Publications Warehouse

Peterjohn, B.G.

2001-01-01

Peterson (2001) used Genetic Algorithm for Rule-set Prediction (GARP) models to predict distribution patterns from Breeding Bird Survey (BBS) data. Evaluations of these models should consider inherent limitations of BBS data: (1) BBS methods may not sample species and habitats equally; (2) using BBS data for both model development and testing may overlook poor fit of some models; and (3) BBS data may not provide the desired spatial resolution or capture temporal changes in species distributions. The predictive value of GARP models requires additional study, especially comparisons with distribution patterns from independent data sets. When employed at appropriate temporal and geographic scales, GARP models show considerable promise for conservation biology applications but provide limited inferences concerning processes responsible for the observed patterns.

Bardet-Biedl syndrome: Mapping of a new locus to chromosome 3 and fine-mapping of the chromosome 16 linked locus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwitek-Black, A.E.; Rokhlina, T.; Nishimura, D.Y.

Bardet-Biedl syndrome (BBS) is a heterogeneous autosomal recessive disorder characterized by mental retardation, post-axial polydactyly, obesity, retinitis pigmentosa, and hypogonadism. Other features of this disease include renal and cardiovascular abnormalities and an increased incidence of hypertension and diabetes mellitus. The molecular etiology for BBS is not known. We previously linked BBS to chromosome 16q13 in a large inbred Bedouin family, and excluded this locus in a second large inbred Bedouin family. We now report linkage of this second family to markers on chromosome 3q, proving non-allelic, genetic heterogeneity in the Bedouin population. A third large inbred Bedouin family was excludedmore » from the 3q and 16q BBS loci. In addition to the identification of a new BBS locus on chromosome 3, we have identified and utilized additional short tandem repeat polymorphisms (STRPs) in the 16q BBS region to narrow the candidate interval to 3 cM. Additional recombinant individuals will allow further refinement of the interval. Identification of genes causing BBS has the potential to provide insight into diverse genetic traits and disease processes including obesity, hypertension, diabetes, retinal degeneration, and abnormal limb, renal and cardiac development.« less

Binaural beats increase interhemispheric alpha-band coherence between auditory cortices.

PubMed

Solcà, Marco; Mottaz, Anaïs; Guggisberg, Adrian G

2016-02-01

Binaural beats (BBs) are an auditory illusion occurring when two tones of slightly different frequency are presented separately to each ear. BBs have been suggested to alter physiological and cognitive processes through synchronization of the brain hemispheres. To test this, we recorded electroencephalograms (EEG) at rest and while participants listened to BBs or a monaural control condition during which both tones were presented to both ears. We calculated for each condition the interhemispheric coherence, which expressed the synchrony between neural oscillations of both hemispheres. Compared to monaural beats and resting state, BBs enhanced interhemispheric coherence between the auditory cortices. Beat frequencies in the alpha (10 Hz) and theta (4 Hz) frequency range both increased interhemispheric coherence selectively at alpha frequencies. In a second experiment, we evaluated whether this coherence increase has a behavioral aftereffect on binaural listening. No effects were observed in a dichotic digit task performed immediately after BBs presentation. Our results suggest that BBs enhance alpha-band oscillation synchrony between the auditory cortices during auditory stimulation. This effect seems to reflect binaural integration rather than entrainment. Copyright © 2015 Elsevier B.V. All rights reserved.

Olfaction evaluation and correlation with brain atrophy in Bardet-Biedl syndrome.

PubMed

Braun, J-J; Noblet, V; Durand, M; Scheidecker, S; Zinetti-Bertschy, A; Foucher, J; Marion, V; Muller, J; Riehm, S; Dollfus, H; Kremer, S

2014-12-01

Bardet-Biedl syndrome (BBS) is a well-recognized ciliopathy characterized by cardinal features namely: early onset retinitis pigmentosa, polydactyly, obesity, hypogonadism, renal and cognitive impairment. Recently, disorders of olfaction (anosmia, hyposmia) have been also described in BBS patients. Moreover, morphological brain anomalies have been reported and prompt for further investigations to determine whether they are primary or secondary to peripheral organ involvement (i.e. visual or olfactory neuronal tissue). The objective of this article is to evaluate olfactory disorders in BBS patients and to investigate putative correlation with morphological cerebral anomalies. To this end, 20 BBS patients were recruited and evaluated for olfaction using the University of Pennsylvania Smell Identification Test (UPSIT). All of them underwent a structural magnetic resonance imaging (MRI) scan. We first investigated brain morphological differences between BBS subjects and 14 healthy volunteers. Then, we showed objective olfaction disorders in BBS patients and highlight correlation between gray matter volume reduction and olfaction dysfunction in several brain areas. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Strategic Plan for the North American Breeding Bird Survey: 2006-2010

USGS Publications Warehouse

,

2007-01-01

Executive Summary The mission of the North American Breeding Bird Survey (BBS) is to provide scientifically credible measures of the status and trends of North American bird populations at continental and regional scales to inform biologically sound conservation and management actions. Determining population trends, relative abundance, and distributions of North American avifauna is critical for identifying conservation priorities, determining appropriate conservation actions, and evaluating those actions. The BBS program, jointly coordinated by the U.S. Geological Survey and Environment Canada?s Canadian Wildlife Service, provides the U.S. and Canadian Federal governments, state and provincial agencies, other conservation practitioners, and the general public with science-based avian population trend estimates and other information for regional and national species' population assessments. Despite the demonstrated value of the BBS for furthering avian conservation across North America, its importance is often underappreciated, and it is underfunded compared with many other government-supported programs that report on status of the environment. Today, BBS resources, adjusted for inflation, are below the amount allocated in the 1970s and are still only sufficient to support two biologists. Yet the number of routes, participants, data, and data requests has quadrupled. Data and information management and delivery requirements and security concerns, non-existent in 1966, impose further demands on BBS resources. In addition, the Mexican expansion of the BBS offers new hope for a truly continental approach to avian conservation, but also brings additional challenges. Meeting the goals of this plan will take cooperation among myriad stakeholders; yet, even with collaboration, most objectives of this plan will be unattainable if BBS program support is not increased. The BBS developed this strategic plan to help set priorities and identify resources required for the program to continue to meet the evolving needs of the conservation community for information on bird population change. By setting clear goals, strategies, and measures of success, this plan provides a cohesive framework and vision for maintenance and development of the BBS. The plan identifies two major goals for the BBS, with a number of strategies and objectives to achieve these goals. Over the next 5 years, progress made in addressing each long-term goal and its associated 5-year strategies and objectives will gage the plan's success. Specific actions, projected outcomes, and measures of success related to accomplishing these are outlined in Table 1, with a timeline in Table 2. The two main goals for the program, with a summary of the strategies to achieve them, are: Goal 1: Collect scientifically credible measures of the status and trends of North American bird populations at continental and regional scales. The North American Breeding Bird Survey will continue to support North American natural resource conservation through the collection of scientifically credible measures of the status and trends of continental bird populations. While doing this, the BBS will work to improve the science behind the program to better meet its mission and the changing needs of the avian conservation community. In partnership with collaborators, the BBS will address detection probability bias and habitat bias, improve analytical methods, and more fully assess and account for observer quality. Moreover, the BBS will improve the quality and breadth of avian population data through strategic increases in route density and the establishment of a Mexican BBS program. Goal 2: Ensure BBS data and analytical results are widely available and easily accessible for use by the avian conservation and management communities. At the heart of the BBS lies a four-million-record database containing more than 40 years of data on more than 600 bird species. These data are of no valu

Is the Berg Balance Scale an effective tool for the measurement of early postural control impairments in patients with Parkinson's disease? Evidence from Rasch analysis.

PubMed

La Porta, F; Giordano, A; Caselli, S; Foti, C; Franchignoni, F

2015-12-01

It is unclear whether the BBS is an effective tool for the measurement of early postural control impairments in patients with Parkinson's disease (PD). The aim of this paper was to evaluate BBS' content validity, internal construct validity, reliability and targeting in patients with PD within the Rasch analysis framework. Observational, cross-sectional study. Outpatient Rehabilitation Unit. A sample of 285 outpatients with PD. The content validity of the BBS was assessed using standard linking techniques. The BBS was administered by trained physiotherapists. The data collected then underwent Rasch analysis. Content validity analysis showed a lack of items assessing postural responses to tripping and slips and stability during walking. On Rasch analysis, the BBS failed the requirements of monotonicity, local independence, unidimensionality and invariance. After rescoring 7 items, grouping of locally dependent items into testlets, and deletion of the static sitting balance item because mistargeted and underdiscriminating, the Rasch-modified BBS for PD (BBS-PD) showed adequate internal construct validity (χ(2)24=39.693; P=0.023), including absence of differential item functioning (DIF) across gender and age, and was, as a whole, sufficiently precise for individual person measurement (PSI=0.894). However, the scale was not well targeted to the sample in view of the prevalence of higher scores. This study demonstrated the internal construct validity and reliability of the BBS-PD as a measurement tool for patients with PD within the Rasch analysis framework. However, the lack of items critical to the assessment of postural control impairments typical of PD, affected negatively the targeting, so that a significant percentage of patients was located in the higher ability range of the measurement continuum, where precision of measurement is reduced. These findings suggest that the BBS, even if modified, may not be an effective tool for the measurement of early postural control in patients with PD.

The role of the North American Breeding Bird Survey in conservation

USGS Publications Warehouse

Hudson, Marie-Anne R.; Francis, Charles M.; Campbell, Kate J.; Downes, Constance M.; Smith, Adam C.; Pardieck, Keith L.

2017-01-01

The North American Breeding Bird Survey (BBS) was established in 1966 in response to a lack of quantitative data on changes in the populations of many bird species at a continental scale, especially songbirds. The BBS now provides the most reliable regional and continental trends and annual indices of abundance available for >500 bird species. This paper reviews some of the ways in which BBS data have contributed to bird conservation in North America over the past 50 yr, and highlights future program enhancement opportunities. BBS data have contributed to the listing of species under the Canadian Species at Risk Act and, in a few cases, have informed species assessments under the U.S. Endangered Species Act. By raising awareness of population changes, the BBS has helped to motivate bird conservation efforts through the creation of Partners in Flight. BBS data have been used to determine priority species and locations for conservation action at regional and national scales through Bird Conservation Region strategies and Joint Ventures. Data from the BBS have provided the quantitative foundation for North American State of the Birds reports, and have informed the public with regard to environmental health through multiple indicators, such as the Canadian Environmental Sustainability Indicators and the U.S. Environmental Protection Agency's Report on the Environment. BBS data have been analyzed with other data (e.g., environmental, land cover, and demographic) to evaluate potential drivers of population change, which have then informed conservation actions. In a few cases, BBS data have contributed to the evaluation of management actions, including informing the management of Mourning Doves (Zenaida macroura), Wood Ducks (Aix sponsa), and Golden Eagles (Aquila chrysaetos). Improving geographic coverage in northern Canada and in Mexico, improving the analytical approaches required to integrate data from other sources and to address variation in detectability, and completing the database, by adding historical bird data at each point count location and pinpointing the current point count locations would further enhance the survey's value.

Hyperphagia among patients with Bardet-Biedl syndrome.

PubMed

Sherafat-Kazemzadeh, R; Ivey, L; Kahn, S R; Sapp, J C; Hicks, M D; Kim, R C; Krause, A J; Shomaker, L B; Biesecker, L G; Han, J C; Yanovski, J A

2013-10-01

The importance of hyperphagia as a cause for energy imbalance in humans with Bardet-Biedl syndrome (BBS) has not been established. We therefore compared hyperphagic symptoms in patients with BBS vs. controls. We studied 13 patients with BBS and 23 non-syndromic controls with similar age, sex and body mass index (BMI) z-score. A 13-item hyperphagia questionnaire was completed by patients' parents/guardians. Total hyperphagia questionnaire score was higher in BBS than controls (27.6 ± 9.0 vs. 19.1 ± 7.9, P = 0.005). Behaviour and drive subscales were higher for BBS than controls (12.5 ± 4.1 vs. 7.8 ± 3.2, P = 0.001, and 11.2 ± 4.1 vs. 8.3 ± 3.8, P = 0.04, respectively); severity was not significantly different between groups (3.8 ± 1.5 vs. 3.0 ± 1.3, P = 0.072). After adjustment for demographic variables and BMI z-score, total and behaviour subscale scores remained significantly different between groups, suggesting food-seeking activity, rather than preoccupation with food may be the main hyperphagic feature among patients with BBS. Appetite dysregulation may contribute to obesity in BBS. © 2013 The Authors. Pediatric Obesity © 2013 International Association for the Study of Obesity.

Comparison of the Mini-Balance Evaluations Systems Test with the Berg Balance Scale in relationship to walking speed and motor recovery post stroke.

PubMed

Madhavan, Sangeetha; Bishnoi, Alka

2017-12-01

The Mini-BESTest is a recently developed balance assessment tool that incorporates challenging dynamic balance tasks. Few studies have compared the psychometric properties of the Mini-BESTest to the commonly used Berg Balance Scale (BBS). However, the utility of these scales in relationship to post stroke walking speeds has not been explored. The purpose of this study was to compare the sensitivity and specificity of the Mini-BESTest and BBS to evaluate walking speeds in individuals with stroke. A retrospective exploratory design. Forty-one individuals with chronic stroke were evaluated with the Mini-BESTest, BBS, and 10-meter self-selected walk test (10MWT). Based on their self-selected gait speeds (below or above 0.8 m/s), participants were classified as slow and fast walkers. Significant linear correlations were observed between the Mini-BESTest vs. BBS (r = 0.72, p ≤ 0.001), Mini-BESTest vs. 10MWT (r = 0.58, p ≤ 0.001), and BBS vs. 10MWT (r = 0.30, p = 0.05). Independent t-tests comparing the balance scores for the slow and fast walkers revealed significant group differences for the Mini-BESTest (p = 0.003), but not for the BBS (p = 0.09). The Mini-BESTest demonstrated higher sensitivity (93%) and specificity (64%) compared to the BBS (sensitivity 81%, specificity 56%) for discriminating participants into slow and fast walkers. The Mini-BESTest has a greater discriminative ability than the BBS to categorize individuals with stroke into slow and fast walkers.

Comparison of the Mini-Balance Evaluations Systems Test with the Berg Balance Scale in relationship to walking speed and motor recovery post stroke

PubMed Central

Madhavan, Sangeetha; Bishnoi, Alka

2017-01-01

Background The Mini-BESTest is a recently developed balance assessment tool that incorporates challenging dynamic balance tasks. Few studies have compared the psychometric properties of the Mini-BESTest to the commonly used Berg Balance Scale (BBS). However, the utility of these scales in relationship to post stroke walking speeds has not been explored. Objectives The purpose of this study was to compare the sensitivity and specificity of the Mini-BESTest and BBS to evaluate walking speeds in individuals with stroke. Design A retrospective exploratory design. Methods Forty-one individuals with chronic stroke were evaluated with the Mini-BESTest, BBS, and 10-meter self-selected walk test (10MWT). Based on their self-selected gait speeds (below or above 0.8 m/s), participants were classified as slow and fast walkers. Results Significant linear correlations were observed between the Mini-BESTest vs. BBS (r = 0.72, p ≤ 0.001), Mini-BESTest vs. 10MWT (r = 0.58, p ≤ 0.001), and BBS vs. 10MWT (r = 0.30, p = 0.05). Independent t-tests comparing the balance scores for the slow and fast walkers revealed significant group differences for the Mini-BESTest (p =0.003), but not for the BBS (p = 0.09). The Mini-BESTest demonstrated higher sensitivity (93%) and specificity (64%) compared to the BBS (sensitivity 81%, specificity 56%) for discriminating participants into slow and fast walkers. No significant results were observed with the FMLE-M scores. Conclusions The Mini-BESTest has a greater discriminative ability than the BBS to categorize individuals with stroke into slow and fast walkers. PMID:28826325

Effects of habitat change along Breeding Bird Survey routes in the central Appalachians on Cerulean Warbler population

USGS Publications Warehouse

McElhone, P.; Wood, P.W.; Dawson, D.

2007-01-01

The cerulean warbler (Dendroica cerulea) is one of the highest priority bird species in the eastern United States because populations have declined 4.3% annually during 1966?2005 based on Breeding Bird Survey (BBS) data. Habitat loss and fragmentation due to land use changes is thought to be one of the major factors contributing to the decline. BBS routes, the primary source for monitoring bird population trends, include 50 sampling stops every 0.8 km. Although data from BBS routes are extrapolated to determine regional trends in bird populations, it is important to understand the effects of habitat changes at the stop-level along BBS routes. Route-level analysis of habitat changes may mask important changes that are occurring at a smaller scale particularly for the cerulean warbler which displays several micro-scale habitat preferences. We are examining cerulean warbler habitat and population changes in its core breeding range of the Ohio Hills and Cumberland Plateau physiographic regions. We quantified land cover changes within 300 m of BBS routes in the core cerulean warbler breeding range of Ohio, West Virginia, and Kentucky by digitizing aerial photographs from two time periods: the 1980s and 2004. We also quantified land cover changes within 300 m of BBS routes with the National Land Cover Dataset (NLCD) from 1992 and 2001. The hand-digitized aerial photos will be compared with the NLCD to determine how similar the two methods are in quantifying land cover changes. We then compared stop-level land cover changes with stop level changes in cerulean warbler detections within the same time periods along the BBS routes. This will allow for a more detailed analysis of how well habitat changes along BBS routes reflect the changes in cerulean warbler populations.

The first 50 years of the North American Breeding Bird Survey

USGS Publications Warehouse

Sauer, John; Ziolkowski, David; Pardieck, Keith L.; Smith, Adam C.; Hudson, Marie-Anne R.; Rodriguez, Vicente; Berlanga, Humberto; Niven, Daniel; Link, William

2017-01-01

The vision of Chandler (Chan) S. Robbins for a continental-scale omnibus survey of breeding birds led to the development of the North American Breeding Bird Survey (BBS). Chan was uniquely suited to develop the BBS. His position as a government scientist had given him experience with designing and implementing continental-scale surveys, his research background made him an effective advocate of the need for a survey to monitor pesticide effects on birds, and his prominence in the birding community gave him connections to infrastructure—a network of qualified volunteer birders who could conduct roadside surveys with standardized point counts. Having started in the eastern United States and the Atlantic provinces of Canada in 1966, the BBS now provides population change information for ∼546 species in the continental United States and Canada, and recently initiated routes in Mexico promise to greatly expand the areas and species covered by the survey. Although survey protocols have remained unchanged for 50 years, the BBS remains relevant in a changing world. Several papers that follow in this Special Section of The Condor: Ornithological Advances review how the BBS has been applied to conservation assessments, especially in combination with other large-scale survey data. A critical feature of the BBS program is an active research program into field and analytical methods to enhance the quality of the count data and to control for factors that influence detectability. Papers in the Special Section also present advances in BBS analyses that improve the utility of this expanding and sometimes controversial survey. In this Perspective, we introduce the Special Section by reviewing the history of the BBS, describing current analyses, and providing summary trend results for all species, highlighting 3 groups of conservation concern: grassland-breeding birds, aridland-breeding birds, and aerial insectivorous birds.

Combining waterfowl and breeding bird survey data to estimate wood duck breeding population size in the Atlantic Flyway

USGS Publications Warehouse

Guthrie Zimmerman,; Sauer, John; Fleming, Kathy; Link, William; Pamela R. Garrettson,

2015-01-01

We combined data from the Atlantic Flyway Breeding Waterfowl Survey (AFBWS) and the North American Breeding Bird Survey (BBS) to estimate the number of wood ducks (Aix sponsa) in the United States portion of the Atlantic Flyway from 1993 to 2013. The AFBWS is a plot-based survey that covers most of the northern and central portions of the Flyway; when analyzed with adjustments for survey time of day effects, these data can be used to estimate population size. The BBS provides an index of wood duck abundance along roadside routes. Although factors influencing change in BBS counts over time can be controlled in BBS analysis, BBS indices alone cannot be used to derive population size estimates. We used AFBWS data to scale BBS indices for Bird Conservation Regions (BCR), basing the scaling factors on the ratio of estimated AFBWS population sizes to regional BBS indices for portions of BCRs that were common to both surveys. We summed scaled BBS results for portions of the Flyway not covered by the AFBWS with AFBWS population estimates to estimate a mean yearly total of 1,295,875 (mean 95% CI: 1,013,940–1,727,922) wood ducks. Scaling factors varied among BCRs from 16.7 to 148.0; the mean scaling factor was 68.9 (mean 95% CI: 53.5–90.9). Flyway-wide, population estimates from the combined analysis were consistent with alternative estimates derived from harvest data, and also provide population estimates within states and BCRs. We recommend their use in harvest and habitat management within the Atlantic Flyway.

Expanding the North American Breeding Bird Survey analysis to include additional species and regions

USGS Publications Warehouse

Sauer, John; Niven, Daniel; Pardieck, Keith L.; Ziolkowski, David; Link, William

2017-01-01

The North American Breeding Bird Survey (BBS) contains data for >700 bird species, but analyses often focus on a core group of ∼420 species. We analyzed data for 122 species of North American birds for which data exist in the North American Breeding Bird Survey (BBS) database but are not routinely analyzed on the BBS Summary and Analysis Website. Many of these species occur in the northern part of the continent, on routes that fall outside the core survey area presently analyzed in the United States and southern Canada. Other species not historically analyzed occur in the core survey area with very limited data but have large portions of their ranges in Mexico and south. A third group of species not historically analyzed included species thought to be poorly surveyed by the BBS, such as rare, coastal, or nocturnal species. For 56 species found primarily in regions north of the core survey area, we expanded the scope of the analysis, using data from 1993 to 2014 during which ≥3 survey routes had been sampled in 6 northern strata (Bird Conservation regions in Alaska, Yukon, and Newfoundland and Labrador) and fitting log-linear hierarchical models for an augmented BBS survey area that included both the new northern strata and the core survey area. We also applied this model to 168 species historically analyzed in the BBS that had data from these additional northern strata. For both groups of species we calculated survey-wide trends for the both core and augmented survey areas from 1993 to 2014; for species that did not occur in the newly defined strata, we computed trends from 1966 to 2014. We evaluated trend estimates in terms of established credibility criteria for BBS results, screening for imprecise trends, small samples, and low relative abundance. Inclusion of data from the northern strata permitted estimation of trend for 56 species not historically analyzed, but only 4 of these were reasonably monitored and an additional 13 were questionably monitored; 39 of these species were likely poorly monitored because of small numbers of samples or very imprecisely estimated trends. Only 4 of 66 “new” species found in the core survey area were reasonably monitored by the BBS; 20 were questionably monitored; and 42 were likely poorly monitored by the BBS because of inefficiency in precision, abundance, or sample size. The hierarchical analyses we present provide a means for reasonable inclusion of the additional species and strata in a common analysis with data from the core area, a critical step in the evolution of the BBS as a continent-scale survey. We recommend that results be presented both 1) from 1993 to the present using the expanded survey area, and 2) from 1966 to the present for the core survey area. Although most of the “new” species we analyzed were poorly monitored by the BBS during 1993–2014, continued expansion of the BBS will improve the quality of information in future analyses for these species and for the many other species presently monitored by the BBS.

Calibrating LOFAR using the Black Board Selfcal System

NASA Astrophysics Data System (ADS)

Pandey, V. N.; van Zwieten, J. E.; de Bruyn, A. G.; Nijboer, R.

2009-09-01

The Black Board SelfCal (BBS) system is designed as the final processing system to carry out the calibration of LOFAR in an efficient way. In this paper we give a brief description of its architectural and software design including its distributed computing approach. A confusion limited deep all sky image (from 38-62 MHz) by calibrating LOFAR test data with the BBS suite is shown as a sample result. The present status and future directions of development of BBS suite are also touched upon. Although BBS is mainly developed for LOFAR, it may also be used to calibrate other instruments once their specific algorithms are plugged in.

Roadside versus remote: Is the habitat sampled by the Breeding Bird Survey in Maryland representative of statewide conditions?

USGS Publications Warehouse

Boone, D.D.; Sauer, J.R.; Thomas, I.; Handley, Lawrence R.; D'Erchia, Frank J.; Charron, Tammy M.

2000-01-01

The North American Breeding Bird Survey (BBS) has received criticism that the bird habitat sampled along the 24.5 mile long roadside transects may not be proportional to regional totals. If true, trends in bird populations recorded by the BBS may not be sensitive predictors of regional or continental change in songbird abundance. To test whether the approximately 60 BBS routes in Maryland representatively sample the state's habitat, a geographic information system (GIS) database was compiled of significant bird habitat identified from remotely sensed landcover and land-use information (e.g., Multi-Resolution Land Characteristics Consortiumclassified Landsat Thematic Mapper imagery, etc.). These GIS data layers were analyzed to determine the statewide acreage of identified habitats as well as the acreage in each of the major physiographic regions of Maryland. Regional and statewide totals were also extracted for the subsample of habitat within 30 m of the BBS transects. The results of the comparison of regional and statewide habitat totals with the BBS sample showed very low proportional difference for nearly all of the identified habitat parameters. For Maryland and perhaps other urbanizing states, the BBS provides an accurate sample of available songbird habitats.

Effect of porcine gastrin releasing peptide on gastric secretion and motility and the release of hormonal peptides in conscious cats.

PubMed

Vagne, M; Collinet, M; Cuber, J C; Bernard, C; Chayvialle, J A; McDonald, T J; Mutt, V

1987-01-01

The effect of porcine gastrin releasing peptide (GRP) was compared to those of bombesin (BBS) and pentagastrin (PG) in conscious cats. GRP and BBS augmented acid and pepsin secretions, as well as antral motility with an early effect comparable to that produced by pentagastrin with an elevation of low amplitude contractions and a diminution of high amplitude contractions. BBS and GRP increased plasma gastrin and pancreatic polypeptide (PP) levels and decreased motilin levels measured by a C terminus-directed antiserum. In all cases, BBS and GRP displayed parallel dose-response curves. PG showed slight differences in the slopes of the dose-response curves slopes of the dose-response curves except for acid secretion stimulation where no difference was noted (PG was the most effective) and for pepsin stimulation where the difference was large (PG was much less effective). According to the different targets studied, BBS was 4 to 9 times more potent than GRP, 6 to 200 times more than PG. Gastrin release, elicited by the lowest ED50 of both BBS and GRP, should be considered as their primary effect in the cat.

A method for mass harvesting islets (Brockmann bodies) from teleost fish.

PubMed

Yang, H; Wright, J R

1995-01-01

In certain species of fish, the insulin-producing tissue is uniquely located in separate structures called Brockmann bodies (BBs). Tilapia BBs have been shown to be a simple and inexpensive source of islet cells for xenotransplantation research. Each donor tilapia contains roughly 12-15 BBs, measuring from 0.3 to 5.0 mm in maximum dimension, in a triangular region of adipose tissue bounded by the liver, stomach, and spleen/gallbladder. At present, the larger BBs (usually 2-4) are harvested by microdissecting these "BB regions" using jeweler's forceps and microvascular scissors while being visualized with the aid of a dissecting microscope. It is a simple but time-consuming task that would not be applicable for harvesting massive amounts of BB tissue for large animal studies. Therefore, we have developed an easier and more efficient method of harvesting BBs based on a standard enzymatic method for isolating human adipocytes. BB regions are harvested from donor fish and pooled into a 50 mL plastic tube containing collagenase Type II (3 mg/mL) in Hank's balanced salt solution (HBSS); the tube is then placed in a 37 degrees C waterbath/shaker for roughly 15 min. The exact length of the digestion interval is determined by visual inspection of the tube to determine whether the BBs have been liberated. The digestion is then stopped by adding excess cold HBSS. The adipocytes float while the BBs and residual connective tissue (i.e., a few blood vessels, nerves, and bile ducts) form a pellet. The pellet is washed several times in HBSS and then placed in a culture dish. The BBs are easily handpicked with a siliconized pipette. Based on functional data and DNA content, this new method roughly doubles or triples our yield of BB tissue per donor fish. To determine whether BBs harvested in this manner functioned in a manner similar to those harvested by microdissection, we performed a series of transplants using mass-harvested BBs. Long-term normoglycemia was achieved in streptozotocin-diabetic nude mice and mean graft survival time was not altered in streptozotocin-diabetic euthymic balb/c mice. However, the total weight of donor fish required per recipient was decreased by 50% in both strains.

Relationship of executive function and educational status with functional balance in older adults.

PubMed

Voos, Mariana Callil; Custódio, Elaine Bazilio; Malaquias, Joel

2011-01-01

The Berg Balance Scale (BBS) is frequently used to assess functional balance in older adults. The relationship of executive function and level of education with the BBS performance has not been described. The aim of this study was to determine whether (1) the performance on a task requiring executive function (part B of the Trail Making Test, TMT-B) influences results of motor and cognitive tests and (2) the number of years of formal education could be related to performance on BBS in older adults. We also explored whether there would be differences, based on performance on TMT-B (high vs low) in motor function (BBS, the timed up and go [TUG]) or cognitive function (TMT-A and TMTDELTA), the Mini Mental State Examination (MMSE), as well as years of education. Participants included 101 older adults (age range, 60-80 years) residing in São Paulo, Brazil. Functional balance was assessed using BBS and TUG. Executive function was assessed using the TMT and MMSE. Educational status was determined by self-report of participant's total number of years of formal education. The BBS scores were inversely related to TMT-A time (r = -0.63, r = 0.40, P < .001) and TMT-B time (r = -0.56, r = 0.31, P < .001). There was a similar relationship with TMTDELTA (r = -0.47, r = 0.22, P < .001). The BBS scores were positively correlated to years of formal education (r = 0.48, r = 0.23, P < .001). There was a ceiling effect on the TMT-B, with many individuals reaching maximum score of 300 seconds. Participants with high levels of executive function had higher BBS and MMSE scores, more education, and lower TMT-A, TMTDELTA and TUG scores (P < .001) than the lower functioning group. Individuals with higher capacity on tasks requiring visuospatial abilities, psychomotor speed, and executive function, such as the TMT, had better performance on BBS. Individuals with a high executive function, measured by TMT-B, also performed better on other motor and cognitive tests.

Ameliorative effects of bombesin and neurotensin on trinitrobenzene sulphonic acid-induced colitis, oxidative damage and apoptosis in rats.

PubMed

Akcan, Alper; Muhtaroglu, Sebahattin; Akgun, Hulya; Akyildiz, Hizir; Kucuk, Can; Sozuer, Erdogan; Yurci, Alper; Yilmaz, Namik

2008-02-28

To investigate the effects of bombesin (BBS) and neurotensin (NTS) on apoptosis and colitis in an ulcerative colitis model. In this study, a total of 50 rats were divided equally into 5 groups. In the control group, no colitis induction or drug administration was performed. Colitis was induced in all other groups. Following the induction of colitis, BBS, NTS or both were applied to three groups of rats. The remaining group (colitis group) received no treatment. On the 11th d after induction of colitis and drug treatment, blood samples were collected for TNF-alpha and IL-6 level studies. Malondialdehyde (MDA), carbonyl, myeloperoxidase (MPO) and caspase-3 activities, as well as histopathological findings, evaluated in colonic tissues. According to the macroscopic and microscopic findings, the study groups treated with BBS, NTS and BBS + NTS showed significantly lower damage and inflammation compared with the colitis group (macroscopic score, 2.1 +/- 0.87, 3.7 +/- 0.94 and 2.1 +/- 0.87 vs 7.3 +/- 0.94; microscopic score, 2.0 +/- 0.66, 3.3 +/- 0.82 and 1.8 +/- 0.63 vs 5.2 +/- 0.78, P < 0.01). TNF-alpha and IL-6 levels were increased significantly in all groups compared with the control group. These increases were significantly smaller in the BBS, NTS and BBS + NTS groups compared with the colitis group (TNF-alpha levels, 169.69 +/- 53.56, 245.86 +/- 64.85 and 175.54 +/- 42.19 vs 556.44 +/- 49.82; IL-6 levels, 443.30 +/- 53.99, 612.80 +/- 70.39 and 396.80 +/- 78.43 vs 1505.90 +/- 222.23, P < 0.05). The colonic MPO and MDA levels were significantly lower in control, BBS, NTS and BBS + NTS groups than in the colitis group (MPO levels, 24.36 +/- 8.10, 40.51 +/- 8.67 and 25.83 +/- 6.43 vs 161.47 +/- 38.24; MDA levels, 4.70 +/- 1.41, 6.55 +/- 1.12 and 4.51 +/- 0.54 vs 15.60 +/- 1.88, P < 0.05). Carbonyl content and caspase-3 levels were higher in the colitis and NTS groups than in control, BBS and BBS + NTS groups (carbonyl levels, 553.99 +/- 59.58 and 336.26 +/- 35.72 vs 209.76 +/- 30.92, 219.76 +/- 25.77 and 220.34 +/- 36.95; caspase-3 levels, 451.70 +/- 68.27 and 216.20 +/- 28.17 vs 28.60 +/- 6.46, 170.50 +/- 32.37 and 166.50 +/- 30.95, P < 0.05). The results of this study suggest BBS and NTS, through their anti-inflammatory actions, support the maintenance of colonic integrity and merit consideration as potential agents for ameliorating colonic inflammation.

Population trends from the North American Breeding Bird Survey

USGS Publications Warehouse

Peterjohn, B.G.; Sauer, J.R.; Robbins, C.S.; Martin, Thomas E.; Finch, Deborah M.

1995-01-01

INTRODUCTION: Most Neotropical migrant birds are difficult to count accurately and are moderately common over large breeding distributions. Consequently, little historical information exists on their large-scale population changes, and most of this information is anecdotal. Surveys begun in this century such as Breeding Bird Censuses and Christmas Bird Counts have the potential to provide this information, but only the North American Breeding Bird Survey (BBS) achieves the extensive continental coverage necessary to document population changes for most Neotropical migrant birds. Conservationists and ecologists have begun to use BBS data to estimate population trends, but there is still widespread confusion over exactly what these data show regarding population changes. In this chapter, we review the current state of knowledge regarding population changes in Neotropical migrant birds and the methods used to analyze these changes. The primary emphasis is on the BBS (Robbins et al. 1986) because this survey provides the best available data for estimating trends of Neotropical migrants on a continental scale. To address questions about methods of analyzing survey data, we review and compare some alternative methods of analyzing BBS data. We also discuss the effectiveness of the BBS in sampling Neotropical migrant species, and review possibilities for use of alternative data sets to verify trends from the BBS.

The relationship between objective balance, perceived sense of balance, and fear of falling in stroke patients.

PubMed

Oguz, Semra; Demirbuken, Ilksan; Kavlak, Bahar; Acar, Gonul; Yurdalan, Saadet Ufuk; Polat, Mine Gulden

2017-10-01

The objective of our study was to investigate the relationship between objective balance, fear of falling, and perceived sense of balance (PSB) in stroke patients. Seventy patients aged 18-65 years with chronically developed hemiplegia or hemiparesis were enrolled in the study. Patients' objective balance scores, fear of falling, and PSB were obtained using the berg balance scale (BBS), the falls efficacy scale (FES), and a visual analog scale, respectively. The Standard Mini-Mental Examination was performed to exclude patients with mental disorders from the study. There was a moderate negative correlation between PSB and BBS scores (p = 0.001, ρ = -0.588); a strong negative correlation between BBS and FES scores (p = 0.001, ρ = -0.808); and a strong positive correlation between PSB and FES scores (p = 0.001, ρ = 0.714). We found that BBS scores had negative correlation with PBS scores in left hemiplegic patients while there was no any relationship between BBS and PBS scores in right hemiplegic patients. PSB assessment, besides the BBS, should be considered among the routine assessment methods that enable the rehabilitation team to be aware of patients' balance capacities.

Clinical Characteristics of Proper Robot-Assisted Gait Training Group in Non-ambulatory Subacute Stroke Patients

PubMed Central

Kim, Soo Jeong; Lee, Hye Jin; Hwang, Seung Won; Pyo, Hannah; Yang, Sung Phil; Lim, Mun-Hee; Park, Gyu Lee

2016-01-01

Objective To identify the clinical characteristics of proper robot-assisted gait training group using exoskeletal locomotor devices in non-ambulatory subacute stroke patients. Methods A total of 38 stroke patients were enrolled in a 4-week robotic training protocol (2 sessions/day, 5 times/week). All subjects were evaluated for their general characteristics, Functional Ambulatory Classification (FAC), Fugl-Meyer Scale (FMS), Berg Balance Scale (BBS), Modified Rankin Scale (MRS), Modified Barthel Index (MBI), and Mini-Mental Status Examination (MMSE) at 0, 2, and 4 weeks. Statistical analysis were performed to determine significant clinical characteristics for improvement of gait function after robot-assisted gait training. Results Paired t-test showed that all functional parameters except MMSE were improved significantly (p<0.05). The duration of disease and baseline BBS score were significantly (p<0.05) correlated with FAC score in multiple regression models. Receiver operating characteristic (ROC) curve showed that a baseline BBS score of '9' was a cutoff value (AUC, 0.966; sensitivity, 91%–100%; specificity, 85%). By repeated-measures ANOVA, the differences in improved walking ability according to time were significant between group of patients who had baseline BBS score of '9' and those who did not have baseline BBS score of '9' Conclusion Our results showed that a baseline BBS score above '9' and a short duration of disease were highly correlated with improved walking ability after robot-assisted gait training. Therefore, baseline BBS and duration of disease should be considered clinically for gaining walking ability in robot-assisted training group. PMID:27152266

Discriminant analysis for predictor of falls in stroke patients by using the Berg Balance Scale.

PubMed

Maeda, Noriaki; Urabe, Yukio; Murakami, Masahito; Itotani, Keisuke; Kato, Junichi

2015-05-01

An observational study was carried out to estimate the strength of the relationships among balance, mobility and falls in hemiplegic stroke inpatients. The objective was to examine factors that may aid in the prediction of the likelihood of falls in stroke patients. A total of 53 stroke patients (30 male, 23 female) aged 67.0 ± 11.1 years were interviewed regarding their fall history. Physical performance was assessed using the Berg Balance Scale (BBS) and the Functional Independence Measure (FIM) scale. Variables that differed between fallers and non-fallers were identified, and a discriminant function analysis was carried out to determine the combination of variables that effectively predicted fall status. Of the 53 stroke patients, 19 were fallers. Compared with the non-fallers, the fallers scored low on the FIM, and differed with respect to age, time from stroke onset, length of hospital stay, Brunnstrom recovery stage and admission BBS score. Discriminant analysis for predicting falls in stroke patients showed that admission BBS score was significantly related to the likelihood of falls. Moreover, discriminant analysis showed that the use of a significant BBS score to classify fallers and non-fallers had an accuracy of 81.1%. The discriminating criterion between the two groups was a score of 31 points on the BBS. The results of this study suggest that BBS score is a strong predictor of falls in stroke patients. As balance is closely related to the risk of falls in hospitalised stroke patients, BBS might be useful in the prediction of falls.

Integrating Breeding Bird Survey and demographic data to estimate Wood Duck population size in the Atlantic Flyway

USGS Publications Warehouse

Zimmerman, Guthrie S.; Sauer, John; Boomer, G. Scott; Devers, Patrick K.; Garrettson, Pamela R.

2017-01-01

The U.S. Fish and Wildlife Service (USFWS) uses data from the North American Breeding Bird Survey (BBS) to assist in monitoring and management of some migratory birds. However, BBS analyses provide indices of population change rather than estimates of population size, precluding their use in developing abundance-based objectives and limiting applicability to harvest management. Wood Ducks (Aix sponsa) are important harvested birds in the Atlantic Flyway (AF) that are difficult to detect during aerial surveys because they prefer forested habitat. We integrated Wood Duck count data from a ground-plot survey in the northeastern U.S. with AF-wide BBS, banding, parts collection, and harvest data to derive estimates of population size for the AF. Overlapping results between the smaller-scale intensive ground-plot survey and the BBS in the northeastern U.S. provided a means for scaling BBS indices to the breeding population size estimates. We applied these scaling factors to BBS results for portions of the AF lacking intensive surveys. Banding data provided estimates of annual survival and harvest rates; the latter, when combined with parts-collection data, provided estimates of recruitment. We used the harvest data to estimate fall population size. Our estimates of breeding population size and variability from the integrated population model (N̄ = 0.99 million, SD = 0.04) were similar to estimates of breeding population size based solely on data from the AF ground-plot surveys and the BBS (N̄ = 1.01 million, SD = 0.04) from 1998 to 2015. Integrating BBS data with other data provided reliable population size estimates for Wood Ducks at a scale useful for harvest and habitat management in the AF, and allowed us to derive estimates of important demographic parameters (e.g., seasonal survival rates, sex ratio) that were not directly informed by data.

Ameliorative effects of bombesin and neurotensin on trinitrobenzene sulphonic acid-induced colitis, oxidative damage and apoptosis in rats

PubMed Central

Akcan, Alper; Muhtaroglu, Sebahattin; Akgun, Hulya; Akyildiz, Hizir; Kucuk, Can; Sozuer, Erdogan; Yurci, Alper; Yilmaz, Namik

2008-01-01

AIM: To investigate the effects of bombesin (BBS) and neurotensin (NTS) on apoptosis and colitis in an ulcerative colitis model. METHODS: In this study, a total of 50 rats were divided equally into 5 groups. In the control group, no colitis induction or drug administration was performed. Colitis was induced in all other groups. Following the induction of colitis, BBS, NTS or both were applied to three groups of rats. The remaining group (colitis group) received no treatment. On the 11th d after induction of colitis and drug treatment, blood samples were collected for TNF-α and IL-6 level studies. Malondialdehyde (MDA), carbonyl, myeloperoxidase (MPO) and caspase-3 activities, as well as histopathological findings, evaluated in colonic tissues. RESULTS: According to the macroscopic and microscopic findings, the study groups treated with BBS, NTS and BBS + NTS showed significantly lower damage and inflammation compared with the colitis group (macroscopic score, 2.1 ± 0.87, 3.7 ± 0.94 and 2.1 ± 0.87 vs 7.3 ± 0.94; microscopic score, 2.0 ± 0.66, 3.3 ± 0.82 and 1.8 ± 0.63 vs 5.2 ± 0.78, P < 0.01). TNF-α and IL-6 levels were increased significantly in all groups compared with the control group. These increases were significantly smaller in the BBS, NTS and BBS + NTS groups compared with the colitis group (TNF-α levels, 169.69 ± 53.56, 245.86 ± 64.85 and 175.54 ± 42.19 vs 556.44 ± 49.82; IL-6 levels, 443.30 ± 53.99, 612.80 ± 70.39 and 396.80 ± 78.43 vs 1505.90 ± 222.23, P < 0.05). The colonic MPO and MDA levels were significantly lower in control, BBS, NTS and BBS + NTS groups than in the colitis group (MPO levels, 24.36 ± 8.10, 40.51 ± 8.67 and 25.83 ± 6.43 vs 161.47 ± 38.24; MDA levels, 4.70 ± 1.41, 6.55 ± 1.12 and 4.51 ± 0.54 vs 15.60 ± 1.88, P < 0.05). Carbonyl content and caspase-3 levels were higher in the colitis and NTS groups than in control, BBS and BBS + NTS groups (carbonyl levels, 553.99 ± 59.58 and 336.26 ± 35.72 vs 209.76 ± 30.92, 219.76 ± 25.77 and 220.34 ± 36.95; caspase-3 levels, 451.70 ± 68.27 and 216.20 ± 28.17 vs 28.60 ± 6.46, 170.50 ± 32.37 and 166.50 ± 30.95, P < 0.05). CONCLUSION: The results of this study suggest BBS and NTS, through their anti-inflammatory actions, support the maintenance of colonic integrity and merit consideration as potential agents for ameliorating colonic inflammation. PMID:18300348

The treatment gap in patients with chronic systolic heart failure: a systematic review of evidence-based prescribing in practice.

PubMed

Chin, Ken Lee; Skiba, Marina; Tonkin, Andrew; Reid, Christopher M; Liew, Danny; Krum, Henry; Hopper, Ingrid

2016-11-01

The extent and impact of under-prescribing of evidence-based pharmacological therapies among heart failure patients with reduced ejection fraction (HFREF) in contemporary practice is unclear. We sought to examine the prescribing patterns of angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), β-blockers (BBs) and mineralocorticoid receptor antagonists (MRAs), and to quantify the estimated 'treatment gap' among HFREF patients in the 'real-world' setting. The MEDLINE, PubMed, EMBASE, CINAHL and CENTRAL databases were searched for registry- or survey-based studies which examined the prescribing rates of ACE inhibitors, ARBs, BBs and MRAs among HFREF patients. Searches were limited to those published in the years 2000-2015. A total of 23 reports, including 83,605 patients, were evaluated. Overall, ACE inhibitors/ARBs, BBs and MRAs were prescribed to 79.8, 81.4 and 36.4 % of patients, respectively. The estimated treatment gaps in the overall population were 13.1 % for ACE inhibitors/ARBs, 3.9 % for BBs and 16.8 % for MRAs. The proportion of patients who received ≥50 % of the guideline-recommended target doses was 72 % for ACE inhibitors, 51 % for ARBs, 49 % for BBs, 53 % for the combination of ACE inhibitors/ARBs and BBs and 83 % for MRAs. Prescribing these drugs according to contemporary guidelines was associated with lower mortality risk. Patients who were elderly, female and with comorbidities were less likely to receive optimal treatment as recommended by the guidelines. ACE inhibitors, ARBs, BBs and MRAs are under-prescribed in eligible HFREF patients. Efforts should be made to improve approaches to closing the treatment gap at both systems of care and individual levels.

Short Berg Balance Scale, BBS-9, as a predictor of fall risk among the aged: a prospective 12-month follow-up study.

PubMed

Hohtari-Kivimäki, Ulla; Salminen, Marika; Vahlberg, Tero; Kivelä, Sirkka-Liisa

2013-12-01

The aim of this study was to assess the adequacy of the short, 9-item Berg Balance Scale (BBS-9) to predict fall risk among the community-dwelling aged. The subjects (n = 519) were derived from the participants in a multifactorial fall prevention intervention conducted in Pori, Finland. Receiver operating characteristic (ROC) analysis was used to determine the cut-off score for BBS-9 (range 0-36) to classify aged people with a fall risk during a 12-month follow-up. Logistic regression was used to analyse the relationship of potential confounders with fall risk. The association between the cut-off score for BBS-9 and fall risk was tested using the Chi-square test. In determining the cut-off score of BBS-9 to classify fall risk, the highest sensitivity (0.51) and specificity (0.57) (when both presumed to be above 0.50) sum score was within the limit range 32 scores or below. The area under curve (AUC) was significantly better in the model adjusted for significant confounders (vision and the number of regularly used drugs) (AUC = 0.64) than in the unadjusted model (AUC = 0.57) (p = 0.045). Among patients who scored 32 or below in BBS-9 the incidence of multiple falls was 20.0 %, whereas among those who scored 33-36 it was 15.7 %. BBS-9 with the cut-off score of 32/33 together with data on vision and the number of regularly used drugs predicted moderately the risk of falling among the community-dwelling aged.

Functional gait assessment and balance evaluation system test: reliability, validity, sensitivity, and specificity for identifying individuals with Parkinson disease who fall.

PubMed

Leddy, Abigail L; Crowner, Beth E; Earhart, Gammon M

2011-01-01

Gait impairments, balance impairments, and falls are prevalent in individuals with Parkinson disease (PD). Although the Berg Balance Scale (BBS) can be considered the reference standard for the determination of fall risk, it has a noted ceiling effect. Development of ceiling-free measures that can assess balance and are good at discriminating "fallers" from "nonfallers" is needed. The purpose of this study was to compare the Functional Gait Assessment (FGA) and the Balance Evaluation Systems Test (BESTest) with the BBS among individuals with PD and evaluate the tests' reliability, validity, and discriminatory sensitivity and specificity for fallers versus nonfallers. This was an observational study of community-dwelling individuals with idiopathic PD. The BBS, FGA, and BESTest were administered to 80 individuals with PD. Interrater reliability (n=15) was assessed by 3 raters. Test-retest reliability was based on 2 tests of participants (n=24), 2 weeks apart. Intraclass correlation coefficients (2,1) were used to calculate reliability, and Spearman correlation coefficients were used to assess validity. Cutoff points, sensitivity, and specificity were based on receiver operating characteristic plots. Test-retest reliability was .80 for the BBS, .91 for the FGA, and .88 for the BESTest. Interrater reliability was greater than .93 for all 3 tests. The FGA and BESTest were correlated with the BBS (r=.78 and r=.87, respectively). Cutoff scores to identify fallers were 47/56 for the BBS, 15/30 for the FGA, and 69% for the BESTest. The overall accuracy (area under the curve) for the BBS, FGA, and BESTest was .79, .80, and .85, respectively. Fall reports were retrospective. Both the FGA and the BESTest have reliability and validity for assessing balance in individuals with PD. The BESTest is most sensitive for identifying fallers.

Bardet-Biedl syndrome: Genetics, molecular pathophysiology, and disease management.

PubMed

Priya, Sathya; Nampoothiri, Sheela; Sen, Parveen; Sripriya, S

2016-09-01

Primary cilia play a key role in sensory perception and various signaling pathways. Any defect in them leads to group of disorders called ciliopathies, and Bardet-Biedl syndrome (BBS, OMIM 209900) is one among them. The disorder is clinically and genetically heterogeneous, with various primary and secondary clinical manifestations, and shows autosomal recessive inheritance and highly prevalent in inbred/consanguineous populations. The disease mapped to at least twenty different genes (BBS1-BBS20), follow oligogenic inheritance pattern. BBS proteins localizes to the centerosome and regulates the biogenesis and functions of the cilia. In BBS, the functioning of various systemic organs (with ciliated cells) gets deranged and results in systemic manifestations. Certain components of the disease (such as obesity, diabetes, and renal problems) when noticed earlier offer a disease management benefit to the patients. However, the awareness of the disease is comparatively low and most often noticed only after severe vision loss in patients, which is usually in the first decade of the patient's age. In the current review, we have provided the recent updates retrieved from various types of scientific literature through journals, on the genetics, its molecular relevance, and the clinical outcome in BBS. The review in nutshell would provide the basic awareness of the disease that will have an impact in disease management and counseling benefits to the patients and their families.

Cycling of the signaling protein phospholipase D through cilia requires the BBSome only for the export phase

PubMed Central

Brown, Jason M.; Sampaio, Julio L.; Craft, Julie M.; Shevchenko, Andrej; Evans, James E.; Witman, George B.

2013-01-01

The BBSome is a complex of seven proteins, including BBS4, that is cycled through cilia by intraflagellar transport (IFT). Previous work has shown that the membrane-associated signaling protein phospholipase D (PLD) accumulates abnormally in cilia of Chlamydomonas reinhardtii bbs mutants. Here we show that PLD is a component of wild-type cilia but is enriched ∼150-fold in bbs4 cilia; this accumulation occurs progressively over time and results in altered ciliary lipid composition. When wild-type BBSomes were introduced into bbs cells, PLD was rapidly removed from the mutant cilia, indicating the presence of an efficient BBSome-dependent mechanism for exporting ciliary PLD. This export requires retrograde IFT. Importantly, entry of PLD into cilia is BBSome and IFT independent. Therefore, the BBSome is required only for the export phase of a process that continuously cycles PLD through cilia. Another protein, carbonic anhydrase 6, is initially imported normally into bbs4 cilia but lost with time, suggesting that its loss is a secondary effect of BBSome deficiency. PMID:23589493

Impact of scalar mesons on the rare B-decays

NASA Astrophysics Data System (ADS)

Issadykov, Aidos; Ivanov, Mikhail A.; Sakhiyev, Sayabek K.

2015-11-01

In the wake of exploring uncertainty in the full angular distribution of the B → Kπ + μ+μ- caused by the presence of the intermediate scalar K0∗ meson, we perform the straightforward calculation of the B(Bs) → S (S is a scalar meson) transition form factors in the full kinematical region within the covariant quark model. We restrict ourselves by the scalar mesons below 1 GeV: a0(980),f0(500),f0(980),K0∗(800). As an application of the obtained results we calculate the widths of the semileptonic and rare decays B(Bs) → Sℓν¯, B(Bs) → Sℓℓ¯ and B(Bs) → Sνν¯. We compare our results with those obtained in other approaches.

[Using exon combined target region capture sequencing chip to detect the disease-causing genes of retinitis pigmentosa].

PubMed

Rong, Weining; Chen, Xuejuan; Li, Huiping; Liu, Yani; Sheng, Xunlun

2014-06-01

To detect the disease-causing genes of 10 retinitis pigmentosa pedigrees by using exon combined target region capture sequencing chip. Pedigree investigation study. From October 2010 to December 2013, 10 RP pedigrees were recruited for this study in Ningxia Eye Hospital. All the patients and family members received complete ophthalmic examinations. DNA was abstracted from patients, family members and controls. Using exon combined target region capture sequencing chip to screen the candidate disease-causing mutations. Polymerase chain reaction (PCR) and direct sequencing were used to confirm the disease-causing mutations. Seventy patients and 23 normal family members were recruited from 10 pedigrees. Among 10 RP pedigrees, 1 was autosomal dominant pedigrees and 9 were autosomal recessive pedigrees. 7 mutations related to 5 genes of 5 pedigrees were detected. A frameshift mutation on BBS7 gene was detected in No.2 pedigree, the patients of this pedigree combined with central obesity, polydactyly and mental handicap. No.2 pedigree was diagnosed as Bardet-Biedl syndrome finally. A missense mutation was detected in No.7 and No.10 pedigrees respectively. Because the patients suffered deafness meanwhile, the final diagnosis was Usher syndrome. A missense mutation on C3 gene related to age-related macular degeneration was also detected in No. 7 pedigrees. A nonsense mutation and a missense mutation on CRB1 gene were detected in No. 1 pedigree and a splicesite mutation on PROM1 gene was detected in No. 5 pedigree. Retinitis pigmentosa is a kind of genetic eye disease with diversity clinical phenotypes. Rapid and effective genetic diagnosis technology combined with clinical characteristics analysis is helpful to improve the level of clinical diagnosis of RP.

Long-term trends in breeding birds in an old-growth Adirondack forest and the surrounding region

USGS Publications Warehouse

McNulty, S.A.; Droege, S.; Masters, R.D.

2008-01-01

Breeding bird populations were sampled between 1954 and 1963, and 1990 and 2000 in an old-growth forest, the Natural Area of Huntington Wildlife Forest (HWF), in the Adirondack Mountains of New York. Trends were compared with data from regional North American Breeding Bird Surveys (BBS) and from a forest plot at Hubbard Brook Experimental Forest, New Hampshire. Trends for 22 species in the HWF Natural Area were negative, eight were positive, and one was zero; 20 were significant. Fifteen of 17 long-distance migrants declined, whereas 7 of 14 short-distance migrants and permanent residents declined. Most (74%) HWF Natural Area species, despite differences in sampling periods and local habitat features, matched in sign of trend when compared to Adirondack BBS routes, 61% matched northeastern BBS routes, and 71% matched eastern United States BBS routes, while 66% matched Hubbard Brook species. The agreement in population trends suggests that forest interior birds, especially long-distance migrants, are affected more by regional than local factors. The analysis indicated that bird trends generated from BBS routes may not be as biased toward roads as previously suggested.

Fidelity by design: Yoctoreactor and binder trap enrichment for small-molecule DNA-encoded libraries and drug discovery.

PubMed

Blakskjaer, Peter; Heitner, Tara; Hansen, Nils Jakob Vest

2015-06-01

DNA-encoded small-molecule library (DEL) technology allows vast drug-like small molecule libraries to be efficiently synthesized in a combinatorial fashion and screened in a single tube method for binding, with an assay readout empowered by advances in next generation sequencing technology. This approach has increasingly been applied as a viable technology for the identification of small-molecule modulators to protein targets and as precursors to drugs in the past decade. Several strategies for producing and for screening DELs have been devised by both academic and industrial institutions. This review highlights some of the most significant and recent strategies along with important results. A special focus on the production of high fidelity DEL technologies with the ability to eliminate screening noise and false positives is included: using a DNA junction called the Yoctoreactor, building blocks (BBs) are spatially confined at the center of the junction facilitating both the chemical reaction between BBs and encoding of the synthetic route. A screening method, known as binder trap enrichment, permits DELs to be screened robustly in a homogeneous manner delivering clean data sets and potent hits for even the most challenging targets. Copyright © 2015 Elsevier Ltd. All rights reserved.

TUDCA Slows Retinal Degeneration in Two Different Mouse Models of Retinitis Pigmentosa and Prevents Obesity in Bardet-Biedl Syndrome Type 1 Mice

PubMed Central

Drack, Arlene V.; Dumitrescu, Alina V.; Bhattarai, Sajag; Gratie, Daniel; Stone, Edwin M.; Mullins, Robert

2012-01-01

Purpose. To evaluate and compare the protective effect of tauroursodeoxycholic acid (TUDCA) on photoreceptor degeneration in different models of retinal degeneration (RD) in mice. Methods. BbsM390R/M390R mice were injected subcutaneously twice a week, from P40 to P120, and rd10 mice were injected every 3 days from P6 to P38 with TUDCA or vehicle (0.15 M NaHCO3). Rd1 and rd16 mice were injected daily from P6 to P30 with TUDCA or vehicle. Retinal structure and function were determined at multiple time points by electroretinography (ERG), optical coherence tomography (OCT), and histology. Results. The amplitude of ERG b-waves was significantly higher in TUDCA-treated Bbs1 and rd10 animals than in controls. Retinal thickness on OCT was slightly greater in treated Bbs1 animals than in the controls. Histologically, outer segments were preserved, and the outer nuclear layer was significantly thicker in the treated Bbs1 and rd10 mice than in the controls. Bbs1M390R/M390R mice developed less obesity than the control Bbs1M390R/M390R while receiving TUDCA. The Rd1 and rd16 mice showed no improvement with TUDCA treatment, and the rd1 mice did not have normal weight gain during treatment. Conclusions. TUDCA treatment preserved ERG b-waves and the outer nuclear layer in Bbs1M390R/M390R mice, and prevented obesity assessed at P120. TUDCA treatment preserved ERG b-waves and the outer nuclear layer in the rd10 mice to P30. TUDCA is a prime candidate for treatment of humans with retinal degeneration, especially those with Bardet-Biedl syndrome, whom it may help not only with the vision loss, but with the debilitating obesity as well. PMID:22110077

Use of North American Breeding Bird Survey data in avian conservation assessments

USGS Publications Warehouse

Rosenberg, Kenneth V.; Blancher, Peter J.; Stanton, Jessica C.; Panjabi, Arvind O.

2017-01-01

Conservation resources are limited, and prioritizing species based on their relative vulnerability and risk of extinction is a fundamental component of conservation planning. In North America, the conservation consortium Partners in Flight (PIF) has developed and implemented a data-driven species assessment process, at global and regional scales, based on quantitative vulnerability criteria. This species assessment process has formed the biological basis for PIF's continental and regional planning and has informed the ranking and legal listing of bird species for conservation protection by state, provincial, and national agencies in Canada, the U.S., and Mexico. Because of its long time series, extensive geographic and species coverage, standardized survey methods, and prompt availability of results, the North American Breeding Bird Survey (BBS) has been an invaluable source of data, allowing PIF to assign objective vulnerability scores calibrated across more than 460 landbird species. BBS data have been most valuable for assessing long-term population trends (PT score). PIF has also developed methods for estimating population size by extrapolating from BBS abundance indices, allowing the assignment of categorical population size (PS) scores for landbird species. At regional scales, BBS relative abundance indices have allowed PIF to assess the area importance (i.e. stewardship responsibility) of each Bird Conservation Region (BCR) for each species, using measures of both relative density and percent of total population in each BCR. Besides direct applicability to assessment scores, PIF has recently used BBS trend data to create new metrics of conservation urgency (e.g., ‘half-life'), as well as for setting population objectives for tracking progress toward meeting conservation goals. Future directions include integrating BBS data with other sources (e.g., eBird) to assess additional species and nonbreeding season measures, working closely with BBS coordinators to expand surveys into Mexico, and providing assessment scores at implementation-relevant scales, such as for migratory bird joint ventures.

The Diagnostic Accuracy of the Berg Balance Scale in Predicting Falls.

PubMed

Park, Seong-Hi; Lee, Young-Shin

2017-11-01

This study aimed to evaluate the predictive validity of the Berg Balance Scale (BBS) as a screening tool for fall risks among those with varied levels of balance. A total of 21 studies reporting predictive validity of the BBS of fall risk were meta-analyzed. With regard to the overall predictive validity of the BBS, the pooled sensitivity and specificity were 0.72 and 0.73, respectively; the accuracy curve area was 0.84. The findings showed statistical heterogeneity among studies. Among the sub-groups, the age group of those younger than 65 years, those with neuromuscular disease, those with 2+ falls, and those with a cutoff point of 45 to 49 showed better sensitivity with statistically less heterogeneity. The empirical evidence indicates that the BBS is a suitable tool to screen for the risk of falls and shows good predictability when used with the appropriate criteria and applied to those with neuromuscular disease.

Feasibility and outcomes of the Berg Balance Scale in older adults with intellectual disabilities.

PubMed

Oppewal, Alyt; Hilgenkamp, Thessa I M; van Wijck, Ruud; Evenhuis, Heleen M

2013-09-01

High incidence of falls and increased risk of fall-related injuries are seen in individuals with intellectual disabilities (ID). The Berg Balance Scale (BBS) is a reliable instrument for balance assessment in the population of (older) adults with ID. The aims of this study were to assess the balance capacities of a large group of older adults with ID with the BBS and look for gender and age effects, as well as reasons for drop-out on separate items, and to identify feasible subtests for subgroups in which the complete BBS is not feasible. The balance capacities of 1050 older clients with borderline to profound ID of three Dutch care-provider services (mean age 61.6 [sd=8.0]) were assessed with the BBS. The participants who completed all items of the BBS (n=508) were the functionally more able part of the study sample. Results showed that even this functionally more able part had poor balance capacities, with a mean BBS score of 47.2, 95% CI [46.3, 48.0], similar to adults in the general population aged around 20 years older. Balance capacities decreased with increasing age and females had poorer balance capacities than males. Difficulties understanding the task and physical limitations were most often the reasons for drop-out. Feasible subtests were identified for the subgroups with very low cognitive levels and wheelchair users. Low balance capacities of older adults with ID show the need for regular screening and the urge for fall prevention programs for individuals with ID. Copyright © 2013 Elsevier Ltd. All rights reserved.

Minimal Clinically Important Difference of Berg Balance Scale in People With Multiple Sclerosis.

PubMed

Gervasoni, Elisa; Jonsdottir, Johanna; Montesano, Angelo; Cattaneo, Davide

2017-02-01

To identify the minimal clinically important difference (MCID) to define clinically meaningful patient's improvement on the Berg Balance Scale (BBS) in people with multiple sclerosis (PwMS) in response to rehabilitation. Cohort study. Neurorehabilitation institute. PwMS (N=110). This study comprised inpatients and outpatients who participated in research on balance and gait rehabilitation. All received 20 rehabilitation sessions with different intensities. Inpatients received daily treatments over a period of 4 weeks, while outpatients received 2 to 3 treatments per week for 10 weeks. An anchor-based approach using clinical global impression of improvement in balance (Activities-specific Balance Confidence [ABC] Scale) was used to determine the MCID of the BBS. The MCID was defined as the minimum change in the BBS total score (postintervention - preintervention) that was needed to perceive at least a 10% improvement on the ABC Scale. Receiver operating characteristic curves were used to define the cutoff of the optimal MCID of the BBS discriminating between improved and not improved subjects. The MCID for change on the BBS was 3 points for the whole sample, 3 points for the inpatients, and 2 points for the outpatients. The area under the curve was .65 for the whole sample, .64 for inpatients, and .68 for outpatients. The MCID for improvement in balance as measured by the BBS was 3 points, meaning that PwMS are likely to perceive that as a reproducible and clinically important change in their balance performance. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

ORD BBS USER'S MANUAL - VERSION 2.0

EPA Science Inventory

The Office of Research and Development's Electronic Bulletin Board System (BBS or ''Board") is designed to facilitate the exchange of technical information and ORD products among EPA Headquarters, laboratory and Regional staff and contractors; States; other Federal agencies, univ...

Use of an adaptive neuro-fuzzy inference system to obtain the correspondence among balance, gait, and depression for Parkinson's disease

NASA Astrophysics Data System (ADS)

Woo, Youngkeun; Lee, Juwon; Hwang, Sujin; Hong, Cheol Pyo

2013-03-01

The purpose of this study was to investigate the associations between gait performance, postural stability, and depression in patients with Parkinson's disease (PD) by using an adaptive neuro-fuzzy inference system (ANFIS). Twenty-two idiopathic PD patients were assessed during outpatient physical therapy by using three clinical tests: the Berg balance scale (BBS), Dynamic gait index (DGI), and Geriatric depression scale (GDS). Scores were determined from clinical observation and patient interviews, and associations among gait performance, postural stability, and depression in this PD population were evaluated. The DGI showed significant positive correlation with the BBS scores, and negative correlation with the GDS score. We assessed the relationship between the BBS score and the DGI results by using a multiple regression analysis. In this case, the GDS score was not significantly associated with the DGI, but the BBS and DGI results were. Strikingly, the ANFIS-estimated value of the DGI, based on the BBS and the GDS scores, significantly correlated with the walking ability determined by using the DGI in patients with Parkinson's disease. These findings suggest that the ANFIS techniques effectively reflect and explain the multidirectional phenomena or conditions of gait performance in patients with PD.

Anchoring of a fully covered self-expandable metal stent with a 5F double-pigtail plastic stent to prevent migration in the management of benign biliary strictures.

PubMed

Park, Jong Kyu; Moon, Jong Ho; Choi, Hyun Jong; Min, Seul Ki; Lee, Tae Hoon; Cheon, Gab Jin; Cheon, Young Koog; Cho, Young Deok; Park, Sang-Heum; Kim, Sun-Joo

2011-10-01

Fully covered self-expandable metal stents (FCSEMSs) can be effectively placed in patients with benign biliary stricture (BBS). However, stent migration is an inherent problem of FCSEMSs. We evaluated the efficacy of anchoring with a 5F double-pigtail plastic stent (anchoring stent) to prevent migration of an FCSEMS in patients with BBS. Between January 2007 and December 2009, 33 of 37 consecutive patients with BBS who had experienced treatment failure of at least one plastic stent placement were prospectively enrolled in this study. The patients with BBS were randomly assigned to undergo FCSEMS placement with or without an anchoring stent (anchoring group: 16 patients; non-anchoring group: 17 patients). The main outcome measures were the stent migration rate and success rates. The technical success rate was 100% in both groups. Significantly less stent migration occurred in the anchoring group (6.3%, 1/16) than in the non-anchoring group (41.2%, 7/17; P=0.024). The median indwelling time was significantly longer in the anchoring group (154 days; range, 86-176 days) than in the non-anchoring group (114 days; range, 19-162 days; P=0.010). Improvement or resolution of the BBS was confirmed in 15 of 16 patients (93.8%) in the anchoring group, and in 12 of 17 patients (70.6%) in the non-anchoring group (P=0.101). The placement of an anchoring stent appears to be a simple and effective method of preventing premature migration of FCSEMSs in patients with BBS. Appropriately powered studies are needed to confirm this finding.

Reliability and validity of the Turkish version of the Berg Balance Scale.

PubMed

Sahin, Fusun; Yilmaz, Figen; Ozmaden, Asli; Kotevolu, Nurdan; Sahin, Tulay; Kuran, Banu

2008-01-01

The purpose of this study was to develop a Turkish version of the Berg Balance Scale (BBS) and assess its reliability and validity. Sixty healthy volunteers older than 65 years were included in to the study. Subjects who had lower extremity amputation, or were armchair or bedridden were excluded. After translation process, the Turkish version of the scale was administered to each participant twice with an interval of 2 weeks. The intraclass correlation coefficient (ICC) was calculated to assess intra- and inter-observer reliability. Chronbach alpha was calculated to evaluate internal consistency of the total BBS score. Interclass correlation coefficient was calcuated to examine test-retest reliability. Convergent validity was assessed by correlating the scale with Modified Barthel Index (MBI) and Timed Up and Go Test (TUG). Construct validity was assessed with factor analysis. The mean age in years of the participants were 77.00+/-5.67 (range: 67-92 yrs). The ICC for intra- and inter- observer reliability was 0.98 (p<0.0001) and 0.97 (p<0.0001), respectively. Chronbach alpha of the Turkish version of the BBS was 0.98. The test-retest reliability (ICC) of the Turkish version of the BBS was determined as 0.98 for the total score, and ranged from 0.86-0.99 for individual items. In terms of validity, the Turkish version of the BBS was correlated with the MBI (in positive direction) and TUG (in negative direction) (r=0.67 p<0.0001; r=-0.75 p<0.0001, respectively). The Turkish version of the BBS is a reliable and valid scale to be used in balance assessment of Turkish older adults.

Tinetti and Berg balance scales correlate with disability in hereditary peripheral neuropathies: a preliminary study.

PubMed

Monti Bragadin, M; Francini, L; Bellone, E; Grandis, M; Reni, L; Canneva, S; Gemelli, C; Ursino, G; Maggi, G; Mori, L; Schenone, A

2015-08-01

The combination of distal muscle weakness, sensory defects and feet deformities leads to disequilibrium in patients affected by Charcot-Marie-Tooth (CMT) neuropathy. Studies relating the outcome of balance scales and clinical severity of CMT are lacking. To evaluate the accuracy of the Tinetti Balance scale (TBS) and Berg Balance scale (BBS) in identifying balance disorders and quantifying disease severity in CMT patients. Observational study. University of Genoa-IRCCS AOU San Martino IST-Department of Neurology, Italy. Nineteen individuals with a diagnosis of CMT (12 females, 7 males, age 41.26±12.42). All subjects underwent an evaluation with both TBS and BBS. Disability was quantified with CMT neuropathy score (CMTNS). Moreover, a complete neurophysiological study was performed. Distal lower limbs strength was evaluated with MRC scale. Pearson rank order correlation was used to determine the correlation between the scores on the two tests and to identify an eventual correlation between TBS or BBS and the CMTNS. Both scales showed a highly significant negative correlation with the CMTNS (r=-0.78, P<0.0005 and r=-0.77, P<0.001, respectively) and distal weakness on the anterior tibial muscles (AT) (TBS: AT left: r=0.65, P<0.005 and AT right: 0.59, P<0.01; BBS: AT left r=+0.71, P<0.001 and AT right r=+0.66, P<0.005). We found also a highly significant, positive correlation between the two different balance scales (r=+0.9, P<0.0001). TBS and BBS strongly correlate with disease disability and distal muscular weakness. Both TBS and BBS may play a relevant role in the assessment of disability in patients affected by CMT. Further studies are needed to validate our results in a larger population.

Management of benign biliary strictures with a novel retrievable self-expandable metal stent.

PubMed

Hu, Bing; Leung, Joseph W; Gao, Dao Jian; Wang, Tian Tian; Wu, Jun

2014-03-01

Endoscopic placement of covered self-expandable metal stent (SEMS) has gained popularity in the management of benign biliary strictures (BBS). The existing SEMS has been designed primarily to palliate malignant biliary obstruction and has a high frequency of stent migration, difficulty in retrieval and stricture recurrence after stent removal. This study aimed to design a novel retrievable SEMS dedicated to the treatment of extrahepatic BBS and evaluate its clinical efficacy and safety. A short fully covered SEMS (FCSEMS) with a retrieval lasso was designed for the specific treatment of BBS. A total of 45 patients with segmental extrahepatic BBS were included in this study. The stent was placed entirely inside the bile duct with only the retrieval lasso extending from the papilla. The stents were recommended to be in situ for 6 to 12 months before removal. The FCSEMS was successfully placed in all 45 patients. In all, 33 patients had their FCSEMS successfully removed after a mean period of 8.6 ± 3.7 (range 2-15.5) months. Stent migration occurred in 9.1% of the patients. During a mean follow-up of 18.9 months after stent removal, recurrent stricture was found in 2 (6.1%) patients and was successfully treated with a second FCSEMS. Overall, the strictures resolved in 30/33 (90.9%) patients. Intraductal placement of a short FCSEMS is suitable for the treatment of segmental extrahepatic BBS. This new removable design offered prolonged stenting and drainage for BBS for up to one year with minimal complications. © 2013 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Alteration of frequency range for binaural beats in acute low-tone hearing loss.

PubMed

Karino, Shotaro; Yamasoba, Tatsuya; Ito, Ken; Kaga, Kimitaka

2005-01-01

The effect of acute low-tone sensorineural hearing loss (ALHL) on the interaural frequency difference (IFD) required for perception of binaural beats (BBs) was investigated in 12 patients with unilateral ALHL and 7 patients in whom ALHL had lessened. A continuous pure tone of 30 dB sensation level at 250 Hz was presented to the contralateral, normal-hearing ear. The presence of BBs was determined by a subjective yes-no procedure as the frequency of a loudness-balanced test tone was gradually adjusted around 250 Hz in the affected ear. The frequency range in which no BBs were perceived (FRNB) was significantly wider in the patients with ALHL than in the controls, and FRNBs became narrower in the recovered ALHL group. Specifically, detection of slow BBs with a small IFD was impaired in this limited (10 s) observation period. The significant correlation between the hearing level at 250 Hz and FRNBs suggests that FRNBs represent the degree of cochlear damage caused by ALHL.

The functional assessment Berg Balance Scale is better capable of estimating fall risk in the elderly than the posturographic Balance Stability System.

PubMed

Pereira, Vanessa Vieira; Maia, Roberto Alcantara; Silva, Sonia Maria Cesar de Azevedo

2013-01-01

The purpose of this study was to verify which instrument better identifies recurrent falls in the elderly. Ninety-eight old people, with an average age of 80 ± 4 years, were submitted to an assessment of balance and fall risk by means of the Berg Balance Scale (BBS) and the posturographic Balance Stability System (BSS). The BBS was correlated with the BSS (r=-0.27; p=0.008), age (r=-0.38; p<0.001) and number of falls (r=-0.25; p=0.013) and the analysis of logistical regression showed that the elderly classified with fall risk on the BBS presented 2.5 (95%CI 1.08-5.78) more chance of identifying who had two falls or more over the last year. The BBS identified that the greater the age the worse the functional balance and demonstrated a greater capacity to identify falls risk suffered over the last year when compared with the BSS.

Characteristics of low polymerization shrinkage flowable resin composites in newly-developed cavity base materials for bulk filling technique.

PubMed

Nitta, Keiko; Nomoto, Rie; Tsubota, Yuji; Tsuchikawa, Masuji; Hayakawa, Tohru

2017-11-29

The purpose of this study was to evaluate polymerization shrinkage and other physical properties of newly-developed cavity base materials for bulk filling technique, with the brand name BULK BASE (BBS). Polymerization shrinkage was measured according to ISO/FDIS 17304. BBS showed the significantly lowest polymerization shrinkage and significantly higher depth of cure than conventional flowable resin composites (p<0.05). The Knoop hardness, flexural strength and elastic modulus of that were significantly lower than conventional flowable resin composites (p<0.05). BBS had the significantly greatest filler content (p<0.05). SEM images of the surface showed failure of fillers. The lowest polymerization shrinkage was due to the incorporation of a new type of low shrinkage monomer, which has urethane moieties. There were no clear correlations between inorganic filler contents and polymerization shrinkage, flexural strength and elastic modulus. In conclusion, the low polymerization shrinkage of BBS will be useful for cavity treatment in dental clinics.

Identification of Behavior Based Safety by Using Traffic Light Analysis to Reduce Accidents

NASA Astrophysics Data System (ADS)

Mansur, A.; Nasution, M. I.

2016-01-01

This work present the safety assessment of a case study and describes an important area within the field production in oil and gas industry, namely behavior based safety (BBS). The company set a rigorous BBS and its intervention program that implemented and deployed continually. In this case, observers requested to have discussion and spread a number of determined questions related with work behavior to the workers during observation. Appraisal of Traffic Light Analysis (TLA) as one tools of risk assessment used to determine the estimated score of BBS questionnaire. Standardization of TLA appraisal in this study are based on Regulation of Minister of Labor and Occupational Safety and Health No:PER.05/MEN/1996. The result shown that there are some points under 84%, which categorized in yellow category and should corrected immediately by company to prevent existing bad behavior of workers. The application of BBS expected to increase the safety performance at work time-by-time and effective in reducing accidents.

White dwarfs in the building blocks of the Galactic spheroid

NASA Astrophysics Data System (ADS)

van Oirschot, Pim; Nelemans, Gijs; Starkenburg, Else; Toonen, Silvia; Helmi, Amina; Zwart, Simon Portegies

2017-11-01

Aims: The Galactic halo likely grew over time in part by assembling smaller galaxies, the so-called building blocks (BBs). We investigate if the properties of these BBs are reflected in the halo white dwarf (WD) population in the solar neighbourhood. Furthermore, we compute the halo WD luminosity functions (WDLFs for four major BBs of five cosmologically motivated stellar haloes). We compare the sum of these to the observed WDLF of the Galactic halo, derived from selected halo WDs in the SuperCOSMOS Sky Survey, aiming to investigate if they match better than the WDLFs predicted by simpler models. Methods: We couple the SeBa binary population synthesis model to the Munich-Groningen semi-analytic galaxy formation model applied to the high-resolution Aquarius dark matter simulations. Although the semi-analytic model assumes an instantaneous recycling approximation, we model the evolution of zero-age main sequence stars to WDs, taking age and metallicity variations of the population into account. To be consistent with the observed stellar halo mass density in the solar neighbourhood (ρ0), we simulate the mass in WDs corresponding to this density, assuming a Chabrier initial mass function (IMF) and a binary fraction of 50%. We also normalize our WDLFs to ρ0. Results: Although the majority of halo stars are old and metal-poor and therefore the WDs in the different BBs have similar properties (including present-day luminosity), we find in our models that the WDs originating from BBs that have young and/or metal-rich stars can be distinguished from WDs that were born in other BBs. In practice, however, it will be hard to prove that these WDs really originate from different BBs, as the variations in the halo WD population due to binary WD mergers result in similar effects. The five joined stellar halo WD populations that we modelled result in WDLFs that are very similar to each other. We find that simple models with a Kroupa or Salpeter IMF fit the observed luminosity function slightly better, since the Chabrier IMF is more top-heavy, although this result is dependent on our choice of ρ0.

Group fitness activities for the elderly: an innovative approach to reduce falls and injuries.

PubMed

Bianco, Antonino; Patti, Antonino; Bellafiore, Marianna; Battaglia, Giuseppe; Sahin, Fatma Nese; Paoli, Antonio; Cataldo, Maria Concetta; Mammina, Caterina; Palma, Antonio

2014-04-01

The aim of this study was to examine the opportunity to adopt, for the elderly, already validated function ability tests to better understand how to prevent falls and injuries and to better plan group fitness activities like ballroom dance classes (e.g., Valzer, Polka, Mazurka). A cross-sectional study was conducted. The Berg Balance Scale (BBS) and the Barthel Index (BI) were administered and the occurrence of falls during the previous 2 years was evaluated by anamnesis. One hundred and twenty-two elderly subjects living in Palermo city participated to the study. According to the anamnesis, subjects were divided into two groups: experimental group (EG) and control group (CG). The EG consisted of 75 subjects attending classes of ballroom dancing (73.0 ± 5.6 years 26.1 ± 3.9 BMI), while the CG included 47 volunteers (74.3 ± 5.4 years, 26.8 ± 4.4 BMI). A threshold of 70 % for both scales (BBS-70 and BI-70 %) was set, according to the aims of the study. STATISTICA software was adopted to perform an unpaired t test. A P value lower than 0.05 was considered to be statistically relevant. The BI and BBS of CG were 76.7 ± 33.08 and 30.9 ± 14.9, respectively, while the BI and BBS of EG were 98.1 ± 6.9 and 50.5 ± 54. In EG the BBS-70 % showed 96.0 % of cases compared to 27.6 % of the CG. The BI showed a similar trend to BBS. In EG the BI-70 % showed 98.6 % of cases, while the BI-70 % of CG showed 70.2 % of cases. Moreover, only 36.0 % of EG reported falls previously, while CG reported 53.2 % of falls during the same period of time. The BBS seems to be a valid and reliable tool able to be adopted also by professionals of the ballroom dancing sector (e.g., Valzer, Polka and Mazurka classes). Instructors may evaluate the functional ability of their attendees through BBS to easily obtain more information and better plan ballroom dance classes. Moreover, we highlight that these conclusions need to be supported by other studies with different cohorts and a larger population scale.

New approaches to the analysis of population trends in land birds: Comment

USGS Publications Warehouse

Link, W.A.; Sauer, J.R.

1997-01-01

James et al. (1996, Ecology 77:13-27) used data from the North American Breeding Bird Survey (BBS) to examine geographic variability in patterns of population change for 26 species of wood warblers. They emphasized the importance of evaluating nonlinear patterns of change in bird populations, proposed LOESS-based non-parametric and semi-parametric analyses of BBS data, and contrasted their results with other analyses, including those of Robbins et al. (1989, Proceedings of the National Academy of Sciences 86: 7658-7662) and Peterjohn et al. (1995, Pages 3-39 in T. E. Martin and D. M. Finch, eds. Ecology and management of Neotropical migratory birds: a synthesis and review of critical issues. Oxford University Press, New York.). In this note, we briefly comment on some of the issues that arose from their analysis of BBS data, suggest a few aspects of the survey that should inspire caution in analysts, and review the differences between the LOESS-based procedures and other procedures (e.g., Link and Sauer 1994). We strongly discourage the use of James et al.'s completely non-parametric procedure, which fails to account for observer effects. Our comparisons of estimators adds to the evidence already present in the literature of the bias associated with omitting observer information in analyses of BBS data. Bias resulting from change in observer abilities should be a consideration in any analysis of BBS data.

Language Use in Asynchronous Computer-Mediated Communication in Taiwan

ERIC Educational Resources Information Center

Huang, Daphne Li-jung

2009-01-01

This paper describes how Chinese-English bilinguals in Taiwan use their languages in asynchronous computer-mediated communication, specifically, via Bulletin Board System (BBS) and email. The main data includes two types: emails collected from a social network and postings collected from two BBS websites. By examining patterns of language choice…

Telecommunications Handbook: Connecting to Newton.

ERIC Educational Resources Information Center

Baker, Christopher; And Others

This handbook was written by the Argonne National Laboratory for use with their electronic bulletin board system (BBS) called Newton. Newton is an educational BBS for use by teachers, students, and parents. Topics range from discussions of science fair topics to online question and answer sessions with scientists. Future capabilities will include…

Marsh birds and the North American Breeding Bird Survey: judging the value of a landscape level survey for habitat specialist species with low detection rates

USGS Publications Warehouse

Sauer, J.R.

1999-01-01

The North American Breeding Bird Survey was started in 1966, and provides information on population change for >400 species of birds. it covers the continental United States, Canada, and Alaska, and is conducted once each year, in June, by volunteer observers. A 39.4 kIn roadside survey route is driven starting 30 min before sunrise, and a 3 min point count is conducted at each of 50 stops spaced every 0.8 kIn. Existing analyses of the data are internet-based (http://www.mbr-pwrc.usgs.govlbbslbbs.html), and include maps of relative abundance, estimates of population change including trends (%/yr), composite annual indices (pattern in time), and maps of population trend (pattern in space). At least 36 species of marsh birds are encountered on the BBS, and the survey provides estimates with greatly varying levels of efficiency for the species. It is often difficult to understand how well the BBS surveys a species. Often, efficiency is judged by estimating trend and its variance for a species, then by calculating power and needed samples to detect a prespecified trend over some time period (e.g., a 2%/yr trend over 31 yr). Unfortunately, this approach is not always valid, as estimated trends and variances can be of little use if the population is poorly sampled. Lurking concerns with BBS data include (1) incomplete coverage of species range; (2) undersampling of habitats; and (3) low and variable visibility of birds during point counts. It is difficult to evaluate these concerns, because known populations do not exist for comparison with counts, and detection rates are time-consuming and costly to estimate. I evaluated the efficiency of the BBS for selected rails (Rallidae) and snipes (Scolopacidae), presenting estimates of population trend over 1966-1996 (T), power to detect 2%/yr trend over 31 yr, needed samples to achieve power of 0.75 with alpha= 0.1, number of survey routes with data for the species (N), average abundance on survey routes (RA), and maps of relative abundance. Examples include Yellow Rail (Coturnicops noveboracensis) (T=12 %/yr; P= 0.0085; N =28; routes; RA=0.05; Power=0.37; Needed samples=85), Black Rail (Laterallus jamaicensis) (No trend data or power information available, N =8), Clapper Rail (Rallus longirostris) (T=1.9%/yr; P=0.55; N =64; RA=0.31; Power=0.35; Needed samples=590), King Rail (Rallus elegans) (T=-4.2 %/yr; P= 0.03; N =76; Power=0.41; Needed samples=159), Sora (Porzana carolina) (T=0.98 %/yr; P= 0.24; N =720; RA= 0.92; Power=0.69; Needed samples= 377), and Common Snipe (Gallinago gallinago) (T=-0.24 %/yr; P= 0.54; N =1412; RA= 2.19; Power=0.98; Needed samples=205). With regard to quality of BBS data, marsh birds fall into 3 categories: (1) almost never encountered on BBS routes; (2) encountered at extremely low abundances on BBS routes; and (3) probably fairly well sampled by BBS roadside counts. BBS data can provide useful information for many marsh bird species, but users should be aware of the limitations of the BBS sample for monitoring species that have low visibility from point counts and prefer habitats not often encountered on roadsides.

Acute flaccid paraparesis (cauda equina syndrome) in a patient with Bardet-Biedl syndrome.

PubMed

Viswanathan, Vibhu Krishnan; Kanna, Rishi Mugesh; Shetty, Ajoy Prasad; Rajasekaran, S

2017-01-01

Bardet-Biedl syndrome (BBS) is a rare, autosomal-recessive, debilitating genetic disorder, which can present with multitudinous systemic clinical features including rod-cone dystrophy, polydactyly, Frohlich-like central obesity, mental retardation, hypogonadism, and renal anomalies. Diverse neuromuscular manifestations in patients afflicted by this heterogeneous disorder include ataxia, cervical, and thoracic canal stenoses, presenting as spastic quadriparesis and other gait disturbances. We report a young patient with BBS, who had presented with acute flaccid paraparesis due to severe primary lumbar canal stenosis. She underwent immediate lumbar decompression and discectomy following which she recovered significantly. Acute cauda equina syndrome due to primary lumbar canal stenosis has not been reported as a clinical feature of BBS previously.

High-efficiency generation of Bessel beams with transmissive metasurfaces

NASA Astrophysics Data System (ADS)

Wang, Zhuo; Dong, Shaohua; Luo, Weijie; Jia, Min; Liang, Zhongzhu; He, Qiong; Sun, Shulin; Zhou, Lei

2018-05-01

Circularly polarized Bessel beams (BBs) are important in biomolecule-sensing-related applications, but the available generators are too bulky in size and/or exhibit low efficiencies. Here, we design and fabricate ultra-thin ( ˜λ /6 ) transmissive Pancharatnam-Berry metasurfaces and perform near-field scanning measurements to show that they can generate circularly polarized BBs within a frequency window of 10.7-12.3 GHz. We experimentally demonstrate that the generated BBs exhibit a self-healing effect, illustrating their non-diffraction characteristics. Finally, we employ far-field measurements to demonstrate that the working efficiency of our devices can reach 91%, while the simulated efficiency reaches 92%. All experimental results are in perfect agreement with full-wave simulations.

U34: driver distraction : an inattention-mitigation component for behavior-based safety programs in commercial vehicle operations (IM-BBS) final report.

DOT National Transportation Integrated Search

2011-09-01

The aim of this research was to develop a comprehensive inattention mitigation component of a behavior-based safety program (IM-BBS) in commercial motor vehicle operations that increases road safety. A key focus was on the use of real-time inattentio...

Electronic Bulletin Boards.

ERIC Educational Resources Information Center

Landberg, Ted

This manual is intended to provide guidance to those interested in establishing an electronic bulletin board system (BBS) that enables users to send and read messages both individually and by teleconferencing, and to transfer files to and from the system. The manual begins with a definition of a BBS and explains its uses and facilities. It then…

The Association Between Fall History and Physical Performance Tests in the Community-Dwelling Elderly: A Cross-Sectional Analysis.

PubMed

Kim, Jin Chul; Chon, Jinmann; Kim, Hee Sang; Lee, Jong Ha; Yoo, Seung Don; Kim, Dong Hwan; Lee, Seung Ah; Han, Yoo Jin; Lee, Hyun Seok; Lee, Bae Youl; Soh, Yun Soo; Won, Chang Won

2017-04-01

To evaluate the association between baseline characteristics, three physical performance tests and fall history in a sample of the elderly from Korean population. A total of 307 participants (mean age, 76.70±4.85 years) were categorized into one of two groups, i.e., fallers and non-fallers. Fifty-two participants who had reported falling unexpectedly at least once in the previous 12 months were assigned to the fallers group. Physical performance tests included Short Physical Performance Battery (SPPB), Berg Balance Scale (BBS), Timed Up and Go test. The differences between the two study groups were compared and we analyzed the correlations between fall histories and physical performance tests. SPPB demonstrated a significant association with fall history. Although the BBS total scores did not show statistical significance, two dynamic balance test items of BBS (B12 and B13) showed a significant association among fallers. This study suggests that SPPB and two dynamic balance test items of the BBS can be used in screening for risk of falls in an ambulatory elderly population.

Measurement of the ratios of branching fractions B(B0s --> Ds- pi+ pi+ pi-)/B(B0-->D- pi+ pi+ pi-) and B(B0s --> Ds- pi+)/B(B0-->D- pi+).

PubMed

Abulencia, A; Adelman, J; Affolder, T; Akimoto, T; Albrow, M G; Ambrose, D; Amerio, S; Amidei, D; Anastassov, A; Anikeev, K; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Arguin, J-F; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Bedeschi, F; Behari, S; Belforte, S; Bellettini, G; Bellinger, J; Belloni, A; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Budroni, S; Burkett, K; Busetto, G; Bussey, P; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carillo, S; Carlsmith, D; Carosi, R; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, I; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Ciljak, M; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Coca, M; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Cyr, D; DaRonco, S; D'Auria, S; Davies, T; D'Onofrio, M; Dagenhart, D; de Barbaro, P; De Cecco, S; Deisher, A; De Lentdecker, G; Dell'Orso, M; Delli Paoli, F; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; Dituro, P; Dörr, C; Donati, S; Donega, M; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, I; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Field, R; Flanagan, G; Foland, A; Forrester, S; Foster, G W; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garcia, J E; Garberson, F; Garfinkel, A F; Gay, C; Gerberich, H; Gerdes, D; Giagu, S; Giannetti, P; Gibson, A; Gibson, K; Gimmell, J L; Ginsburg, C; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Goldstein, J; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Griffiths, M; Grinstein, S; Grosso-Pilcher, C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Holloway, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ishizawa, Y; Ivanov, A; Iyutin, B; James, E; Jang, D; Jayatilaka, B; Jeans, D; Jensen, H; Jeon, E J; Jindariani, S; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Karchin, P E; Kato, Y; Kemp, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kovalev, A; Kraan, A C; Kraus, J; Kravchenko, I; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhlmann, S E; Kuhr, T; Kusakabe, Y; Kwang, S; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; LeCompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Loverre, P; Lu, R-S; Lucchesi, D; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; MacQueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Manca, G; Margaroli, F; Marginean, R; Marino, C; Marino, C P; Martin, A; Martin, M; Martin, V; Martínez, M; Maruyama, T; Mastrandrea, P; Masubuchi, T; Matsunaga, H; Mattson, M E; Mazini, R; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miles, J; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyamoto, A; Moed, S; Moggi, N; Mohr, B; Moore, R; Morello, M; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Nachtman, J; Nagano, A; Naganoma, J; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nigmanov, T; Nodulman, L; Norniella, O; Nurse, E; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Pagliarone, C; Palencia, E; Papadimitriou, V; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ranjan, N; Rappoccio, S; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Sabik, S; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Saltzberg, D; Sánchez, C; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savard, P; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyrla, A; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Sjolin, J; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; Staveris-Polykalas, A; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sun, H; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Takikawa, K; Tanaka, M; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tsuchiya, R; Tsuno, S; Turini, N; Ukegawa, F; Unverhau, T; Uozumi, S; Usynin, D; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Veramendi, G; Veszpremi, V; Vidal, R; Vila, I; Vilar, R; Vine, T; Vollrath, I; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner, J; Wagner, W; Wallny, R; Wang, S M; Warburton, A; Waschke, S; Waters, D; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zhou, J; Zucchelli, S

2007-02-09

Using 355 pb;{-1} of data collected by the CDF II detector in pp[over ] collisions at sqrt[s]=1.96 TeV at the Fermilab Tevatron, we study the fully reconstructed hadronic decays B_{(s)};{0}-->D_{(s)};{-}pi;{+} and B_{(s)};{0}-->D_{(s)};{-}pi;{+}pi;{+}pi;{-}. We present the first measurement of the ratio of branching fractions B(B_{s};{0}-->D_{s};{-}pi;{+}pi;{+}pi;{-})/B(B;{0}-->D;{-}pi;{+}pi;{+}pi;{-})=1.05+/-0.10(stat)+/-0.22(syst). We also update our measurement of B(B_{s};{0}-->D_{s};{-}pi;{+})/B(B;{0}-->D;{-}pi;{+}) to 1.13+/-0.08(stat)+/-0.23(syst), improving the statistical uncertainty by more than a factor of 2. We find B(B_{s};{0}-->D_{s};{-}pi;{+})=[3.8+/-0.3(stat)+/-1.3(syst)]x10;{-3} and B(B_{s};{0}-->D_{s};{-}pi;{+}pi;{+}pi;{-})=[8.4+/-0.8(stat)+/-3.2(syst)]x10;{-3}.

Evaluating the effectiveness of Behavior-Based Safety education methods for commercial vehicle drivers.

PubMed

Wang, Xuesong; Xing, Yilun; Luo, Lian; Yu, Rongjie

2018-08-01

Risky driving behavior is one of the main causes of commercial vehicle related crashes. In order to achieve safer vehicle operation, safety education for drivers is often provided. However, the education programs vary in quality and may not always be successful in reducing crash rates. Behavior-Based Safety (BBS) education is a popular approach found effective by numerous studies, but even this approach varies as to the combination of frequency, mode and content used by different education providers. This study therefore evaluates and compares the effectiveness of BBS education methods. Thirty-five drivers in Shanghai, China, were coached with one of three different BBS education methods for 13 weeks following a 13-week baseline phase with no education. A random-effects negative binomial (NB) model was built and calibrated to investigate the relationship between BBS education and the driver at-fault safety-related event rate. Based on the results of the random-effects NB model, event modification factors (EMF) were calculated to evaluate and compare the effectiveness of the methods. Results show that (1) BBS education was confirmed to be effective in safety-related event reduction; (2) the most effective method among the three applied monthly face-to-face coaching, including feedback with video and statistical data, and training on strategies to avoid driver-specific unsafe behaviors; (3) weekly telephone coaching using statistics and strategies was rated by drivers as the most convenient delivery mode, and was also significantly effective. Copyright © 2018 Elsevier Ltd. All rights reserved.

Reliability of the Berg Balance Scale as a Clinical Measure of Balance in Community-Dwelling Older Adults with Mild to Moderate Alzheimer Disease: A Pilot Study.

PubMed

Muir-Hunter, Susan W; Graham, Laura; Montero Odasso, Manuel

2015-08-01

To measure test-retest and interrater reliability of the Berg Balance Scale (BBS) in community-dwelling adults with mild to moderate Alzheimer disease (AD). Method : A sample of 15 adults (mean age 80.20 [SD 5.03] years) with AD performed three balance tests: the BBS, timed up-and-go test (TUG), and Functional Reach Test (FRT). Both relative reliability, using the intra-class correlation coefficient (ICC), and absolute reliability, using standard error of measurement (SEM) and minimal detectable change (MDC95) values, were calculated; Bland-Altman plots were constructed to evaluate inter-tester agreement. The test-retest interval was 1 week. Results : For the BBS, relative reliability values were 0.95 (95% CI, 0.85-0.98) for test-retest reliability and 0.72 (95% CI, 0.31-0.91) for interrater reliability; SEM was 6.01 points and MDC95 was 16.66 points; and interrater agreement was 16.62 points. The BBS performed better in test-retest reliability than the TUG and FRT, tests with established reliability in AD. Between 33% and 50% of participants required cueing beyond standardized instructions because they were unable to remember test instructions. Conclusions : The BBS achieved relative reliability values that support its clinical utility, but MDC95 and agreement values indicate the scale has performance limitations in AD. Further research to optimize balance assessment for people with AD is required.

The design and synthesis of a novel compound of berberine and baicalein that inhibits the efficacy of lipid accumulation in 3T3-L1 adipocytes.

PubMed

Hao, Mengjiao; Li, Yan; Liu, Lixian; Yuan, Xiao; Gao, Ying; Guan, Zhuoji; Li, Weimin

2017-10-15

The combination of berberine and baicalein may have a better therapeutic effect against disease. To explore the combined effect of baicalein and berberine in the treatment of obesity, we designed and synthesized a hybrid compound, and its biological activities were evaluated in 3T3-L1 adipocytes. The structures of the berberine-baicalein (BBS) compounds were confirmed by 1 H NMR, 13 C NMR, ultraviolet spectroscopy and high resolution mass spectrometry (HRMS). The present study showed that the IC 50 values of the inhibitory effects of baicalein, berberine and BBS against 3T3-L1 cells were 29.81±0.90, 21.84±1.67 and 9.42±0.60µM, respectively. The expression of mRNAs related to lipolysis and lipogenesis were examined by quantitative real-time PCR. The results showed that BBS could up-regulate the expression of the Atgl gene and down-regulate the mRNA expression of Srebp-1c, Fasn, Scd1, and Acc in 3T3-L1 adipocytes. These results indicate that BBS may have a stronger effect than baicalein and berberine on the viability of 3T3-L1 preadipocytes. In addition, BBS may have therapeutic effects and pharmacological activities against obesity. This "medicine couple" may be beneficial for studies of traditional Chinese medicine. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multicenter trial evaluating the use of covered self-expanding metal stents in benign biliary strictures: time to revisit our therapeutic options?

PubMed

Kahaleh, Michel; Brijbassie, Alan; Sethi, Amrita; Degaetani, Marisa; Poneros, John M; Loren, David E; Kowalski, Thomas E; Sejpal, Divyesh V; Patel, Sandeep; Rosenkranz, Laura; McNamara, Kevin N; Raijman, Isaac; Talreja, Jayant P; Gaidhane, Monica; Sauer, Bryan G; Stevens, Peter D

2013-09-01

Covered self-expanding metal stents are being used more frequently in benign biliary strictures (BBS). We report the results of a multicenter study with fully covered self-expanding metal stent (FCSEMS) placement for the management of BBS. : To prospectively evaluate the efficacy and safety of FCSEMS in the management of BBS. Patients with BBS from 6 tertiary care centers who received FCSEMS with flared ends between April 2009 and October 2010 were included in this retrospective study.Efficacy was measured after removal of FCSEMS by evaluating stricture resolution on the basis of symptom resolution, imaging, laboratory studies, and/or choledochoscopy at removal. Safety profile was evaluated by assessing postprocedural complications. A total of 133 patients (78, 58.6% males) with a mean age of 59.2±14.8 years with BBS received stents. Of the 133 stents placed, 97 (72.9%) were removed after a mean stent duration of 95.5±48.7 days. Stricture resolution after FCSEMS removal was as follows: postsurgical, 11/12 (91.6%); gallstone-related disease, 16/19 (84.2%); chronic pancreatitis, 26/31 (80.7%); other etiology, 4/5 (80.0%); and anastomotic strictures, 19/31(61.2%). Ninety-four patients were included in the logistic regression analyses. Patients who had indwelling stents for >90 days were 4.3 times more likely to have resolved strictures [odds ratio, 4.3 (95% confidence interval, 1.24-15.09)] and patients with nonmigrated stents were 5.4 times more likely to have resolved strictures [odds ratio, 5.4 (95% confidence interval, 1.001-29.29)]. FCSEMS for BBS had an acceptable rate of stricture resolution for postsurgical strictures, gallstone-related strictures, and those due to chronic pancreatitis. Predictors for stricture resolution include longer indwell time and absence of migration. Further study is warranted to assess long-term efficacy in a prospective manner with longer than 3-month time of stent indwelling time.

[Comparison of the performance-oriented mobility assessment and the Berg balance scale. Assessment tools in geriatrics and geriatric rehabilitation].

PubMed

Schülein, S

2014-02-01

In order to develop and coordinate an integrated plan for treatment of hospitalized elderly patients in danger of future falls it is of utmost importance to ensure using the assessment that best targets people who are at risk for falling. For this purpose the performance-oriented mobility assessment (POMA) and the Berg balance scale (BBS) can be used. The purpose of this study was to collate the results of articles published on these assessment tools in order to appraise whether one of them could be favored under the viewpoint of practicability and expressiveness. A literature search was conducted for studies examining the two assessment tools published since 1986 through December 2011 in English and German language. Reference sections were also inspected for additional citations. Overall 19 studies were retrieved in order to answer the posed question. Of the total number of 1,455 patients in the identified articles, 712 with an average age of 74.1 years were included in the BBS trials and the POMA was assessed using 743 patients with an average age of 75.7 years. The BBS was good at identifying elderly people who are at risk for falling (sensitivity 84-95.5 %) and those who are not at-risk for falling (specificity 76.5-95.5 %. The demonstrated results for the POMA ranged from relatively poor to good (sensitivity 64-95.5 %) and from poor to very high (specificity 60-100 %). The BBS demonstrated its strengths in the more precise survey for monitoring balance and predicting risk for falling. Weaknesses of the BBS were the higher average time of processing and the inability to detect changes in gait. The advantages of the POMA was the short processing time, the possibility for separate identification of balance and gait and the high accuracy in recognition of gait changes. The results suggest that the POMA can be used as a fast screening tool to evaluate risk for falling or changes in gait ability. Geriatric patients who screen positive for risks of falls using the POMA should be selected for further assessment using the BBS. The BBS is a concise assessment tool for monitoring balance and to predict a person's current risk for falling.

Human basal body basics.

PubMed

Vertii, Anastassiia; Hung, Hui-Fang; Hehnly, Heidi; Doxsey, Stephen

2016-01-01

In human cells, the basal body (BB) core comprises a ninefold microtubule-triplet cylindrical structure. Distal and subdistal appendages are located at the distal end of BB, where they play indispensable roles in cilium formation and function. Most cells that arrest in the G0 stage of the cell cycle initiate BB docking at the plasma membrane followed by BB-mediated growth of a solitary primary cilium, a structure required for sensing the extracellular environment and cell signaling. In addition to the primary cilium, motile cilia are present in specialized cells, such as sperm and airway epithelium. Mutations that affect BB function result in cilia dysfunction. This can generate syndromic disorders, collectively called ciliopathies, for which there are no effective treatments. In this review, we focus on the features and functions of BBs and centrosomes in Homo sapiens.

Muscle Dysmorphia Symptomatology and Associated Psychological Features in Bodybuilders and Non-Bodybuilder Resistance Trainers: A Systematic Review and Meta-Analysis.

PubMed

Mitchell, Lachlan; Murray, Stuart B; Cobley, Stephen; Hackett, Daniel; Gifford, Janelle; Capling, Louise; O'Connor, Helen

2017-02-01

Muscle dysmorphia (MD) is associated with a self-perceived lack of size and muscularity, and is characterized by a preoccupation with and pursuit of a hyper-mesomorphic body. MD symptoms may hypothetically be more prevalent in bodybuilders (BBs) than in non-bodybuilder resistance trainers (NBBRTs). Our objective was to compare MD symptomatology in BBs versus NBBRTs and identify psychological and other characteristics associated with MD in these groups. We searched relevant databases from earliest record to February 2015 for studies examining MD symptoms in BBs and/or NBBRTs. Included studies needed to assess MD using a psychometrically validated assessment tool. Study quality was evaluated using an adapted version of the validated Downs and Black tool. We calculated between-group standardized mean difference (effect sizes [ESs]) and 95 % confidence intervals (CIs) for each MD subscale, and performed meta-analysis when five or more studies used the same MD tool. We also extracted data describing psychological or other characteristics associated with MD. Of the 2135 studies initially identified, 31 analyzing data on 5880 participants (BBs: n = 1895, NBBRTs: n = 3523, controls: n = 462) were eligible for inclusion, though study quality was generally poor-moderate (range 7-19/22). Most participants were male (90 %). Eight different MD assessment tools were used. Meta-analysis for five studies all using the Muscle Dysmorphia Inventory (MDI) revealed there was a medium to large pooled ES for greater MD symptomatology in BBs than in NBBRTs on all MDI subscales (ES 0.53-1.12; p ≤ 0.01). Competitive BBs scored higher than non-competitive BBs (ES 1.21, 95 % CI 0.82-1.60; p < 0.001). MD symptoms were associated with anxiety (r 0.32-0.42; p ≤ 0.01), social physique anxiety (r 0.26-0.75; p < 0.01), depression (r 0.23-0.53; p ≤ 0.01), neuroticism (r 0.38; p < 0.001), and perfectionism (r 0.35; p < 0.05) and were inversely associated with self-concept (r -0.32 to -0.36; p < 0.01) and self-esteem (r -0.42 to -0.47; p < 0.01). MD symptomatology was greater in BBs than in NBBRTs. Anxiety and social physique anxiety, depression, neuroticism, and perfectionism were positively associated with MD, while self-concept and self-esteem were negatively associated. It remains unclear whether these characteristics are exacerbated by bodybuilding, or whether individuals with these characteristics are attracted to the bodybuilding context.

Acute flaccid paraparesis (cauda equina syndrome) in a patient with Bardet–Biedl syndrome

PubMed Central

Viswanathan, Vibhu Krishnan; Kanna, Rishi Mugesh; Shetty, Ajoy Prasad; Rajasekaran, S

2017-01-01

Bardet–Biedl syndrome (BBS) is a rare, autosomal-recessive, debilitating genetic disorder, which can present with multitudinous systemic clinical features including rod-cone dystrophy, polydactyly, Frohlich-like central obesity, mental retardation, hypogonadism, and renal anomalies. Diverse neuromuscular manifestations in patients afflicted by this heterogeneous disorder include ataxia, cervical, and thoracic canal stenoses, presenting as spastic quadriparesis and other gait disturbances. We report a young patient with BBS, who had presented with acute flaccid paraparesis due to severe primary lumbar canal stenosis. She underwent immediate lumbar decompression and discectomy following which she recovered significantly. Acute cauda equina syndrome due to primary lumbar canal stenosis has not been reported as a clinical feature of BBS previously. PMID:28566787

First observation of the decay Bs0-->Ds-Ds+ and measurement of its branching ratio.

PubMed

Aaltonen, T; Adelman, J; Akimoto, T; Albrow, M G; Alvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Apresyan, A; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Beauchemin, P-H; Bedeschi, F; Bednar, P; Behari, S; Bellettini, G; Bellinger, J; Belloni, A; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Bridgeman, A; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Dagenhart, D; Datta, M; Davies, T; de Barbaro, P; De Cecco, S; Deisher, A; De Lentdecker, G; De Lorenzo, G; Dell'Orso, M; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Ferrazza, C; Field, R; Flanagan, G; Forrest, R; Forrester, S; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garberson, F; Garcia, J E; Garfinkel, A F; Gerberich, H; Gerdes, D; Giagu, S; Giakoumopolou, V; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C M; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, D; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Hays, C; Heck, M; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hewamanage, S; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; Iyutin, B; James, E; Jayatilaka, B; Jeans, D; Jeon, E J; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Kar, D; Karchin, P E; Kato, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Koay, S A; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kraus, J; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhlmann, S E; Kuhr, T; Kulkarni, N P; Kusakabe, Y; Kwang, S; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; Lecompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Linacre, J; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Lovas, L; Lu, R-S; Lucchesi, D; Lueck, J; Luci, C; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; Macqueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis, A; Margaroli, F; Marino, C; Marino, C P; Martin, A; Martin, M; Martin, V; Martínez, M; Martínez-Ballarín, R; Maruyama, T; Mastrandrea, P; Masubuchi, T; Mattson, M E; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miles, J; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyake, H; Moed, S; Moggi, N; Moon, C S; Moore, R; Morello, M; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Nagano, A; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nodulman, L; Norman, M; Norniella, O; Nurse, E; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Pagan Griso, S; Pagliarone, C; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M A; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyria, A; Shalhout, S Z; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sun, H; Suslov, I; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thompson, G A; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tu, Y; Turini, N; Ukegawa, F; Uozumi, S; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Vellidis, C; Veszpremi, V; Vidal, M; Vidal, R; Vila, I; Vilar, R; Vine, T; Vogel, M; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner-Kuhr, J; Wagner, W; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zheng, Y; Zucchelli, S

2008-01-18

We report the observation of the exclusive decay Bs0-->Ds-Ds+ at the 7.5 standard deviation level using 355 pb(-1) of data collected by the CDF II detector in pp collisions at sqrt[s]=1.96 TeV at the Fermilab Tevatron. We measure the relative branching ratio B(Bs0-->Ds-Ds+)/B(B0-->D-Ds+)=1.44(-0.44)(+0.48). Using the world average value for B(B0-->D-Ds+), we find B(Bs0-->Ds-Ds+)=(9.4(-4.2)(+4.4))x10(-3). This provides a lower bound DeltaGammasCP/Gammas>or=2B(Bs0-->Ds-Ds+)>1.2x10(-2) at 95% C.L.

Lesion location associated with balance recovery and gait velocity change after rehabilitation in stroke patients.

PubMed

Moon, Hyun Im; Lee, Hyo Jeong; Yoon, Seo Yeon

2017-06-01

Impaired gait function after stroke contributes strongly to overall patient disability. However, the response to rehabilitation varies between individuals. The aims of this study were to identify predictors of gait velocity change and to elucidate lesion location associated with change of balance and gait function. We reviewed 102 stroke patients. The patients were divided into two groups according to gait ability post-rehabilitation, and we analyzed differences in their characteristics, such as demographic information, lesion factors, and initial balance function. Multivariate regression analyses were performed to examine the predictors of rehabilitation response. Lesion location and volume were measured on brain magnetic resonance images. We generated statistical maps of the lesions related to functional gains in gait and balance using voxel-based lesion symptom mapping (VLSM). The group of patients who regained independent ambulation function showed a smaller lesion size, a shorter duration from stroke onset, and higher initial balance function. In the regression model, gait velocity changes were predicted with the initial Berg balance scale (BBS) and duration post-onset. Absolute BBS changes were also correlated with the duration post-onset and initial BBS, and relative BBS changes were predicted by the baseline BBS. Using VLSM, lesion locations associated with gait velocity changes and balance adjusting for other factors were the insula, internal capsule, and adjacent white matter. Initial balance function as well as the interval between stroke onset and the initiation of therapy might influence balance recovery and gait velocity changes. Damage to the insula and internal capsule also affected gait velocity change after rehabilitation.

A comparison of Boolean-based retrieval to the WAIS system for retrieval of aeronautical information

NASA Technical Reports Server (NTRS)

Marchionini, Gary; Barlow, Diane

1994-01-01

An evaluation of an information retrieval system using a Boolean-based retrieval engine and inverted file architecture and WAIS, which uses a vector-based engine, was conducted. Four research questions in aeronautical engineering were used to retrieve sets of citations from the NASA Aerospace Database which was mounted on a WAIS server and available through Dialog File 108 which served as the Boolean-based system (BBS). High recall and high precision searches were done in the BBS and terse and verbose queries were used in the WAIS condition. Precision values for the WAIS searches were consistently above the precision values for high recall BBS searches and consistently below the precision values for high precision BBS searches. Terse WAIS queries gave somewhat better precision performance than verbose WAIS queries. In every case, a small number of relevant documents retrieved by one system were not retrieved by the other, indicating the incomplete nature of the results from either retrieval system. Relevant documents in the WAIS searches were found to be randomly distributed in the retrieved sets rather than distributed by ranks. Advantages and limitations of both types of systems are discussed.

"Cooking the books"--behavior-based safety at the San Francisco Bay Bridge.

PubMed

Brown, Garrett D; Barab, Jordan

2007-01-01

Practitioners of Behavior-Based Safety (BBS) claim dramatic reductions in worker injuries and illnesses through modifying workers' "unsafe behaviors." This case study of a BBS program implemented by KFM, a giant construction consortium rebuilding the eastern span of the San Francisco Bay Bridge in California, documents how BBS was used to suppress reporting of worker injuries and illnesses on site. The key elements of KFM's BBS "injury prevention" strategy included: 1) cash incentives to workers and supervisors who do not report injuries; 2) reprisals and threats of reprisals against those employees who do report injuries; 3) selection and use of employer friendly occupational health clinics and workers compensation insurance administrators; 4) strict limits on the activities of contract industrial hygiene consultants; and 5) a secretive management committee that decides whether reported injuries and illnesses are legitimate and recordable. KFM reported injury and illness rates 55% to 72% lower than other bridge builders in the Bay Area, but the California Division of Occupational Safety and Health (Cal/OSHA) issued Willful citations to the consortium in June 2006 for failing to record 13 worker injuries on its "OSHA Log 300," as required by law.

Regional analysis of population trajectories from the North American Breeding Bird Survey

USGS Publications Warehouse

Sauer, J.R.; Link, W.A.; Helbig, Andreas J.; Flade, Martin

1999-01-01

The North American Breeding Bird Survey (BBS) was started in 1966, and provides information on population change and distribution for most of the birds in North America. The geographic extent of the survey, and the logistical compromises needed to survey such a large area, present many challenges for estimation from BBS data. In this paper, we describe the survey and discuss some of the limitations of the survey design and implementation. Analysis of the survey has evolved over time as new statistical methods and insights into the analysis of count data are developed. Survey results and analysis tools for the BBS are now available over intemet; we present new methods that use generalized linear models for estimation of population change and empirical Bayes procedures for regional summaries.

Enhancing the value of the breeding bird survey: reply to Sauer et al. (2005)

Treesearch

Charles M. Francis; Jonathan Bart; Erica H. Dunn; Kenneth P. Burnham; C. John Ralph

2005-01-01

Bart et al (2004a) proposed several approaches for enhancing the considerable value of the Breeding Bird Survey (BBS). Sauer et al. (2005) critiqued some of these approaches, and emphasized alternative goals for the survey. We agree with many of the suggestions of Sauer et al. (2005); notably that multispecies, large-scale surveys such as the BBS are most valuable for...

Atlas of climate change effects in 150 bird species of the Eastern United States

Treesearch

Stephen Matthews; Raymond O' Connor; Louis R. Iverson; Anantha M. Prasad

2004-01-01

NOTE: Instructions for navigating this publication can be found on the front cover. This atlas documents the current and potential future distribution of 150 common bird species in the Eastern United States. Distribution data for individual species were derived from the Breeding Bird Survey (BBS) from 1981 to 1990. Regression tree analysis was used to model the BBS...

A Usability Survey of a Contents-Based Video Retrieval System by Combining Digital Video and an Electronic Bulletin Board

ERIC Educational Resources Information Center

Haga, Hirohide; Kaneda, Shigeo

2005-01-01

This article describes the survey of the usability of a novel content-based video retrieval system. This system combines video streaming and an electronic bulletin board system (BBS). Comments submitted to the BBS are used to index video data. Following the development of the prototype system an experimental survey with ten subjects was performed.…

A Multi-Level Simultaneous Analysis of How Student and School Characteristics Are Related to Students' English Language Achievement

ERIC Educational Resources Information Center

Güvendir, Emre

2015-01-01

This study examines how student and school characteristics are related to Turkish students' English language achievement in Evaluation of Student Achievement Test (ÖBBS) of 2009. The participants of the study involve 43707 ninth year students who were required to take ÖBBS in 2009. For data analysis two level hierarchical linear modeling was…

In Rwandese Women with Low Iron Status, Iron Absorption from Low-Phytic Acid Beans and Biofortified Beans Is Comparable, but Low-Phytic Acid Beans Cause Adverse Gastrointestinal Symptoms.

PubMed

Petry, Nicolai; Rohner, Fabian; Gahutu, Jean Bosco; Campion, Bruno; Boy, Erick; Tugirimana, Pierrot L; Zimmerman, Michael Bruce; Zwahlen, Christian; Wirth, James P; Moretti, Diego

2016-05-01

Phytic acid (PA) is a major inhibitor of iron bioavailability from beans, and high PA concentrations might limit the positive effect of biofortified beans (BBs) on iron status. Low-phytic acid (lpa) bean varieties could increase iron bioavailability. We set out to test whether lpa beans provide more bioavailable iron than a BB variety when served as part of a composite meal in a bean-consuming population with low iron status. Dietary iron absorption from lpa, iron-biofortified, and control beans (CBs) (regular iron and PA concentrations) was compared in 25 nonpregnant young women with low iron status with the use of a multiple-meal crossover design. Iron absorption was measured with stable iron isotopes. PA concentration in lpa beans was ∼10% of BBs and CBs, and iron concentration in BBs was ∼2- and 1.5-fold compared with CBs and lpa beans, respectively. Fractional iron absorption from lpa beans [8.6% (95% CI: 4.8%, 15.5%)], BBs [7.3% (95% CI: 4.0%, 13.4%)], and CBs [8.0% (95% CI: 4.4%, 14.6%)] did not significantly differ. The total amount of iron absorbed from lpa beans and BBs was 421 μg (95% CI: 234, 756 μg) and 431 μg (95% CI: 237, 786 μg), respectively, and did not significantly differ, but was >50% higher (P < 0.005) than from CBs (278 μg; 95% CI: 150, 499 μg). In our trial, the lpa beans were hard to cook, and their consumption caused transient adverse digestive side effects in ∼95% of participants. Gel electrophoresis analysis showed phytohemagglutinin L (PHA-L) residues in cooked lpa beans. BBs and lpa beans provided more bioavailable iron than control beans and could reduce dietary iron deficiency. Digestive side effects of lpa beans were likely caused by PHA-L, but it is unclear to what extent the associated digestive problems reduced iron bioavailability. This trial was registered at clinicaltrials.gov as NCT02215278. © 2016 American Society for Nutrition.

Endoscopic treatment of benign biliary strictures using covered self-expandable metal stents (CSEMS).

PubMed

Irani, Shayan; Baron, Todd H; Akbar, Ali; Lin, Otto S; Gluck, Michael; Gan, Ian; Ross, Andrew S; Petersen, Bret T; Topazian, Mark; Kozarek, Richard A

2014-01-01

Traditional endoscopic management of benign biliary strictures (BBS) consists of placement of one or more plastic stents. Emerging data support the use of covered self-expandable metal stents (CSEMS). We sought to assess outcome of endoscopic temporary placement of CSEMS in patients with BBS. This was a retrospective study of CSEMS placement for BBS between May 2005 and July 2012 from two tertiary care centers. A total of 145 patients (81 males, median age 59 years) with BBS were identified; 73 of which were classified as extrinsic and were caused by chronic pancreatitis, and 70 were intrinsic. Main outcome measures were resolution of stricture and adverse events (AEs) due to self-expandable metal stents (SEMS)-related therapy. Fully covered and partially covered 8-10 mm diameter SEMS were placed and subsequently removed in 121/125 (97 %) attempts in BBS (failure to remove four partially covered stents). Stricture resolution occurred in 83/125 (66 %) patients after a median stent duration of 26 weeks (median follow-up 90 weeks). Resolution of extrinsic strictures was significantly lower compared to intrinsic strictures (31/65, 48 % vs. 52/60, 87 %, p = 0.004) despite longer median stent duration (30 vs. 20 weeks). Thirty-seven AEs occurred in 25 patients (17 %), with 12 developing multiple AEs including cholangitis (n = 17), pancreatitis (n = 5), proximal stent migration (n = 3), cholecystitis (n = 2), pain requiring SEMS removal and/or hospitalization (n = 3), inability to remove (n = 4), and new stricture formation (n = 3). Benign biliary strictures can be effectively treated with CSEMS. Successful resolution of biliary strictures due to extrinsic disease is seen significantly less often than those due to intrinsic disease. Removal is successful in all patients with fully covered SEMS.

Bbs8, together with the planar cell polarity protein Vangl2, is required to establish left-right asymmetry in zebrafish.

PubMed

May-Simera, Helen L; Kai, Masatake; Hernandez, Victor; Osborn, Daniel P S; Tada, Masazumi; Beales, Philip L

2010-09-15

Laterality defects such as situs inversus are not uncommonly encountered in humans, either in isolation or as part of another syndrome, but can have devastating developmental consequences. The events that break symmetry during early embryogenesis are highly conserved amongst vertebrates and involve the establishment of unidirectional flow by cilia within an organising centre such as the node in mammals or Kupffer's vesicle (KV) in teleosts. Disruption of this flow can lead to the failure to successfully establish left-right asymmetry. The correct apical-posterior cellular position of each node/KV cilium is critical for its optimal radial movement which serves to sweep fluid (and morphogens) in the same direction as its neighbours. Planar cell polarity (PCP) is an important conserved process that governs ciliary position and posterior tilt; however the underlying mechanism by which this occurs remains unclear. Here we show that Bbs8, a ciliary/basal body protein important for intraciliary/flagellar transport and the core PCP protein Vangl2 interact and are required for establishment and maintenance of left-right asymmetry during early embryogenesis in zebrafish. We discovered that loss of bbs8 and vangl2 results in laterality defects due to cilia disruption at the KV. We showed that perturbation of cell polarity following abrogation of vangl2 causes nuclear mislocalisation, implying defective centrosome/basal body migration and apical docking. Moreover, upon loss of bbs8 and vangl2, we observed defective actin organisation. These data suggest that bbs8 and vangl2 act synergistically on cell polarization to establish and maintain the appropriate length and number of cilia in the KV and thereby facilitate correct LR asymmetry. (c) 2010. Published by Elsevier Inc.

Tele-Assessment of the Berg Balance Scale: Effects of Transmission Characteristics.

PubMed

Venkataraman, Kavita; Morgan, Michelle; Amis, Kristopher A; Landerman, Lawrence R; Koh, Gerald C; Caves, Kevin; Hoenig, Helen

2017-04-01

To compare Berg Balance Scale (BBS) rating using videos with differing transmission characteristics with direct in-person rating. Repeated-measures study for the assessment of the BBS in 8 configurations: in person, high-definition video with slow motion review, standard-definition videos with varying bandwidths and frame rates (768 kilobytes per second [kbps] videos at 8, 15, and 30 frames per second [fps], 30 fps videos at 128, 384, and 768 kbps). Medical center. Patients with limitations (N=45) in ≥1 of 3 specific aspects of motor function: fine motor coordination, gross motor coordination, and gait and balance. Not applicable. Ability to rate the BBS in person and using videos with differing bandwidths and frame rates in frontal and lateral views. Compared with in-person rating (7%), 18% (P=.29) of high-definition videos and 37% (P=.03) of standard-definition videos could not be rated. Interrater reliability for the high-definition videos was .96 (95% confidence interval, .94-.97). Rating failure proportions increased from 20% in videos with the highest bandwidth to 60% (P<.001) in videos with the lowest bandwidth, with no significant differences in proportions across frame rate categories. Both frontal and lateral views were critical for successful rating using videos, with 60% to 70% (P<.001) of videos unable to be rated on a single view. Although there is some loss of information when using videos to rate the BBS compared to in-person ratings, it is feasible to reliably rate the BBS remotely in standard clinical spaces. However, optimal video rating requires frontal and lateral views for each assessment, high-definition video with high bandwidth, and the ability to carry out slow motion review. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Conservation landmarks: bureau of biological survey and national biological service

USGS Publications Warehouse

Friend, M.

1995-01-01

A century separates the recent development of the National Biological Service (NBS) and an early predecessor, the Bureau of Biological Survey (BBS). Both organizations were established at critical crossroads for the conservation of the nation's living biological resources and are conservation landmarks of their times. The BBS of the 192()'s was described as 'a government Bureau of the first rank, handling affairs of great scientific, educational, social, and above all, economic importance throughout the United States and its outlying possessions'' (Cameron 1929:144-145). This stature was achieved at a time of great social, economic, and ecological change. BBS had the vision to pioneer new approaches that led to enhanced understanding of the relation between people, other living things, and the environment. The NBS faces similar challenges to address the issues of the 1990's and beyond.

First observation of B(s)(0) --> D(s)(+/-)K(-/+) and measurement of the ratio of branching fractions B(B(s)(0) --> D(s)(+/-)K(-/+)/B(B(s)(0) --> D(s)(+)pi(-)).

PubMed

Aaltonen, T; Adelman, J; Akimoto, T; Albrow, M G; Alvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Apollinari, G; Apresyan, A; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Azzurri, P; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Bartsch, V; Bauer, G; Beauchemin, P-H; Bedeschi, F; Bednar, P; Beecher, D; Behari, S; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Beringer, J; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Bridgeman, A; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Calancha, C; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavaliere, V; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Compostella, G; Convery, M E; Conway, J; Copic, K; Cordelli, M; Cortiana, G; Cox, D J; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Dagenhart, D; Datta, M; Davies, T; de Barbaro, P; De Cecco, S; Deisher, A; De Lorenzo, G; Dell'Orso, M; Deluca, C; Demortier, L; Deng, J; Deninno, M; Derwent, P F; di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Elagin, A; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Ferrazza, C; Field, R; Flanagan, G; Forrest, R; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garberson, F; Garcia, J E; Garfinkel, A F; Genser, K; Gerberich, H; Gerdes, D; Gessler, A; Giagu, S; Giakoumopoulou, V; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C M; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Group, R C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, D; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Hays, C; Heck, M; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hewamanage, S; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; James, E; Jayatilaka, B; Jeon, E J; Jha, M K; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Kar, D; Karchin, P E; Kato, Y; Kephart, R; Keung, J; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Knuteson, B; Ko, B R; Koay, S A; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kreps, M; Kroll, J; Krop, D; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhr, T; Kulkarni, N P; Kurata, M; Kusakabe, Y; Kwang, S; Laasanen, A T; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; LeCompte, T; Lee, E; Lee, H S; Lee, S W; Leone, S; Lewis, J D; Lin, C S; Linacre, J; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, C; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Lovas, L; Lu, R-S; Lucchesi, D; Lueck, J; Luci, C; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; MacQueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis-Katsikakis, A; Margaroli, F; Marino, C; Marino, C P; Martin, A; Martin, V; Martínez, M; Martínez-Ballarín, R; Maruyama, T; Mastrandrea, P; Masubuchi, T; Mattson, M E; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzione, A; Merkel, P; Mesropian, C; Miao, T; Miladinovic, N; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyake, H; Moggi, N; Moon, C S; Moore, R; Morello, M J; Morlok, J; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Nagano, A; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nodulman, L; Norman, M; Norniella, O; Nurse, E; Oakes, L; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Orava, R; Osterberg, K; Pagan Griso, S; Pagliarone, C; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Pianori, E; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Pueschel, E; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rodriguez, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Safonov, A; Sakumoto, W K; Saltó, O; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, A; Schmidt, E E; Schmidt, M A; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyrla, A; Shalhout, S Z; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shiraishi, S; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spreitzer, T; Squillacioti, P; Stanitzki, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Suslov, I; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thompson, G A; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Totaro, P; Tourneur, S; Tu, Y; Turini, N; Ukegawa, F; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Vellidis, C; Veszpremi, V; Vidal, M; Vidal, R; Vila, I; Vilar, R; Vine, T; Vogel, M; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner-Kuhr, J; Wagner, W; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Xie, S; Yagil, A; Yamamoto, K; Yamaoka, J; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zheng, Y; Zucchelli, S

2009-11-06

A combined mass and particle identification fit is used to make the first observation of the decay B(s)(0) --> D(s)(+/-)K(-/+) and measure the branching fraction of B(s)(0) --> D(s)(+/-)K(-/+) relative to B(s)(0) --> D(s)(+)pi(-). This analysis uses 1.2 fb(-1) integrated luminosity of pp collisions at square root(s) = 1.96 TeV collected with the CDF II detector at the Fermilab Tevatron collider. We observe a B(s)(0) --> D(s)(+/-)K(-/+) signal with a statistical significance of 8.1 sigma and measure B(B(s)(0) --> D(s)(+/-)K(-/+) /B(B(s)(0) --> D(s)(+)pi(-) 0.097+/-0.018(stat) +/- 0.009(syst).

North American Breeding Bird Survey Annual Summary, 1989

USGS Publications Warehouse

Droege, S.; Sauer, J.R.

1990-01-01

The North American Breeding Bird Survey (BBS) is run by approximately 2,000 skilled amateur ornithologists and is coordinated cooperatively by the U.S. Fish and Wildlife Service and the Canadian Wildlife Service. Since 1966, BBS cooperators have been collecting standardized information on North American bird populations. The BBS is a roadside survey, comprised of permanent routes that are surveyed yearly. Each route is 39.4 km (24.5 miles) long and consists of 50 stops spaced 0.8 km (0.5 mile) apart. All birds heard or seen during a 3-min observation period at each stop are recorded, and, for each species, the sum of the counts on individual stops is used as an index of species density on the route. Survey routes occur throughout the continental United States and most of Canada. Here, we present the population changes of the 251 bird species reported on the 50 or more BBS routes in the survey region during 1988 and 1989. Population trends for 1966-89 are presented for comparison. The direction and significance of population changes between the years for the 306 species occurring on 10 or more routes within States and Provinces are summarized in Appendix B. The pattern of population changes for selected species is graphically summarized on maps by physiographic stratum.

North American Breeding Bird Survey Annual Summary, 1988

USGS Publications Warehouse

Droege, S.; Sauer, J.R.

1989-01-01

Introduction: The North American Breeding Bird Survey (BBS) is run by approximately 2,000 skilled amateur ornithologists, and is coordinated cooperatively by the U.S. Fish and Wildlife Service and the Canadian Wildlife Service. Beginning in 1966, BBS cooperators have been collecting standardized information on North American bird populations. The BBS is a roadside survey, comprised of permanent routes that are surveyed yearly. Each route is 39.4 km (24.5 miles) long and consists of 50 stops spaced 0.8 km (0.5 mile) apart. All birds heard or seen during a 3-min observation period at each stop are recorded, and the sum of the individual stops for each species is used as an index of species density on the route. In this report, we present the population changes of the 222 bird species reported on > 50 BBS routes during 1987 and 1988. Population trends for 1966-87 are presented for comparison. Owing to space constraints, trends are not reported for States, Provinces, or physiographic regions. Instead, we present maps illustrating patterns of population change for selected species, and summarize State and physiographic strata patterns of population change as the proportion of species that increased in each region. Detailed State, Provincial, and physiographic strata changes arc available to interested readers.

Explicit Building-Block Multiobjective Genetic Algorithms: Theory, Analysis, and Development

DTIC Science & Technology

2003-03-01

Member Date Dr. (Maj) David A. Van Veldhuizen Committee Member Date Dr. Richard F. Deckro Dean’s Representative Date Accepted: Robert A. Calico, Jr...results in increased throughput and vice-versa. Van Veldhuizen validated the concept that BBs exist and are useful in the multiob- jective domain [184...extended to multiobjective functions. Van Veldhuizen states that BBs are not handled differently by MOEAs as compared to EAs. Even though an MOEA

Communication network analysis in maternity hospital bulletin board system.

PubMed

Suto, Shunji; Ashida, Nobuyuki; Higashi, Terumasa; Takemura, Hideo; Kurimoto, Koji; Yorifuji, Shiro

2007-04-01

Recent changes in Japanese social environments consequently dropped total fertility rate, and poor interpersonal relationships in local communities have aggravated the environments for childbirth and child-rearing. Under such circumstances, we introduced a bulletin board system (BBS) to an official web-site of a maternity hospital to set up a community for its patients for communication regarding childbirth and the like. Based on the logs from BBS, we graphed types of communication among its users with to describe topologies. Additionally, we calculated degrees of centralization of entire networks and found the hospital role as the administrator becomes smaller as inter-user communication becomes more brisk. The analysis of contents of respective threads also revealed that main topics shifted from gestational matters to postnatal and child-rearing as communication became more brisk, which indicates those postnatal users are also strongly conscious with gestational and progestational contents and contribute to supporting the entire BBS.

Extremes in ecology: Avoiding the misleading effects of sampling variation in summary analyses

USGS Publications Warehouse

Link, W.A.; Sauer, J.R.

1996-01-01

Surveys such as the North American Breeding Bird Survey (BBS) produce large collections of parameter estimates. One's natural inclination when confronted with lists of parameter estimates is to look for the extreme values: in the BBS, these correspond to the species that appear to have the greatest changes in population size through time. Unfortunately, extreme estimates are liable to correspond to the most poorly estimated parameters. Consequently, the most extreme parameters may not match up with the most extreme parameter estimates. The ranking of parameter values on the basis of their estimates are a difficult statistical problem. We use data from the BBS and simulations to illustrate the potential misleading effects of sampling variation in rankings of parameters. We describe empirical Bayes and constrained empirical Bayes procedures which provide partial solutions to the problem of ranking in the presence of sampling variation.

Cystic fibrosis transmembrane conductance regulator modulators: precision medicine in cystic fibrosis.

PubMed

Burgener, Elizabeth B; Moss, Richard B

2018-06-01

The aim of this study was to describe the newest development in cystic fibrosis (CF) care, CF transmembrane conductance regulator (CFTR) modulator therapies. Phase II results showing CFTR modulator triple therapies are more effective than current CFTR modulators. CFTR modulator therapy targets the protein defective in CF and boosts its function, but the drug must match mutation pathobiology. Ivacaftor, a CFTR potentiator, was the first modulator approved in 2012, with impressive improvement in lung function and other measures of disease in patients with gating and other residual function mutations (∼10% of CF patients). In 2015, the combination of lumacaftor, a CFTR corrector, and ivacaftor was approved for patients homozygous for the F508del mutation (∼40-50% of the CF population) with positive but less impressive clinical response and 10-20% incidence of intolerance. A next-generation CFTR corrector, tezacaftor, with ivacaftor equally effective and better tolerated than lumacaftor, has also received US Food and Drug Administration approval. Novel CFTR correctors, entering Phase 3 trials in triple modulator combination with tezacaftor-ivacaftor, appear substantially more effective for patients who are homozygous for the F508del mutation and can provide benefit for patients with a single F508del mutation. This offers promise of effective CFTR modulator therapy for nearly 90% of CF patients.

Mutational landscape of antibody variable domains reveals a switch modulating the interdomain conformational dynamics and antigen binding

PubMed Central

Koenig, Patrick; Lee, Chingwei V.; Walters, Benjamin T.; Janakiraman, Vasantharajan; Stinson, Jeremy; Patapoff, Thomas W.; Fuh, Germaine

2017-01-01

Somatic mutations within the antibody variable domains are critical to the immense capacity of the immune repertoire. Here, via a deep mutational scan, we dissect how mutations at all positions of the variable domains of a high-affinity anti-VEGF antibody G6.31 impact its antigen-binding function. The resulting mutational landscape demonstrates that large portions of antibody variable domain positions are open to mutation, and that beneficial mutations can be found throughout the variable domains. We determine the role of one antigen-distal light chain position 83, demonstrating that mutation at this site optimizes both antigen affinity and thermostability by modulating the interdomain conformational dynamics of the antigen-binding fragment. Furthermore, by analyzing a large number of human antibody sequences and structures, we demonstrate that somatic mutations occur frequently at position 83, with corresponding domain conformations observed for G6.31. Therefore, the modulation of interdomain dynamics represents an important mechanism during antibody maturation in vivo. PMID:28057863

Mutations in histone modulators are associated with prolonged survival during azacitidine therapy

PubMed Central

Tobiasson, Magnus; McLornan, Donal P.; Karimi, Mohsen; Dimitriou, Marios; Jansson, Monika; Azenkoud, Asmaa Ben; Jädersten, Martin; Lindberg, Greger; Abdulkadir, Hani; Kulasekararaj, Austin; Ungerstedt, Johanna; Lennartsson, Andreas; Ekwall, Karl; Mufti, Ghulam J.; Hellström-Lindberg, Eva

2016-01-01

Early therapeutic decision-making is crucial in patients with higher-risk MDS. We evaluated the impact of clinical parameters and mutational profiles in 134 consecutive patients treated with azacitidine using a combined cohort from Karolinska University Hospital (n=89) and from King's College Hospital, London (n=45). While neither clinical parameters nor mutations had a significant impact on response rate, both karyotype and mutational profile were strongly associated with survival from the start of treatment. IPSS high-risk cytogenetics negatively impacted overall survival (median 20 vs 10 months; p<0.001), whereas mutations in histone modulators (ASXL1, EZH2) were associated with prolonged survival (22 vs 12 months, p=0.01). This positive association was present in both cohorts and remained highly significant in the multivariate cox model. Importantly, patients with mutations in histone modulators lacking high-risk cytogenetics showed a survival of 29 months compared to only 10 months in patients with the opposite pattern. While TP53 was negatively associated with survival, neither RUNX1-mutations nor the number of mutations appeared to influence survival in this cohort. We propose a model combining histone modulator mutational screening with cytogenetics in the clinical decision-making process for higher-risk MDS patients eligible for treatment with azacitidine. PMID:26959885

Optimising mobility outcome measures in Huntington's disease.

PubMed

Busse, Monica; Quinn, Lori; Khalil, Hanan; McEwan, Kirsten

2014-01-01

Many of the performance-based mobility measures that are currently used in Huntington's disease (HD) were developed for assessment in other neurological conditions such as stroke. We aimed to assess the individual item-response of commonly used performance-based mobility measures, with a view to optimizing the scales for specific application in Huntington's Disease (HD). Data from a larger multicentre, observational study were used. Seventy-five people with HD (11 pre-manifest & 64 manifest) were assessed on the Six-Minute Walk Test, 10-Meter Walk Test, Timed "Up & Go" Test (TUG), Berg Balance Scale (BBS), Physical Performance Test (PPT), Four Square Step Test, and Tinetti Mobility Test (TMT). The Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, Functional Assessment Scale and Total Functional Capacity scores were recorded, alongside cognitive measures. Standard regression analysis was used to assess predictive validity. Individual item responses were investigated using a sequence of approaches to allow for gradual removal of items and the subsequent creation of shortened versions. Psychometric properties (reliability and discriminant ability) of the shortened scales were assessed. TUG (β 0.46, CI 0.20-3.47), BBS (β -0.35, CI -2.10-0.14), and TMT (β -0.45, CI -3.14-0.64) were good disease-specific mobility measures. PPT was the best measure of functional performance (β 0.42, CI 0.00-0.43 for TFC & β 0.57 CI 0.15-0.81 for FAS). Shortened versions of BBS and TMT were developed based on item analysis. The resultant BBS and TMT shortened scales were reliable for use in manifest HD. ROC analysis showed that shortened scales were able to discriminate between manifest and pre-manifest disease states. Our data suggests that the PPT is appropriate as a general measure of function in individuals with HD, and we have identified shortened versions of the BBS and TMT that measure the unique gait and balance impairments in HD. These scales, alongside the TUG, may therefore be important measures to consider in future clinical trials.

Knee and ankle strength and lower extremity power in adolescent female ballet dancers.

PubMed

Kenne, Ellinor; Unnithan, Viswanath B

2008-01-01

The aims of this study were twofold: (1) to compare the strength of four muscle groups of the lower limb (quadriceps [Q], hamstrings [H], plantar flexors [PF], and dorsiflexors [DF]) between female adolescent ballet dancers (BALs) and basketball players (BBs) over three angular velocities (30 degrees, 60 degrees and 90 degrees/sec) and two types of contraction (eccentric and concentric); and (2) to compare peak and mean power between the BALs and BBs. Eleven BALs (age: 15.8 +/- 1.2 years; stature: 163.9 +/- 6.2 cm; body mass: 56.3 +/- 5.7 kg; Tanner stage 4: N=10, stage 5: N=1) and ten BBs (age: 15.8 +/- 1.0 years; stature: 172.5 +/- 5.8 cm; body mass: 63.2 +/- 10.0 kg; Tanner stage 4: N=7, stage 5: N=3) volunteered to participate. Each participant performed one habituation session and one testing session on a Biodex isokinetic dynamometer to determine peak torque. Three angular velocities (30 degrees, 60 degrees and 90 degrees/sec) were used for each muscle group. To determine absolute and relative peak and mean power, participants performed a 30 second anaerobic Wingate test on a cycle ergometer. There were no significant differences in peak torque for Q, H, PF, and DF between the groups. Basketball players produced greater absolute peak power [569.7 +/- 82.2 vs. 454.6 +/- 79.3 W (p < .05)], relative peak power [9.1 +/- 1.3 vs. 8.1 +/- 1.0 W/kg body mass (p < .05)], absolute mean power [428.4 +/- 53.9 vs. 333.7 +/- 68.2 W (p < .05)] and relative mean power [6.83 +/- 0.7 vs. 5.9 +/- 0.7 W/kg (p < .05)] than BALs. Ballet dancers and BBs had similar isokinetically measured lower extremity muscular strength, but BALs generated lower levels of peak power and mean power compared to BBs.

Efficacy of self-expandable metal stents in management of benign biliary strictures and comparison with multiple plastic stents: a meta-analysis.

PubMed

Khan, Muhammad Ali; Baron, Todd H; Kamal, Faisal; Ali, Bilal; Nollan, Richard; Ismail, Mohammad Kashif; Tombazzi, Claudio; Artifon, Everson L A; Repici, Alessandro; Khashab, Mouen A

2017-07-01

Background and study aims  There is burgeoning interest in the utilization of covered self-expandable metal stents (CSEMSs) for managing benign biliary stricture (BBS). This systematic review and meta-analysis evaluated cumulative stricture resolution and recurrence rates using CSEMSs and compared performance of CSEMSs and multiple plastic stents (MPS) in BBS management. Method  Searches in several databases identified studies including ≥ 10 patients that utilized CSEMSs for BBS treatment. Weighted pooled rates were calculated for stricture resolution and recurrence. Pooled risk ratios (RRs) comparing CSEMSs with MPS were calculated for stricture resolution, stricture recurrence, and adverse events. Pooled difference in means was calculated to compare number of endoscopic retrograde cholangiopancreatographies (ERCPs) in each group.  Results  The meta-analysis included 22 studies with 1298 patients. Weighted pooled rate for BBS resolution with CSEMS was 83 % (95 % confidence limits [95 %CLs] 78 %, 87 %; I 2  = 72 %). On meta-regression analysis, resolution in chronic pancreatitis patients and post-orthotopic liver transplant patients were significant predictors of heterogeneity. Weighted pooled rate for stricture recurrence with CSEMSs was 16 % (11 %, 22 %). Overall rate of adverse events requiring intervention and/or hospitalization was 15 %. Four randomized controlled trials with 213 patients compared CSEMSs with MPS: the pooled RRs for stricture resolution, recurrence, and adverse events were 1.07 (0.97, 1.18), 0.88 (0.48, 1.63), and 1.16 (0.71, 1.88), respectively with no heterogeneity. Pooled difference in means for number of ERCPs was - 1.71 ( - 2.33, - 1.09) in favor of CSEMS. Conclusions  CSEMSs appear to have excellent efficacy in BBS management. They are as effective as MPS but require fewer ERCPs to achieve clinical success. © Georg Thieme Verlag KG Stuttgart · New York.

The Mini-Balance Evaluation Systems Test (Mini-BESTest) Demonstrates Higher Accuracy in Identifying Older Adult Participants With History of Falls Than Do the BESTest, Berg Balance Scale, or Timed Up and Go Test.

PubMed

Yingyongyudha, Anyamanee; Saengsirisuwan, Vitoon; Panichaporn, Wanvisa; Boonsinsukh, Rumpa

2016-01-01

Balance deficits a significant predictor of falls in older adults. The Balance Evaluation Systems Test (BESTest) and the Mini-Balance Evaluation Systems Test (Mini-BESTest) are tools that may predict the likelihood of a fall, but their capabilities and accuracies have not been adequately addressed. Therefore, this study aimed at examining the capabilities of the BESTest and Mini-BESTest for identifying older adult with history of falls and comparing the participants with history of falls identification accuracy of the BESTest, Mini-BESTest, Berg Balance Scale (BBS), and the Timed Up and Go Test (TUG) for identifying participants with a history of falls. Two hundred healthy older adults with a mean age of 70 years were classified into participants with and without history of fall groups on the basis of their 12-month fall history. Their balance abilities were assessed using the BESTest, Mini-BESTest, BBS, and TUG. An analysis of the resulting receiver operating characteristic curves was performed to calculate the area under the curve (AUC), sensitivity, specificity, cutoff score, and posttest accuracy of each. The Mini-BESTest showed the highest AUC (0.84) compared with the BESTest (0.74), BBS (0.69), and TUG (0.35), suggesting that the Mini-BESTest had the highest accuracy in identifying older adult with history of falls. At the cutoff score of 16 (out of 28), the Mini-BESTest demonstrated a posttest accuracy of 85% with a sensitivity of 85% and specificity of 75%. The Mini-BESTest had the highest posttest accuracy, with the others having results of 76% (BESTest), 60% (BBS), and 65% (TUG). The Mini-BESTest is the most accurate tool for identifying older adult with history of falls compared with the BESTest, BBS, and TUG.

Technical Note: Robust measurement of the slice-sensitivity profile in breast tomosynthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maki, Aili K., E-mail: aili.maki@sri.utoronto.ca

2016-08-15

Purpose: The purpose of this work is to improve the repeatability of the measurement of the slice-sensitivity profile (SSP) in reconstructed breast tomosynthesis volumes. Methods: A grid of aluminum ball-bearings (BBs) within a PMMA phantom was imaged on breast tomosynthesis systems from three different manufacturers. The full-width half-maximum (FWHM) values were measured for the SSPs of the BBs in the reconstructed volumes. The effect of transforming the volumes from a Cartesian coordinate system (CCS) to a cone-beam coordinate system (CBCS) on the variability in the FWHM values was assessed. Results: Transforming the volumes from a CCS to a CBCS beforemore » measuring the SSPs reduced the coefficient of variation (COV) in the measurements of FWHM in repeated measurements by 56% and reduced the dependence of the FWHM values on the location of the BBs within the reconstructed volume by 76%. Conclusions: Measuring the SSP in the volumes in a CBCS improves the robustness of the measurement.« less

Selected Manpower Statistics, FY-65

DTIC Science & Technology

1966-04-11

o 0.1 • • O.T 0.1 0.1 MM ID Ja* UH OWtStWWllfl) tarn JB y Lit, «•&. ■nvV M».». MUWT ClflUM U,I ».» 15 1.0 >,*T) 8:8 J:J 5:S ^8 i.« t.» ».I...8» «8» »»» i M*4I fjßl ISS iss saa SBJS aas ma Bias SS »««ü 1KB W« 5!K 5BB5 B»B KB» ! BJB 5«B! t| •»«« SUM 33313 SS9IS 9(1119 199911 llttil II99M...v«vw 3N’M*«*M’ <f<r«v<r ««*«««« «MVfr«v ttm* ****** ****** S «8 5^5 JSB B« ffl« BBS? SSäi »BJ! S5J135 g «IS JBS BBS SB! »BB MBB BBS iBBJ SB

Effect of bilateral lower limb strengthening exercise on balance and walking in hemiparetic patients after stroke: a randomized controlled trial.

PubMed

Jeon, Hye Joo; Hwang, Byong Yong

2018-02-01

[Purpose] To evaluate the effect of bilateral lower limb strengthening designed to improve balance and walking in stroke patients. [Subjects and Methods] Twenty hemiparetic stroke patients were divided into two groups: a unilateral therapy group (UTG) (n=10) and a bilateral therapy group (BTG) (n=10). The UTG completed strength training only in the paretic lower limb. The BTG completed strength training in the paretic and non-paretic lower limbs. Assessment tools included the functional reach test (FRT), the Berg balance scale (BBS), the timed up and go (TUG) test, and a 10-meter walk test (10MWT). [Results] In both groups, the lower limb strengthening exercise for balance and walking significantly improved the FRT, BBS, TUG, and 10MWT scores. Compared with UTG, the BTG attained significantly improved FRT and BBS scores. [Conclusion] Bilateral therapy using this lower limb strengthening exercise effectively promotes balance in hemiparetic stroke patients.

Effect of bilateral lower limb strengthening exercise on balance and walking in hemiparetic patients after stroke: a randomized controlled trial

PubMed Central

Jeon, Hye Joo; Hwang, Byong Yong

2018-01-01

[Purpose] To evaluate the effect of bilateral lower limb strengthening designed to improve balance and walking in stroke patients. [Subjects and Methods] Twenty hemiparetic stroke patients were divided into two groups: a unilateral therapy group (UTG) (n=10) and a bilateral therapy group (BTG) (n=10). The UTG completed strength training only in the paretic lower limb. The BTG completed strength training in the paretic and non-paretic lower limbs. Assessment tools included the functional reach test (FRT), the Berg balance scale (BBS), the timed up and go (TUG) test, and a 10-meter walk test (10MWT). [Results] In both groups, the lower limb strengthening exercise for balance and walking significantly improved the FRT, BBS, TUG, and 10MWT scores. Compared with UTG, the BTG attained significantly improved FRT and BBS scores. [Conclusion] Bilateral therapy using this lower limb strengthening exercise effectively promotes balance in hemiparetic stroke patients. PMID:29545693

The North American Breeding Bird Survey

USGS Publications Warehouse

Bystrak, D.; Ralph, C. John; Scott, J. Michael

1981-01-01

A brief history of the North American Breeding Bird Survey (BBS) and a discussion of the technique are presented. The approximately 2000 random roadside routes conducted yearly during the breeding season throughout North America produce an enormous bank of data on distribution and abundance of breeding birds with great potential use. Data on about one million total birds of 500 species per year are on computer tape to facilitate accessibility and are available to any serious investigator. The BBS includes the advantages of wide geographic coverage, sampling of most habitat types, standardization of data collection, and a relatively simple format. The Survey is limited by placement of roads (e.g., marshes and rugged mountainous areas are not well sampled), traffic noise interference in some cases and preference of some bird species for roadside habitats. These and other problems and biases of the BBS are discussed. The uniformity of the technique allows for detecting changes in populations and for creation of maps of relative abundance. Examples of each are presented.

Characterization of Courtesy Stigma Perceived by Parents of Overweight Children with Bardet-Biedl Syndrome.

PubMed

Hamlington, Barbara; Ivey, Lauren E; Brenna, Ethan; Biesecker, Leslie G; Biesecker, Barbara B; Sapp, Julie C

2015-01-01

A child's obesity is generally perceived by the public to be under the control of the child's parents. While the health consequences of childhood obesity are well understood, less is known about psychological and social effects of having an obese child on parents. We set out to characterize stigma and courtesy stigma experiences surrounding obesity among children with Bardet-Biedl syndrome (BBS), a multisystem genetic disorder, and their parents. Twenty-eight parents of children with BBS participated in semi-structured interviews informed by social stigmatization theory, which describes courtesy stigma as parental perception of stigmatization by association with a stigmatized child. Parents were asked to describe such experiences. Parents of children with BBS reported the child's obesity as the most frequent target of stigmatization. They perceived health care providers as the predominant source of courtesy stigma, describing interactions that resulted in feeling devalued and judged as incompetent parents. Parents of children with BBS feel blamed by others for their child's obesity and described experiences that suggest health care providers may contribute to courtesy stigma and thus impede effective communication about managing obesity. Health care providers may reinforce parental feelings of guilt and responsibility by repeating information parents may have previously heard and ignoring extremely challenging barriers to weight management, such as a genetic predisposition to obesity. Strategies to understand and incorporate parents' perceptions and causal attributions of their children's weight may improve communication about weight control.

The level of physical activity affects the health of older adults despite being active

PubMed Central

Fernandez-Alonso, Lorena; Muñoz-García, Daniel; La Touche, Roy

2016-01-01

Health care in the ageing population is becoming a crucial issue, due to the quality of life. Physical activity, is of primary importance for older adults. This report compared the physical activity in two active older adults population with functionality, quality of life, and depression symptoms. A cross-sectional study was developed with 64 older adults. Physical activity was assessed through the Yale Physical Activity Survey for classification into a less activity (LA) group and a more activity (MA) group. Afterwards, the other health variables were measured through specific questionnaires: the quality of life with the EuroQol (EuroQol five dimensions questionnaire, EQ-5D), functionality with the Berg balance scale (BBS) and depression symptoms with the geriatric depression scale (GDS). There is a statistical significant difference between groups for the BBS (t=2.21; P=0.03, d=0.27). The Pearson correlation analysis shows in LA group a moderate correlation between the BBS and age (r=−0.539; P<0.01) and EQ-5D (r=0.480; P<0.01). Moreover, both groups had a moderate negative correlation between GDS and the the EQ-5D time trade-off (r=−0.543; P=0.02). Active older adults with different amounts of physical activity differ in the BBS. This functional score was higher in the MA group. When observing to quality of life, only the LA group was negatively associated with age while in both groups were associated with depression index. PMID:27419115

Validity and Relative Ability of 4 Balance Tests to Identify Fall Status of Older Adults With Type 2 Diabetes.

PubMed

Marques, Alda; Silva, Alexandre; Oliveira, Ana; Cruz, Joana; Machado, Ana; Jácome, Cristina

The Berg Balance Scale (BBS), the Balance Evaluation Systems Test (BESTest), the Mini-BESTest, and the Brief-BESTest are useful tests to assess balance; however, their clinimetric properties have not been studied well in older adults with type 2 diabetes (T2D). This study compared the validity and relative ability of the BBS, BESTest, Mini-BESTest, and Brief-BESTest to identify fall status in older adults with T2D. This study involved a cross-sectional design. Sixty-six older adults with T2D (75 ± 7.6 years) were included and asked to report the number of falls during the previous 12 months and to complete the Activities-specific Balance Confidence scale. The BBS and the BESTest were administered, and the Mini-BESTest and Brief-BESTest scores were computed based on the BESTest performance. Receiver operating characteristics were used to assess the ability of each balance test to differentiate between participants with and without a history of falls. The 4 balance tests were able to identify fall status (areas under the curve = 0.74-0.76), with similar sensitivity (60%-67%) and specificity (71%-76%). The 4 balance tests were able to differentiate between older adults with T2D with and without a history of falls. As the BBS and the BESTest require longer application time, the Brief-BESTest may be an appropriate choice to use in clinical practice to detect fall risk.

Potential roadside biases due to habitat changes along Breeding Bird Survey routes

USGS Publications Warehouse

Keller, C.M.E.; Scallan, J.T.

1999-01-01

Breeding Bird Surveys (BBS) are conducted along roadside routes to enable a large geographic area to be surveyed. Yet the potential biases of sampling populations only from roadsides have received little attention. We sampled aerial photography of BBS routes taken in the mid-1960s and late-1980s to evaluate whether habitat changes that occurred along roadsides were also occurring in the surrounding area, and whether the frequency of habitats encountered along roadsides were similar to that off-route. We examined 28 routes in Maryland and 25 routes in Ohio, and defined roadside area as within 200 m of the road, and off-route as 200-1,600 m from the road. Most habitat changes that occurred along BBS roadsides also were occurring in the off-route areas. However, increases in urban cover was significantly greater along the road in Maryland where urbanization of farmland was the predominant habitat change. The small increase in urban cover in Ohio was not significantly greater along the road. Construction of single family homes was greater along BBS roadsides in both states. In Ohio, the greatest change in habitat was the conversion of farmland back to forest, which was not significantly greater along the road. Changes associated with urbanization were more biased towards roadsides than the reforestation of farmland. Within one time period, roadside areas had less forest and more agricultural and urban cover types than occurred off-route.

Individualized treadmill and strength training for chronic stroke rehabilitation: effects of imbalance.

PubMed

Al-Jarrah, Muhammed; Shaheen, Samira; Harries, Netta; Kissani, Najib; Molteni, Franco; Bar Haim, Simona

2014-01-01

Stroke survivors often have significant walking limitations and are at high risk for falling. Treadmill training, as a rehabilitation approach in stroke survivors, and its relationship to balance ability has not been widely studied. The main goal of this study was to investigate the effectiveness of an individualized treadmill-strength training protocol on functional outcomes in chronic stroke survivors. Thirty adult participants with chronic stroke were recruited from 1 European and 4 Middle Eastern countries. Each completed 36 sessions of treadmill-strength training. The rehabilitation protocol was individualized according to each patient's cardiovascular fitness. Ten-meter walk test (10MWT), Berg Balance Scale (BBS), and 6-minute walk test (6MWT) were measured before (T0) and after training (T1) and 6 months later (T2). Paired t tests were used to test differences with training (T1 - T0) and retention after training (T2 - T1). Increases in all 3 measures from T0 to T1 were significant. There were no changes in 10MWT and BBS from T1 to T2, but 6MWT tended to increase. Separate analyses for subjects with BBS scores <41 at T0 demonstrated comparatively greater improvements from T0 to T1 than in those with BBS scores ≯40. Those with low scores also significantly increased from T1 to T2 in both walk tests. These findings suggest that a protocol combining treadmill with strength training has beneficial long-term effects on functional walking measures after chronic stroke, especially in patients who initially have low balance ability.

The Additive Effects of Core Muscle Strengthening and Trunk NMES on Trunk Balance in Stroke Patients

PubMed Central

Ko, Eun Jae; Kim, Dae Yul; Yi, Jin Hwa; Kim, Won; Hong, Jayoung

2016-01-01

Objective To investigate an additive effect of core muscle strengthening (CMS) and trunk neuromuscular electrical stimulation (tNEMS) on trunk balance in stroke patients. Methods Thirty patients with acute or subacute stroke who were unable to maintain static sitting balance for >5 minutes were enrolled and randomly assigned to 3 groups, i.e., patients in the CMS (n=10) group received additional CMS program; the tNMES group (n=10) received additional tNMES over the posterior back muscles; and the combination (CMS and tNMES) group (n=10) received both treatments. Each additional treatment was performed 3 times per week for 20 minutes per day over 3 weeks. Korean version of Berg Balance Scale (K-BBS), total score of postural assessment scale for stroke patients (PASS), Trunk Impairment Scale (TIS), and Korean version of Modified Barthel Index (K-MBI) were evaluated before and after 3 weeks of therapeutic intervention. Results All 3 groups showed improvements in K-BBS, PASS, TIS, and K-MBI after therapeutic interventions, with some differences. The combination group showed more improvements in K-BBS and the dynamic sitting balance of TIS, as compared to the CMS group; and more improvement in K-BBS, as compared to the tNMES group. Conclusion The results indicated an additive effect of CMS and tNMES on the recovery of trunk balance in patients with acute or subacute stroke who have poor sitting balance. Simultaneous application of CMS and tNMES should be considered when designing a rehabilitation program to improve trunk balance in stroke patients. PMID:26949681

How are patients with heart failure treated in primary care?
.

PubMed

Vaillant-Roussel, Hélène; Pereira, Bruno; Gibot-Boeuf, Sylvaine; Eschalier, Romain; Dubray, Claude; Boussageon, Rémy; Vorilhon, Philippe

2018-05-24

The aim of this study was to assess the adherence of general practitioners (GPs) to guidelines in patients with heart failure with reduced ejection fraction (HFrEF) and to describe GPs' prescribing behavior regarding patients with heart failure with preserved ejection fraction (HFpEF). Cross-sectional study as part of the ETIC trial. Five classes of drugs were described: angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs); β-blockers (BBs); mineralocorticoid receptor antagonists (MRAs); diuretics (thiazide or loop diuretics); and digoxin. 178 patients were studied: their mean age was 73.5 years (± 10.6). Of the 128 patients with HFpEF, 81.3% received ACEIs or ARBs, 63.3% received BBs, 13.3% received MRAs, 75.8% received diuretics, and 12.5% received digoxin. Of the 50 patients with HFrEF, 84% received ACEIs or ARBs, 74% received BBs, 20% received MRAs, 76% received diuretics, and 2% received digoxin. 25% of the patients were given a drug in accordance with the recommendations for drug class but not a drug authorized for the HFrEF indication. Among the patients with HFrEF who were treated in accordance with the recommendations, target doses were achieved in 1/3 given ACEIs/ARBs, 1/4 given BBs, and 1/2 given MRAs. Only 6% of the patients had a perfect Global Adherence Indicator-3 (GAI-3) with all target doses achieved. Several drugs were prescribed even though they were not recommended, and few patients were treated optimally. It seems to be necessary to develop a pragmatic tool to help GPs and cardiologists in optimizing treatment.
.

Reliability of blood color and blood gases in discriminating arterial from venous puncture during cardiopulmonary resuscitation.

PubMed

Park, Je Sung; Lee, Byung Kook; Jeung, Kyung Woon; Choi, Sung Soo; Park, Sang Wook; Song, Kyung Hwan; Lee, Sung Min; Heo, Tag; Min, Yong Il

2015-04-01

We investigated the use of blood color brightness and blood gas variables for discriminating arterial from venous puncture during cardiopulmonary resuscitation (CPR). The study's aims were to determine if discrimination using Po2 is superior to using blood color brightness, and if blood color brightness, Po2, and acid-base variables derived from blood gas analysis accurately discriminate arterial from venous blood during CPR. Fifteen pigs underwent ventricular fibrillation followed by CPR. During CPR, paired femoral arterial and venous blood samples were obtained, and 2 blinded observers were asked to identify the blood's origin. Blood color brightness was measured using a blood brightness scale (BBS). The discriminatory performances of the BBS and blood gas variables were evaluated by calculating the area under receiver operating characteristic curves (AUC). The observers accurately discriminated arterial from venous blood with a sensitivity of 97.0% (84.7%-99.5%) and specificity of 84.9% (69.1%-93.4%). The BBS (AUC = 0.983) and Po2 (AUC = 0.981) methods both showed comparable and excellent discriminatory performances. pH, Pco2, and HCO3(-) all discriminated arterial from venous blood (AUC = 0.831, 0.971, and 0.652, respectively). The AUC for Pco2 was comparable to that for Po2 but significantly larger than that for pH (P = .002) or HCO3(-) (P < .001). The BBS and Po2 methods showed comparable and excellent discrimination performances. Using pH, Pco2, and HCO3(-) levels also discriminated arterial from venous blood during CPR with statistical significance. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of caffeine and Bombesin on ethanol and food intake

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dietze, M.A.; Kulkosky, P.J.

1991-01-01

The methylxanthine caffeine and ethyl alcohol are widely used and powerful psychotropic drugs, but their interactions are not well understood. Bombesin is a brain-gut neuropeptide which is thought to function as a neurochemical factor in the inhibitory control of voluntary alcohol ingestion. We assessed the effects of combinations of intraperitoneal doses of caffeine and bombesin on 5% w/v ethanol solution and food intake in deprived rats. Deprived male and female Wistar rats received access to 5% ethanol or Purina chow for 30 minutes after i.p. injections. In single doses, CAF and BBS significantly decreased both ethanol and food consumption, atmore » 50 mg/kg and 10 {mu}g/kg, respectively. CAF and BBS combinations produced infra-additive, or less-than-expected inhibitory effects on ethanol intake, but simple additive inhibitory effects on food intake. This experimental evidence suggests a reciprocal blocking of effects of CAF and BBS on ethanol intake but not food intake. Caffeine, when interacting and bombesin, increases alcohol consumption beyond expected values. Caffeine could affect the operation of endogenous satisfy signals for alcohol consumption.« less

The effects of a multi-axis balance board intervention program in an elderly population.

PubMed

Dougherty, John; Kancel, Anne; Ramar, Cassandra; Meacham, Crystal; Derrington, Stephen

2011-01-01

Balance is a major issue facing the geriatric population. Nine participants from a local community center for seniors completed a five-week study to assess improvement in balance. Measures of balance, performance times, and scores on the Berg Balance Scale (BBS) and the Wii Fit Age (WFA) were recorded before and after the entire intervention. An analysis of variance (ANOVA) with repeated measures was used to assess change in BBS and WFA scores. An analysis of covariance with repeated measures was used to asses the impact of possible contributing factors of age, gender, BMI and total balance board training time over the five-week period. The analysis indicated that use of the Indo Balance Board three times a week for ten minutes can significantly improve balance and potentially decrease the risk of falls, as measured by the BBS. Age was the only factor that significantly influenced balance (p = .006). These improvements are postulated to be due to an increase in subjects' core and lower extremity muscle strength and improved proprioception; a result of balance board usage.

Neuropeptide Y family receptors traffic via the Bardet-Biedl syndrome pathway to signal in neuronal primary cilia.

PubMed

Loktev, Alexander V; Jackson, Peter K

2013-12-12

Human monogenic obesity syndromes, including Bardet-Biedl syndrome (BBS), implicate neuronal primary cilia in regulation of energy homeostasis. Cilia in hypothalamic neurons have been hypothesized to sense and regulate systemic energy status, but the molecular mechanism of this signaling remains unknown. Here, we report a comprehensive localization screen of 42 G-protein-coupled receptors (GPCR) revealing seven ciliary GPCRs, including the neuropeptide Y (NPY) receptors NPY2R and NPY5R. We show that mice modeling BBS disease or obese tubby mice fail to localize NPY2R to cilia in the hypothalamus and that BBS mutant mice fail to activate c-fos or decrease food intake in response to the NPY2R ligand PYY3-36. We find that cells with ciliary NPY2R show augmented PYY3-36-dependent cAMP signaling. Our data demonstrate that ciliary targeting of NPY receptors is important for controlling energy balance in mammals, revealing a physiologically defined ligand-receptor pathway signaling within neuronal cilia. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Traffic effects on bird counts on North American Breeding Bird Survey routes

USGS Publications Warehouse

Griffith, Emily H.; Sauer, John R.; Royle, J. Andrew

2010-01-01

The North American Breeding Bird Survey (BBS) is an annual roadside survey used to estimate population change in >420 species of birds that breed in North America. Roadside sampling has been criticized, in part because traffic noise can interfere with bird counts. Since 1997, data have been collected on the numbers of vehicles that pass during counts at each stop. We assessed the effect of traffic by modeling total vehicles as a covariate of counts in hierarchical Poisson regression models used to estimate population change. We selected species for analysis that represent birds detected at low and high abundance and birds with songs of low and high frequencies. Increases in vehicle counts were associated with decreases in bird counts in most of the species examined. The size and direction of these effects remained relatively constant between two alternative models that we analyzed. Although this analysis indicated only a small effect of incorporating traffic effects when modeling roadside counts of birds, we suggest that continued evaluation of changes in traffic at BBS stops should be a component of future BBS analyses.

Post-cholecystectomy biliary strictures: not always benign.

PubMed

Sharma, Ajay; Behari, Anu; Sikora, Sadiq S; Kumar, Ashok; Saxena, Rajan; Kapoor, Vinay K

2008-07-01

Post-cholecystectomy malignant biliary obstruction masquerading as benign biliary stricture (BBS) has not been reported in the literature; it presents a diagnostic and management challenge. Of the 349 post-cholecystectomy BBS managed at a tertiary care hospital in northern India between 1989 and 2004, 11 patients were found to have biliary malignancy. Records of these 11 patients were analyzed retrospectively for the purpose of this study. Mean age of patients with malignant biliary strictures was significantly higher (52 vs 38 years, P = 0.000); they were more likely to have jaundice (100% vs 78%, P = 0.008) and pruritus (82% vs 48%, P = 0.03). Unlike most patients with BBS referred from elsewhere to us, they had had a smooth postoperative course uncomplicated by bile leak, had a longer cholecystectomy-presentation interval, and were more likely to have high strictures ((Bismuth type III/IV) 91% vs 49%, P = 0.008). Post-cholecystectomy biliary obstruction is not always benign. High bilirubin levels and hilar strictures, especially after an uneventful cholecystectomy, in a middle-aged patient should raise a suspicion of underlying missed malignancy.

[B-BS and occupational health and safety management systems: the SGSL certification].

PubMed

Calabrese, G; Candura, G

2010-01-01

The social costs deriving from the lack of occupational safety, which nowadays constitute approximately 2.8% of the GDP, tend not to come down despite the regulations, the inspections and the sanctions. The problems may be ascribed both to a shortage of systemic actions and to inappropriate training of the workers. Possible solutions are represented by the adoption of organizational models (D. Lgs. 81 art. 30) and by the implementation of protocols such as the Behavior-Based Safety (B-BS). Organisational and Management Models have been introduced with art. 30 D.Lgs. 81/2008 and with art. 6 D.Lgs. 231/2001. The comparison between their requisites and the ones specified by the OHSAS 18001 standards, confirms the partial overlapping of the Organizational Models with the Occupational Health & Safety Management Systems. Nevertheless such Systems are rarely adopted by Italian companies and their implementation still doesn't grant complete effectiveness. The B-BS protocol is proving to be a tool of extraordinary value to increase the level of safety, especially when used along with the known Health & Safety Management Systems.

Bottom Backscattering Strengths Measured in Shallow and Deep Water

DTIC Science & Technology

2017-01-18

basically the same experimental set up (Fig. 2-1) as the BBS experiments that form the basis of the shallow-water portion of this report1. Their dates...6 experiments in 5 distinct environments from 1993 to 2005. This report presents the BBS results from these experiments , as well as empirical fits...Test Operations…………………………………………………………..50 B Measured Bottom Backscattering Strengths…………………...……..50 7 CROSS- EXPERIMENT EPL-FIT VALUES (SHALLOW

Effect of beta-blocker therapy on heart rate response in patients with hypertension and newly diagnosed untreated obstructive sleep apnea syndrome.

PubMed

Wolf, Jacek; Drozdowski, Jacek; Czechowicz, Krzysztof; Winklewski, Paweł J; Jassem, Ewa; Kara, Tomas; Somers, Virend K; Narkiewicz, Krzysztof

2016-01-01

Beta1-receptor antagonists (BBs) are commonly administered in the treatment of cardiovascular disease (CVD). The reported benefits of BB use in CVD patients with concomitant obstructive sleep apnea (OSA) may be limited by their impact on apnea-induced bradycardias. Therefore the aim of the study was to test the influence of BBs on periapneic heart rate (HR) fluctuations in hypertensive patients with newly-detected and untreated OSA. We studied 88 hypertensive patients (56 on BBs and 32 BB naive) with newly-diagnosed moderate-to-severe OSA who were free of major pulmonary comorbidities and did not require antiarrhythmic therapy. ECGs recorded during sleep were investigated for heart rate (HR) responses to apneas allowing to compare extreme HR accelerations and decelerations between the groups. Average sleep-time HR was comparable in BB-naive (BB-) and BB-treated (BB+) patients. Direct comparisons showed that HR decelerations were also similar in the two subgroups (53.8±9.6 vs. 54.4±7.8 bpm; P=0.78, for BB- and BB+, respectively) however, BBs blunted the OSA-induced HR accelerations (82.3±12.2 vs. 74.3±10.0; P=0.003). After adjusting for baseline HR and magnitude of desaturations, HR decelerations were more evident in BB-naive group whereas tachycardic responses remained blunted in the BB+ group. The incidence of ectopies and conduction abnormalities were comparable across two groups. Beta-blockers do not potentiate apnea-induced HR decelerations, attenuate apnea-induced increases in heart rate and do not influence incidence of ectopies and conduction abnormalities in patients with hypertension and moderate-to-severe, untreated OSA. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Pediatric surgeons on the Internet: a multi-institutional experience.

PubMed

Wulkan, M L; Smith, S D; Whalen, T V; Hardin, W D

1997-04-01

An estimated 24 million people, or 11% of the North American population over 16 years of age, use the Internet. An estimated 40% of households have computers, and 37 million people have Internet access. The experience of three pediatric surgery Internet sites are reviewed to evaluate current practices and future potential of the Internet to practicing pediatric surgeons. The sites reviewed are the Pediatric Surgery Bulletin Board System (BBS), the Pediatric Surgery List Server, and the Pediatric Surgery Website. Statistics were collected at each site to characterize the number of users, traffic load, topics of interest, and times of peak use. There are currently 79 subscribers to the Pediatric Surgery BBS and 100 subscribers to the Pediatric Surgery List Server. The average user of the BBS is a young man who has placed an average of 52 calls to the BBS since joining. There have been 1413 Internet electronic mail messages sent. Twenty-five percent of the traffic has been related to clinical problems and 5% to research, teaching, and career issues. Traffic at this site has been increasing exponentially with most of the dialogue concentrated on clinical issues and problem cases. In a 3-month period the Pediatric Surgery Website received 16,270 hits. The most commonly accessed areas include an electronic mail directory, case studies, the job board, information on the pediatric surgical residency, and information on upcoming meetings. Pediatric surgeons are exploring the Internet and using available pediatric surgery resources. The scope of professional information available to pediatric surgeons on the Internet is still limited but is increasing rapidly. The Internet will impact the way physicians practice medicine through education and communication.

Salmonella DIVA vaccine reduces disease, colonization and shedding due to virulent S. Typhimurium infection in swine

PubMed Central

Bearson, Shawn M. D; Brunelle, Brian W; Bayles, Darrell O; Lee, In Soo; Kich, Jalusa D

2017-01-01

Purpose Non-host-adapted Salmonella serovars, including the common human food-borne pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), are opportunistic pathogens that can colonize food-producing animals without causing overt disease. Interventions against Salmonella are needed to enhance food safety, protect animal health and allow the differentiation of infected from vaccinated animals (DIVA). Methodology An attenuated S. Typhimurium DIVA vaccine (BBS 866) was characterized for the protection of pigs following challenge with virulent S. Typhimurium. The porcine transcriptional response to BBS 866 vaccination was evaluated. RNA-Seq analysis was used to compare gene expression between BBS 866 and its parent; phenotypic assays were performed to confirm transcriptional differences observed between the strains. Results Vaccination significantly reduced fever and interferon-gamma (IFNγ) levels in swine challenged with virulent S. Typhimurium compared to mock-vaccinated pigs. Salmonella faecal shedding and gastrointestinal tissue colonization were significantly lower in vaccinated swine. RNA-Seq analysis comparing BBS 866 to its parental S. Typhimurium strain demonstrated reduced expression of the genes involved in cellular invasion and bacterial motility; decreased invasion of porcine-derived IPEC-J2 cells and swimming motility for the vaccine strain was consistent with the RNA-Seq analysis. Numerous membrane proteins were differentially expressed, which was an anticipated gene expression pattern due to the targeted deletion of several regulatory genes in the vaccine strain. RNA-Seq analysis indicated that genes involved in the porcine immune and inflammatory response were differentially regulated at 2 days post-vaccination compared to pre-vaccination. Conclusion Evaluation of the S. Typhimurium DIVA vaccine indicates that vaccination will provide both swine health and food safety benefits. PMID:28516860

Pre-Stroke Use of Beta-Blockers Does Not Lower Post-Stroke Infection Rate: An Exploratory Analysis of the Preventive Antibiotics in Stroke Study.

PubMed

Westendorp, Willeke F; Vermeij, Jan-Dirk; Brouwer, Matthijs C; Roos, Y B W E M; Nederkoorn, Paul J; van de Beek, Diederik

2016-01-01

Stroke-associated infections occur frequently and are associated with unfavorable outcome. Previous cohort studies suggest a protective effect of beta-blockers (BBs) against infections. A sympathetic drive may increase immune suppression and infections. This study is aimed at investigating the association between BB treatment at baseline and post-stroke infection in the Preventive Antibiotics in Stroke Study (PASS), a prospective clinical trial. We performed an exploratory analysis in PASS, 2,538 patients with acute phase of stroke (24 h after onset) were randomized to ceftriaxone (intravenous, 2 g per day for 4 days) in addition to stroke unit care, or standard stroke unit care without preventive antibiotic treatment. All clinical data, including use of BBs, was prospectively collected. Infection was diagnosed by the treating physician, and independently by an expert panel blinded for all other data. Multivariable analysis was performed to investigate the relation between BB treatment and infection rate. Infection, as defined by the physician, occurred in 348 of 2,538 patients (14%). Multivariable analysis showed that the use of BBs at baseline was associated with the development of infection during clinical course (adjusted OR (aOR) 1.61, 95% CI 1.19-2.18; p < 0.01). BB use at baseline was also associated with the development of pneumonia (aOR 1.56, 95% CI 1.05-2.30; p = 0.03). Baseline BB use was not associated with mortality (aOR 1.14, 95% CI 0.84-1.53; p = 0.41) or unfavorable outcome at 3 months (aOR 1.10, 95% CI 0.89-1.35; p = 0.39). Patients treated with BBs prior to stroke have a higher rate of infection and pneumonia. © 2016 S. Karger AG, Basel.

Measuring standing balance in multiple sclerosis: Further progress towards an automatic and reliable method in clinical practice.

PubMed

Keune, Philipp M; Young, William R; Paraskevopoulos, Ioannis T; Hansen, Sascha; Muenssinger, Jana; Oschmann, Patrick; Müller, Roy

2017-08-15

Balance deficits in multiple sclerosis (MS) are often monitored by means of observer-rated tests. These may provide reliable data, but may also be time-consuming, subject to inter-rater variability, and potentially insensitive to mild fluctuations throughout the clinical course. On the other hand, laboratory assessments are often not available. The Nintendo Wii Balance Board (WBB) may represent a low-cost solution. The purpose of the current study was to examine the methodological quality of WBB data in MS (internal consistency, test-retest reliability), convergent validity with observer-rated tests (Berg Balance Scale, BBS; Timed-Up and Go Test, TUG), and discriminative validity concerning clinical status (Expanded Disability Status Scale, EDSS). Standing balance was assessed with the WBB for 4min in 63 MS patients at two assessment points, four months apart. Additionally, patients were examined with the BBS, TUG and the EDSS. A period of 4min on the WBB provided data characterized by excellent internal consistency and test-retest reliability. Significant correlations between WBB data and results of the BBS and TUG were obtained after merely 2min on the board. An EDSS median-split revealed that higher EDSS values (>3) were associated with significantly increased postural sway on the WBB. WBB measures reflecting postural sway are methodologically robust in MS, involving excellent internal consistency and test-retest reliability. They are also characterized by convergent validity with other considerably lengthier observer-rated balance measures (BBS) and sensitive to broader clinical characteristics (EDSS). The WBB may hence represent an effective, easy-to-use monitoring tool for MS patients in clinical practice. Copyright © 2017 Elsevier B.V. All rights reserved.

Covered self-expanding metal stents may be preferable to plastic stents in the treatment of chronic pancreatitis-related biliary strictures: a systematic review comparing 2 methods of stent therapy in benign biliary strictures.

PubMed

Siiki, Antti; Helminen, Mika; Sand, Juhani; Laukkarinen, Johanna

2014-08-01

Covered self-expanding metal stents (CSEMS) are being increasingly used in the endoscopic treatment of benign biliary strictures (BBS). There is no solid evidence yet to support their routine use. To evaluate feasibility, success rate, and complications of CSEMS compared with multiple plastic stents (PS) in BBS in a systematic review. A systematic search of electronic databases (Medline, Scopus, and Embase) for studies published from 2000 to 2012 combined to hand-search of reference lists resulted 4977 articles. Out of 99 potentially relevant studies selected for full-text review, 12 CSEMS (376 patients) and 13 PS studies (570 patients) met the final inclusion criteria. A systematic review comparing the 2 methods was made using proportion meta-analysis. A tendency to successful use of CSEMS in strictures related to chronic pancreatitis (CP) was shown: clinical success of 77% and 33% [95% confidence interval (CI), 61%-94% vs. 4%-63%, P=0.06] was achieved with CSEMS and PS at 12 months follow-up, respectively. There were no differences in the success rates of other etiologies except CP or in the early complications. In CSEMS, incidence of late adverse events was lower in CP-related strictures (3% vs. 67%, 95% CI, 0%-13% vs. 17%-99%, P=0.02). The median number of endoscopic retrograde cholangiopancreatographies was lower with CSEMSs: 1.5 versus 3.9 (P=0.002). Improved clinical success with fewer endoscopic sessions and corresponding complication rate may be achieved with CSEMS treatment compared with PS in BBS secondary to CP. In other BBS etiologies, this systematic review remains inconclusive.

[Functional assessment of patients with vertigo and dizziness in occupational medicine].

PubMed

Zamysłowska-Szmytke, Ewa; Szostek-Rogula, Sylwia; Śliwińska-Kowalska, Mariola

2018-03-09

Balance assessment relies on symptoms, clinical examination and functional assessment and their verification in objective tests. Our study was aimed at calculating the assessment compatibility between questionnaires, functional scales and objective vestibular and balance examinations. A group of 131 patients (including 101 women; mean age: 59±14 years) of the audiology outpatient clinic was examined. Benign paroxysmal positional vertigo, phobic vertigo and central dizziness were the most common diseases observed in the study group. Patients' symptoms were tested using the questionnaire on Cawthworne-Cooksey exercises (CC), Dizziness Handicap Inventory (DHI) and Duke Anxiety-Depression Scale. Berg Balance Scale (BBS), Dynamic Gait Index (DGI), the Tinetti test, Timed Up and Go test (TUG), and Dynamic Visual Acuity (DVA) were used for the functional balance assessment. Objective evaluation included: videonystagmography caloric test and static posturography. The study results revealed statistically significant but moderate compatibility between functional tests BBS, DGI, TUG, DVA and caloric results (Kendall's W = 0.29) and higher for posturography (W = 0.33). The agreement between questionnaires and objective tests were very low (W = 0.08-0.11).The positive predictive values of BBS were 42% for caloric and 62% for posturography tests, of DGI - 46% and 57%, respectively. The results of functional tests (BBS, DGI, TUG, DVA) revealed statistically significant correlations with objective balance tests but low predictive values did not allow to use these tests in vestibular damage screening. Only half of the patients with functional disturbances revealed abnormal caloric or posturography tests. The qualification to work based on objective tests ignore functional state of the worker, which may influence the ability to work. Med Pr 2018;69(2):179-189. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Hierarchical modeling of population stability and species group attributes from survey data

USGS Publications Warehouse

Sauer, J.R.; Link, W.A.

2002-01-01

Many ecological studies require analysis of collections of estimates. For example, population change is routinely estimated for many species from surveys such as the North American Breeding Bird Survey (BBS), and the species are grouped and used in comparative analyses. We developed a hierarchical model for estimation of group attributes from a collection of estimates of population trend. The model uses information from predefined groups of species to provide a context and to supplement data for individual species; summaries of group attributes are improved by statistical methods that simultaneously analyze collections of trend estimates. The model is Bayesian; trends are treated as random variables rather than fixed parameters. We use Markov Chain Monte Carlo (MCMC) methods to fit the model. Standard assessments of population stability cannot distinguish magnitude of trend and statistical significance of trend estimates, but the hierarchical model allows us to legitimately describe the probability that a trend is within given bounds. Thus we define population stability in terms of the probability that the magnitude of population change for a species is less than or equal to a predefined threshold. We applied the model to estimates of trend for 399 species from the BBS to estimate the proportion of species with increasing populations and to identify species with unstable populations. Analyses are presented for the collection of all species and for 12 species groups commonly used in BBS summaries. Overall, we estimated that 49% of species in the BBS have positive trends and 33 species have unstable populations. However, the proportion of species with increasing trends differs among habitat groups, with grassland birds having only 19% of species with positive trend estimates and wetland birds having 68% of species with positive trend estimates.

Balance, functional mobility, and fall occurrence in patients with human T-cell lymphotropic virus type-1-associated myelopathy/tropical spastic paraparesis: a cross-sectional study.

PubMed

Fonseca, Erika Pedreira da; Sá, Katia Nunes; Nunes, Rebeca Freitas Reis; Ribeiro Junior, Antônio Carlos; Lira, Síntia Freitas Bastos; Pinto, Elen Beatriz

2018-01-01

Human T-cell lymphotropic virus type-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) may lead to reduced functional mobility and balance. It is important to establish specific parameters that identify these changes and predict the risk of falls in these patients. The aim was to compare balance, functional mobility, and occurrence of falls among patients with and without HAM/TSP and to suggest values to predict the risk of falls in these patients. A cross-sectional study in patients with and without HAM/TSP involved balance assessments based on the berg balance scale (BBS) and functional mobility evaluation based on the timed up and go (TUG) test. From reports of falls, the sensitivity, specificity, and best cutoff points for the risk of falls assessed by these instruments were established using the receiver-operating characteristic (ROC) curve; 5% alpha was considered. We selected 42 participants: 29 with HAM/TSP and 13 without HAM/TSP. There was a statistically significant difference in the occurrence of falls, balance, and functional mobility between the groups (p<0.05). Good accuracy was determined for the BBS (77%) and TUG test (70%) and the cutoff points for the risk of falls were defined as 50 points for the BBS and 12.28 seconds for the TUG test. Patients with HAM/TSP present reduced functional mobility and balance in relation to those without HAM/TSP. The risk of falls increased for these patients can be evaluated by the values ​​of 50 points using the BBS and 12.28 seconds using the TUG test.

Balance measured by the sway balance smart-device application does not discriminate between older persons with and without a fall history.

PubMed

Vincenzo, Jennifer L; Glenn, Jordan M; Gray, Stephanie M; Gray, Michelle

2016-08-01

Clinical functional assessments of balance often lack specificity and sensitivity in discriminating and predicting falls among community-dwelling older adults. We determined the feasibility of using a smart-device application measuring balance to discriminate fall status among older adults. We also evaluated differences between smart-device balance measurements when secured with or without a harness. A cross-sectional study design to determine the ability of the Sway Balance smart-device application (SWAY) to discriminate older adults based on fall history. The Berg Balance Scale (BBS) and Activities-Specific Balance Confidence Scale (ABC) were used as comparative, clinically based assessments. Community-dwelling older adults with (n = 25) and without (n = 32) a history of fall(s) participated. Multivariate analysis of variance was used to determine differences among assessments based on fall history. Logistic regression models determined the ability of each assessment to discriminate fall history. Older adults with and without a history of falls were not significantly different on SWAY (P = 0.92) but were different on BBS (P = 0.01), and ABC (P < 0.001). Similarly, SWAY did not discriminate fall history (P = 0.92), while BBS and ABC both discriminated fall history (P < 0.01). Paired t tests between SWAY scores with and without a harness indicated no differences (P ≥ 0.05). Among the older adults studied, the BBS and ABC measures discriminated groups defined by fall history, while the SWAY smart-device balance application did not. Modifications to the application may improve the discriminating ability of the measure in the recognition of fall status in older adults.

Comparison of mobility and user satisfaction between a microprocessor knee and a standard prosthetic knee: a summary of seven single-subject trials.

PubMed

Howard, Charla L; Wallace, Chris; Perry, Bonnie; Stokic, Dobrivoje S

2018-03-01

Insufficient evidence of the benefits provided by costlier microprocessor knees (MPKs) over nonmicroprocessor knees (NMPKs) often causes concern when considering MPK prescription. Thus, more studies are needed to demonstrate differences between MPKs and NMPKs and define sensitive outcomes to guide MPK prescription. The aim of this study was to evaluate the impact of switching from NMPK to MPK on measures of mobility and preference. Seven long-term NMPK users (all men, ages 50-84, 3-64 years postamputation) participated in this study, which use a single-subject design (ABA or BAB; A=NMPK, B=MPK). Mobility was assessed with the Amputee Mobility Predictor, Berg Balance Scale (BBS), L-Test, 6-Min Walk Test (6MWT) with Physiological Cost Index, and self-selected normal and very fast gait speeds. The preference between NMPK and MPK was evaluated by the Prosthesis Evaluation Questionnaire (PEQ) and the visual analog scale. Mobility improved with the MPK in six of seven participants, which was most often captured with BBS (median: +6 points) and 6MWT (median: +63 m). These improvements typically exceeded minimal clinically important difference or minimal detectable change thresholds. Most participants scored the MPK higher on the PEQ (median: +20 points) and six of seven expressed a global preference toward MPK. In the BAB group, the Amputee Mobility Predictor and BBS correlated with perception of change on several PEQ domains (Ρ≥0.59). In conclusion, MPKs may provide better outcomes and user satisfaction, particularly in those with lower mobility function. BBS and 6MWT were found to be the most sensitive measures to capture changes in mobility while using MPK for several weeks.

The reliability and validity of the Turkish version of Fullerton Advanced Balance (FAB-T) scale.

PubMed

Iyigun, Gozde; Kirmizigil, Berkiye; Angin, Ender; Oksuz, Sevim; Can, Filiz; Eker, Levent; Rose, Debra J

2018-06-04

The aim of this study was to evaluate the reliability and validity of the Turkish version of the FAB(FAB-T) scale in the older Turkish adults. The reliability and validity of the scale was tested on 200 community-dwelling older adults. FAB-T scale was scored by different physiotherapists on different days to evaluate inter-rater and intrarater reliability. The Berg Balance Scale (BBS) was used for the evaluation of convergent validity, and the content validity of the FAB-T scale was investigated. The FAB-T scale showed very high inter- and intra-rater reliability. For inter-rater agreement, on the individual test items and total score ICC values were 0.92 (95 %CI; 0.90-0.94) and 0.96 (95% CI; 0.95-0.97) respectively. The intra-rater agreement, on the individual test items and total score ICC values were 0.93 (95 %CI; 0.91- 0.95) and 0.96 (95% CI; 0.95- 0.97) respectively. There was a good agreement between the FAB-T and BBS scales. A high correlation was found between the BBS and FAB-T scales [rho = 0.70 (%95 CI; 0.62-0.76)] indicating good convergent validity. Considering the content validity of the FAB-T scale, no floor (floor score: 0%) or ceiling (ceiling score: 6.5%) effect was detected. The FAB-T scale was successfully translated from the original English version (FAB) and demonstrated strong psychometric features. It was found that the FAB-T scale has very high inter-rater and intra-rater reliability. Considering the convergent validity, the scale has high correlation with the BBS. The FAB-T has no floor and ceiling effect. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of expiring reimbursability of pentaerythrityl tetranitrate (PETN, pentalong®) on anti-anginal therapy: an observational study.

PubMed

Grimmsmann, Thomas; Chenot, Jean-François; Angelow, Aniela

2015-08-01

Pentaerythrityl tetranitrate (PETN) was the most commonly prescribed long-acting nitrate in Germany. We aimed to assess whether the discontinuation of PETN reimbursability in 2011 resulted in alternative prescriptions of anti-anginal medications or in a discontinuation of anti-anginal therapy. This is an observational study using health claims data from one German federal state analysing all patients discontinuing a PETN treatment. Patients starting a new alternative anti-anginal treatment (long-acting nitrates, molsidome, ivabradine and ranolazine) were compared with patients without a new anti-anginal treatment with respect to use of short-acting nitrates, beta blockers (BBs) and calcium channel blockers (CCBs). Out of 12,909 patients, 12,763 (99%) discontinued PETN until 12/2012. Of these, 52% started an alternative anti-anginal treatment, 43% did not receive any alternative treatment and 5% were excluded from analysis. Before termination of PETN reimbursability, 65% of patients received BBs, 29% CCBs and 10% short-acting nitrates. In patients started on alternative anti-anginal treatment, prescription rates for short-acting nitrates, BBs and CCBs remained constant after discontinuing PETN. In patients without any alternative anti-anginal treatment, prescription rates for BBs and CCBs did not change meaningfully (<3%), and prescription rates for short-acting nitrates decreased from 9% to 6%. Half of the patients discontinued PETN without alternative. This did not lead to increased prescription rates of standard IHD medications or total medication number indicating that there might still be a high percentage of ischaemic heart disease patients treated unnecessarily with long-acting nitrates. The undertreatment with prognostically relevant first-line medications indicates a need for better guideline implementation activities. Copyright © 2015 John Wiley & Sons, Ltd.

[Effects of physical activity on cognitive functions, balance and risk of falls in elderly patients with Alzheimer's dementia].

PubMed

Hernandez, Salma S S; Coelho, Flávia G M; Gobbi, Sebastião; Stella, Florindo

2010-01-01

To analyze the effects of regular, systematic and supervised activity on the cognitive functions, balance and risk of falls of elderly patients with Alzheimer's Dementia (AD). Sixteen elderly patients (mean age 78.5+/-6.8 years) were divided into two groups: intervention group (IG; n=9) and routine group (RG; n=7). The IG exercised systematically for six months, and both groups were submitted to the following tests: Mini-Mental State Examination (MMSE), Berg Balance Scale (BBS), Timed Up-and-Go (TUG) and the agility/dynamic balance (AGIBAL) item of the American Alliance for Health, Physical Education, Recreation and Dance (AAHPERD) test battery. There was a statistically significant interaction (two-way ANOVA; F1,14=32.07; p=0.01) between groups and moments for the AGIBAL. The Mann Whitney U test indicated significant differences between groups (p=0.03), only at the post-intervention moment for the TUG measured in steps and for BBS. Therefore, no significant intergroup differences were found for the TUG, BBS and MMSE at the pre-intervention moment or at post-intervention moment for the TUG measured in seconds and MMSE. The intragroup analysis by means of the Wilcoxon test showed a significant decline in the TUG, BBS and MMSE for the RG, but not for the IG. Spearman's coefficient showed a significant correlation between the results of the MMSE and AGIBAL. Physical activity may be an important non-pharmacological approach that can benefit cognitive functions and balance and reduce the risk of falls. Moreover, agility and balance are associated with cognitive functions in elderly patients with AD.

Comparison of Modules of Wild Type and Mutant Huntingtin and TP53 Protein Interaction Networks: Implications in Biological Processes and Functions

PubMed Central

Basu, Mahashweta; Bhattacharyya, Nitai P.; Mohanty, Pradeep K.

2013-01-01

Disease-causing mutations usually change the interacting partners of mutant proteins. In this article, we propose that the biological consequences of mutation are directly related to the alteration of corresponding protein protein interaction networks (PPIN). Mutation of Huntingtin (HTT) which causes Huntington's disease (HD) and mutations to TP53 which is associated with different cancers are studied as two example cases. We construct the PPIN of wild type and mutant proteins separately and identify the structural modules of each of the networks. The functional role of these modules are then assessed by Gene Ontology (GO) enrichment analysis for biological processes (BPs). We find that a large number of significantly enriched () GO terms in mutant PPIN were absent in the wild type PPIN indicating the gain of BPs due to mutation. Similarly some of the GO terms enriched in wild type PPIN cease to exist in the modules of mutant PPIN, representing the loss. GO terms common in modules of mutant and wild type networks indicate both loss and gain of BPs. We further assign relevant biological function(s) to each module by classifying the enriched GO terms associated with it. It turns out that most of these biological functions in HTT networks are already known to be altered in HD and those of TP53 networks are altered in cancers. We argue that gain of BPs, and the corresponding biological functions, are due to new interacting partners acquired by mutant proteins. The methodology we adopt here could be applied to genetic diseases where mutations alter the ability of the protein to interact with other proteins. PMID:23741403

Modulation of protein stability and aggregation properties by surface charge engineering.

PubMed

Raghunathan, Govindan; Sokalingam, Sriram; Soundrarajan, Nagasundarapandian; Madan, Bharat; Munussami, Ganapathiraman; Lee, Sun-Gu

2013-09-01

An attempt to alter protein surface charges through traditional protein engineering approaches often affects the native protein structure significantly and induces misfolding. This limitation is a major hindrance in modulating protein properties through surface charge variations. In this study, as a strategy to overcome such a limitation, we attempted to co-introduce stabilizing mutations that can neutralize the destabilizing effect of protein surface charge variation. Two sets of rational mutations were designed; one to increase the number of surface charged amino acids and the other to decrease the number of surface charged amino acids by mutating surface polar uncharged amino acids and charged amino acids, respectively. These two sets of mutations were introduced into Green Fluorescent Protein (GFP) together with or without stabilizing mutations. The co-introduction of stabilizing mutations along with mutations for surface charge modification allowed us to obtain functionally active protein variants (s-GFP(+15-17) and s-GFP(+5-6)). When the protein properties such as fluorescent activity, folding rate and kinetic stability were assessed, we found the possibility that the protein stability can be modulated independently of activity and folding by engineering protein surface charges. The aggregation properties of GFP could also be altered through the surface charge engineering.

A genome-wide association study identifies susceptibility loci for non-syndromic sagittal craniosynostosis near BMP2 and within BBS9

PubMed Central

Justice, Cristina M.; Yagnik, Garima; Kim, Yoonhee; Peter, Inga; Jabs, Ethylin Wang; Erazo, Monica; Ye, Xiaoqian; Ainehsazan, Edmond; Shi, Lisong; Cunningham, Michael L.; Kimonis, Virginia; Roscioli, Tony; Wall, Steven A.; Wilkie, Andrew O.M.; Stoler, Joan; Richtsmeier, Joan T.; Heuzé, Yann; Sanchez-Lara, Pedro A.; Buckley, Michael F.; Druschel, Charlotte M.; Mills, James L.; Caggana, Michele; Romitti, Paul A.; Kay, Denise M.; Senders, Craig; Taub, Peter J.; Klein, Ophir D.; Boggan, James; Zwienenberg-Lee, Marike; Naydenov, Cyril; Kim, Jinoh; Wilson, Alexander F.; Boyadjiev, Simeon A.

2013-01-01

Sagittal craniosynostosis is the most common form of craniosynostosis, affecting approximately one of 5,000 newborns. We conducted the first genome-wide association study (GWAS) for non-syndromic sagittal craniosynostosis (sNSC) using 130 non-Hispanic white (NHW) case-parent trios. Robust associations were observed in a 120 kb region downstream of BMP2, flanked by rs1884302 (P = 1.13 × 10−14; odds ratio [OR] = 4.58) and rs6140226 (P = 3.40 × 10−11; OR = 0.24) and within a 167 kb region of BBS9 between rs10262453 (P = 1.61 × 10−10; OR=0.19) and rs17724206 (P = 1.50 × 10−8; OR = 0.22). We replicated the associations to both loci [rs1884302 (P = 4.39 × 10−31); rs10262453 (P = 3.50 × 10−14)] in an independent NHW population of 172 unrelated sNSC probands and 548 controls. Both BMP2 and BBS9 are genes with a role in skeletal development warranting functional studies to further understand the etiology of sNSC. PMID:23160099

Model selection for the North American Breeding Bird Survey: A comparison of methods

USGS Publications Warehouse

Link, William; Sauer, John; Niven, Daniel

2017-01-01

The North American Breeding Bird Survey (BBS) provides data for >420 bird species at multiple geographic scales over 5 decades. Modern computational methods have facilitated the fitting of complex hierarchical models to these data. It is easy to propose and fit new models, but little attention has been given to model selection. Here, we discuss and illustrate model selection using leave-one-out cross validation, and the Bayesian Predictive Information Criterion (BPIC). Cross-validation is enormously computationally intensive; we thus evaluate the performance of the Watanabe-Akaike Information Criterion (WAIC) as a computationally efficient approximation to the BPIC. Our evaluation is based on analyses of 4 models as applied to 20 species covered by the BBS. Model selection based on BPIC provided no strong evidence of one model being consistently superior to the others; for 14/20 species, none of the models emerged as superior. For the remaining 6 species, a first-difference model of population trajectory was always among the best fitting. Our results show that WAIC is not reliable as a surrogate for BPIC. Development of appropriate model sets and their evaluation using BPIC is an important innovation for the analysis of BBS data.

Buteos

USGS Publications Warehouse

Titus, K.; Fuller, M.R.; Stauffer, D.F.; Sauer, J.R.; Pendleton, Beth Giron; LeFranc, Maurice N.=; Moss, Mary Beth

1989-01-01

Red-tailed, red-shouldered, and broad-winged hawks nest throughout the 11 northeastern states, and red-tailed, red-shouldered, and rough-legged hawks winter in this region. Historical and present ranges of these species are similar, although red-shouldered and broad-winged hawk ranges now have more vacant patches at a local and regional level. Only the red-shouldered hawk is of special concern or officially listed as threatened by some state agencies. Analysis of Breeding Bird Survey (BBS) data indicated positive trends in counts of red-tailed hawks along the more developed Northeast corridor. No trends were found in analyses of BBS data for red-shouldered hawks in either more- or less-developed regions of the Northeast. Based on the BBS, we found a decreasing trend in counts of broad-winged hawks along the more-developed Northeast corridor, and an increasing trend in less-developed regions of the Northeast. Our analyses of Christmas Bird Count data indicated no trend in counts of red-shouldered nor rough-legged hawks, but an increase in counts of red-tailed hawks from 1962 to 1983. Many individuals believe that species such as the red-shouldered hawk are declining in the Northeast, but no trends were detected in our analyses.

Bile duct injury repair: when? what? who?

PubMed

Kapoor, Vinay K

2007-01-01

Laparoscopic cholecystectomy is associated with a two-to-four times higher risk of bile duct injury (BDI) than open cholecystectomy. BDI can lead to significant morbidity and even mortality. The first priority in BDI is to control peritoneal and biliary sepsis and to convert an acute BDI to a controlled external biliary fistula (EBF) - this can be achieved by endoscopic and/ or radiological intervention in most cases. This should be followed by assessment of the extent of injury - both biliary and vascular. Immediate management of BDI recognized during cholecystectomy depends on the type of injury, the condition of the patient, and the experience of the surgeon. For BDI recognized after cholecystectomy, early repair is not recommended, as the results are poor. The EBF may evolve into a benign biliary stricture (BBS), which should be electively repaired by a Roux-en-Y hepatico-jejunostomy. The use of an endoscopic stent as definitive management of BDI is not recommended. Long-term follow-up is essential after the repair of a BBS, as recurrence can occur several years after repair. Recurrent BBS is best treated with endoscopic balloon dilatation. Excellent early and long-term results can be obtained in specialized units at tertiary care referral centers.

[Evaluation of angiogenic activity in sera from patients with interstitial lung diseases].

PubMed

Zielonka, T M; Demkow, U; Kowalski, J; Kuś, J; Krychniak-Soszka, A; Radzikowska, E; Skopińska-Rózewska, E; Rowińska-Zakrzewska, E

1997-01-01

Angiogenesis is a process of new blood vessels' formation occurring in many physiological and pathological conditions. Neovascularisation is the principal vascular response in chronic inflammation and concomitant fibrotic process. Microvascular changes in various organ sites in sarcoidosis (BBS) and some of the symptoms of the disease may be related to microangiopathy. Moreover, vascular alterations were also observed in lung specimens from idiopathic pulmonary fibrosis (IPF) and avian fanciers lung (AFL) patients. The present study was aimed at testing the effects of serum from 43 patients with ILD (24 BBS, 8 AFL, 8 IPF, 3 DIPF--drug induced pulmonary fibrosis) and 11 healthy controls on angiogenic capability of normal blood peripheral mononuclear cells (PBMC) in the murine intradermal angiogenesis assay (according to Sidky and Auerbach). The data demonstrated that sera from ILD patients significantly enhanced angiogenic capacity of normal PBMC as compared to control sera (p < 0.001). The effect was more pronounced for AFL patients than for BBS and IPF ones (p < 0.05). Sera from DIPF did not stimulate angiogenesis compared to control sera. The data showed that sera from ILD patients constitute sources of mediators participating in angiogenesis. This phenomenon may play role in pathogenesis of chronic immunological processes in lung.

A Big-Data-based platform of workers' behavior: Observations from the field.

PubMed

Guo, S Y; Ding, L Y; Luo, H B; Jiang, X Y

2016-08-01

Behavior-Based Safety (BBS) has been used in construction to observe, analyze and modify workers' behavior. However, studies have identified that BBS has several limitations, which have hindered its effective implementation. To mitigate the negative impact of BBS, this paper uses a case study approach to develop a Big-Data-based platform to classify, collect and store data about workers' unsafe behavior that is derived from a metro construction project. In developing the platform, three processes were undertaken: (1) a behavioral risk knowledge base was established; (2) images reflecting workers' unsafe behavior were collected from intelligent video surveillance and mobile application; and (3) images with semantic information were stored via a Hadoop Distributed File System (HDFS). The platform was implemented during the construction of the metro-system and it is demonstrated that it can effectively analyze semantic information contained in images, automatically extract workers' unsafe behavior and quickly retrieve on HDFS as well. The research presented in this paper can enable construction organizations with the ability to visualize unsafe acts in real-time and further identify patterns of behavior that can jeopardize safety outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of walking with a cane on balance and social participation among community-dwelling post-stroke individuals.

PubMed

Hamzat, T K; Kobiri, A

2008-06-01

Walking devices such as canes and frames are often prescribed to post-stroke individuals to enhance their balance and walking, and thus facilitate community reintegration and social participation. The aim of this study was to observe social participation and balance in post-stroke hemiparetic patients and compare the performance of those walking with a cane (AD group) and without a cane (WAD group). The relationships between cane usage and activity participation and balance were also studied. In this ex post facto research study, balance and social participation were evaluated using the Berg Balance Scale (BBS) and the Craig Handicap Assessment and Reporting Technique (CHART) in 50 individuals with hemiparesis secondary to first incidence hemispheric stroke. The study included 25 AD subjects (mean age 59.88+/-12.04 years) and 25 WAD subjects (mean age 55.84+/-11.30 years) who were consecutively recruited from the physiotherapy units of Korle Bu Teaching Hospital (KBTH) and the 37 Military Hospital in Accra (Ghana). Before recruitment into the study, both groups of subjects were matched for age, height, weight, BBS and CHART scores at the point of discharge from the inpatient units of the two hospitals, the duration of stroke, and the duration of physiotherapy post-stroke. Mann-Whitney U statistics showed that the AD group had comparatively higher mean participation scores (U=22.37; P=0.00) and lower mean balance performance (BBS score U=30.68; P=0.00) than their WAD counterparts. Spearman's correlation coefficient also revealed a significant negative correlation between the BBS and CHART scores in both groups (AD rho=-0.063; P=0.00 and WAD rho=-0.037; P=0.05). These findings indicate that post-stroke individuals who used a cane to aid in walking had poorer balance and less social participation than their age-matched counterparts who walked unaided. As balance improved (higher BBS score), participation also improved (lower CHART score) in both groups. In spite of the small sample size, the outcome of this study suggests that prescription of a cane for a post-stroke individual should be carefully considered by the physiotherapist, especially if the focus of rehabilitation includes restoration of balance functions and social participation.

The effect of dietary phosphorus level and phytase supplementation on growth performance, bone-breaking strength, and litter phosphorus concentration in broilers.

PubMed

Powell, S; Johnston, S; Gaston, L; Southern, L L

2008-05-01

This research was conducted to determine the effects of feeding different P levels with and without phytase supplementation on broiler growth performance, bone-breaking strength (BBS), and litter P concentration. An experiment with 4 trials was conducted with 7,840 Ross x Ross straight-run broilers. For each trial, 1,960 broilers were allotted on d 0 to treatments, with 7 replications each and with 70 broilers per replication. The broilers were fed a 4-period feeding program consisting of starter (0 to 14 d), grower (14 to 32 d), finisher (32 to 41 d), and withdrawal (41 to 50 d) periods. For each trial, the same pen was used continuously for each treatment-replication combination, and the litter was not removed between trials. Broilers were fed a control diet [0.43, 0.40, 0.36, or 0.32% nonphytate P (nPP)] in the starter, grower, finisher, and withdrawal periods, respectively, a low Ca and P (LCaP) diet with a 0.05% reduction in nPP in each period, and these 2 diets supplemented with phytase at 600 phytase units/kg (nPP and Ca were reduced by 0.094% in diets with phytase). Diet did not affect (P > 0.10) broiler performance in the starter or withdrawal periods. Generally, both phytase addition and the LCaP diet decreased some aspects of growth performance during the grower and finisher periods. There was no main effect of phytase on BBS, but BBS was decreased in the broilers fed the LCaP diet with phytase addition (nPP x phytase, P < 0.01) in the grower period, and BBS was decreased in the finisher (P < 0.02) and withdrawal (P < 0.01) periods for broilers fed the LCaP diet. Total P, soluble P (SP), and reactive soluble P (RSP) were decreased (P < 0.04) in the litter of broilers fed the LCaP diets. Total P, SP, and RSP were decreased (P < 0.01) in the litter of broilers fed phytase. These data indicate that phytase supplementation at 600 phytase units/kg reduces growth in some periods, has no effect on BBS, and reduces total P, SP, and RSP in the litter.

Use of carbon steel ball bearings to determine the effect of biocides and corrosion inhibitors on microbiologically influenced corrosion under flow conditions.

PubMed

Pinnock, Tijan; Voordouw, Johanna; Voordouw, Gerrit

2018-05-10

A consortium of sulfate-reducing bacteria consisting mostly of Desulfovibrio, Desulfomicrobium, and Desulfocurvus from oil field produced water was cultivated in a chemostat, receiving medium with 20 mM formate and 10 mM sulfate as the energy and 1 mM acetate as the carbon source. The chemostat effluent, containing 5 mM sulfide and 0.5 mM of residual acetate, was passed through 1-ml syringe columns with 60 carbon steel ball bearings (BBs) of 53.6 ± 0.1 mg each at a flow rate of 0.8 ml/h per column. These were treated every 5 days with 1.6 ml of 300 ppm of glutaraldehyde (Glut), tetrakis(hydroxymethyl)phosphonium sulfate (THPS), benzalkonium chloride (BAC), or Glut/BAC, a mixture of Glut and BAC. Alternatively, BBs were treated with 33% (v/v) of a water-soluble (CR_W) or an oil-soluble (CR_O1 or CR_O3) corrosion inhibitor for 20 s after which the corrosion inhibitor was drained off and BBs were packed into columns. The effluent of untreated control columns had no acetate. Treatment with the chemically reactive biocides Glut and THPS, as well as with Glut/BAC, gave a transient increase of acetate indicating decreased microbial activity. This was not seen with BAC alone indicating it to be the least effective biocide. Relative to untreated BBs (100%), those treated periodically with Glut, THPS, BAC, or Glut/BAC had a general weight loss corrosion rate of 91, 81, 45, and 36% of the untreated rate of 0.104 ± 0.004 mm/year, respectively. Single treatment with corrosion inhibitors decreased corrosion to 48, 2, and 1% of the untreated rate for CR_W, CR_O1 and CR_O3, respectively. Analysis of the distribution of corrosion rates from the weight loss of individual BBs (N = 120) indicated the presence of a more slowly and a more rapidly corroding group. BAC treatment prevented emergence of the latter, and this quaternary ammonium detergent appeared most effective in decreasing corrosion not because of its biocidal properties, but because of its corrosion inhibitory properties.

Golden eagle population trends in the western United States: 1968-2010

USGS Publications Warehouse

Millsap, Brian A.; Zimmerman, Guthrie S.; Sauer, John R.; Nielson, Ryan M.; Otto, Mark; Bjerre, Emily; Murphy, Robert K.

2013-01-01

In 2009, the United States Fish and Wildlife Service promulgated permit regulations for the unintentional lethal take (anthropogenic mortality) and disturbance of golden eagles (Aquila chrysaetos). Accurate population trend and size information for golden eagles are needed so agency biologists can make informed decisions when eagle take permits are requested. To address this need with available data, we used a log-linear hierarchical model to average data from a late-summer aerial-line-transect distance-sampling survey (WGES) of golden eagles in the United States portions of Bird Conservation Region (BCR) 9 (Great Basin), BCR 10 (Northern Rockies), BCR 16 (Southern Rockies/Colorado Plateau), and BCR 17 (Badlands and Prairies) from 2006 to 2010 with late-spring, early summer Breeding Bird Survey (BBS) data for the same BCRs and years to estimate summer golden eagle population size and trends in these BCRs. We used the ratio of the density estimates from the WGES to the BBS index to calculate a BCR-specific adjustment factor that scaled the BBS index (i.e., birds per route) to a density estimate. Our results indicated golden eagle populations were generally stable from 2006 to 2010 in the 4 BCRs, with an estimated average rate of population change of −0.41% (95% credible interval [CI]: −4.17% to 3.40%) per year. For the 4 BCRs and years, we estimated annual golden eagle population size to range from 28,220 (95% CI: 23,250–35,110) in 2007 to 26,490 (95% CI: 21,760–32,680) in 2008. We found a general correspondence in trends between WGES and BBS data for these 4 BCRs, which suggested BBS data were providing useful trend information. We used the overall adjustment factor calculated from the 4 BCRs and years to scale BBS golden eagle counts from 1968 to 2005 for the 4 BCRs and for 1968 to 2010 for the 8 other BCRs (without WGES data) to estimate golden eagle population size and trends across the western United States for the period 1968 to 2010. In general, we noted slightly declining trends in southern BCRs and slightly increasing trends in northern BCRs. However, we estimated the average rate of golden eagle population change across all 12 BCRs for the period 1968–2010 as +0.40% per year (95% CI = −0.27% to 1.00%), suggesting a stable population. We also estimated the average rate of population change for the period 1990–2010 was +0.5% per year (95% CI = −0.33% to 1.3%). Our annual estimates of population size for the most recent decade range from 31,370 (95% CI: 25,450–39,310) in 2004 to 33,460 (95% CI: 27,380–41,710) in 2007. Our results clarify that golden eagles are not declining widely in the western United States. © 2013 The Wildlife Society.

Integrating Safety with Science,Technology and Innovation at Los Alamos National Laboratory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rich, Bethany M

2012-04-02

The mission of Los Alamos National Laboratory (LANL) is to develop and apply science, technology and engineering solutions to ensure the safety, security, and reliability of the U.S. nuclear deterrent; reduce global threats; and solve emerging national security challenges. The most important responsibility is to direct and conduct efforts to meet the mission with an emphasis on safety, security, and quality. In this article, LANL Environmental, Safety, and Health (ESH) trainers discuss how their application and use of a kinetic learning module (learn by doing) with a unique fall arrest system is helping to address one the most common industrialmore » safety challenges: slips and falls. A unique integration of Human Performance Improvement (HPI), Behavior Based Safety (BBS) and elements of the Voluntary Protection Program (VPP) combined with an interactive simulator experience is being used to address slip and fall events at Los Alamos.« less

Genomic Context Analysis of de Novo STXBP1 Mutations Identifies Evidence of Splice Site DNA-Motif Associated Hotspots.

PubMed

Uddin, Mohammed; Woodbury-Smith, Marc; Chan, Ada J S; Albanna, Ammar; Minassian, Berge; Boelman, Cyrus; Scherer, Stephen W

2018-03-28

Mutations within STXBP1 have been associated with a range of neurodevelopmental disorders implicating the pleotropic impact of this gene. Although the frequency of de novo mutations within STXBP1 for selective cohorts with early onset epileptic encephalopathy is more than 1%, there is no evidence for a hotspot within the gene. In this study, we analyzed the genomic context of de novo STXBP1 mutations to examine whether certain motifs indicated a greater risk of mutation. Through a comprehensive context analysis of 136 de novo /rare mutation (SNV/Indels) sites in this gene, strikingly 26.92% of all SNV mutations occurred within 5bp upstream or downstream of a 'GTA' motif ( P < 0.0005). This implies a genomic context modulated mutagenesis. Moreover, 51.85% (14 out of 27) of the 'GTA' mutations are splicing compared to 14.70% (20 out of 136) of all reported mutations within STXBP1 We also noted that 11 of these 14 'GTA' associated mutations are de novo in origin. Our analysis provides strong evidence of DNA motif modulated mutagenesis for STXBP1 de novo splicing mutations. Copyright © 2018 Uddin et al.

WHY DOES OLDER ADULTS' BALANCE BECOME LESS STABLE WHEN WALKING AND PERFORMING A SECONDARY TASK? EXAMINATION OF ATTENTIONAL SWITCHING ABILITIES

PubMed Central

Hawkes, Teresa D; Siu, Ka-Chun; Silsupadol, Patima; Woollacott, Marjorie H.

2011-01-01

Previous research using dual-task paradigms indicates balance-impaired older adults (BIOA) are less able to flexibly shift attentional focus between a cognitive and motor task than healthy older adults (HOA). Shifting attention is a component of executive function. Task switch tests assess executive attention function. This multivariate study asked if BIOAs demonstrate greater task switching deficits than HOAs. A group of 39 HOA (65–80 yrs) and BIOA (65–87 yrs) subjects performed a visuo-spatial task switch. A sub-group of subjects performed a dual-task obstacle avoidance paradigm. All participants completed the Berg Balance Scale (BBS) and Timed Up and Go (TUG). We assessed differences by group for: 1) visuo-spatial task switch reaction times (switch/no-switch), and performance on the BBS and TUG. Our balance groups differed significantly on BBS score (p < .001) and switch reaction time (p = .032), but not the TUG. This confirmed our hypothesis that neuromuscular and executive attention function differs between these two groups. For our BIOA sub-group, gait velocity correlated negatively with performance on the switch condition (p=.036). This suggests that BIOA efficiency of attentional allocation in dual task settings should be further explored. PMID:21964051

A randomized controlled trial of Turkish folklore dance on the physical performance, balance, depression and quality of life in older women.

PubMed

Eyigor, Sibel; Karapolat, Hale; Durmaz, Berrin; Ibisoglu, Ugur; Cakir, Serap

2009-01-01

The present study has been carried out to investigate the effects of group-based Turkish folkloric dances on physical performance, balance, depression and quality of life (QoL) in 40 healthy adult elderly females over the age of 65 years. Subjects were randomly allocated into Group 1 (folkloric dance-based exercise) and Group 2 (control). A 8-week dance-based exercise program was performed. Outcome measures included a 20-m walk test, a 6-min walk test, stair climbing and chair rise time, Berg balance scale (BBS), the Medical Outcomes Study (MOS) 36-item short form health survey (SF-36), and geriatric depression scale (GDS) questionnaires. In Group 1 statistically significant improvements were found in most of the physical performance tests, BBS and some SF-36 subscales after the exercise (p<0.05). In the Group 2 there was no clinically significant change in the variables. Comparing the groups, significant improvements in favor of Group 1 have emerged in most of the functional performance tests, in some of the SF-36 subscales and BBS score (p<0.05). We achieved improvements in physical performance, balance and QoL in elderly females. Application of folkloric dance specific to countries as an exercise program for elderly people may be helpful.

Cohort differences in the availability of informal caregivers: are the Boomers at risk?

PubMed

Ryan, Lindsay H; Smith, Jacqui; Antonucci, Toni C; Jackson, James S

2012-04-01

We compare the close family resources of Baby Boomers (BBs) to previous cohorts of older adults at population level and then examine individual-level cohort comparisons of age-related trajectories of informal care availability from midlife into old age. Population data from the U.S. Census and from the Health and Retirement Study (HRS) are used to identify a cohort similar to the BBs on marital status and fertility rates. Using generalized linear mixed models and 10-year longitudinal data from Depression and WWII parents (DWP; n = 1,052) and the parents of BBs (PBB; n = 3,573) in the HRS, we examine cohort differences in the time-varying likelihoods of being married and of having an adult child living within 10 miles. The DWP had similar informal care resources at entry to old age as is expected in the BB. Longitudinal analyses of the DWP and PBB cohorts in HRS reveal that the availability of family changes over time and that the DWP cohort was significantly less likely to have a spouse or a grown child living nearby. These findings, and future projections based on them, have significant implications for institutions and public policy concerned with the informal caregiving needs of the Boomer cohort as they age.

Influence of educational status on executive function and functional balance in individuals with Parkinson disease.

PubMed

Souza, Carolina de Oliveira; Voos, Mariana Callil; Francato, Débora Valente; Chien, Hsin Fen; Barbosa, Egberto Reis

2013-03-01

This study investigated whether educational status influenced how people with Parkinson disease (PD) performed on Parts A, B, and DELTA of the Trail Making Test (TMT) and on the Berg Balance Scale (BBS). Recent studies have shown that educational status may influence cognitive and motor test performance. We gave the TMT and the BBS to assess executive function and functional balance in 28 people with PD (Hoehn and Yahr score between 2 and 3) and 30 healthy elderly people. Participants reported their number of years of formal education. We divided each group of participants by educational status: low (4 to 10 years of education) or high (≥11 years). In both the PD (P=0.018) and control (P=0.003) groups, participants with low educational status performed worse on the TMT Part B than did those with high educational status. Within the PD group, the less-educated participants scored worse on the BBS than did the more educated (P<0.001); this difference was not significant between the more- and less-educated controls (P=0.976). Whether or not they had PD, less-educated people performed worse than more-educated people on the TMT Part B. Educational status affected executive function, but PD status did not. Among individuals with PD, educational status influenced functional balance.

Balance ability measured with the Berg balance scale: a determinant of fall history in community-dwelling adults with leg amputation.

PubMed

Wong, Christopher Kevin; Chen, Christine C; Blackwell, Wren M; Rahal, Rana T; Benoy, Stephany A

2015-01-01

Falls are common among adults with leg amputations and associated with balance confidence. But subjective confidence is not equivalent with physical ability. This multivariate analyses of community-dwelling adults with leg amputations examined relationships among individual characteristics, falls, balance ability and balance confidence. Cross-sectional study. Community-dwelling adults with leg amputations recruited from a support group and prosthetic clinic. Subjects provided self-reported medical/fall history, prosthetic functional use, and Activities-specific Balance Confidence (ABC) questionnaire data. Balance ability was assessed with the Berg Balance Scale (BBS). Fall incidence was categorized as any fall (one or more) and recurrent falls (more than one). Multivariate logistic regression analyzed relationships within the two fall categories. Cross tabulations and ANOVA analyzed differences among subcategories. Fifty-four subjects (mean age 56.8) with various etiologies, amputation levels, and balance abilities participated. 53.7% had any fall; 25.9% had recurrent falls. Models for both fall categories correctly classified fall history in > 70% of subjects with combinations of the variables ABC, BBS, body-mass-index, and amputation level. Falls occurred regardless of clinical characteristics. Total BBS and select item scores were independent determinants of fall history. Unlike other balance-impaired populations, adults with leg amputation and better balance ability had greater odds of falling.

Comparison of jump-landing protocols with Biodex Balance System as measures of dynamic postural stability in athletes.

PubMed

Krkeljas, Zarko

2017-07-21

The objective of the study was to determine whether a relationship exists between the two common methods for assessing postural stability in athletes: the time-to-stabilisation (TTS) via force-plate and the Biodex Balance System (BBS). The conditions under which these measurements assess dynamic postural control may not provide sufficient feedback to practitioners. Fourty-four amateur soccer players with no history of musculoskeletal disorders volunteered for the study. Pearson correlation was used to compare the anterior-posterior (AP), medio-lateral (ML), and the overall stability indexes measured by BBS, with the corresponding parameters of TTS assessed via force plate. There was no significant correlation between any parameters of dynamic stability measured by force-plate and the stability indexes. However, there was a significant correlation between the resulting vectors and the AP component of TTS for each jump protocol. Furthermore, forward drop landing exhibited shortest TTS in AP direction, while lateral drop landing resulted in longer ML TTS relative to both forward jumps (p < 0.001). These results demonstrate that the TTS and BBS stability indexes should be used as distinct measures of dynamic postural stability. TTS protocols may be modified to target a specific training conditions or athletic population.

Traditional Chinese Mind and Body Exercises for Promoting Balance Ability of Old Adults: A Systematic Review and Meta-Analysis

PubMed Central

Zhang, Yanjie; Wang, Yong Tai; Liu, Xiao Lei

2016-01-01

The purpose of this study was to provide a quantitative evaluation of the effectiveness of traditional Chinese mind and body exercises in promoting balance ability for old adults. The eligible studies were extensively searched from electronic databases (Medline, CINAHL, SportDicus, and Web of Science) until 10 May 2016. Reference lists of relevant publications were screened for future hits. The trials used randomized controlled approaches to compare the effects of traditional Chinese mind and body exercise (TCMBE) on balance ability of old adults that were included. The synthesized results of Berg Balance Scale (BBS), Timed Up and Go Test (TUG), and static balance with 95% confidence intervals were counted under a random-effects model. Ten studies were selected based on the inclusion criteria, and a total of 1,798 participants were involved in this review. The results of the meta-analysis showed that TCMBE had no significant improvement on BBS and TUG, but the BBS and TUG could be obviously improved by prolonging the intervention time. In addition, the results showed that TCMBE could significantly improve the static balance compared to control group. In conclusion, old adults who practiced TCMBE with the time not less than 150 minutes per week for more than 15 weeks could promote the balance ability. PMID:27990168

Traditional Chinese Mind and Body Exercises for Promoting Balance Ability of Old Adults: A Systematic Review and Meta-Analysis.

PubMed

Chen, Shihui; Zhang, Yanjie; Wang, Yong Tai; Liu, Xiao Lei

2016-01-01

The purpose of this study was to provide a quantitative evaluation of the effectiveness of traditional Chinese mind and body exercises in promoting balance ability for old adults. The eligible studies were extensively searched from electronic databases (Medline, CINAHL, SportDicus, and Web of Science) until 10 May 2016. Reference lists of relevant publications were screened for future hits. The trials used randomized controlled approaches to compare the effects of traditional Chinese mind and body exercise (TCMBE) on balance ability of old adults that were included. The synthesized results of Berg Balance Scale (BBS), Timed Up and Go Test (TUG), and static balance with 95% confidence intervals were counted under a random-effects model. Ten studies were selected based on the inclusion criteria, and a total of 1,798 participants were involved in this review. The results of the meta-analysis showed that TCMBE had no significant improvement on BBS and TUG, but the BBS and TUG could be obviously improved by prolonging the intervention time. In addition, the results showed that TCMBE could significantly improve the static balance compared to control group. In conclusion, old adults who practiced TCMBE with the time not less than 150 minutes per week for more than 15 weeks could promote the balance ability.

Structure and evolution of online social relationships: Heterogeneity in unrestricted discussions.

PubMed

Goh, K-I; Eom, Y-H; Jeong, H; Kahng, B; Kim, D

2006-06-01

With the advancement in the information age, people are using electronic media more frequently for communications, and social relationships are also increasingly resorting to online channels. While extensive studies on traditional social networks have been carried out, little has been done on online social networks. Here we analyze the structure and evolution of online social relationships by examining the temporal records of a bulletin board system (BBS) in a university. The BBS dataset comprises of 1908 boards, in which a total of 7446 students participate. An edge is assigned to each dialogue between two students, and it is defined as the appearance of the name of a student in the from- and to-field in each message. This yields a weighted network between the communicating students with an unambiguous group association of individuals. In contrast to a typical community network, where intracommunities (intercommunities) are strongly (weakly) tied, the BBS network contains hub members who participate in many boards simultaneously but are strongly tied, that is, they have a large degree and betweenness centrality and provide communication channels between communities. On the other hand, intracommunities are rather homogeneously and weakly connected. Such a structure, which has never been empirically characterized in the past, might provide a new perspective on the social opinion formation in this digital era.

Creation and formation mechanism of new carbon phases constructed by amorphous carbon

NASA Astrophysics Data System (ADS)

Yao, Mingguang; Cui, Wen; Liu, Bingbing

Our recent effort is focusing on the creation of new hard/superhard carbon phases constructed by disordered carbons or amorphous carbon clusters under high pressure. We showed that the pressure-induced amorphous hard carbon clusters from collapsed fullerenes can be used as building blocks (BBs) for constructing novel carbon structures. This new strategy has been verified by compressing a series of intercalated fullerides, pre-designed by selecting various dopants with special features. We demonstrate that the boundaries of the amorphous BBs are mediated by intercalated dopants and several new superhard materials have been prepared. We also found that the dopant-mediated BBs can be arranged in either ordered or disordered structures, both of which can be hard enough to indent the diamond anvils. The hardening mechanisms of the new phases have also been discussed. For the glassy carbon (GC) constructructed by disordered fullerene-like nanosized fragments, we also found that these disordered fragments can bond and the compressed GC transformed into a transparent superhard phase. Such pressure-induced transformation has been discovered to be driven by a novel mechanism (unpublished). By understanding the mechanisms we can clarify the controversial results on glassy carbon reported recently. The authors would like to thank the financial support from the National Natural Science Foundation of China (No. 11474121, 51320105007).

Search for the decays B_{(s)};{0} --> e;{+} micro;{-} and B_{(s)};{0} --> e;{+} e;{-} in CDF run II.

PubMed

Aaltonen, T; Adelman, J; Akimoto, T; Alvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Apollinari, G; Apresyan, A; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Azzurri, P; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Bartsch, V; Bauer, G; Beauchemin, P-H; Bedeschi, F; Beecher, D; Behari, S; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Beringer, J; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Bridgeman, A; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burke, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Calancha, C; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carls, B; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavaliere, V; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Chwalek, T; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Compostella, G; Convery, M E; Conway, J; Cordelli, M; Cortiana, G; Cox, C A; Cox, D J; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Dagenhart, D; Datta, M; Davies, T; de Barbaro, P; De Cecco, S; Deisher, A; De Lorenzo, G; Dell'orso, M; Deluca, C; Demortier, L; Deng, J; Deninno, M; Derwent, P F; di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Elagin, A; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Ferrazza, C; Field, R; Flanagan, G; Forrest, R; Frank, M J; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garberson, F; Garcia, J E; Garfinkel, A F; Genser, K; Gerberich, H; Gerdes, D; Gessler, A; Giagu, S; Giakoumopoulou, V; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C M; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Han, B-Y; Han, J Y; Happacher, F; Hara, K; Hare, D; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hays, C; Heck, M; Heijboer, A; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hewamanage, S; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Hussein, M; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; James, E; Jang, D; Jayatilaka, B; Jeon, E J; Jha, M K; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Kar, D; Karchin, P E; Kato, Y; Kephart, R; Keung, J; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, H W; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Knuteson, B; Ko, B R; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kreps, M; Kroll, J; Krop, D; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhr, T; Kulkarni, N P; Kurata, M; Kwang, S; Laasanen, A T; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; Lecompte, T; Lee, E; Lee, H S; Lee, S W; Leone, S; Lewis, J D; Lin, C-S; Linacre, J; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, C; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Lovas, L; Lucchesi, D; Luci, C; Lueck, J; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Macqueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis-Katsikakis, A; Margaroli, F; Marino, C; Marino, C P; Martin, A; Martin, V; Martínez, M; Martínez-Ballarín, R; Maruyama, T; Mastrandrea, P; Masubuchi, T; Mathis, M; Mattson, M E; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzione, A; Merkel, P; Mesropian, C; Miao, T; Miladinovic, N; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyake, H; Moggi, N; Moon, C S; Moore, R; Morello, M J; Morlock, J; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Nagano, A; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Necula, V; Nett, J; Neu, C; Neubauer, M S; Neubauer, S; Nielsen, J; Nodulman, L; Norman, M; Norniella, O; Nurse, E; Oakes, L; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Orava, R; Osterberg, K; Griso, S Pagan; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Peiffer, T; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Pianori, E; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Pueschel, E; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Renton, P; Renz, M; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rodriguez, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Rutherford, B; Saarikko, H; Safonov, A; Sakumoto, W K; Saltó, O; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savoy-Navarro, A; Schlabach, P; Schmidt, A; Schmidt, E E; Schmidt, M A; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sforza, F; Sfyrla, A; Shalhout, S Z; Shears, T; Shepard, P F; Shimojima, M; Shiraishi, S; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spreitzer, T; Squillacioti, P; Stanitzki, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Strycker, G L; Stuart, D; Suh, J S; Sukhanov, A; Suslov, I; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thompson, G A; Thomson, E; Tipton, P; Ttito-Guzmán, P; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Totaro, P; Tourneur, S; Trovato, M; Tsai, S-Y; Tu, Y; Turini, N; Ukegawa, F; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Vellidis, C; Vidal, M; Vidal, R; Vila, I; Vilar, R; Vine, T; Vogel, M; Volobouev, I; Volpi, G; Wagner, P; Wagner, R G; Wagner, R L; Wagner, W; Wagner-Kuhr, J; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Weinelt, J; Wenzel, H; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Wilbur, S; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Würthwein, F; Xie, S; Yagil, A; Yamamoto, K; Yamaoka, J; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zhang, X; Zheng, Y; Zucchelli, S

2009-05-22

We report results from a search for the lepton flavor violating decays B_{s};{0} --> e;{+} micro;{-} and B;{0} --> e;{+} micro;{-}, and the flavor-changing neutral-current decays B_{s};{0} --> e;{+} e;{-} and B;{0} --> e;{+} e;{-}. The analysis uses data corresponding to 2 fb;{-1} of integrated luminosity of pp[over ] collisions at sqrt[s] = 1.96 TeV collected with the upgraded Collider Detector (CDF II) at the Fermilab Tevatron. The observed number of B0 and B_{s};{0} candidates is consistent with background expectations. The resulting Bayesian upper limits on the branching ratios at 90% credibility level are B(B_{s};{0} --> e;{+} micro;{-}) < 2.0 x 10;{-7}, B(B;{0} --> e;{+} micro;{-}) < 6.4 x 10;{-8}, B(B_{s};{0} --> e;{+} e;{-}) < 2.8 x 10;{-7}, and B(B;{0} --> e;{+} e;{-}) < 8.3 x 10;{-8}. From the limits on B(B_{(s)};{0} --> e;{+} micro;{-}), the following lower bounds on the Pati-Salam leptoquark masses are also derived: M_{LQ}(B_{s};{0} --> e;{+} micro;{-}) > 47.8 TeV/c;{2}, and M_{LQ}(B;{0} --> e;{+} micro;{-}) > 59.3 TeV / c;{2}, at 90% credibility level.

Estimating population trends with a linear model: Technical comments

USGS Publications Warehouse

Sauer, John R.; Link, William A.; Royle, J. Andrew

2004-01-01

Controversy has sometimes arisen over whether there is a need to accommodate the limitations of survey design in estimating population change from the count data collected in bird surveys. Analyses of surveys such as the North American Breeding Bird Survey (BBS) can be quite complex; it is natural to ask if the complexity is necessary, or whether the statisticians have run amok. Bart et al. (2003) propose a very simple analysis involving nothing more complicated than simple linear regression, and contrast their approach with model-based procedures. We review the assumptions implicit to their proposed method, and document that these assumptions are unlikely to be valid for surveys such as the BBS. One fundamental limitation of a purely design-based approach is the absence of controls for factors that influence detection of birds at survey sites. We show that failure to model observer effects in survey data leads to substantial bias in estimation of population trends from BBS data for the 20 species that Bart et al. (2003) used as the basis of their simulations. Finally, we note that the simulations presented in Bart et al. (2003) do not provide a useful evaluation of their proposed method, nor do they provide a valid comparison to the estimating- equations alternative they consider.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

Contents: commentary; noteworthy governmental happenings; notes on nps technology; notes on watershed management; news from the states; agricultural notes; nps electronic bulletin board (bbs) news; reviews; and announcements of interest.

Mathematical modelling of digesta passage rate, mean retention time and in vivo apparent digestibility of two different lengths of hay and big-bale grass silage in ponies.

PubMed

Moore-Colyer, M J S; Morrow, H J; Longland, A C

2003-07-01

Welsh-cross pony geldings (about 300 kg live weight) were used in a 4x4 Latin square experiment to determine the rate of passage and apparent digestibility of unchopped big-bale grass silage (BBL), chopped big-bale grass silage (BBS), unchopped grass hay (HL) and chopped grass hay (HS) offered at approximately 15 g/kg live weight per d. On day 1 of collection weeks, ponies were fed 85 g ytterbium chloride hexahydrate-marked feed 1.5 h after the morning meal. Total faecal collections commenced 8 h later and continued for 168 h. Apparent digestibilities of feed DM, organic matter (OM), crude protein (CP, Nx6.25), acid-detergent fibre (ADF) and neutral-detergent fibre (NDF) were also determined. Faecal excretion data were subjected to the models of Pond et al. (1988) and digesta mean retention time (MRT) calculated from these models and using the algebraic method of Thielmans et al. (1978). Silage had significantly (P<0.05) higher digestibilities of DM, OM, CP, ADF and NDF than hay; however, chop length had no effect. All the models of Pond et al. (1988) accurately described (R(2)>0.8) the pattern of faecal marker excretion. MRT of BBL (29.0 h)>BBS(27 h)>HS and HL (26 h). Compartmental analysis using the G3 model of Pond et al. (1988) showed BBL and HS diets had longer MRT in the time-dependent compartment, whereas BBS and HL had longer MRT in the time-independent compartment. Results from this experiment indicate that BBL and BBS are readily accepted and digested by ponies. While Yb is a successful external marker for determining total tract MRT and for modelling faecal excretion curves in horses, the results did not allow any definite conclusions to be drawn on digesta MRT within the different compartments of the equid gut.

Gait and Balance Measures Can Identify Change From a Cerebrospinal Fluid Tap Test in Idiopathic Normal Pressure Hydrocephalus.

PubMed

Gallagher, Ryan; Marquez, Jodie; Osmotherly, Peter

2018-04-25

To identify in patients with idiopathic normal pressure hydrocephalus (iNPH) undergoing a cerebrospinal fluid (CSF) tap test (TT) for consideration of a ventricular peritoneal (VP) shunt: (1) gait and balance measures, which identify symptom change; (2) differences present between pre- and post-CSF TT scores between patients classified as responders and nonresponder; (3) ability of patients with iNPH to accurately quantify change in their gait and balance symptoms from a CSF TT. Prospective observational study. Post-CSF TT assessment was completed 2-4 hours post. Tertiary referral neurological and neurosurgical hospital. Patients (N=74) with iNPH receiving a 30 mL CSF TT for consideration of a VP shunt. Patients underwent a battery of gait and balance measures pre- and post-CSF TT and indicated their perceived change on a global rating of change (GRC). Patients deemed to improve and offered VP shunt insertion by a neurologist or neurosurgeon were labeled responders. Performance oriented mobility assessment (Tinetti), Berg Balance Scale (BBS), timed Up and Go (TUG), 10-meter walk test (10MWT), GRC. Forty patients were classified responders, 34 nonresponders. Significant differences were identified for responders: Tinetti (3.88 points), TUG (3.98 seconds), 10MWT (0.08 m/sec), and BBS (5.29 points). Significant differences were found for nonresponders for the Tinetti (0.91 points) and BBS (2.06 points). Change scores for responders and nonresponders were significantly different for all tests between responders and nonresponders. GRC scores for gait (+2 for responders, 0 for nonresponders) and balance (+2.5 for responders, 0 for nonresponders) were both significantly different. The Tinetti, BBS, and TUG can identify change in patients undergoing a CSF TT for iNPH. Patients appear to be able to accurately identify if change has occurred. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Computational genomic analysis of PARK7 interactome reveals high BBS1 gene expression as a prognostic factor favoring survival in malignant pleural mesothelioma.

PubMed

Vavougios, Georgios D; Solenov, Evgeniy I; Hatzoglou, Chrissi; Baturina, Galina S; Katkova, Liubov E; Molyvdas, Paschalis Adam; Gourgoulianis, Konstantinos I; Zarogiannis, Sotirios G

2015-10-01

The aim of our study was to assess the differential gene expression of Parkinson protein 7 (PARK7) interactome in malignant pleural mesothelioma (MPM) using data mining techniques to identify novel candidate genes that may play a role in the pathogenicity of MPM. We constructed the PARK7 interactome using the ConsensusPathDB database. We then interrogated the Oncomine Cancer Microarray database using the Gordon Mesothelioma Study, for differential gene expression of the PARK7 interactome. In ConsensusPathDB, 38 protein interactors of PARK7 were identified. In the Gordon Mesothelioma Study, 34 of them were assessed out of which SUMO1, UBC3, KIAA0101, HDAC2, DAXX, RBBP4, BBS1, NONO, RBBP7, HTRA2, and STUB1 were significantly overexpressed whereas TRAF6 and MTA2 were significantly underexpressed in MPM patients (network 2). Furthermore, Kaplan-Meier analysis revealed that MPM patients with high BBS1 expression had a median overall survival of 16.5 vs. 8.7 mo of those that had low expression. For validation purposes, we performed a meta-analysis in Oncomine database in five sarcoma datasets. Eight network 2 genes (KIAA0101, HDAC2, SUMO1, RBBP4, NONO, RBBP7, HTRA2, and MTA2) were significantly differentially expressed in an array of 18 different sarcoma types. Finally, Gene Ontology annotation enrichment analysis revealed significant roles of the PARK7 interactome in NuRD, CHD, and SWI/SNF protein complexes. In conclusion, we identified 13 novel genes differentially expressed in MPM, never reported before. Among them, BBS1 emerged as a novel predictor of overall survival in MPM. Finally, we identified that PARK7 interactome is involved in novel pathways pertinent in MPM disease. Copyright © 2015 the American Physiological Society.

Effects of Exergames on Balance, Functional Mobility, and Quality of Life of Geriatrics Versus Home Exercise Programme: Randomized Controlled Study.

PubMed

Karahan, Ali Yavuz; Tok, Fatih; Taşkın, Halil; Kuçuksaraç, Seher; Başaran, Aynur; Yıldırım, Pelin

2015-11-01

To compare the effects of exergames (EGs) using the Xbox Kinect™ device and home exercise (HE) on balance, functional mobility, and quality of life of individuals aged 65 years or older. One hundred participants who met the inclusion criteria were randomized to the EG or HE group. The EG group took part in a 6-week programme using the Xbox360Kinect™ device, and the HE group took part in a 6-week balance exercise programme at home 5 days a week. The Berg Balance Scale (BBS) was used to assess balance, the Timed Up and Go (TUG) test was used to evaluate functional walking, and the Short Form 36 (SF-36) was used to assess quality of life. Forty-eight participants in the EG group and 42 participants in the HE group completed the study. The groups were similar in terms of age, sex, and pretreatment values of BBS, TUG, and SF-36. Although the BBS scores of both groups improved significantly (all p<0.05), the post-treatment scores of the EG group were better than those of the HE group. The TUG scores improved only in the EG group (p<0.05). The increase in the BBS scores and decrease in the TUG test scores were significant only in the EG group (all p<0.05). A significant improvement was also observed in the quality of life parameters of physical functioning, social role functioning, physical role restriction, general health perceptions, and physical component scores in the post-exercise evaluations of the EG group. The participants commented that they found the EG programme very entertaining. The EG can be considered a safe, entertaining and sustainable alternative to HE programmes, and it may have positive effects on balance, functional walking and quality of life in geriatric subjects. Copyright© by the National Institute of Public Health, Prague 2015.

Comparison of the Fullerton Advanced Balance Scale, Mini-BESTest, and Berg Balance Scale to Predict Falls in Parkinson Disease.

PubMed

Schlenstedt, Christian; Brombacher, Stephanie; Hartwigsen, Gesa; Weisser, Burkhard; Möller, Bettina; Deuschl, Günther

2016-04-01

The correct identification of patients with Parkinson disease (PD) at risk for falling is important to initiate appropriate treatment early. This study compared the Fullerton Advanced Balance (FAB) scale with the Mini-Balance Evaluation Systems Test (Mini-BESTest) and Berg Balance Scale (BBS) to identify individuals with PD at risk for falls and to analyze which of the items of the scales best predict future falls. This was a prospective study to assess predictive criterion-related validity. The study was conducted at a university hospital in an urban community. Eighty-five patients with idiopathic PD (Hoehn and Yahr stages: 1-4) participated in the study. Measures were number of falls (assessed prospectively over 6 months), FAB scale, Mini-BESTest, BBS, and Unified Parkinson's Disease Rating Scale. The FAB scale, Mini-BESTest, and BBS showed similar accuracy to predict future falls, with values for area under the curve (AUC) of the receiver operating characteristic (ROC) curve of 0.68, 0.65, and 0.69, respectively. A model combining the items "tandem stance," "rise to toes," "one-leg stance," "compensatory stepping backward," "turning," and "placing alternate foot on stool" had an AUC of 0.84 of the ROC curve. There was a dropout rate of 19/85 participants. The FAB scale, Mini-BESTest, and BBS provide moderate capacity to predict "fallers" (people with one or more falls) from "nonfallers." Only some items of the 3 scales contribute to the detection of future falls. Clinicians should particularly focus on the item "tandem stance" along with the items "one-leg stance," "rise to toes," "compensatory stepping backward," "turning 360°," and "placing foot on stool" when analyzing postural control deficits related to fall risk. Future research should analyze whether balance training including the aforementioned items is effective in reducing fall risk. © 2016 American Physical Therapy Association.

Effect of exposure to evidence-based pharmacotherapy on outcomes after acute myocardial infarction in older adults.

PubMed

Zuckerman, Ilene H; Yin, Xianghua; Rattinger, Gail B; Gottlieb, Stephen S; Simoni-Wastila, Linda; Pierce, Sarah A; Huang, Ting-Ying; Shenolikar, Rahul; Stuart, Bruce

2012-10-01

To assess the effect of exposure to evidence-based medication after hospital discharge for Medicare beneficiaries with acute myocardial infarction (AMI). A discrete-time hazard model was used to estimate time to outcome associated with exposure to four drug classes (angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin-II receptor blockers (ARBs), beta-blockers (BBs), statins, and clopidogrel) used for post-AMI secondary prevention of cardiovascular events and mortality. Medicare administrative data for a 5% random sample of beneficiaries. Medicare beneficiaries (N = 9,538) hospitalized for an AMI between April 1, 2006, and December 31, 2007, who survived for at least 30 days after discharge. The cohort was followed until death or December 31, 2008. Time-varying exposure was measured as proportion of days covered (PDC) for each quarter during the follow-up period. PDC was classified into five categories (0-0.2, 0.2-0.4, 0.4-0.6, 0.6-0.8, 0.8-1.0). Outcomes were mortality and a composite outcome of death or post-AMI hospitalization. Over a median follow-up of 18 months, mean PDC rates ranged from 0.37 (clopidogrel) to 0.50 (statins). When comparing the highest versus lowest categories of exposure, the hazard of the composite outcome was significantly lower for all drug classes except BBs (statins, adjusted hazard ratio (aHR) = 0.71, ACEIs/ARBs, aHR = 0.81, clopidogrel, aHR = 0.85, BBs, aHR = 0.93). All four drug classes were significantly associated with reductions in mortality; the magnitude of effect for the mortality outcome was largest for statins and smallest for BBs. Age modified the effect of statins on mortality. Use of evidence-based medications for secondary prevention after AMI is suboptimal in the Medicare population, and low exposure rates are associated with significantly higher risk for subsequent hospitalization and death. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

Adherence to optimal heart rate control in heart failure with reduced ejection fraction: insight from a survey of heart rate in heart failure in Sweden (HR-HF study).

PubMed

Fu, M; Ahrenmark, U; Berglund, S; Lindholm, C J; Lehto, A; Broberg, A Månsson; Tasevska-Dinevska, G; Wikstrom, G; Ågard, A; Andersson, B

2017-12-01

Despite that heart rate (HR) control is one of the guideline-recommended treatment goals for heart failure (HF) patients, implementation has been painstakingly slow. Therefore, it would be important to identify patients who have not yet achieved their target heart rates and assess possible underlying reasons as to why the target rates are not met. The survey of HR in patients with HF in Sweden (HR-HF survey) is an investigator-initiated, prospective, multicenter, observational longitudinal study designed to investigate the state of the art in the control of HR in HF and to explore potential underlying mechanisms for suboptimal HR control with focus on awareness of and adherence to guidelines for HR control among physicians who focus on the contributing role of beta-blockers (BBs). In 734 HF patients the mean HR was 68 ± 12 beats per minute (bpm) (37.2% of the patients had a HR >70 bpm). Patients with HF with reduced ejection fraction (HFrEF) (n = 425) had the highest HR (70 ± 13 bpm, with 42% >70 bpm), followed by HF with preserved ejection fraction and HF with mid-range ejection fraction. Atrial fibrillation, irrespective of HF type, had higher HR than sinus rhythm. A similar pattern was observed with BB treatment. Moreover, non-achievement of the recommended target HR (<70 bpm) in HFrEF and sinus rhythm was unrelated to age, sex, cardiovascular risk factors, cardiovascular diseases, and comorbidities, but was related to EF and the clinical decision of the physician. Approximately 50% of the physicians considered a HR of >70 bpm optimal and an equal number considered a HR of >70 bpm too high, but without recommending further action. Furthermore, suboptimal HR control cannot be attributed to the use of BBs because there was neither a difference in use of BBs nor an interaction with BBs for HR >70 bpm compared with HR <70 bpm. Suboptimal control of HR was noted in HFrEF with sinus rhythm, which appeared to be attributable to physician decision making rather than to the use of BBs. Therefore, our results underline the need for greater attention to HR control in patients with HFrEF and sinus rhythm and thus a potential for improved HF care.

Improved Blackbody Temperature Sensors for a Vacuum Furnace

NASA Technical Reports Server (NTRS)

Farmer, Jeff; Coppens, Chris; O'Dell, J. Scott; McKechnie, Timothy N.; Schofield, Elizabeth

2009-01-01

Some improvements have been made in the design and fabrication of blackbody sensors (BBSs) used to measure the temperature of a heater core in a vacuum furnace. Each BBS consists of a ring of thermally conductive, high-melting-temperature material with two tantalum-sheathed thermocouples attached at diametrically opposite points. The name "blackbody sensor" reflects the basic principle of operation. Heat is transferred between the ring and the furnace heater core primarily by blackbody radiation, heat is conducted through the ring to the thermocouples, and the temperature of the ring (and, hence, the temperature of the heater core) is measured by use of the thermocouples. Two main requirements have guided the development of these BBSs: (1) The rings should have as high an emissivity as possible in order to maximize the heat-transfer rate and thereby maximize temperature-monitoring performance and (2) the thermocouples must be joined to the rings in such a way as to ensure long-term, reliable intimate thermal contact. The problem of fabricating a BBS to satisfy these requirements is complicated by an application-specific prohibition against overheating and thereby damaging nearby instrumentation leads through the use of conventional furnace brazing or any other technique that involves heating the entire BBS and its surroundings. The problem is further complicated by another application-specific prohibition against damaging the thin tantalum thermocouple sheaths through the use of conventional welding to join the thermocouples to the ring. The first BBS rings were made of graphite. The tantalum-sheathed thermocouples were attached to the graphite rings by use of high-temperature graphite cements. The ring/thermocouple bonds thus formed were found to be weak and unreliable, and so graphite rings and graphite cements were abandoned. Now, each BBS ring is made from one of two materials: either tantalum or a molybdenum/titanium/zirconium alloy. The tantalum-sheathed thermocouples are bonded to the ring by laser brazing. The primary advantage of laser brazing over furnace brazing is that in laser brazing, it is possible to form a brazed connection locally, without heating nearby parts to the flow temperature of the brazing material. Hence, it is possible to comply with the prohibition against overheating nearby instrumentation leads. Also, in laser brazing, unlike in furnace brazing, it is possible to exert control over the thermal energy to such a high degree that it becomes possible to braze the thermocouples to the ring without burning through the thin tantalum sheaths on the thermocouples. The brazing material used in the laser brazing process is a titanium-boron paste. This brazing material can withstand use at temperatures up to about 1,400 C. In thermal-cycling tests performed thus far, no debonding between the rings and thermocouples has been observed. Emissivity coatings about 0.001 in. (.0.025 mm) thick applied to the interior surfaces of the rings have been found to improve the performance of the BBS sensors by raising the apparent emissivities of the rings. In thermal-cycling tests, the coatings were found to adhere well to the rings.

Targeting a genetic defect: cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis.

PubMed

Derichs, Nico

2013-03-01

Cystic fibrosis (CF) is caused by genetic mutations that affect the cystic fibrosis transmembrane conductance regulator (CFTR) protein. These mutations can impact the synthesis and transfer of the CFTR protein to the apical membrane of epithelial cells, as well as influencing the gating or conductance of chloride and bicarbonate ions through the channel. CFTR dysfunction results in ionic imbalance of epithelial secretions in several organ systems, such as the pancreas, gastrointestinal tract, liver and the respiratory system. Since discovery of the CFTR gene in 1989, research has focussed on targeting the underlying genetic defect to identify a disease-modifying treatment for CF. Investigated management strategies have included gene therapy and the development of small molecules that target CFTR mutations, known as CFTR modulators. CFTR modulators are typically identified by high-throughput screening assays, followed by preclinical validation using cell culture systems. Recently, one such modulator, the CFTR potentiator ivacaftor, was approved as an oral therapy for CF patients with the G551D-CFTR mutation. The clinical development of ivacaftor not only represents a breakthrough in CF care but also serves as a noteworthy example of personalised medicine.

The effect of Nintendo® Wii® on balance in people with multiple sclerosis: a pilot randomized control study.

PubMed

Brichetto, Giampaolo; Spallarossa, Patricio; de Carvalho, Maria L Lopes; Battaglia, Mario A

2013-08-01

Improvement of sensory strategies is a relevant part of balance rehabilitation in multiple sclerosis (MS). This study aimed to Assess the effectiveness of visual-feedback exercises in improving balance in MS. We divided 36 patients into Wii and control-treated groups that underwent balance rehabilitation. Outcomes were obtained for Berg Balance Scale (BBS), Modified Fatigue Impact Scale, and sway area under conditions of opened and closed eyes. BBS showed a statistically significant improvement (from 49.6 to 54.6 points, p < 0.05) in the Wii group. Interactive visual-feedback exercises such as Wii could be more effective than the current standard protocol in improving balance disorders in MS.

Discovering Multimodal Behavior in Ms. Pac-Man through Evolution of Modular Neural Networks.

PubMed

Schrum, Jacob; Miikkulainen, Risto

2016-03-12

Ms. Pac-Man is a challenging video game in which multiple modes of behavior are required: Ms. Pac-Man must escape ghosts when they are threats and catch them when they are edible, in addition to eating all pills in each level. Past approaches to learning behavior in Ms. Pac-Man have treated the game as a single task to be learned using monolithic policy representations. In contrast, this paper uses a framework called Modular Multi-objective NEAT (MM-NEAT) to evolve modular neural networks. Each module defines a separate behavior. The modules are used at different times according to a policy that can be human-designed (i.e. Multitask) or discovered automatically by evolution. The appropriate number of modules can be fixed or discovered using a genetic operator called Module Mutation. Several versions of Module Mutation are evaluated in this paper. Both fixed modular networks and Module Mutation networks outperform monolithic networks and Multitask networks. Interestingly, the best networks dedicate modules to critical behaviors (such as escaping when surrounded after luring ghosts near a power pill) that do not follow the customary division of the game into chasing edible and escaping threat ghosts. The results demonstrate that MM-NEAT can discover interesting and effective behavior for agents in challenging games.

Discovering Multimodal Behavior in Ms. Pac-Man through Evolution of Modular Neural Networks

PubMed Central

Schrum, Jacob; Miikkulainen, Risto

2015-01-01

Ms. Pac-Man is a challenging video game in which multiple modes of behavior are required: Ms. Pac-Man must escape ghosts when they are threats and catch them when they are edible, in addition to eating all pills in each level. Past approaches to learning behavior in Ms. Pac-Man have treated the game as a single task to be learned using monolithic policy representations. In contrast, this paper uses a framework called Modular Multi-objective NEAT (MM-NEAT) to evolve modular neural networks. Each module defines a separate behavior. The modules are used at different times according to a policy that can be human-designed (i.e. Multitask) or discovered automatically by evolution. The appropriate number of modules can be fixed or discovered using a genetic operator called Module Mutation. Several versions of Module Mutation are evaluated in this paper. Both fixed modular networks and Module Mutation networks outperform monolithic networks and Multitask networks. Interestingly, the best networks dedicate modules to critical behaviors (such as escaping when surrounded after luring ghosts near a power pill) that do not follow the customary division of the game into chasing edible and escaping threat ghosts. The results demonstrate that MM-NEAT can discover interesting and effective behavior for agents in challenging games. PMID:27030803

Suppressor Mutations for Presenilin 1 Familial Alzheimer Disease Mutants Modulate γ-Secretase Activities.

PubMed

Futai, Eugene; Osawa, Satoko; Cai, Tetsuo; Fujisawa, Tomoya; Ishiura, Shoichi; Tomita, Taisuke

2016-01-01

γ-Secretase is a multisubunit membrane protein complex containing presenilin (PS1) as a catalytic subunit. Familial Alzheimer disease (FAD) mutations within PS1 were analyzed in yeast cells artificially expressing membrane-bound substrate, amyloid precursor protein, or Notch fused to Gal4 transcriptional activator. The FAD mutations, L166P and G384A (Leu-166 to Pro and Gly-384 to Ala substitution, respectively), were loss-of-function in yeast. We identified five amino acid substitutions that suppress the FAD mutations. The cleavage of amyloid precursor protein or Notch was recovered by the secondary mutations. We also found that secondary mutations alone activated the γ-secretase activity. FAD mutants with suppressor mutations, L432M or S438P within TMD9 together with a missense mutation in the second or sixth loops, regained γ-secretase activity when introduced into presenilin null mouse fibroblasts. Notably, the cells with suppressor mutants produced a decreased amount of Aβ42, which is responsible for Alzheimer disease. These results indicate that the yeast system is useful to screen for mutations and chemicals that modulate γ-secretase activity. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Modulation of Caenorhabditis elegans transcription factor activity by HIM-8 and the related Zinc-Finger ZIM proteins.

PubMed

Sun, Hongliu; Nelms, Brian L; Sleiman, Sama F; Chamberlin, Helen M; Hanna-Rose, Wendy

2007-10-01

The previously reported negative regulatory activity of HIM-8 on the Sox protein EGL-13 is shared by the HIM-8-related ZIM proteins. Furthermore, mutation of HIM-8 can modulate the effects of substitution mutations in the DNA-binding domains of at least four other transcription factors, suggesting broad regulatory activity by HIM-8.

The Genomic Evolution of Prostate Cancer

DTIC Science & Technology

2014-10-01

Mutation characteristics. (a) Number of high-confidence somatic mutations across all foci. Non- silent , non- silent mutations; Unique, number of unique...genes harboring a non- silent mutation; Reported, gene reported to be mutated in references 9–12 and 14. (b) Spectrum of unique high confidence somatic...epigenetic and micr- oRNA-mediated inactivation of LRP1B, a modulator of the extracellular environment of thyroid cancer cells. Oncogene 2011; 30

[Deregulation of pre-messenger RNA splicing and rare diseases].

PubMed

de la Grange, Pierre

2016-12-01

Most of protein-coding human genes are subjected to alternative pre-mRNA splicing. This mechanism is highly regulated to precisely modulate detection of specific splice sites. This regulation is under control of the spliceosome and several splicing factors are also required to modulate the alternative usage of splice sites. Splicing factors and spliceosome components recognize splicing signals and regulatory sequences of the pre-mRNAs. These splicing sequences make splicing susceptible to polymorphisms and mutations. Examples of associations between human rare diseases and defects in pre-messenger RNA splicing are accumulating. Although many alterations are caused by mutations in splicing sequence (i.e., cis acting mutations), recent studies described the disruptive impact of mutations within spliceosome components or splicing factors (i.e., trans acting mutations). Following growing of knowledge regarding splicing regulation, several approaches have been developed to compensate for the effect of deleterious mutations and to restore sufficient amounts of functional protein. © 2016 médecine/sciences – Inserm.

Histopathology and culturable bacteria associated with "big belly" and "skin nodule" syndromes in ornamental Siamese fighting fish, Betta splendens.

PubMed

Dong, H T; Senapin, S; Phiwsaiya, K; Techatanakitarnan, C; Dokladda, K; Ruenwongsa, P; Panijpan, B

2018-06-02

The Siamese fighting fish (Betta splendens) is one of the popular aquarium ornamental fish in the global trade. Large numbers of ornamental fish farmed in central Thailand suffered from two common syndromes; preliminarily named skin nodule syndrome (SNS) and big belly syndrome (BBS): they showed noticeable clinical signs of abnormal appearances resulting in depressed saleability. Since very few specifics are known about causative agents of these syndromes, this study aimed at investigating histopathological features and culturable bacteria associated with these fish infected in the process of farming. Histopathologically, SNS fish consistently exhibited necrosis and severe melanization in the muscles and multiple internal organs. Whereas BBS fish exhibited either typical granulomas or tissue damage associated with acid-fast stained bacteria and Gram negative bacteria, respectively. Six different Gram negative bacterial species were recovered from BBS fish while 23 bacterial species belonging to 14 genera were recovered from fish suffering from SNS. Most of the culturable bacteria are new to betta fish and some of them are known to be marine bacteria, suggesting possible entry route via a contaminated live feed, commercial Artemia shrimp. The true causative agents of these syndromes remain unclear. However, histopathological changes and existence of a wide range of bacteria associated with the naturally diseased fish suggest involvement of multiple bacterial infections. Copyright © 2018 Elsevier Ltd. All rights reserved.

Kinesin 1 regulates cilia length through an interaction with the Bardet-Biedl syndrome related protein CCDC28B.

PubMed

Novas, Rossina; Cardenas-Rodriguez, Magdalena; Lepanto, Paola; Fabregat, Matías; Rodao, Magela; Fariello, María Inés; Ramos, Mauricio; Davison, Camila; Casanova, Gabriela; Alfaya, Lucía; Lecumberry, Federico; González-Sapienza, Gualberto; Irigoín, Florencia; Badano, Jose L

2018-02-14

Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinal degeneration, obesity, polydactyly, renal disease and mental retardation. CCDC28B is a BBS-associated protein that we have previously shown plays a role in cilia length regulation whereby its depletion results in shortened cilia both in cells and Danio rerio (zebrafish). At least part of that role is achieved by its interaction with the mTORC2 component SIN1, but the mechanistic details of this interaction and/or additional functions that CCDC28B might play in the context of cilia remain poorly understood. Here we uncover a novel interaction between CCDC28B and the kinesin 1 molecular motor that is relevant to cilia. CCDC28B interacts with kinesin light chain 1 (KLC1) and the heavy chain KIF5B. Notably, depletion of these kinesin 1 components results in abnormally elongated cilia. Furthermore, through genetic interaction studies we demonstrate that kinesin 1 regulates ciliogenesis through CCDC28B. We show that kinesin 1 regulates the subcellular distribution of CCDC28B, unexpectedly, inhibiting its nuclear accumulation, and a ccdc28b mutant missing a nuclear localization motif fails to rescue the phenotype in zebrafish morphant embryos. Therefore, we uncover a previously unknown role of kinesin 1 in cilia length regulation that relies on the BBS related protein CCDC28B.

Effect of pulmonary rehabilitation on balance in persons with chronic obstructive pulmonary disease.

PubMed

Beauchamp, Marla K; O'Hoski, Sachi; Goldstein, Roger S; Brooks, Dina

2010-09-01

To describe within-subject effects of pulmonary rehabilitation (PR) on balance in persons with chronic obstructive pulmonary disease (COPD) and to determine whether any observed changes in balance were associated with change in exercise tolerance or health-related quality of life. Single-arm longitudinal study. Inpatient PR center. Subjects with COPD (N=29; mean +/- SD age, 69.8+/-10.3y; forced expiratory volume in 1 second, 46.3%+/-22.3% predicted; 59% men [n=17]). A standardized 6-week multidisciplinary PR program (exercise training, breathing exercises, education, and psychologic support). Balance was assessed using the Berg Balance Scale (BBS), Timed Up and Go (TUG) test, and the Activities-Specific Balance Confidence (ABC) scale. Exercise tolerance was determined from the 6-minute walk test (6MWT), and health-related quality of life from the Chronic Respiratory Questionnaire (CRQ). Subjects showed small improvements in BBS (2.8+/-2.8 points; P<.001) and TUG (-1.5+/-2.4s; P=.003) scores, but not in ABC scores (4.8+/-15.4 points; P>.05). There was a weak relationship between change in BBS and change in CRQ scores (r=.40; P=.045) and no relationship with change in 6MWT. PR contributed to minor improvements in balance and had no effect on balance confidence in subjects with COPD. Further work is warranted to determine the optimal intervention for improving balance in this population.

Tailored balance exercises on people with multiple sclerosis: A pilot randomized, controlled study.

PubMed

Brichetto, Giampaolo; Piccardo, Elisa; Pedullà, Ludovico; Battaglia, Mario Alberto; Tacchino, Andrea

2015-07-01

Altered integration of signals from visual (VIS), somatosensory (PROP) and vestibular system (VEST) lead to balance control impairments affecting the daily living activities of patients with multiple sclerosis (PwMS). As a consequence, tailored interventions could be crucial in improving efficacy of balance rehabilitation treatments. The objective of this paper is to assess the efficacy of tailored rehabilitation treatments for balance disorders based on visual, somatosensory and vestibular deficits versus traditional rehabilitation exercises. Thirty-two PwMS were assessed with the Berg Balance Scale (BBS), the composite score (CS) obtained by computerized dynamic posturography (CDP) test and the Modified Fatigue Impact Scale (MFIS). Based on CDP analysis, prevalent VIS, PROP or VEST deficits were identified and patients randomly allocated to a personalized (PRG) or traditional (TRG) rehabilitation group. BBS score showed a significant difference between pre- and post-treatment scores of 6.3 and 2.0 points respectively for PRG and TRG. CS showed a significant difference between pre- and post-treatment scores of 16.6 and 7.6 points respectively for PRG and TRG. No interaction effect was found for MFIS score. BBS and CS showed changes in the PRG group that met clinical relevant difference, underlining that tailored rehabilitation interventions based on patient-specific sensory system impairment could improve balance and postural control in PwMS. © The Author(s), 2015.

Cohort Differences in the Availability of Informal Caregivers: Are the Boomers at Risk?

PubMed Central

Ryan, Lindsay H.; Smith, Jacqui; Antonucci, Toni C.; Jackson, James S.

2012-01-01

Purpose of the Study: We compare the close family resources of Baby Boomers (BBs) to previous cohorts of older adults at population level and then examine individual-level cohort comparisons of age-related trajectories of informal care availability from midlife into old age. Design and Methods: Population data from the U.S. Census and from the Health and Retirement Study (HRS) are used to identify a cohort similar to the BBs on marital status and fertility rates. Using generalized linear mixed models and 10-year longitudinal data from Depression and WWII parents (DWP; n = 1,052) and the parents of BBs (PBB; n = 3,573) in the HRS, we examine cohort differences in the time-varying likelihoods of being married and of having an adult child living within 10 miles. Results: The DWP had similar informal care resources at entry to old age as is expected in the BB. Longitudinal analyses of the DWP and PBB cohorts in HRS reveal that the availability of family changes over time and that the DWP cohort was significantly less likely to have a spouse or a grown child living nearby. Implications: These findings, and future projections based on them, have significant implications for institutions and public policy concerned with the informal caregiving needs of the Boomer cohort as they age. PMID:22298747

Wii-Fit for Improving Gait and Balance in an Assisted Living Facility: A Pilot Study

PubMed Central

Padala, Kalpana P.; Padala, Prasad R.; Malloy, Timothy R.; Geske, Jenenne A.; Dubbert, Patricia M.; Dennis, Richard A.; Garner, Kimberly K.; Bopp, Melinda M.; Burke, William J.; Sullivan, Dennis H.

2012-01-01

Objectives. To determine the effects on balance and gait of a Wii-Fit program compared to a walking program in subjects with mild Alzheimer's dementia (AD). Methods. A prospective randomized (1 : 1) pilot study with two intervention arms was conducted in an assisted living facility with twenty-two mild AD subjects. In both groups the intervention occurred under supervision for 30 minutes daily, five times a week for eight weeks. Repeated measures ANOVA and paired t-tests were used to analyze changes. Results. Both groups showed improvement in Berg Balance Scale (BBS), Tinetti Test (TT) and Timed Up and Go (TUG) over 8 weeks. However, there was no statistically significant difference between the groups over time. Intragroup analysis in the Wii-Fit group showed significant improvement on BBS (P = 0.003), and TT (P = 0.013). The walking group showed a trend towards improvement on BBS (P = 0.06) and TUG (P = 0.07) and significant improvement in TT (P = 0.06). Conclusion. This pilot study demonstrates the safety and efficacy of Wii-Fit in an assisted living facility in subjects with mild AD. Use of Wii-Fit resulted in significant improvements in balance and gait comparable to those in the robust monitored walking program. These results need to be confirmed in a larger, methodologically sound study. PMID:22745909

Supervised Versus Home Exercise Training Programs on Functional Balance in Older Subjects.

PubMed

Youssef, Enas Fawzy; Shanb, Alsayed Abd Elhameed

2016-11-01

Aging is associated with a progressive decline in physical capabilities and a disturbance of both postural control and daily living activities. The aim of this study was to evaluate the effects of supervised versus home exercise programs on muscle strength, balance and functional activities in older participants. Forty older participants were equally assigned to a supervised exercise program (group-I) or a home exercise program (group-II). Each participant performed the exercise program for 35-45 minutes, two times per week for four months. Balance indices and isometric muscle strength were measured with the Biodex Balance System and Hand-Held Dynamometer. Functional activities were evaluated by the Berg Balance Scale (BBS) and the timed get-up-and-go test (TUG). The mean values of the Biodex balance indices and the BBS improved significantly after both the supervised and home exercise programs ( P < 0.05). However, the mean values of the TUG and muscle strength at the ankle, knee and hip improved significantly only after the supervised program. A comparison between the supervised and home exercise programs revealed there were only significant differences in the BBS, TUG and muscle strength. Both the supervised and home exercise training programs significantly increased balance performance. The supervised program was superior to the home program in restoring functional activities and isometric muscle strength in older participants.

Effects of individual and group exercise programs on pain, balance, mobility and perceived benefits in rheumatoid arthritis with pain and foot deformities.

PubMed

do Carmo, Carolina Mendes; Almeida da Rocha, Bruna; Tanaka, Clarice

2017-11-01

[Purpose] To verify the effects of individual and group exercise programs on pain, balance, mobility and perceived benefits of rheumatoid arthritis patients (RA) with pain and foot deformities. [Subjects and Methods] Thirty patients with RA pain and foot deformity were allocated into two groups: G1: individual exercise program and G2: group exercise program. The variables analyzed were Numerical Rating Scale (NRS) for pain, Berg Balance Scale (BBS) for balance, Timed Up & Go Test (TUG) and Functional Reach (FR) for mobility, and Foot Health Status Questionnaire (FHSQ-Br) for perceived benefits. Both exercise programs consisted of functional rehabilitation exercises and self-care guidance aimed at reducing pain and improving balance and mobility. Intragroup comparisons of variables between A1 (pre-intervention) and A2 (post-intervention) were performed. [Results] Patients in both groups were similar in A1 (pre-intervention) in all the variables analyzed. Comparison between A1 and A2 for each variable showed improvement for G1 in the NRS, BBS, FR, TUG and in four out of ten domains of FHSQ-Br. G2 showed improvement in the NRS, BBS and eight out of ten domains of FHSQ-Br. [Conclusion] Both individual and group programs revealed benefits for patients with RA, however, group exercise programs showed better perception of benefits.

Efficacy of Aquatic Treadmill Training on Gait Symmetry and Balance in Subacute Stroke Patients

PubMed Central

2017-01-01

Objective To determine the efficacy of aquatic treadmill training (ATT) as a new modality for stroke rehabilitation, by assessing changes in gait symmetry, balance function, and subjective balance confidence for the paretic and non-paretic leg in stroke patients. Methods Twenty-one subacute stroke patients participated in 15 intervention sessions of aquatic treadmill training. The Comfortable 10-Meter Walk Test (CWT), spatiotemporal gait parameters, Berg Balance Scale (BBS), and Activities-specific Balance Confidence scale (ABC) were assessed pre- and post-interventions. Results From pre- to post-intervention, statistically significant improvements were observed in the CWT (0.471±0.21 to 0.558±0.23, p<0.001), BBS (39.66±8.63 to 43.80±5.21, p<0.001), and ABC (38.39±13.46 to 46.93±12.32, p<0.001). The step-length symmetry (1.017±0.25 to 0.990±0.19, p=0.720) and overall temporal symmetry (1.404±0.36 to 1.314±0.34, p=0.218) showed improvement without statistical significance. Conclusion ATT improves the functional aspects of gait, including CWT, BBS and ABC, and spatiotemporal gait symmetry, though without statistical significance. Further studies are required to examine and compare the potential benefits of ATT as a new modality for stroke therapy, with other modalities. PMID:28758074

Efficacy of Aquatic Treadmill Training on Gait Symmetry and Balance in Subacute Stroke Patients.

PubMed

Lee, Mi Eun; Jo, Geun Yeol; Do, Hwan Kwon; Choi, Hee Eun; Kim, Woo Jin

2017-06-01

To determine the efficacy of aquatic treadmill training (ATT) as a new modality for stroke rehabilitation, by assessing changes in gait symmetry, balance function, and subjective balance confidence for the paretic and non-paretic leg in stroke patients. Twenty-one subacute stroke patients participated in 15 intervention sessions of aquatic treadmill training. The Comfortable 10-Meter Walk Test (CWT), spatiotemporal gait parameters, Berg Balance Scale (BBS), and Activities-specific Balance Confidence scale (ABC) were assessed pre- and post-interventions. From pre- to post-intervention, statistically significant improvements were observed in the CWT (0.471±0.21 to 0.558±0.23, p<0.001), BBS (39.66±8.63 to 43.80±5.21, p<0.001), and ABC (38.39±13.46 to 46.93±12.32, p<0.001). The step-length symmetry (1.017±0.25 to 0.990±0.19, p=0.720) and overall temporal symmetry (1.404±0.36 to 1.314±0.34, p=0.218) showed improvement without statistical significance. ATT improves the functional aspects of gait, including CWT, BBS and ABC, and spatiotemporal gait symmetry, though without statistical significance. Further studies are required to examine and compare the potential benefits of ATT as a new modality for stroke therapy, with other modalities.

Free energy landscape remodeling of the cardiac pacemaker channel explains the molecular basis of familial sinus bradycardia

PubMed Central

Boulton, Stephen; Akimoto, Madoka; Akbarizadeh, Sam; Melacini, Giuseppe

2017-01-01

The hyperpolarization-activated and cyclic nucleotide-modulated ion channel (HCN) drives the pacemaker activity in the heart, and its malfunction can result in heart disorders. One such disorder, familial sinus bradycardia, is caused by the S672R mutation in HCN, whose electrophysiological phenotypes include a negative shift in the channel activation voltage and an accelerated HCN deactivation. The outcomes of these changes are abnormally low resting heart rates. However, the molecular mechanism underlying these electrophysiological changes is currently not fully understood. Crystallographic investigations indicate that the S672R mutation causes limited changes in the structure of the HCN intracellular gating tetramer, but its effects on protein dynamics are unknown. Here, we utilize comparative S672R versus WT NMR analyses to show that the S672R mutation results in extensive perturbations of the dynamics in both apo- and holo-forms of the HCN4 isoform, reflecting how S672R remodels the free energy landscape for the modulation of HCN4 by cAMP, i.e. the primary cyclic nucleotide modulator of HCN channels. We show that the S672R mutation results in a constitutive shift of the dynamic auto-inhibitory equilibrium toward inactive states of HCN4 and broadens the free-energy well of the apo-form, enhancing the millisecond to microsecond dynamics of the holo-form at sites critical for gating cAMP binding. These S672R-induced variations in dynamics provide a molecular basis for the electrophysiological phenotypes of this mutation and demonstrate that the pathogenic effects of the S672R mutation can be rationalized primarily in terms of modulations of protein dynamics. PMID:28174302

Observation of new charmless decays of bottom hadrons.

PubMed

Aaltonen, T; Adelman, J; Akimoto, T; Alvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Apollinari, G; Apresyan, A; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Azzurri, P; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Bartsch, V; Bauer, G; Beauchemin, P-H; Bedeschi, F; Beecher, D; Behari, S; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Beringer, J; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Bridgeman, A; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burke, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Calancha, C; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carls, B; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavaliere, V; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Chwalek, T; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Compostella, G; Convery, M E; Conway, J; Cordelli, M; Cortiana, G; Cox, C A; Cox, D J; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Dagenhart, D; Datta, M; Davies, T; de Barbaro, P; De Cecco, S; Deisher, A; De Lorenzo, G; Dell'Orso, M; Deluca, C; Demortier, L; Deng, J; Deninno, M; Derwent, P F; di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Elagin, A; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Ferrazza, C; Field, R; Flanagan, G; Forrest, R; Frank, M J; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garberson, F; Garcia, J E; Garfinkel, A F; Genser, K; Gerberich, H; Gerdes, D; Gessler, A; Giagu, S; Giakoumopoulou, V; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C M; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Han, B-Y; Han, J Y; Happacher, F; Hara, K; Hare, D; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hays, C; Heck, M; Heijboer, A; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hewamanage, S; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Hussein, M; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; James, E; Jang, D; Jayatilaka, B; Jeon, E J; Jha, M K; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Kar, D; Karchin, P E; Kato, Y; Kephart, R; Keung, J; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, H W; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Knuteson, B; Ko, B R; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kreps, M; Kroll, J; Krop, D; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhr, T; Kulkarni, N P; Kurata, M; Kwang, S; Laasanen, A T; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; LeCompte, T; Lee, E; Lee, H S; Lee, S W; Leone, S; Lewis, J D; Lin, C-S; Linacre, J; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, C; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Lovas, L; Lucchesi, D; Luci, C; Lueck, J; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Macqueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis-Katsikakis, A; Margaroli, F; Marino, C; Marino, C P; Martin, A; Martin, V; Martínez, M; Martínez-Ballarín, R; Maruyama, T; Mastrandrea, P; Masubuchi, T; Mathis, M; Mattson, M E; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzione, A; Merkel, P; Mesropian, C; Miao, T; Miladinovic, N; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyake, H; Moggi, N; Moon, C S; Moore, R; Morello, M J; Morlock, J; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Nagano, A; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Necula, V; Nett, J; Neu, C; Neubauer, M S; Neubauer, S; Nielsen, J; Nodulman, L; Norman, M; Norniella, O; Nurse, E; Oakes, L; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Orava, R; Osterberg, K; Griso, S Pagan; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Peiffer, T; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Pianori, E; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Pueschel, E; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Renton, P; Renz, M; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rodriguez, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Safonov, A; Sakumoto, W K; Saltó, O; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savoy-Navarro, A; Schlabach, P; Schmidt, A; Schmidt, E E; Schmidt, M A; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sforza, F; Sfyrla, A; Shalhout, S Z; Shears, T; Shepard, P F; Shimojima, M; Shiraishi, S; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spreitzer, T; Squillacioti, P; Stanitzki, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Strycker, G L; Stuart, D; Suh, J S; Sukhanov, A; Suslov, I; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Tesarek, R; Thom, J; Thompson, A S; Thompson, G A; Thomson, E; Tipton, P; Ttito-Guzmán, P; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Totaro, P; Tourneur, S; Trovato, M; Tsai, S-Y; Tu, Y; Turini, N; Ukegawa, F; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Vellidis, C; Vidal, M; Vidal, R; Vila, I; Vilar, R; Vine, T; Vogel, M; Volobouev, I; Volpi, G; Wagner, P; Wagner, R G; Wagner, R L; Wagner, W; Wagner-Kuhr, J; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Weinelt, J; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Wilbur, S; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Würthwein, F; Xie, S; Yagil, A; Yamamoto, K; Yamaoka, J; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zhang, X; Zheng, Y; Zucchelli, S

2009-07-17

We search for new charmless decays of neutral b hadrons to pairs of charged hadrons, using 1 fb(-1) of data collected by the CDF II detector at the Fermilab Tevatron. We report the first observation of the Bs0-->K-pi+ decay and measure B(Bs0-->K-pi+)=(5.0+/-0.7(stat)+/-0.8(syst))x10(-6). We also report the first observation of charmless b-baryon decays, and measure B(Lambdab0-->ppi-)=(3.5+/-0.6(stat)+/-0.9(syst))x10(-6) and B(Lambdab0-->pK-)=(5.6+/-0.8(stat)+/-1.5(syst))x10(-6). No evidence is found for other modes, and we set the limit B(Bs0-->pi+pi;-)<1.2x10(-6) at 90% C.L.

Detection of CFTR function and modulation in primary human nasal cell spheroids.

PubMed

Brewington, John J; Filbrandt, Erin T; LaRosa, F J; Ostmann, Alicia J; Strecker, Lauren M; Szczesniak, Rhonda D; Clancy, John P

2018-01-01

Expansion of CFTR modulators to patients with rare/undescribed mutations will be facilitated by patient-derived models quantifying CFTR function and restoration. We aimed to generate a personalized model system of CFTR function and modulation using non-surgically obtained nasal epithelial cells (NECs). NECs obtained by curettage from healthy volunteers and CF patients were expanded and grown in 3-dimensional culture as spheroids, characterized, and stimulated with cAMP-inducing agents to activate CFTR. Spheroid swelling was quantified as a proxy for CFTR function. NEC spheroids recapitulated characteristics of pseudostratified respiratory epithelia. When stimulated with forskolin/IBMX, spheroids swelled in the presence of functional CFTR, and shrank in its absence. Spheroid swelling quantified mutant CFTR restoration in F508del homozygous cells using clinically available CFTR modulators. NEC spheroids hold promise for understanding rare CFTR mutations and personalized modulator testing to drive evaluation for CF patients with common, rare or undescribed mutations. Portions of this data have previously been presented in abstract form at the 2016 meetings of the American Thoracic Society and the 2016 North American Cystic Fibrosis Conference. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Assessment of balance and risk for falls in a sample of community-dwelling adults aged 65 and older

PubMed Central

Hawk, Cheryl; Hyland, John K; Rupert, Ronald; Colonvega, Makasha; Hall, Stephanie

2006-01-01

Background Falls are a major health concern for older adults and their impact is a significant public health problem. The chief modifiable risk factors for falls in community-dwellers are psychotropic drugs, polypharmacy, environmental hazards, poor vision, lower extremity impairments, and balance impairments. This study focused on balance impairments. Its purpose was to assess the feasibility of recruiting older adults with possible balance problems for research conducted at a chiropractic research center, and to explore the utility of several widely used balance instruments for future studies of the effect of chiropractic care on balance in older adults. Methods This descriptive study was conducted from September through December 2004. Participants were recruited through a variety of outreach methods, and all were provided with an educational intervention. Data were collected at each of two visits through questionnaires, interviews, and physical examinations. Balance was assessed on both visits using the Activities-specific Balance Confidence Scale (ABCS), the Berg Balance Scale (BBS), and the One Leg Standing Test (OLST). Results A total of 101 participants enrolled in the study. Advertising in the local senior newspaper was the most effective method of recruitment (46%). The majority of our participants were white (86%) females (67%). About one third (32%) of participants had a baseline BBS score below 46, the cut-off point for predicting risk of falling. A mean improvement in BBS scores of 1.7 points was observed on the second visit. For the subgroup with baseline scores below 46, the mean change was 4.5 points, but the group mean remained below 46 (42.5). Conclusion Recruitment of community-dwelling seniors for fall-related research conducted at a chiropractic research center appears feasible, and the most successful recruitment strategies for this center appeared to be a combination of targeted newspaper ads and personal contact through senior centers. The BBS and OLST appear to be promising screening and assessment instruments, which might have utility in future investigations of the possible effects of chiropractic care on balance. PMID:16441893

Assessment of balance and risk for falls in a sample of community-dwelling adults aged 65 and older.

PubMed

Hawk, Cheryl; Hyland, John K; Rupert, Ronald; Colonvega, Makasha; Hall, Stephanie

2006-01-27

Falls are a major health concern for older adults and their impact is a significant public health problem. The chief modifiable risk factors for falls in community-dwellers are psychotropic drugs, polypharmacy, environmental hazards, poor vision, lower extremity impairments, and balance impairments. This study focused on balance impairments. Its purpose was to assess the feasibility of recruiting older adults with possible balance problems for research conducted at a chiropractic research center, and to explore the utility of several widely used balance instruments for future studies of the effect of chiropractic care on balance in older adults. This descriptive study was conducted from September through December 2004. Participants were recruited through a variety of outreach methods, and all were provided with an educational intervention. Data were collected at each of two visits through questionnaires, interviews, and physical examinations. Balance was assessed on both visits using the Activities-specific Balance Confidence Scale (ABCS), the Berg Balance Scale (BBS), and the One Leg Standing Test (OLST). A total of 101 participants enrolled in the study. Advertising in the local senior newspaper was the most effective method of recruitment (46%). The majority of our participants were white (86%) females (67%). About one third (32%) of participants had a baseline BBS score below 46, the cut-off point for predicting risk of falling. A mean improvement in BBS scores of 1.7 points was observed on the second visit. For the subgroup with baseline scores below 46, the mean change was 4.5 points, but the group mean remained below 46 (42.5). Recruitment of community-dwelling seniors for fall-related research conducted at a chiropractic research center appears feasible, and the most successful recruitment strategies for this center appeared to be a combination of targeted newspaper ads and personal contact through senior centers. The BBS and OLST appear to be promising screening and assessment instruments, which might have utility in future investigations of the possible effects of chiropractic care on balance.

The use of virtual reality for balance among individuals with chronic stroke: a systematic review and meta-analysis.

PubMed

Iruthayarajah, Jerome; McIntyre, Amanda; Cotoi, Andreea; Macaluso, Steven; Teasell, Robert

2017-01-01

Virtual reality (VR) is becoming a popular alternative to traditional upper and lower limb rehabilitation following a stroke. To conduct a systematic review and meta-analysis on the effectiveness of VR interventions for improving balance in a chronic stroke (≥6 months) population. A literature search of Pubmed, Scopus, CINAHL, Embase, Psycinfo, and Web of Science databases was conducted. English randomized controlled trials published up to September 2015 assessing balance with VR in chronic stroke participants. Mean and standard deviations from outcome measures were extracted. Pooled standard mean differences ± standard error were calculated for the Berg Balance Scale (BBS) and the Timed Up and Go test (TUG). In total, 20 studies were selected which assessed the Nintendo ® Wii Fit balance board (n = 7), treadmill training and VR (n = 7), and postural training using VR (n = 6). Significant improvements were found for VR interventions evaluating the BBS (n = 12; MD = 2.94 ± 0.57; p < 0.001) and TUG (n = 13; MD = 2.49 ± 0.57; p < 0.001). Sub-analyses revealed postural VR interventions had a significant effect on BBS (n = 5) and TUG (n = 3) scores (BBS: MD = 3.82 ± 0.79; p < 0.001 and TUG: MD = 3.74 ± 0.97; p < 0.001). VR and treadmill training (n = 5) had a significant effect on TUG scores (MD = 2.15 ± 0.89, p = 0.016). Overall, VR interventions compared to conventional rehabilitation had significant improvements. The meta-analyses also suggest that the Nintendo ® Wii Fit balance board may not be effective, although further confirmatory studies are necessary. Results should be interpreted with caution due to differences in therapy intensities and effect sizes within the included studies.

Reliability, Validity, and Ability to Identify Fall Status of the Balance Evaluation Systems Test, Mini-Balance Evaluation Systems Test, and Brief-Balance Evaluation Systems Test in Older People Living in the Community.

PubMed

Marques, Alda; Almeida, Sara; Carvalho, Joana; Cruz, Joana; Oliveira, Ana; Jácome, Cristina

2016-12-01

To assess the reliability, validity, and ability to identify fall status of the Balance Evaluation Systems Test (BESTest), Mini-BESTest, and Brief-BESTest, compared with the Berg Balance Scale (BBS), in older people living in the community. Cross-sectional. Community centers. Older adults (N=122; mean age ± SD, 76±9y). Not applicable. Participants reported on falls history in the preceding year and completed the Activities-Specific Balance Confidence (ABC) Scale. The BBS, BESTest, and the Five Times Sit-To-Stand Test were administered. Interrater (2 physiotherapists) and test-retest relative (48-72h) and absolute reliabilities were explored with the intraclass correlation coefficient (ICC) equation (2,1) and the Bland and Altman method. Minimal detectable changes at the 95% confidence level (MDC 95 ) were established. Validity was assessed by correlating the balance tests with each other and with the ABC Scale (Spearman correlation coefficients-ρ). Receiver operating characteristics assessed the ability of each balance test to differentiate between people with and without a history of falls. All balance tests presented good to excellent interrater (ICC=.71-.93) and test-retest (ICC=.50-.82) relative reliability, with no evidence of bias. MDC 95 values were 4.6, 9, 3.8, and 4.1 points for the BBS, BESTest, Mini-BESTest, and Brief-BESTest, respectively. All tests were significantly correlated with each other (ρ=.83-.96) and with the ABC Scale (ρ=.46-.61). Acceptable ability to identify fall status (areas under the curve, .71-.78) was found for all tests. Cutoff points were 48.5, 82, 19.5, and 12.5 points for the BBS, BESTest, Mini-BESTest, and Brief-BESTest, respectively. All balance tests are reliable, valid, and able to identify fall status in older people living in the community. Therefore, the choice of which test to use will depend on the level of balance impairment, purpose, and time availability. Copyright © 2016. Published by Elsevier Inc.

Validity, Reliability, and Ability to Identify Fall Status of the Berg Balance Scale, BESTest, Mini-BESTest, and Brief-BESTest in Patients With COPD.

PubMed

Jácome, Cristina; Cruz, Joana; Oliveira, Ana; Marques, Alda

2016-11-01

The Berg Balance Scale (BBS), Balance Evaluation Systems Test (BESTest), Mini-BESTest, and Brief-BESTest are useful in the assessment of balance. Their psychometric properties, however, have not been tested in patients with chronic obstructive pulmonary disease (COPD). This study aimed to compare the validity, reliability, and ability to identify fall status of the BBS, BESTest, Mini-BESTest, and the Brief-BESTest in patients with COPD. A cross-sectional study was conducted. Forty-six patients (24 men, 22 women; mean age=75.9 years, SD=7.1) were included. Participants were asked to report their falls during the previous 12 months and to fill in the Activity-specific Balance Confidence (ABC) Scale. The BBS and the BESTest were administered. Mini-BESTest and Brief-BESTest scores were computed based on the participants' BESTest performance. Validity was assessed by correlating balance tests with each other and with the ABC Scale. Interrater reliability (2 raters), intrarater reliability (48-72 hours), and minimal detectable changes (MDCs) were established. Receiver operating characteristics assessed the ability of each balance test to differentiate between participants with and without a history of falls. Balance test scores were significantly correlated with each other (Spearman correlation rho=.73-.90) and with the ABC Scale (rho=.53-.75). Balance tests presented high interrater reliability (intraclass correlation coefficient [ICC]=.85-.97) and intrarater reliability (ICC=.52-.88) and acceptable MDCs (MDC=3.3-6.3 points). Although all balance tests were able to identify fall status (area under the curve=0.74-0.84), the BBS (sensitivity=73%, specificity=77%) and the Brief-BESTest (sensitivity=81%, specificity=73%) had the higher ability to identify fall status. Findings are generalizable mainly to older patients with moderate COPD. The 4 balance tests are valid, reliable, and valuable in identifying fall status in patients with COPD. The Brief-BESTest presented slightly higher interrater reliability and ability to differentiate participants' fall status. © 2016 American Physical Therapy Association.

SU-E-T-300: Spatial Variations of Multiple Off-Axial Targets for a Single Isocenter SRS Treatment Plan in ExacTrac 6D Robotic Couch System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, S; Tseng, T

2014-06-01

Purpose: To evaluate the spatial variations of multiple off-axial targets for a single isocenter stereotactic radiosurgery (SRS) treatment plan in ExacTrac 6D robotic couch system (BrainLab AG). Methods: Five metallic ball bearing (BB) markers were placed sparsely in 3D off-axial locations (non-coplanar) inside a skull phantom as the representatives of multiple targets mimicking multiple brain metastases. The locations of the BB markers were carefully chosen to minimize overlapping of each other in a port imaging detector plane. The skull phantom was immobilized by a frameless mask and CT scanned with a BrainLab Head and Neck Localizer using a GE Optimamore » MDCT scanner. The CT images were exported to iPlan software (BrainLab AG) and a multiple target PTV was drawn by combining all the contours of the BBs. The margin of the MLC opening was selected as 3 mm expansion outward. Two coplanar arc beams were placed to generate a single isocenter SRS plan to treat the PTV. The arc beams were delivered using Novalis Tx system with portal imaging acquisition mode per 10% temporal resolution. The locations of the BBs were visualized and analyzed with respect to the MLC aperture in the treatment plan similar to the Winston-Lutz test. Results: All the BBs were clearly identified inside the MLC openings. The positional errors for the BBs were overall less than 1 mm along the rotational path of the two arcs. Conclusion: This study verified that the spatial deviations of multiple off-axial targets for a single isocenter SRS treatment plan is within sub-millimeter range in ExacTrac 6D robotic couch system. Accompanied with the Winston-Lutz test, this test will quality-assure the spatial accuracies of the isocenter as well as the positions of multiple off-axial targets for the SRS treatment using a single isocenter multiple target treatment plan.« less

From biowaste to magnet-responsive materials for water remediation from polycyclic aromatic hydrocarbons.

PubMed

Nisticò, Roberto; Cesano, Federico; Franzoso, Flavia; Magnacca, Giuliana; Scarano, Domenica; Funes, Israel G; Carlos, Luciano; Parolo, Maria E

2018-07-01

Composted urban biowaste-derived substances (BBS-GC) are used as carbon sources for the preparation of carbon-coated magnet-sensitive nanoparticles obtained via co-precipitation method and the subsequent thermal treatment at 550 °C under nitrogen atmosphere. A multitechnique approach has been applied to investigate the morphology, magnetic properties, phase composition, thermal stability of the obtained magnet-sensitive materials. In particular, pyrolysis-induced modifications affecting the BBS-GC/carbon shell were highlighted. The adsorption capacity of such bio-derivative magnetic materials for the removal of hydrophobic contaminants such as polycyclic aromatic hydrocarbons was evaluated in order to verify their potential application in wastewater remediation process. The promising results suggest their use as a new generation of magnet-responsive easily-recoverable adsorbents for water purification treatments. Copyright © 2018 Elsevier Ltd. All rights reserved.

Efficient statistical mapping of avian count data

USGS Publications Warehouse

Royle, J. Andrew; Wikle, C.K.

2005-01-01

We develop a spatial modeling framework for count data that is efficient to implement in high-dimensional prediction problems. We consider spectral parameterizations for the spatially varying mean of a Poisson model. The spectral parameterization of the spatial process is very computationally efficient, enabling effective estimation and prediction in large problems using Markov chain Monte Carlo techniques. We apply this model to creating avian relative abundance maps from North American Breeding Bird Survey (BBS) data. Variation in the ability of observers to count birds is modeled as spatially independent noise, resulting in over-dispersion relative to the Poisson assumption. This approach represents an improvement over existing approaches used for spatial modeling of BBS data which are either inefficient for continental scale modeling and prediction or fail to accommodate important distributional features of count data thus leading to inaccurate accounting of prediction uncertainty.

Case report: Physical therapy management of axial dystonia.

PubMed

Voos, Mariana Callil; Oliveira, Tatiana de Paula; Piemonte, Maria Elisa Pimentel; Barbosa, Egberto Reis

2014-01-01

Few studies have described physical therapy approaches to provide functional independence and reduce pain in individuals with dystonia. This report describes the physical therapy treatment of a 46-year-old woman diagnosed with idiopathic segmental axial dystonia. For two years, the patient was treated with kinesiotherapy (active and resisted movements and stretching of neck and trunk muscles), abdominal taping (kinesiotaping techniques), functional training, and sensory tricks. She was assessed with parts I, II and III of Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-I, TWSTRS-II and TWSTRS-III), Berg Balance Scale (BBS), Six-Minute Walk Test (6-MWT), and the motor domain of Functional Independence Measure (FIM-motor) before and after the two-year treatment and after the one year follow-up. Postural control and symmetry improved (TWSTRS-I: from 30 to 18), functional independence increased (TWSTRS-II: from 27 to 15; BBS: from 36 to 46; 6-MWT: from 0 to 480 meters (m); FIM-motor: from 59 to 81), and the pain diminished (TWSTRS-III: from 12 to 5). The functional improvement was retained after one year (TWSTRS-I: 14/35; TWRTRS-II: 12/30; TWRTRS-III: 5/20; BBS: 48/56; 6-MWT: 450 m; FIM-motor: 81/91). This program showed efficacy on providing a better control of the dystonic muscles and thus the doses of botulinum toxin needed to treat them could be reduced. Outcomes support the therapeutic strategies used to deal with this type of dystonia.

Therapeutic Effects of Mechanical Horseback Riding on Gait and Balance Ability in Stroke Patients

PubMed Central

Han, Jun Young; Kim, Shin Kyoung; Chung, Jin Sang; Lee, Hyun-Cheol; Lim, Jae Kuk; Lee, Jiwon; Park, Kawn Yong

2012-01-01

Objective To investigate the therapeutic effects of mechanical horseback riding for gait and balance parameters in post-stroke patients. Method This study was a non randomized prospective positive-controlled trial over a 12 week period. From May 2011 to October 2011, 37 stroke patients were recruited from our outpatient clinic and divided into two groups. The control group received the conventional physiotherapy while the intervention group received the conventional physiotherapy along with mechanical horseback riding therapy for 12 weeks. Outcome measurements of gait included the Functional Ambulation Category (FAC) and gait part of the Performance Oriented Mobility Assessment (G-POMA) while those of balance included the Berg Balance Scale (BBS) and the balance part of the Performance Oriented Mobility Assessment (B-POMA). These measurements were taken before and after treatment. Results There were no significant differences in the baseline characteristics and initial values between the two groups. When comparing baseline and 12 weeks post treatment in each group, the intervention group showed significant improvement on BBS (39.9±5.7 → 45.7±4.8, p=0.001) and B-POMA (10.4±2.6 → 12.6±2.1, p=0.001), but significant improvement on gait parameters. When comparing the groups, the dynamic balance category of BBS in post treatment showed significant difference (p=0.02). Conclusion This study suggests that mechanical horseback riding therapy may be an effective treatment tool for enhancing balance in adults with stroke. PMID:23342307

Feasibility of Wii Fit training to improve clinical measures of balance in older adults.

PubMed

Bieryla, Kathleen A; Dold, Neil M

2013-01-01

Numerous interventions have been proposed to improve balance in older adults with varying degrees of success. A novel approach may be to use an off-the-shelf video game system utilizing real-time force feedback to train older adults. The purpose of this study is to investigate the feasibility of using Nintendo's Wii Fit for training to improve clinical measures of balance in older adults and to retain the improvements after a period of time. Twelve healthy older adults (aged >70 years) were randomly divided into two groups. The experimental group completed training using Nintendo's Wii Fit game three times a week for 3 weeks while the control group continued with normal activities. Four clinical measures of balance were assessed before training, 1 week after training, and 1 month after training: Berg Balance Scale (BBS), Fullerton Advanced Balance (FAB) scale, Functional Reach (FR), and Timed Up and Go (TUG). Friedman two-way analysis of variance by ranks was conducted on the control and experimental group to determine if training using the Wii Balance Board with Wii Fit had an influence on clinical measures of balance. Nine older adults completed the study (experimental group n = 4, control group n = 5). The experimental group significantly increased their BBS after training while the control group did not. There was no significant change for either group with FAB, FR, and TUG. Balance training with Nintendo's Wii Fit may be a novel way for older adults to improve balance as measured by the BBS.

Effect of the addition of B{sub 2}O{sub 3} and BaO-B{sub 2}O{sub 3}-SiO{sub 2} glasses on the microstructure and dielectric properties of giant dielectric constant material CaCu{sub 3}Ti{sub 4}O{sub 12}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shri Prakash, B.; Varma, K.B.R.

2007-06-15

The effect of the addition of glassy phases on the microstructure and dielectric properties of CaCu{sub 3}Ti{sub 4}O{sub 12} (CCTO) ceramics was investigated. Both single-component (B{sub 2}O{sub 3}) and multi-component (30 wt% BaO-60 wt% B{sub 2}O{sub 3}-10 wt% SiO{sub 2} (BBS)) glass systems were chosen to study their effect on the density, microstructure and dielectric properties of CCTO. Addition of an optimum amount of B{sub 2}O{sub 3} glass facilitated grain growth and an increase in dielectric constant. However, further increase in the B{sub 2}O{sub 3} content resulted in its segregation at the grain boundaries associated with a reduction in themore » grain size. In contrast, BBS glass addition resulted in well-faceted grains and increase in the dielectric constant and decrease in the dielectric loss. An internal barrier layer capacitance (IBLC) model was invoked to correlate the dielectric constant with the grain size in these samples. - Graphical abstract: Scanning electron micrograph of 30 wt% BaO-60 wt% B{sub 2}O{sub 3}-10 wt% SiO{sub 2} (BBS) glass-added CaCu{sub 3}Ti{sub 4}O{sub 12} ceramic on sintering.« less

Population trajectory of burrowing owls (Athene cunicularia) in eastern Washington

USGS Publications Warehouse

Conway, C.J.; Pardieck, K.L.

2006-01-01

Anecdotal evidence suggests that burrowing owls have declined in Washington. The Washington Department of Fish and Wildlife is currently conducting a status review for burrowing owls which will help determine whether they should be listed as threatened or endangered in the state. To provide insights into the current status of burrowing owls (Athene cunicularia), we analyzed data from the North American Breeding Bird Survey using two analytical approaches to determine their current population trajectory in eastern Washington. We used a one-sample t-test to examine whether trend estimates across all BBS routes in Washington differed from zero. We also used a mixed model analysis to estimate the rate of decline in number of burrowing owls detected between 1968 and 2005. The slope in number of burrowing owls detected was negative for 12 of the 16 BBS routes in Washington that have detected burrowing owls. Numbers of breeding burrowing owls detected in eastern Washington declined at a rate of 1.5% annually. We suggest that all BBS routes that have detected burrowing owls in past years in eastern Washington be surveyed annually and additional surveys conducted to track population trends of burrowing owls at finer spatial scales in eastern Washington. In the meantime, land management and regulatory agencies should ensure that publicly managed areas with breeding burrowing owls are not degraded and should implement education and outreach programs to promote protection of privately owned areas with breeding owls.

Effects of coordination and manipulation therapy for patients with Parkinson disease.

PubMed

Zhao, Mingming; Hu, Caiyou; Wu, Zhixin; Chen, Yu; Li, Zhengming; Zhang, Mingsheng

2017-09-01

To determine the effects of a new exercise training regimen, i.e. coordination and manipulation therapy (CMT), on motor, balance, and cardiac functions in patients with Parkinson disease (PD). We divided 36 PD patients into the CMT (n = 22) and control (n = 14) groups. The patients in the CMT group performed dry-land swimming (imitation of the breaststroke) and paraspinal muscle stretching for 30 min/workday for 1 year. The control subjects did not exercise regularly. The same medication regimen was maintained in both groups during the study. Clinical characteristics, Unified Parkinson's Disease Rating Scale (UPDRS) scores, Berg balance scale (BBS) scores, mechanical balance measurements, timed up and go (TUG) test, and left ventricular ejection fraction (LVEF) were compared at 0 (baseline), 6, and 12 months. Biochemical test results were compared at 0 and 12 months. The primary outcome was motor ability. The secondary outcome was cardiac function. In the CMT group, UPDRS scores significantly improved, TUG test time and step number significantly decreased, BBS scores significantly increased, and most mechanical balance measurements significantly improved after 1 year of regular exercise therapy (all p < 0.05). In the control group, UPDRS scores significantly deteriorated, TUG test time and step number significantly increased, BBS scores significantly decreased, and most mechanical balance measurements significantly worsened after 1 year (all P < 0.05). LVEF improved in the CMT group only (P = 0.01). This preliminary study suggests that CMT effectively improved mobility disorder, balance, and cardiac function in PD patients over a 1-year period.

Mirror Therapy with Neuromuscular Electrical Stimulation for improving motor function of stroke survivors: A pilot randomized clinical study.

PubMed

Lee, DongGeon; Lee, GyuChang; Jeong, JiSim

2016-07-27

This study was to investigate the effects of Mirror Therapy (MT) combined with Neuromuscular Electrical Stimulation (NMES) on muscle strength and tone, motor function, balance, and gait ability in stroke survivors with hemiplegia. This study was a randomized controlled trial. Twenty-seven hemiplegic stroke survivors from a rehabilitation center participated in the study. The participants were randomly assigned to either an experimental or a control group. The experimental group (n = 14) underwent MT combined with NMES and conventional physical therapy, and the control group (n = 13) underwent conventional physical therapy alone. Muscle strength and tone, balance, and gait ability were examined at baseline and after 4 weeks of intervention. A hand-held dynamometer was used to assess muscle strength, the Modified Ashworth Scale (MAS) was used to assess muscle tone, the Berg Balance Scale (BBS) and Timed Up and Go test (TUG) were used to ascertain balance, and the 6-m Walk Test (6mWT) was used to examine gait ability. After the intervention, compared to baseline values, there were significant improvements in muscle strength and MAS, BBS, TUG, and 6mWT values in the experimental group (P< 0.05). In addition, at post-intervention, there were significant differences between the two groups in muscle strength and BBS (P< 0.05). MT combined with NMES may effectively improve muscle strength and balance in hemiplegic stroke survivors. However, further studies are necessary to demonstrate brain reorganization after MT combined with NMES.

Rehabilitation of balance disturbances due to chemotherapy-induced peripheral neuropathy: a pilot study.

PubMed

Cammisuli, Sharon; Cavazzi, Enrico; Baldissarro, Eleonora; Leandri, Massimo

2016-08-01

Cancer patients with chemotherapy-induced peripheral neuropathy (CIPN) have sensory and motor deficits leading to inappropriate proprioceptive feedback, impaired postural control, and fall risk. Balance training with computerized force platforms has been successfully used in rehabilitation of balance disturbances, but programs specifically developed for CIPN patients are lacking. This pilot study evaluated a rehabilitation protocol exclusively based on visual computer-feedback balance training (VCFBT) to improve balance in patients with CIPN. Open-label, non-randomized pilot study, 4-week intervention with pre- vs. post-treatment evaluation. Outpatients of the Rehabilitation Institute of the Salvatore Maugeri Foundation, in Genoa, Italy. Seven out-patients with clinical-instrumental diagnosis of CIPN. At admission, patients were administered the Berg Balance Scale (BBS) and underwent static-dynamic posturography using a computerized force platform to objectively quantify their balance impairment. Their performance was compared to values of a normal age-matched population. Patients then underwent 4 weeks of VCFBT (three 60-minute sessions/week). At discharge, BBS and posturography were repeated and the results compared with those at admission. A significant pre- vs. post-treatment improvement was found in balance as measured by static-dynamic posturography (P=0.004) and BBS (P<0.002). Despite caution needed for the low sample size, this pilot study has shown preliminary evidence that intensive rehabilitation, based on VCFBT can produce a significant improvement in balance outcomes. To our knowledge, this is the first report in CIPN patients of a rehabilitation program based exclusively on VCFBT.

Splinters and Other Foreign Bodies in the Skin

MedlinePlus

... FBs: Bullets, BBs, nails, sewing needles, pins, tacks. Fiberglass spicules. Fishhooks: May have a barbed point that ... need removal Tiny plant stickers, cactus spines, or fiberglass spicules that need removal Minor sliver, splinter, or ...

The UMD-p53 database: new mutations and analysis tools.

PubMed

Béroud, Christophe; Soussi, Thierry

2003-03-01

The tumor suppressor gene TP53 (p53) is the most extensively studied gene involved in human cancers. More than 1,400 publications have reported mutations of this gene in 150 cancer types for a total of 14,971 mutations. To exploit this huge bulk of data, specific analytic tools were highly warranted. We therefore developed a locus-specific database software called UMD-p53. This database compiles all somatic and germline mutations as well as polymorphisms of the TP53 gene which have been reported in the published literature since 1989, or unpublished data submitted to the database curators. The database is available at www.umd.necker.fr or at http://p53.curie.fr/. In this paper, we describe recent developments of the UMD-p53 database. These developments include new fields and routines. For example, the analysis of putative acceptor or donor splice sites is now automated and gives new insight for the causal role of "silent mutations." Other routines have also been created such as the prescreening module, the UV module, and the cancer distribution module. These new improvements will help users not only for molecular epidemiology and pharmacogenetic studies but also for patient-based studies. To achieve theses purposes we have designed a procedure to check and validate data in order to reach the highest quality data. Copyright 2003 Wiley-Liss, Inc.

iBEST: intelligent Balance assessment and Stability Training system using smartphone.

PubMed

Wai, Aung Aung Phyo; Duc, Pham Duy; Syin, Chan; Zhang, Haihong

2014-01-01

Patients with postural instability could lead to falls and injuries while walking due to balance disorders. So those patients need regular balance training and evaluation to improve and examine balance deficiencies. But many do not notice such balance issues; resulting lack of timely preventive measures. This shows the needs of affordable and accessible solution for balance training and assessment. So iBEST (intelligent Balance assessment and Stability Training) is proposed enabling to train and assess balance conveniently anywhere anytime. Moreover, therapists can remotely evaluate and manage their recovery progress. These benefits can be realized leveraging sensors from smartphone, cloud-based data analytics and web applications. iBEST employs sensorised automated balance assessment in digitizing Berg Balance Scale (BBS) clinical risk assessment tool. The initial feasibility study showed average accuracy of 90.22% using smartphone in classifying the specified BBS test items.

Population densities of painted buntings in the southeastern United States

USGS Publications Warehouse

Meyers, J. Michael

2011-01-01

The eastern population trend of Passerina ciris (Painted Bunting) declined 3.5% annually during the first 30 yrs of the Breeding Bird Survey (BBS, 1966–1996). Recently, the US Fish and Wildlife Service listed Painted Buntings as a focal species. Surveys for this focal species for the next 10 yrs (BBS, 1997–2007), however, are too low (2 in young pine plantations to 42 per km2 in maritime shrub. Effective detection radii for habitats varied from 64 to 90 m and were slightly higher in developed than in undeveloped habitats. Distance sampling is recommended to determine densities of Painted Buntings; however, large sample sizes (70–100 detections/habitat type) are required to monitor Painted Bunting densities in most habitats in the Atlantic coastal region of the southeastern United States. Special attention should be given to maritime shrub habitats, which may be important to maintaining the Painted Bunting population in the southeastern US.

Structural insight to mutation effects uncover a common allosteric site in class C GPCRs.

PubMed

Harpsøe, Kasper; Boesgaard, Michael W; Munk, Christian; Bräuner-Osborne, Hans; Gloriam, David E

2017-04-15

Class C G protein-coupled receptors (GPCRs) regulate important physiological functions and allosteric modulators binding to the transmembrane domain constitute an attractive and, due to a lack of structural insight, a virtually unexplored potential for therapeutics and the food industry. Combining pharmacological site-directed mutagenesis data with the recent class C GPCR experimental structures will provide a foundation for rational design of new therapeutics. We uncover one common site for both positive and negative modulators with different amino acid layouts that can be utilized to obtain selectivity. Additionally, we show a large potential for structure-based modulator design, especially for four orphan receptors with high similarity to the crystal structures. All collated mutagenesis data is available in the GPCRdb mutation browser at http://gpcrdb.org/mutations/ and can be analyzed online or downloaded in excel format. david.gloriam@sund.ku.dk. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Breakthrough Therapies: Cystic Fibrosis (CF) Potentiators and Correctors

PubMed Central

Solomon, George M.; Marshall, Susan G.; Ramsey, Bonnie W.; Rowe, Steven M.

2015-01-01

Cystic Fibrosis is caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene resulting in abnormal protein function. Recent advances of targeted molecular therapies and high throughput screening have resulted in multiple drug therapies that target many important mutations in the CFTR protein. In this review, we provide the latest results and current progress of CFTR modulators for the treatment of cystic fibrosis, focusing on potentiators of CFTR channel gating and Phe508del processing correctors for the Phe508del CFTR mutation. Special emphasis is placed on the molecular basis underlying these new therapies and emerging results from the latest clinical trials. The future directions for augmenting the rescue of Phe508del with CFTR modulators is also emphasized. PMID:26097168

Land Plus Aquatic Therapy Versus Land-Based Rehabilitation Alone for the Treatment of Balance Dysfunction in Parkinson Disease: A Randomized Controlled Study With 6-Month Follow-Up.

PubMed

Palamara, Grazia; Gotti, Francesco; Maestri, Roberto; Bera, Rossana; Gargantini, Roberto; Bossio, Fabiola; Zivi, Ilaria; Volpe, Daniele; Ferrazzoli, Davide; Frazzitta, Giuseppe

2017-06-01

To assess whether a specific land-based physical intervention with the inclusion of aquatic therapy is more effective than land-based rehabilitation alone for the treatment of balance dysfunction in patients with Parkinson disease (PD), immediately after therapy and at 6 months' follow-up. Randomized controlled study with 6-month follow-up. A PD and brain injury rehabilitation department in a general hospital. Patients (N=34) with moderate-stage PD. Seventeen patients underwent a land-based rehabilitation protocol called multidisciplinary intensive rehabilitation treatment (MIRT), and 17 underwent MIRT plus aquatic therapy (MIRT-AT). The primary outcome measure was the Berg Balance Scale (BBS); secondary outcome measures were the Unified Parkinson Disease Rating Scale parts II and III (UPDRS II/III) and the Timed Up and Go (TUG) test. These measures were assessed in both groups at admission, at discharge, and after 6 months. BBS improved after treatment in both groups. Even though no statistically significant difference between groups was observed at each observation time, BBS scores at follow-up were significantly higher than at baseline in MIRT-AT patients. Both groups also showed an improvement in UPDRS II/III and TUG at the end of treatment compared with baseline, but these findings were lost at the 6-month follow-up. Aquatic therapy added to land-based rehabilitation could provide a contribution to the treatment of balance dysfunction in patients with moderate-stage PD. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Feasibility study of short-term effects of chiropractic manipulation on older adults with impaired balance.

PubMed

Hawk, Cheryl; Pfefer, Mark T; Strunk, Richard; Ramcharan, Michael; Uhl, Nathan

2007-12-01

The purpose of this study was to collect preliminary information on the effects of chiropractic spinal manipulation on reducing risk of falls in older adults with impaired balance, as assessed by the Berg Balance Scale (BBS). This information is necessary to develop a line of investigation into the role of chiropractic care on reduction of fall risk in this population. Randomized, 2-group pretest/posttest design feasibility study with a target sample size of 10 (5 per group), conducted within the outpatient health center of a chiropractic college. Inclusion criteria were as follows: aged 60 years or older, able to stand on one leg <5 seconds, and able to attend all sessions. Patients were assigned to chiropractic care (CMT) or supervised exercise (EX) and scheduled for 2 visits per week for 8 weeks. A total of 26 people responded to recruitment; and 11 were enrolled: 6 in the CMT and 5 in the EX group. Two patients dropped out at the baseline visit when they were assigned to the EX group. One CMT patient dropped out in the seventh week because of a fall at home resulting in a leg fracture. All remaining patients were compliant with treatment protocols. Five of 6 CMT patients and 4 of 5 EX patients had baseline BBS scores <45, indicating increased risk of falls. At visit 16, 2 CMT and 1 of the 3 remaining EX patients had BBS scores <45. One mild and transient adverse event was noted. Further investigation of the possible role of chiropractic care in reducing fall risk in this population appears feasible.

Temporary placement of fully covered self-expandable metal stents in benign biliary strictures.

PubMed

Ryu, Choong Heon; Kim, Myung Hwan; Lee, Sang Soo; Park, Do Hyun; Seo, Dong Wan; Lee, Sung Koo

2013-07-01

Benign biliary strictures (BBSs) have been endoscopically managed with plastic stent placement. However, data regarding fully covered self-expandable metal stents (FCSEMSs) in BBS patients remain scarce in Korea. Forty-one patients (21 men, 65.9%) with BBSs underwent FCSEMS placement between February 2007 and July 2010 in Asan Medical Center. Efficacy and safety were evaluated retrospectively. Patients were considered to have resolution if they showed evidence of stricture resolution on cholangiography and if an inflated retrieval balloon easily passed through the strictures at FCSEMS removal. The mean FCSEMS placement time was 3.2 (1.9-6.2) months. Patients were followed for a mean of 10.2 (1.0-32.0) months after FCSEMS removal. The BBS resolution rate was confirmed in 38 of 41 (92.7%) patients who underwent FCSEMS removal. After FCSEMS removal, 6 of 38 (15.8%) patients experienced symptomatic recurrent stricture and repeat stenting was performed. When a breakdown by etiology of stricture was performed, 14 of 15 (93.3%) patients with chronic pancreatitis, 17 of 19 (89.5%) with gall stone-related disease, 4 of 4 (100%) with surgical procedures, and 2 of 2 (100%) with BBSs of other etiology had resolution at FCSEMS removal. Complications related to stent therapy occurred in 12 (29%) patients, including post-ERCP pancreatitis (n=4), proximal migration (n=3), distal migration (n=3), and occlusion (n=2). Temporary FCSEMS placement in BBS patients offers a potential alternative to plastic stenting. However, because of the significant complications and modest resolution rates, the potential benefits and risks should be evaluated in further investigations.

Feasibility of Wii Fit training to improve clinical measures of balance in older adults

PubMed Central

Bieryla, Kathleen A; Dold, Neil M

2013-01-01

Background and purpose Numerous interventions have been proposed to improve balance in older adults with varying degrees of success. A novel approach may be to use an off-the-shelf video game system utilizing real-time force feedback to train older adults. The purpose of this study is to investigate the feasibility of using Nintendo’s Wii Fit for training to improve clinical measures of balance in older adults and to retain the improvements after a period of time. Methods Twelve healthy older adults (aged >70 years) were randomly divided into two groups. The experimental group completed training using Nintendo’s Wii Fit game three times a week for 3 weeks while the control group continued with normal activities. Four clinical measures of balance were assessed before training, 1 week after training, and 1 month after training: Berg Balance Scale (BBS), Fullerton Advanced Balance (FAB) scale, Functional Reach (FR), and Timed Up and Go (TUG). Friedman two-way analysis of variance by ranks was conducted on the control and experimental group to determine if training using the Wii Balance Board with Wii Fit had an influence on clinical measures of balance. Results Nine older adults completed the study (experimental group n = 4, control group n = 5). The experimental group significantly increased their BBS after training while the control group did not. There was no significant change for either group with FAB, FR, and TUG. Conclusion Balance training with Nintendo’s Wii Fit may be a novel way for older adults to improve balance as measured by the BBS. PMID:23836967

A US Multicenter Study of Safety and Efficacy of Fully Covered Self-Expandable Metallic Stents in Benign Extrahepatic Biliary Strictures.

PubMed

Saxena, Payal; Diehl, David L; Kumbhari, Vivek; Shieh, Frederick; Buscaglia, Jonathan M; Sze, Wilson; Kapoor, Sumit; Komanduri, Srinadh; Nasr, John; Shin, Eun Ji; Singh, Vikesh; Lennon, Anne Marie; Kalloo, Anthony N; Khashab, Mouen A

2015-11-01

Endoscopic therapy is considered first line for management of benign biliary strictures (BBSs). Placement of plastic stents has been effective but limited by their short-term patency and need for repeated procedures. Fully covered self-expandable metallic stents (FCSEMSs) offer longer-lasting biliary drainage without the need for frequent exchanges. The aim of this study was to assess the efficacy and safety of FCSEMS in patients with BBS. A retrospective review of all patients who underwent ERCP and FCSEMS placement at five tertiary referral US hospitals was performed. Stricture resolution and adverse events related to ERCP and/or stenting were recorded. A total of 123 patients underwent FCSEMS placement for BBS and 112 underwent a subsequent follow-up ERCP. The mean age was 62 years (±15.6), and 57% were males. Stricture resolution occurred in 81% of patients after a mean of 1.2 stenting procedures (mean stent dwell time 24.4 ± 2.3 weeks), with a mean follow-up of 18.5 months. Stricture recurrence occurred in 5 patients, and 3 patients required surgery for treatment of refractory strictures. Stent migration (9.7%) was the most common complication, followed by stent occlusion (4.9%), cholangitis (4.1%), and pancreatitis (3.3%). There was one case of stent fracture during removal, and one stent could not be removed. There was one death due to cholangitis. Majority of BBS can be successfully managed with 1-2 consecutive FCSEMS with stent dwell time of 6 months.

Updated branching fraction measurements of B ( s) 0 → K S 0 h + h ' - decays

NASA Astrophysics Data System (ADS)

Aaij, R.; Adeva, B.; Adinolfi, M.; Ajaltouni, Z.; Akar, S.; Albrecht, J.; Alessio, F.; Alexander, M.; Ali, S.; Alkhazov, G.; Alvarez Cartelle, P.; Alves, A. A.; Amato, S.; Amerio, S.; Amhis, Y.; An, L.; Anderlini, L.; Andreassi, G.; Andreotti, M.; Andrews, J. E.; Appleby, R. B.; Archilli, F.; d'Argent, P.; Arnau Romeu, J.; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Baalouch, M.; Babuschkin, I.; Bachmann, S.; Back, J. J.; Badalov, A.; Baesso, C.; Baker, S.; Balagura, V.; Baldini, W.; Baranov, A.; Barlow, R. J.; Barschel, C.; Barsuk, S.; Barter, W.; Baryshnikov, F.; Baszczyk, M.; Batozskaya, V.; Batsukh, B.; Battista, V.; Bay, A.; Beaucourt, L.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Beiter, A.; Bel, L. J.; Bellee, V.; Belloli, N.; Belous, K.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Beranek, S.; Berezhnoy, A.; Bernet, R.; Bertolin, A.; Betancourt, C.; Betti, F.; Bettler, M.-O.; van Beuzekom, M.; Bezshyiko, Ia.; Bifani, S.; Billoir, P.; Birnkraut, A.; Bitadze, A.; Bizzeti, A.; Blake, T.; Blanc, F.; Blouw, J.; Blusk, S.; Bocci, V.; Boettcher, T.; Bondar, A.; Bondar, N.; Bonivento, W.; Bordyuzhin, I.; Borgheresi, A.; Borghi, S.; Borisyak, M.; Borsato, M.; Bossu, F.; Boubdir, M.; Bowcock, T. J. V.; Bowen, E.; Bozzi, C.; Braun, S.; Britton, T.; Brodzicka, J.; Buchanan, E.; Burr, C.; Bursche, A.; Buytaert, J.; Cadeddu, S.; Calabrese, R.; Calvi, M.; Calvo Gomez, M.; Camboni, A.; Campana, P.; Campora Perez, D. H.; Capriotti, L.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carniti, P.; Carson, L.; Carvalho Akiba, K.; Casse, G.; Cassina, L.; Castillo Garcia, L.; Cattaneo, M.; Cavallero, G.; Cenci, R.; Chamont, D.; Charles, M.; Charpentier, Ph.; Chatzikonstantinidis, G.; Chefdeville, M.; Chen, S.; Cheung, S. F.; Chobanova, V.; Chrzaszcz, M.; Chubykin, A.; Cid Vidal, X.; Ciezarek, G.; Clarke, P. E. L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Coco, V.; Cogan, J.; Cogneras, E.; Cogoni, V.; Cojocariu, L.; Collins, P.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombs, G.; Coquereau, S.; Corti, G.; Corvo, M.; Costa Sobral, C. M.; Couturier, B.; Cowan, G. A.; Craik, D. C.; Crocombe, A.; Cruz Torres, M.; Cunliffe, S.; Currie, R.; D'Ambrosio, C.; Da Cunha Marinho, F.; Dall'Occo, E.; Dalseno, J.; Davis, A.; De Bruyn, K.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Serio, M.; De Simone, P.; Dean, C. T.; Decamp, D.; Deckenhoff, M.; Del Buono, L.; Dembinski, H.-P.; Demmer, M.; Dendek, A.; Derkach, D.; Deschamps, O.; Dettori, F.; Dey, B.; Di Canto, A.; Di Nezza, P.; Dijkstra, H.; Dordei, F.; Dorigo, M.; Dosil Suárez, A.; Dovbnya, A.; Dreimanis, K.; Dufour, L.; Dujany, G.; Dungs, K.; Durante, P.; Dzhelyadin, R.; Dziewiecki, M.; Dziurda, A.; Dzyuba, A.; Déléage, N.; Easo, S.; Ebert, M.; Egede, U.; Egorychev, V.; Eidelman, S.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; Ely, S.; Esen, S.; Evans, H. M.; Evans, T.; Falabella, A.; Farley, N.; Farry, S.; Fay, R.; Fazzini, D.; Ferguson, D.; Fernandez, G.; Fernandez Prieto, A.; Ferrari, F.; Ferreira Rodrigues, F.; Ferro-Luzzi, M.; Filippov, S.; Fini, R. A.; Fiore, M.; Fiorini, M.; Firlej, M.; Fitzpatrick, C.; Fiutowski, T.; Fleuret, F.; Fohl, K.; Fontana, M.; Fontanelli, F.; Forshaw, D. C.; Forty, R.; Franco Lima, V.; Frank, M.; Frei, C.; Fu, J.; Funk, W.; Furfaro, E.; Färber, C.; Gabriel, E.; Gallas Torreira, A.; Galli, D.; Gallorini, S.; Gambetta, S.; Gandelman, M.; Gandini, P.; Gao, Y.; Garcia Martin, L. M.; García Pardiñas, J.; Garra Tico, J.; Garrido, L.; Garsed, P. J.; Gascon, D.; Gaspar, C.; Gavardi, L.; Gazzoni, G.; Gerick, D.; Gersabeck, E.; Gersabeck, M.; Gershon, T.; Ghez, Ph.; Gianì, S.; Gibson, V.; Girard, O. G.; Giubega, L.; Gizdov, K.; Gligorov, V. V.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gorelov, I. V.; Gotti, C.; Govorkova, E.; Graciani Diaz, R.; Granado Cardoso, L. A.; Graugés, E.; Graverini, E.; Graziani, G.; Grecu, A.; Greim, R.; Griffith, P.; Grillo, L.; Gruber, L.; Gruberg Cazon, B. R.; Grünberg, O.; Gushchin, E.; Guz, Yu.; Gys, T.; Göbel, C.; Hadavizadeh, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S. C.; Hamilton, B.; Han, X.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Harrison, J.; Hatch, M.; He, J.; Head, T.; Heister, A.; Hennessy, K.; Henrard, P.; Henry, L.; van Herwijnen, E.; Heß, M.; Hicheur, A.; Hill, D.; Hombach, C.; Hopchev, P. H.; Huard, Z.-C.; Hulsbergen, W.; Humair, T.; Hushchyn, M.; Hutchcroft, D.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jalocha, J.; Jans, E.; Jawahery, A.; Jiang, F.; John, M.; Johnson, D.; Jones, C. R.; Joram, C.; Jost, B.; Jurik, N.; Kandybei, S.; Karacson, M.; Kariuki, J. M.; Karodia, S.; Kecke, M.; Kelsey, M.; Kenzie, M.; Ketel, T.; Khairullin, E.; Khanji, B.; Khurewathanakul, C.; Kirn, T.; Klaver, S.; Klimaszewski, K.; Klimkovich, T.; Koliiev, S.; Kolpin, M.; Komarov, I.; Kopecna, R.; Koppenburg, P.; Kosmyntseva, A.; Kotriakhova, S.; Kozachuk, A.; Kozeiha, M.; Kravchuk, L.; Kreps, M.; Krokovny, P.; Kruse, F.; Krzemien, W.; Kucewicz, W.; Kucharczyk, M.; Kudryavtsev, V.; Kuonen, A. K.; Kurek, K.; Kvaratskheliya, T.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lanfranchi, G.; Langenbruch, C.; Latham, T.; Lazzeroni, C.; Le Gac, R.; van Leerdam, J.; Leflat, A.; Lefrançois, J.; Lefèvre, R.; Lemaitre, F.; Lemos Cid, E.; Leroy, O.; Lesiak, T.; Leverington, B.; Li, T.; Li, Y.; Li, Z.; Likhomanenko, T.; Lindner, R.; Lionetto, F.; Liu, X.; Loh, D.; Longstaff, I.; Lopes, J. H.; Lucchesi, D.; Lucio Martinez, M.; Luo, H.; Lupato, A.; Luppi, E.; Lupton, O.; Lusiani, A.; Lyu, X.; Machefert, F.; Maciuc, F.; Maev, O.; Maguire, K.; Malde, S.; Malinin, A.; Maltsev, T.; Manca, G.; Mancinelli, G.; Manning, P.; Maratas, J.; Marchand, J. F.; Marconi, U.; Marin Benito, C.; Marinangeli, M.; Marino, P.; Marks, J.; Martellotti, G.; Martin, M.; Martinelli, M.; Martinez Santos, D.; Martinez Vidal, F.; Martins Tostes, D.; Massacrier, L. M.; Massafferri, A.; Matev, R.; Mathad, A.; Mathe, Z.; Matteuzzi, C.; Mauri, A.; Maurice, E.; Maurin, B.; Mazurov, A.; McCann, M.; McNab, A.; McNulty, R.; Meadows, B.; Meier, F.; Melnychuk, D.; Merk, M.; Merli, A.; Michielin, E.; Milanes, D. A.; Minard, M.-N.; Mitzel, D. S.; Mogini, A.; Molina Rodriguez, J.; Monroy, I. A.; Monteil, S.; Morandin, M.; Morello, M. J.; Morgunova, O.; Moron, J.; Morris, A. B.; Mountain, R.; Muheim, F.; Mulder, M.; Mussini, M.; Müller, D.; Müller, J.; Müller, K.; Müller, V.; Naik, P.; Nakada, T.; Nandakumar, R.; Nandi, A.; Nasteva, I.; Needham, M.; Neri, N.; Neubert, S.; Neufeld, N.; Neuner, M.; Nguyen, T. D.; Nguyen-Mau, C.; Nieswand, S.; Niet, R.; Nikitin, N.; Nikodem, T.; Nogay, A.; O'Hanlon, D. P.; Oblakowska-Mucha, A.; Obraztsov, V.; Ogilvy, S.; Oldeman, R.; Onderwater, C. J. G.; Ossowska, A.; Otalora Goicochea, J. M.; Owen, P.; Oyanguren, A.; Pais, P. R.; Palano, A.; Palutan, M.; Papanestis, A.; Pappagallo, M.; Pappalardo, L. L.; Pappenheimer, C.; Parker, W.; Parkes, C.; Passaleva, G.; Pastore, A.; Patel, M.; Patrignani, C.; Pearce, A.; Pellegrino, A.; Penso, G.; Pepe Altarelli, M.; Perazzini, S.; Perret, P.; Pescatore, L.; Petridis, K.; Petrolini, A.; Petrov, A.; Petruzzo, M.; Picatoste Olloqui, E.; Pietrzyk, B.; Pikies, M.; Pinci, D.; Pistone, A.; Piucci, A.; Placinta, V.; Playfer, S.; Plo Casasus, M.; Poikela, T.; Polci, F.; Poli Lener, M.; Poluektov, A.; Polyakov, I.; Polycarpo, E.; Pomery, G. J.; Ponce, S.; Popov, A.; Popov, D.; Popovici, B.; Poslavskii, S.; Potterat, C.; Price, E.; Prisciandaro, J.; Prouve, C.; Pugatch, V.; Puig Navarro, A.; Punzi, G.; Qian, C.; Qian, W.; Quagliani, R.; Rachwal, B.; Rademacker, J. H.; Rama, M.; Ramos Pernas, M.; Rangel, M. S.; Raniuk, I.; Ratnikov, F.; Raven, G.; Ravonel Salzgeber, M.; Reboud, M.; Redi, F.; Reichert, S.; dos Reis, A. C.; Remon Alepuz, C.; Renaudin, V.; Ricciardi, S.; Richards, S.; Rihl, M.; Rinnert, K.; Rives Molina, V.; Robbe, P.; Rodrigues, A. B.; Rodrigues, E.; Rodriguez Lopez, J. A.; Rodriguez Perez, P.; Rogozhnikov, A.; Roiser, S.; Rollings, A.; Romanovskiy, V.; Romero Vidal, A.; Ronayne, J. W.; Rotondo, M.; Rudolph, M. S.; Ruf, T.; Ruiz Valls, P.; Saborido Silva, J. J.; Sadykhov, E.; Sagidova, N.; Saitta, B.; Salustino Guimaraes, V.; Sanchez Gonzalo, D.; Sanchez Mayordomo, C.; Sanmartin Sedes, B.; Santacesaria, R.; Santamarina Rios, C.; Santimaria, M.; Santovetti, E.; Sarti, A.; Satriano, C.; Satta, A.; Saunders, D. M.; Savrina, D.; Schael, S.; Schellenberg, M.; Schiller, M.; Schindler, H.; Schlupp, M.; Schmelling, M.; Schmelzer, T.; Schmidt, B.; Schneider, O.; Schopper, A.; Schreiner, H. F.; Schubert, K.; Schubiger, M.; Schune, M.-H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Semennikov, A.; Sergi, A.; Serra, N.; Serrano, J.; Sestini, L.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, V.; Siddi, B. G.; Silva Coutinho, R.; Silva de Oliveira, L.; Simi, G.; Simone, S.; Sirendi, M.; Skidmore, N.; Skwarnicki, T.; Smith, E.; Smith, I. T.; Smith, J.; Smith, M.; Soares Lavra, l.; Sokoloff, M. D.; Soler, F. J. P.; Souza De Paula, B.; Spaan, B.; Spradlin, P.; Sridharan, S.; Stagni, F.; Stahl, M.; Stahl, S.; Stefko, P.; Stefkova, S.; Steinkamp, O.; Stemmle, S.; Stenyakin, O.; Stevens, H.; Stoica, S.; Stone, S.; Storaci, B.; Stracka, S.; Stramaglia, M. E.; Straticiuc, M.; Straumann, U.; Sun, L.; Sutcliffe, W.; Swientek, K.; Syropoulos, V.; Szczekowski, M.; Szumlak, T.; T'Jampens, S.; Tayduganov, A.; Tekampe, T.; Tellarini, G.; Teubert, F.; Thomas, E.; van Tilburg, J.; Tilley, M. J.; Tisserand, V.; Tobin, M.; Tolk, S.; Tomassetti, L.; Tonelli, D.; Topp-Joergensen, S.; Toriello, F.; Tourinho Jadallah Aoude, R.; Tournefier, E.; Tourneur, S.; Trabelsi, K.; Traill, M.; Tran, M. T.; Tresch, M.; Trisovic, A.; Tsaregorodtsev, A.; Tsopelas, P.; Tully, A.; Tuning, N.; Ukleja, A.; Ustyuzhanin, A.; Uwer, U.; Vacca, C.; Vagnoni, V.; Valassi, A.; Valat, S.; Valenti, G.; Vazquez Gomez, R.; Vazquez Regueiro, P.; Vecchi, S.; van Veghel, M.; Velthuis, J. J.; Veltri, M.; Veneziano, G.; Venkateswaran, A.; Verlage, T. A.; Vernet, M.; Vesterinen, M.; Viana Barbosa, J. V.; Viaud, B.; Vieira, D.; Vieites Diaz, M.; Viemann, H.; Vilasis-Cardona, X.; Vitti, M.; Volkov, V.; Vollhardt, A.; Voneki, B.; Vorobyev, A.; Vorobyev, V.; Voß, C.; de Vries, J. A.; Vázquez Sierra, C.; Waldi, R.; Wallace, C.; Wallace, R.; Walsh, J.; Wang, J.; Ward, D. R.; Wark, H. M.; Watson, N. K.; Websdale, D.; Weiden, A.; Whitehead, M.; Wicht, J.; Wilkinson, G.; Wilkinson, M.; Williams, M.; Williams, M. P.; Williams, M.; Williams, T.; Wilson, F. F.; Wimberley, J.; Winn, M. A.; Wishahi, J.; Wislicki, W.; Witek, M.; Wormser, G.; Wotton, S. A.; Wraight, K.; Wyllie, K.; Xie, Y.; Xing, Z.; Xu, Z.; Yang, Z.; Yang, Z.; Yao, Y.; Yin, H.; Yu, J.; Yuan, X.; Yushchenko, O.; Zarebski, K. A.; Zavertyaev, M.; Zhang, L.; Zhang, Y.; Zhelezov, A.; Zheng, Y.; Zhu, X.; Zhukov, V.; Zonneveld, J. B.; Zucchelli, S.

2017-11-01

The charmless three-body decays B ( s) 0 → K S 0 h + h ' - (where h (') = π, K) are analysed using a sample of pp collision data recorded by the LHCb experiment, corresponding to an integrated luminosity of 3 fb-1. The branching fractions are measured relative to that of the B 0 → K S 0 π + π - decay, and are determined to be: B({B}^0\\to {K}S^0{K}^{± /π^{∓})}{B({B}^0\\to {K}S^0{K}+{π}-)}=0.123± 0.009(stat)± 0.015(syst), B({B}^0\\to {K}S^0{K}^{+/K-)}{B({B}^0\\to {K}S^0{π}+{π}-)}=0.549± 0.018(stat)± 0.033(syst), B({B}_s^0\\to {K}S^0{π}^{+/π-)}{B({B}^0\\to {K}S^0{π}+{π}-)}=0.191± 0.027(stat)± 0.031(syst)± 0.011({f}_s/{f}_d), B({B}_s^0\\to {K}S^0{K}^{± /π^{∓})}{B({B}^0\\to {K}S^0{π}+{π}-)}=1.70± 0.07(stat)± 0.11(syst)± 0.10({f}_s/{f}_d), B({B}_s^0\\to {K}S^0{K}^{+/K-)}{B({B}^0\\to {K}S^0{π}+{π}-)}\\in [0.008-0.051] at 90% confidence level, where f s / f d represents the ratio of hadronisation fractions of the B s 0 and B 0 mesons. [Figure not available: see fulltext.

Balance Assessment in Deaf Children and Teenagers Prior to and Post Capoeira Practice through the Berg Balance Scale.

PubMed

Lima, Rubianne

2017-12-01

Hearing loss changes the functionality and body structure a disability that limits activity and restricts the participation of the individual in situations of daily life. It is believed that capoeira can help people with visual disabilities to minimize these deficits. BSE is a low specificity scale that evaluates objectively and functionally aspects of balance and risk of falls in the elderly and children, including the effect of environment on balance function. The objective of the research is to analyze deaf children and adolescents prior to and post-practice of capoeira using the Berg Balance Scale (BBS). Quantitative, clinical and observational studies. Twenty five deaf children between 10 and 16 years old of both genders were assessed. BBS was applied in two stages: before starting capoeira and after 6 months of training. The one-hour classes were held once a week for quantitative evaluation purposes. The subjects were divided and evaluated in two groups (10-13 years old and 14-16 years old). There was a significant statistical difference in BBS scores. The general group and the group of 10-13 years old (p = 0.0251) showed an increase in scores after practicing capoeira (p = 0.0039). There were no statistically significant differences in the group from 14 to 16 years of age (p = 0.0504). Using the Berg Balance Scale, it was possible to observe an improvement in the balance of the group of children and adolescents who practiced capoeira, and consequently, a decrease in the risk of falling.

Effect of Sling Exercise Training on Balance in Patients with Stroke: A Meta-Analysis

PubMed Central

Peng, Qiyuan; Chen, Jingjie; Zou, Yucong; Liu, Gang

2016-01-01

Objective This study aims to evaluate the effect of sling exercise training (SET) on balance in patients with stroke. Methods PubMed, Cochrane Library, Ovid LWW, CBM, CNKI, WanFang, and VIP databases were searched for randomized controlled trials of the effect of SET on balance in patients with stroke. The study design and participants were subjected to metrological analysis. Berg balance Scale (BBS), Barthel index score (BI), and Fugl-Meyer Assessment (FMA) were used as independent parameters for evaluating balance function, activities of daily living(ADL) and motor function after stroke respectively, and were subjected to meta-analysis by RevMan5.3 software. Results Nine studies with 460 participants were analyzed. Results of meta-analysis showed that the SET treatment combined with conventional rehabilitation was superior to conventional rehabilitation treatments, with increased degrees of BBS (WMD = 3.81, 95% CI [0.15, 7.48], P = 0.04), BI (WMD = 12.98, 95% CI [8.39, 17.56], P < 0.00001), and FMA (SMD = 0.76, 95% CI [0.41, 1.11], P < 0.0001). Conclusion Based on limited evidence from 9 trials, the SET treatment combined with conventional rehabilitation was superior to conventional rehabilitation treatments, with increased degrees of BBS, BI and FMA, So the SET treatment can improvement of balance function after stroke, but the interpretation of our findings is required to be made with caution due to limitations in included trials such as small sample sizes and the risk of bias. Therefore, more multi-center and large-sampled randomized controlled trials are needed to confirm its clinical applications. PMID:27727288

The relationship between balance and vitamin 25(OH)D in fibromyalgia patients.

PubMed

Kasapoğlu Aksoy, Meliha; Altan, Lale; Ökmen Metin, Burcu

2017-09-01

Fibromyalgia syndrome (FMS) is a chronic disease characterized by diffuse pain of unknown cause, fatigue, sleep disorders, cognitive dysfunction, and sensitivity. Fibromyalgia was shown to be associated with balance problems and increased incidence of falls. There are many theoretical mechanisms related to the impact of vitamin D on postural control. The aim of the current study was to investigate the relationship between vitamin 25(OH)D levels and pain, balance and daily activities in patients with FMS. Patients aged 35-65 years who were diagnosed with FMS according to 1990 ACR diagnostic criteria were screened. Seventy patients diagnosed with FMS and 60 healthy controls with comparable age and gender were included in the study. Fibromyalgia impact scale (FIQ), Berg Balance Scale (BBS), the Nottingham Health Profile (NHP), and visual analog scale (VAS) were applied to the subjects. The subjects were divided into two groups by vitamin 25(OH)D level being above or below 30 ng/ml. A statistically significant difference was established between VAS, BBS value and all NHP subscale and NHP total values of FMS patients and those of healthy control group. The relationship between BBS and the level of vitamin 25(OH)D of all participants was investigated, a positive statistically significant relationship was found with Vit-D at r = 0.481 level (p < 0.05). It was observed that low vitamin D levels affected balance in both FMS group and healthy control group. It should be kept in mind that vitamin D level is likely to negatively affect balance and VAS values in FMS.

The potential application of behavior-based safety in the trucking industry

DOT National Transportation Integrated Search

2000-04-01

Behavior-based safety (BBS) is a set of methods to improve safety performance in the workplace by engaging workers in the improvement process, identifying critical safety behaviors, performing observations to gather data, providing feedback to encour...

Statistical mapping of count survey data

USGS Publications Warehouse

Royle, J. Andrew; Link, W.A.; Sauer, J.R.; Scott, J. Michael; Heglund, Patricia J.; Morrison, Michael L.; Haufler, Jonathan B.; Wall, William A.

2002-01-01

We apply a Poisson mixed model to the problem of mapping (or predicting) bird relative abundance from counts collected from the North American Breeding Bird Survey (BBS). The model expresses the logarithm of the Poisson mean as a sum of a fixed term (which may depend on habitat variables) and a random effect which accounts for remaining unexplained variation. The random effect is assumed to be spatially correlated, thus providing a more general model than the traditional Poisson regression approach. Consequently, the model is capable of improved prediction when data are autocorrelated. Moreover, formulation of the mapping problem in terms of a statistical model facilitates a wide variety of inference problems which are cumbersome or even impossible using standard methods of mapping. For example, assessment of prediction uncertainty, including the formal comparison of predictions at different locations, or through time, using the model-based prediction variance is straightforward under the Poisson model (not so with many nominally model-free methods). Also, ecologists may generally be interested in quantifying the response of a species to particular habitat covariates or other landscape attributes. Proper accounting for the uncertainty in these estimated effects is crucially dependent on specification of a meaningful statistical model. Finally, the model may be used to aid in sampling design, by modifying the existing sampling plan in a manner which minimizes some variance-based criterion. Model fitting under this model is carried out using a simulation technique known as Markov Chain Monte Carlo. Application of the model is illustrated using Mourning Dove (Zenaida macroura) counts from Pennsylvania BBS routes. We produce both a model-based map depicting relative abundance, and the corresponding map of prediction uncertainty. We briefly address the issue of spatial sampling design under this model. Finally, we close with some discussion of mapping in relation to habitat structure. Although our models were fit in the absence of habitat information, the resulting predictions show a strong inverse relation with a map of forest cover in the state, as expected. Consequently, the results suggest that the correlated random effect in the model is broadly representing ecological variation, and that BBS data may be generally useful for studying bird-habitat relationships, even in the presence of observer errors and other widely recognized deficiencies of the BBS.

The modular architecture of protein-protein binding interfaces.

PubMed

Reichmann, D; Rahat, O; Albeck, S; Meged, R; Dym, O; Schreiber, G

2005-01-04

Protein-protein interactions are essential for life. Yet, our understanding of the general principles governing binding is not complete. In the present study, we show that the interface between proteins is built in a modular fashion; each module is comprised of a number of closely interacting residues, with few interactions between the modules. The boundaries between modules are defined by clustering the contact map of the interface. We show that mutations in one module do not affect residues located in a neighboring module. As a result, the structural and energetic consequences of the deletion of entire modules are surprisingly small. To the contrary, within their module, mutations cause complex energetic and structural consequences. Experimentally, this phenomenon is shown on the interaction between TEM1-beta-lactamase and beta-lactamase inhibitor protein (BLIP) by using multiple-mutant analysis and x-ray crystallography. Replacing an entire module of five interface residues with Ala created a large cavity in the interface, with no effect on the detailed structure of the remaining interface. The modular architecture of binding sites, which resembles human engineering design, greatly simplifies the design of new protein interactions and provides a feasible view of how these interactions evolved.

Effects of HCM cTnI Mutation R145G on Troponin Structure and Modulation by PKA Phosphorylation Elucidated by Molecular Dynamics Simulations

PubMed Central

Lindert, Steffen; Cheng, Yuanhua; Kekenes-Huskey, Peter; Regnier, Michael; McCammon, J. Andrew

2015-01-01

Cardiac troponin (cTn) is a key molecule in the regulation of human cardiac muscle contraction. The N-terminal cardiac-specific peptide of the inhibitory subunit of troponin, cTnI (cTnI1-39), is a target for phosphorylation by protein kinase A (PKA) during β-adrenergic stimulation. We recently presented evidence indicating that this peptide interacts with the inhibitory peptide (cTnl137–147) when S23 and S24 are phosphorylated. The inhibitory peptide is also the target of the point mutation cTnI-R145G, which is associated with hypertrophic cardiomyopathy (HCM), a disease associated with sudden death in apparently healthy young adults. It has been shown that both phosphorylation and this mutation alter the cTnC-cTnI (C-I) interaction, which plays a crucial role in modulating contractile activation. However, little is known about the molecular-level events underlying this modulation. Here, we computationally investigated the effects of the cTnI-R145G mutation on the dynamics of cTn, cTnC Ca2+ handling, and the C-I interaction. Comparisons were made with the cTnI-R145G/S23D/S24D phosphomimic mutation, which has been used both experimentally and computationally to study the cTnI N-terminal specific effects of PKA phosphorylation. Additional comparisons between the phosphomimic mutations and the real phosphorylations were made. For this purpose, we ran triplicate 150 ns molecular dynamics simulations of cTnI-R145G Ca2+-bound cTnC1-161-cTnI1-172-cTnT236-285, cTnI-R145G/S23D/S24D Ca2+-bound cTnC1-161-cTnI1-172-cTnT236-285, and cTnI-R145G/PS23/PS24 Ca2+-bound cTnC1-161-cTnI1-172-cTnT236-285, respectively. We found that the cTnI-R145G mutation did not impact the overall dynamics of cTn, but stabilized crucial Ca2+-coordinating interactions. However, the phosphomimic mutations increased overall cTn fluctuations and destabilized Ca2+ coordination. Interestingly, cTnI-R145G blunted the intrasubunit interactions between the cTnI N-terminal extension and the cTnI inhibitory peptide, which have been suggested to play a crucial role in modulating troponin function during β-adrenergic stimulation. These findings offer a molecular-level explanation for how the HCM mutation cTnI-R145G reduces the modulation of cTn by phosphorylation of S23/S24 during β-adrenergic stimulation. PMID:25606687

Effects of HCM cTnI mutation R145G on troponin structure and modulation by PKA phosphorylation elucidated by molecular dynamics simulations.

PubMed

Lindert, Steffen; Cheng, Yuanhua; Kekenes-Huskey, Peter; Regnier, Michael; McCammon, J Andrew

2015-01-20

Cardiac troponin (cTn) is a key molecule in the regulation of human cardiac muscle contraction. The N-terminal cardiac-specific peptide of the inhibitory subunit of troponin, cTnI (cTnI(1-39)), is a target for phosphorylation by protein kinase A (PKA) during β-adrenergic stimulation. We recently presented evidence indicating that this peptide interacts with the inhibitory peptide (cTnl(137-147)) when S23 and S24 are phosphorylated. The inhibitory peptide is also the target of the point mutation cTnI-R145G, which is associated with hypertrophic cardiomyopathy (HCM), a disease associated with sudden death in apparently healthy young adults. It has been shown that both phosphorylation and this mutation alter the cTnC-cTnI (C-I) interaction, which plays a crucial role in modulating contractile activation. However, little is known about the molecular-level events underlying this modulation. Here, we computationally investigated the effects of the cTnI-R145G mutation on the dynamics of cTn, cTnC Ca(2+) handling, and the C-I interaction. Comparisons were made with the cTnI-R145G/S23D/S24D phosphomimic mutation, which has been used both experimentally and computationally to study the cTnI N-terminal specific effects of PKA phosphorylation. Additional comparisons between the phosphomimic mutations and the real phosphorylations were made. For this purpose, we ran triplicate 150 ns molecular dynamics simulations of cTnI-R145G Ca(2+)-bound cTnC(1-161)-cTnI(1-172)-cTnT(236-285), cTnI-R145G/S23D/S24D Ca(2+)-bound cTnC(1-161)-cTnI(1-172)-cTnT(236-285), and cTnI-R145G/PS23/PS24 Ca(2+)-bound cTnC(1-161)-cTnI(1-172)-cTnT(236-285), respectively. We found that the cTnI-R145G mutation did not impact the overall dynamics of cTn, but stabilized crucial Ca(2+)-coordinating interactions. However, the phosphomimic mutations increased overall cTn fluctuations and destabilized Ca(2+) coordination. Interestingly, cTnI-R145G blunted the intrasubunit interactions between the cTnI N-terminal extension and the cTnI inhibitory peptide, which have been suggested to play a crucial role in modulating troponin function during β-adrenergic stimulation. These findings offer a molecular-level explanation for how the HCM mutation cTnI-R145G reduces the modulation of cTn by phosphorylation of S23/S24 during β-adrenergic stimulation. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Modulation of Radiogenic Damage by Microgravity: Results From STS-76

NASA Technical Reports Server (NTRS)

Nelson, Gregory; Kazarians, Gayane; Schubert, Wayne; Kern, Roger; Schranck, David; Hartman, Philip; Hlavacek, Anthony; Wilde, Honor; Lewicki, Dan; Benton, Eugene;

Behavior-based safety at Amtrak-Chicago associated with reduced injuries and costs.

DOT National Transportation Integrated Search

2007-02-01

The Federal Railroad Administration (FRA) Human Factors Research and Development (R&D) Program is sponsoring the Clear Signal for Action Program (CSA) to evaluate whether an approach that combines behavior-based safety (BBS) and continuous improvemen...

Adaptation to High Ethanol Reveals Complex Evolutionary Pathways

PubMed Central

Das, Anupam; Espinosa-Cantú, Adriana; De Maeyer, Dries; Arslan, Ahmed; Van Pee, Michiel; van der Zande, Elisa; Meert, Wim; Yang, Yudi; Zhu, Bo; Marchal, Kathleen; DeLuna, Alexander; Van Noort, Vera; Jelier, Rob; Verstrepen, Kevin J.

2015-01-01

Tolerance to high levels of ethanol is an ecologically and industrially relevant phenotype of microbes, but the molecular mechanisms underlying this complex trait remain largely unknown. Here, we use long-term experimental evolution of isogenic yeast populations of different initial ploidy to study adaptation to increasing levels of ethanol. Whole-genome sequencing of more than 30 evolved populations and over 100 adapted clones isolated throughout this two-year evolution experiment revealed how a complex interplay of de novo single nucleotide mutations, copy number variation, ploidy changes, mutator phenotypes, and clonal interference led to a significant increase in ethanol tolerance. Although the specific mutations differ between different evolved lineages, application of a novel computational pipeline, PheNetic, revealed that many mutations target functional modules involved in stress response, cell cycle regulation, DNA repair and respiration. Measuring the fitness effects of selected mutations introduced in non-evolved ethanol-sensitive cells revealed several adaptive mutations that had previously not been implicated in ethanol tolerance, including mutations in PRT1, VPS70 and MEX67. Interestingly, variation in VPS70 was recently identified as a QTL for ethanol tolerance in an industrial bio-ethanol strain. Taken together, our results show how, in contrast to adaptation to some other stresses, adaptation to a continuous complex and severe stress involves interplay of different evolutionary mechanisms. In addition, our study reveals functional modules involved in ethanol resistance and identifies several mutations that could help to improve the ethanol tolerance of industrial yeasts. PMID:26545090

Corin mutations K317E and S472G from preeclamptic patients alter zymogen activation and cell surface targeting. [Corrected].

PubMed

Dong, Ningzheng; Zhou, Tiantian; Zhang, Yue; Liu, Meng; Li, Hui; Huang, Xiaoyi; Liu, Zhenzhen; Wu, Yi; Fukuda, Koichi; Qin, Jun; Wu, Qingyu

2014-06-20

Corin is a membrane-bound serine protease that acts as the atrial natriuretic peptide (ANP) convertase in the heart. Recent studies show that corin also activates ANP in the pregnant uterus to promote spiral artery remodeling and prevent pregnancy-induced hypertension. Two CORIN gene mutations, K317E and S472G, were identified in preeclamptic patients and shown to have reduced activity in vitro. In this study, we carried out molecular modeling and biochemical experiments to understand how these mutations impair corin function. By molecular modeling, the mutation K317E was predicted to alter corin LDL receptor-2 module conformation. Western blot analysis of K317E mutant in HEK293 cells showed that the mutation did not block corin expression on the cell surface but inhibited corin zymogen activation. In contrast, the mutation S472G was predicted to abolish a β-sheet critical for corin frizzled-2 module structure. In Western blot analysis and flow cytometry, S472G mutant was not detected on the cell surface in transfected HEK293 cells. By immunostaining, the S472G mutant was found in the ER, indicating that the mutation S472G disrupted the β-sheet, causing corin misfolding and ER retention. Thus, these results show that mutations in the CORIN gene may impair corin function by entirely different mechanisms. Together, our data provide important insights into the molecular basis underlying corin mutations that may contribute to preeclampsia in patients. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Pathogenic adaptation of intracellular bacteria by rewiring a cis-regulatory input function.

PubMed

Osborne, Suzanne E; Walthers, Don; Tomljenovic, Ana M; Mulder, David T; Silphaduang, Uma; Duong, Nancy; Lowden, Michael J; Wickham, Mark E; Waller, Ross F; Kenney, Linda J; Coombes, Brian K

2009-03-10

The acquisition of DNA by horizontal gene transfer enables bacteria to adapt to previously unexploited ecological niches. Although horizontal gene transfer and mutation of protein-coding sequences are well-recognized forms of pathogen evolution, the evolutionary significance of cis-regulatory mutations in creating phenotypic diversity through altered transcriptional outputs is not known. We show the significance of regulatory mutation for pathogen evolution by mapping and then rewiring a cis-regulatory module controlling a gene required for murine typhoid. Acquisition of a binding site for the Salmonella pathogenicity island-2 regulator, SsrB, enabled the srfN gene, ancestral to the Salmonella genus, to play a role in pathoadaptation of S. typhimurium to a host animal. We identified the evolved cis-regulatory module and quantified the fitness gain that this regulatory output accrues for the bacterium using competitive infections of host animals. Our findings highlight a mechanism of pathogen evolution involving regulatory mutation that is selected because of the fitness advantage the new regulatory output provides the incipient clones.

Pathogenic adaptation of intracellular bacteria by rewiring a cis-regulatory input function

PubMed Central

Osborne, Suzanne E.; Walthers, Don; Tomljenovic, Ana M.; Mulder, David T.; Silphaduang, Uma; Duong, Nancy; Lowden, Michael J.; Wickham, Mark E.; Waller, Ross F.; Kenney, Linda J.; Coombes, Brian K.

2009-01-01

The acquisition of DNA by horizontal gene transfer enables bacteria to adapt to previously unexploited ecological niches. Although horizontal gene transfer and mutation of protein-coding sequences are well-recognized forms of pathogen evolution, the evolutionary significance of cis-regulatory mutations in creating phenotypic diversity through altered transcriptional outputs is not known. We show the significance of regulatory mutation for pathogen evolution by mapping and then rewiring a cis-regulatory module controlling a gene required for murine typhoid. Acquisition of a binding site for the Salmonella pathogenicity island-2 regulator, SsrB, enabled the srfN gene, ancestral to the Salmonella genus, to play a role in pathoadaptation of S. typhimurium to a host animal. We identified the evolved cis-regulatory module and quantified the fitness gain that this regulatory output accrues for the bacterium using competitive infections of host animals. Our findings highlight a mechanism of pathogen evolution involving regulatory mutation that is selected because of the fitness advantage the new regulatory output provides the incipient clones. PMID:19234126

In vivo levels of S-adenosylmethionine modulate C:G to T:A mutations associated with repeat-induced point mutation in Neurospora crassa.

PubMed

Rosa, Alberto Luis; Folco, Hernán Diego; Mautino, Mario Ricardo

2004-04-14

In Neurospora crassa, the mutagenic process termed repeat-induced point mutation (RIP) inactivates duplicated DNA sequences during the sexual cycle by the introduction of C:G to T:A transition mutations. In this work, we have used a collection of N. crassa strains exhibiting a wide range of cellular levels of S-adenosylmethionine (AdoMet), the universal donor of methyl groups, to explore whether frequencies of RIP are dependent on the cellular levels of this metabolite. Mutant strains met-7 and eth-1 carry mutations in genes of the AdoMet pathway and have low levels of AdoMet. Wild type strains with high levels of AdoMet were constructed by introducing a chimeric transgene of the AdoMet synthetase (AdoMet-S) gene fused to the constitutive promoter trpC from Aspergillus nidulans. Crosses of these strains against tester duplications of the pan-2 and am genes showed that frequencies of RIP, as well as the total number of C:G to T:A transition mutations found in randomly selected am(RIP) alleles, are inversely correlated to the cellular level of AdoMet. These results indicate that AdoMet modulates the biochemical pathway leading to RIP.

A Gene Module-Based eQTL Analysis Prioritizing Disease Genes and Pathways in Kidney Cancer.

PubMed

Yang, Mary Qu; Li, Dan; Yang, William; Zhang, Yifan; Liu, Jun; Tong, Weida

2017-01-01

Clear cell renal cell carcinoma (ccRCC) is the most common and most aggressive form of renal cell cancer (RCC). The incidence of RCC has increased steadily in recent years. The pathogenesis of renal cell cancer remains poorly understood. Many of the tumor suppressor genes, oncogenes, and dysregulated pathways in ccRCC need to be revealed for improvement of the overall clinical outlook of the disease. Here, we developed a systems biology approach to prioritize the somatic mutated genes that lead to dysregulation of pathways in ccRCC. The method integrated multi-layer information to infer causative mutations and disease genes. First, we identified differential gene modules in ccRCC by coupling transcriptome and protein-protein interactions. Each of these modules consisted of interacting genes that were involved in similar biological processes and their combined expression alterations were significantly associated with disease type. Then, subsequent gene module-based eQTL analysis revealed somatic mutated genes that had driven the expression alterations of differential gene modules. Our study yielded a list of candidate disease genes, including several known ccRCC causative genes such as BAP1 and PBRM1 , as well as novel genes such as NOD2, RRM1, CSRNP1, SLC4A2, TTLL1 and CNTN1. The differential gene modules and their driver genes revealed by our study provided a new perspective for understanding the molecular mechanisms underlying the disease. Moreover, we validated the results in independent ccRCC patient datasets. Our study provided a new method for prioritizing disease genes and pathways.

γ-Secretase Modulators and APH1 Isoforms Modulate γ-Secretase Cleavage but Not Position of ε-Cleavage of the Amyloid Precursor Protein (APP).

PubMed

Lessard, Christian B; Cottrell, Barbara A; Maruyama, Hiroko; Suresh, Suraj; Golde, Todd E; Koo, Edward H

2015-01-01

The relative increase in Aβ42 peptides from familial Alzheimer disease (FAD) linked APP and PSEN mutations can be related to changes in both ε-cleavage site utilization and subsequent step-wise cleavage. Cleavage at the ε-site releases the amyloid precursor protein (APP) intracellular domain (AICD), and perturbations in the position of ε-cleavage are closely associated with changes in the profile of amyloid β-protein (Aβ) species that are produced and secreted. The mechanisms by which γ-secretase modulators (GSMs) or FAD mutations affect the various γ-secretase cleavages to alter the generation of Aβ peptides have not been fully elucidated. Recent studies suggested that GSMs do not modulate ε-cleavage of APP, but the data were derived principally from recombinant truncated epitope tagged APP substrate. Here, using full length APP from transfected cells, we investigated whether GSMs modify the ε-cleavage of APP under more native conditions. Our results confirmed the previous findings that ε-cleavage is insensitive to GSMs. In addition, fenofibrate, an inverse GSM (iGSM), did not alter the position or kinetics of ε-cleavage position in vitro. APH1A and APH1B, a subunit of the γ-secretase complex, also modulated Aβ42/Aβ40 ratio without any alterations in ε-cleavage, a result in contrast to what has been observed with PS1 and APP FAD mutations. Consequently, GSMs and APH1 appear to modulate γ-secretase activity and Aβ42 generation by altering processivity but not ε-cleavage site utilization.

Increased Trunk Extension Endurance is Associated with Meaningful Improvement in Balance among Older Adults with Mobility Problems

PubMed Central

Suri, Pradeep; Kiely, Dan K.; Leveille, Suzanne G.; Frontera, Walter R.; Bean, Jonathan. F.

2011-01-01

Objective To determine if trunk extension endurance changes with training are associated with clinically meaningful improvements in balance among mobility-limited older adults. Design Longitudinal data from a randomized clinical trial. Setting Outpatient rehabilitation research center. Participants Community-dwelling older adults (N=64; mean age 75.9 y) with mobility limitations as defined by a score of 4 to 10 on the Short Physical Performance Battery. Interventions 16 weeks of progressive resistance training. Main Outcome Measures Outcomes were the Berg Balance Scale (BBS) and the Unipedal Stance Test (UST). Predictors included leg strength, leg power, trunk extension endurance and the product of heart rate and blood pressure (RPP) at the final stage of an exercise tolerance test. We performed an analysis of data from participants who completed 16 weeks of training using binary outcomes defined by a clinically meaningful change from baseline to completion of the intervention (CMC) (BBS= 4 units; UST= 5 seconds). The association of predictor variables with balance outcomes was examined separately and together in multivariate adjusted logistic regression models. Results Trunk extension endurance in seconds (1.04 [1.00– 1.09]) was independently associated with CMC on the BBS. Trunk extension endurance (1.02 [1.00– 1.03]) was independently associated with CMC on the UST. Other physical attributes were not associated with meaningful change in balance. Conclusions Improvements in trunk extension endurance were independently associated with clinically meaningful changes in balance in older adults. Leg strength, leg power, and RPP were not associated with CMC in balance. Poor trunk extension endurance may be a rehabilitative impairment worthy of further study as a modifiable factor linked to balance among older adults. PMID:21636073

Increased trunk extension endurance is associated with meaningful improvement in balance among older adults with mobility problems.

PubMed

Suri, Pradeep; Kiely, Dan K; Leveille, Suzanne G; Frontera, Walter R; Bean, Jonathan F

2011-07-01

To determine whether trunk extension endurance changes with training are associated with clinically meaningful improvements in balance among mobility-limited older adults. Longitudinal data from a randomized controlled trial. Outpatient rehabilitation research center. Community-dwelling older adults (N=64; mean age, 75.9y) with mobility limitations as defined by a score of 4 to 10 on the Short Physical Performance Battery. Sixteen weeks of progressive resistance training. Outcomes were the Berg Balance Scale (BBS) and the Unipedal Stance Time (UST). Predictors included leg strength, leg power, trunk extension endurance, and the product of heart rate and blood pressure (RPP) at the final stage of an exercise tolerance test. We performed an analysis of data from participants who completed 16 weeks of training by using binary outcomes defined by a clinically meaningful change (CMC) from baseline to completion of the intervention (BBS=4 units; UST=5s). The association of predictor variables with balance outcomes was examined separately and together in multivariate adjusted logistic regression models. Trunk extension endurance in seconds (1.04 [1.00-1.09]) was independently associated with CMC on the BBS. Trunk extension endurance (1.02 [1.00-1.03]) was independently associated with CMC on the UST. Other physical attributes were not associated with meaningful change in balance. Improvements in trunk extension endurance were independently associated with CMCs in balance in older adults. Leg strength, leg power, and RPP were not associated with CMC in balance. Poor trunk extension endurance may be a rehabilitative impairment worthy of further study as a modifiable factor linked to balance among older adults. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Long-term outcomes of covered self-expandable metal stents for treating benign biliary strictures.

PubMed

Park, Jin-Seok; Lee, Sang Soo; Song, Tae Jun; Park, Do Hyun; Seo, Dong-Wan; Lee, Sung Koo; Han, Seungbong; Kim, Myung-Hwan

2016-05-01

Fully covered, self-expandable metal stents (FCSEMSs) are acceptable tools for treating benign biliary stricture (BBS). However, little is known about the long-term outcomes of this technique. The aim of the present study was to evaluate the procedural and long-term outcomes of FCSEMSs for treating BBSs. A total of 134 consecutive patients (median age 56 years; range 21 - 83) with BBS were retrospectively reviewed. The main outcomes were technical and clinical success, stricture resolution, recurrence, and adverse events. Outcomes were analyzed by reviewing patient medical records. The success rates of FCSEMS placement and removal were 99.3 % and 98.2 %, respectively. Stricture resolution occurred in 103/132 (78.0 %) of the patients (median stent duration, 93 days; range 1 - 489). The associated factors for stricture resolution were longer stent indwelling period (≥ 120 days) and absence of stent migration. Stricture recurrence was seen in 26/103 patients (25.2 %; 95 % confidence interval [CI] 0.17 - 0.34) within a median of 390 days (range 4 - 903 days). Chronic pancreatitis was associated with stricture recurrence (hazard ratio [HR] 2.59, 95 %CI 1.20 - 5.61; P = 0.02). Stent migration occurred in 41/132 patients (31.1 %; 95 %CI 0.23 - 0.39). The FCSEMS with anchoring flaps appeared to protect against stent migration (HR 0.22, 95 %CI 0.08 - 0.63; P < 0.01). FCSEMSs had a high success rate for BBS resolution. Longer indwelling periods and the absence of stent migration might be important factors for stricture resolution. © Georg Thieme Verlag KG Stuttgart · New York.

Functional capacity and dependency in transfer and dressing are associated with depressive symptoms in older people.

PubMed

Boström, Gustaf; Conradsson, Mia; Rosendahl, Erik; Nordström, Peter; Gustafson, Yngve; Littbrand, Håkan

2014-01-01

This study examined associations between depressive symptoms and functional capacity, overall dependency in personal activities of daily living (ADLs), and dependency in individual ADL tasks, respectively, in people with a high mean age, large range of functional capacity, and wide spectrum of dependency in ADLs. Cross-sectional data from three studies were used. A total of 392 individuals living in community and residential care facilities were included. Mean age was 86.2 years, 72% were women, 75% were dependent in ADLs, 42% had depression, and 39% had dementia. Depressive symptoms were assessed with the 15-item Geriatric Depression Scale (GDS-15), functional capacity with the Berg Balance Scale (BBS), and ADLs with the Barthel ADL Index. Multiple linear regression analyses with comprehensive adjustments were performed between GDS-15 and BBS, GDS-15 and Barthel ADL Index, and GDS-15 and each individual ADL task, separately. GDS-15 score was associated with BBS score (unstandardized b =-0.03, P=0.008), but not with Barthel ADL Index score (unstandardized b =-0.07, P=0.068). No significant interaction effects of sex, dementia, or living conditions were found in these associations. Among individual ADL tasks, dependency in transfer (unstandardized b =-1.03, P=0.007) and dressing (unstandardized b =-0.70, P=0.035) were associated with depressive symptoms. Functional capacity seems to be independently associated with depressive symptoms in older people living in community and residential care facilities, whereas overall ADL performance may not be associated. Dependency in the individual ADL tasks of transfer and dressing appear to be independently associated with depressive symptoms and may be an important focus of future interdisciplinary multifactorial intervention studies.

Functional capacity and dependency in transfer and dressing are associated with depressive symptoms in older people

PubMed Central

Boström, Gustaf; Conradsson, Mia; Rosendahl, Erik; Nordström, Peter; Gustafson, Yngve; Littbrand, Håkan

2014-01-01

Background This study examined associations between depressive symptoms and functional capacity, overall dependency in personal activities of daily living (ADLs), and dependency in individual ADL tasks, respectively, in people with a high mean age, large range of functional capacity, and wide spectrum of dependency in ADLs. Methods Cross-sectional data from three studies were used. A total of 392 individuals living in community and residential care facilities were included. Mean age was 86.2 years, 72% were women, 75% were dependent in ADLs, 42% had depression, and 39% had dementia. Depressive symptoms were assessed with the 15-item Geriatric Depression Scale (GDS-15), functional capacity with the Berg Balance Scale (BBS), and ADLs with the Barthel ADL Index. Multiple linear regression analyses with comprehensive adjustments were performed between GDS-15 and BBS, GDS-15 and Barthel ADL Index, and GDS-15 and each individual ADL task, separately. Results GDS-15 score was associated with BBS score (unstandardized b =−0.03, P=0.008), but not with Barthel ADL Index score (unstandardized b =−0.07, P=0.068). No significant interaction effects of sex, dementia, or living conditions were found in these associations. Among individual ADL tasks, dependency in transfer (unstandardized b =−1.03, P=0.007) and dressing (unstandardized b =−0.70, P=0.035) were associated with depressive symptoms. Conclusion Functional capacity seems to be independently associated with depressive symptoms in older people living in community and residential care facilities, whereas overall ADL performance may not be associated. Dependency in the individual ADL tasks of transfer and dressing appear to be independently associated with depressive symptoms and may be an important focus of future interdisciplinary multifactorial intervention studies. PMID:24523582

Reliability and minimal detectable change of physical performance measures in individuals with pre-manifest and manifest Huntington disease.

PubMed

Quinn, Lori; Khalil, Hanan; Dawes, Helen; Fritz, Nora E; Kegelmeyer, Deb; Kloos, Anne D; Gillard, Jonathan W; Busse, Monica

2013-07-01

Clinical intervention trials in people with Huntington disease (HD) have been limited by a lack of reliable and appropriate outcome measures. The purpose of this study was to determine the reliability and minimal detectable change (MDC) of various outcome measures that are potentially suitable for evaluating physical functioning in individuals with HD. This was a multicenter, prospective, observational study. Participants with pre-manifest and manifest HD (early, middle, and late stages) were recruited from 8 international sites to complete a battery of physical performance and functional measures at 2 assessments, separated by 1 week. Test-retest reliability (using intraclass correlation coefficients) and MDC values were calculated for all measures. Seventy-five individuals with HD (mean age=52.12 years, SD=11.82) participated in the study. Test-retest reliability was very high (>.90) for participants with manifest HD for the Six-Minute Walk Test (6MWT), 10-Meter Walk Test, Timed "Up & Go" Test (TUG), Berg Balance Scale (BBS), Physical Performance Test (PPT), Barthel Index, Rivermead Mobility Index, and Tinetti Mobility Test (TMT). Many MDC values suggested a relatively high degree of inherent variability, particularly in the middle stage of HD. Minimum detectable change values for participants with manifest HD that were relatively low across disease stages were found for the BBS (5), PPT (5), and TUG (2.98). For individuals with pre-manifest HD (n=11), the 6MWT and Four Square Step Test had high reliability and low MDC values. The sample size for the pre-manifest HD group was small. The BBS, PPT, and TUG appear most appropriate for clinical trials aimed at improving physical functioning in people with manifest HD. Further research in people with pre-manifest HD is necessary.

Interpretability of Change Scores in Measures of Balance in People With COPD.

PubMed

Beauchamp, Marla K; Harrison, Samantha L; Goldstein, Roger S; Brooks, Dina

2016-03-01

Balance deficits and an increased fall risk are well documented in individuals with COPD. Despite evidence that balance training programs can improve performance on clinical balance tests, their minimal clinically important difference (MCID) is unknown. The aim of this study was to determine the MCID of the Berg Balance Scale (BBS), Balance Evaluation Systems Test (BESTest), and Activities-Specific Balance Confidence (ABC) scale in patients with COPD undergoing pulmonary rehabilitation. We performed a secondary analysis of data from two studies of balance training in COPD (n = 55). The MCID for each balance measure was estimated using the following anchor and distribution-based approaches: (1) mean change scores on a patient-reported global change in balance scale, (2) optimal cut-point from receiver operating characteristic curves (ROCs), and (3) the minimal detectable change with 95% confidence (MDC95). Data from 55 patients with COPD (mean age, 71.2 ± 7.1 y; mean FEV1, 39.2 ± 15.8% predicted) were used in the analysis. The smallest estimate of MCID was from the ROC method. Anchor-based estimates of the MCID ranged from 3.5 to 7.1 for the BBS, 10.2 to 17.4 for the BESTest, and 14.2 to 18.5 for the ABC scale; their MDC95 values were 5.0, 13.1, and 18.9, respectively. Among patients with COPD undergoing pulmonary rehabilitation, a change of 5 to 7 points for the BBS, 13 to 17 points for the BESTest, and 19 points for the ABC scale is required to be both perceptible to patients and beyond measurement error. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Defining the Human Macula Transcriptome and Candidate Retinal Disease Genes UsingEyeSAGE

PubMed Central

Rickman, Catherine Bowes; Ebright, Jessica N.; Zavodni, Zachary J.; Yu, Ling; Wang, Tianyuan; Daiger, Stephen P.; Wistow, Graeme; Boon, Kathy; Hauser, Michael A.

2009-01-01

Purpose To develop large-scale, high-throughput annotation of the human macula transcriptome and to identify and prioritize candidate genes for inherited retinal dystrophies, based on ocular-expression profiles using serial analysis of gene expression (SAGE). Methods Two human retina and two retinal pigment epithelium (RPE)/choroid SAGE libraries made from matched macula or midperipheral retina and adjacent RPE/choroid of morphologically normal 28- to 66-year-old donors and a human central retina longSAGE library made from 41- to 66-year-old donors were generated. Their transcription profiles were entered into a relational database, EyeSAGE, including microarray expression profiles of retina and publicly available normal human tissue SAGE libraries. EyeSAGE was used to identify retina- and RPE-specific and -associated genes, and candidate genes for retina and RPE disease loci. Differential and/or cell-type specific expression was validated by quantitative and single-cell RT-PCR. Results Cone photoreceptor-associated gene expression was elevated in the macula transcription profiles. Analysis of the longSAGE retina tags enhanced tag-to-gene mapping and revealed alternatively spliced genes. Analysis of candidate gene expression tables for the identified Bardet-Biedl syndrome disease gene (BBS5) in the BBS5 disease region table yielded BBS5 as the top candidate. Compelling candidates for inherited retina diseases were identified. Conclusions The EyeSAGE database, combining three different gene-profiling platforms including the authors’ multidonor-derived retina/RPE SAGE libraries and existing single-donor retina/RPE libraries, is a powerful resource for definition of the retina and RPE transcriptomes. It can be used to identify retina-specific genes, including alternatively spliced transcripts and to prioritize candidate genes within mapped retinal disease regions. PMID:16723438

Defining the human macula transcriptome and candidate retinal disease genes using EyeSAGE.

PubMed

Bowes Rickman, Catherine; Ebright, Jessica N; Zavodni, Zachary J; Yu, Ling; Wang, Tianyuan; Daiger, Stephen P; Wistow, Graeme; Boon, Kathy; Hauser, Michael A

2006-06-01

To develop large-scale, high-throughput annotation of the human macula transcriptome and to identify and prioritize candidate genes for inherited retinal dystrophies, based on ocular-expression profiles using serial analysis of gene expression (SAGE). Two human retina and two retinal pigment epithelium (RPE)/choroid SAGE libraries made from matched macula or midperipheral retina and adjacent RPE/choroid of morphologically normal 28- to 66-year-old donors and a human central retina longSAGE library made from 41- to 66-year-old donors were generated. Their transcription profiles were entered into a relational database, EyeSAGE, including microarray expression profiles of retina and publicly available normal human tissue SAGE libraries. EyeSAGE was used to identify retina- and RPE-specific and -associated genes, and candidate genes for retina and RPE disease loci. Differential and/or cell-type specific expression was validated by quantitative and single-cell RT-PCR. Cone photoreceptor-associated gene expression was elevated in the macula transcription profiles. Analysis of the longSAGE retina tags enhanced tag-to-gene mapping and revealed alternatively spliced genes. Analysis of candidate gene expression tables for the identified Bardet-Biedl syndrome disease gene (BBS5) in the BBS5 disease region table yielded BBS5 as the top candidate. Compelling candidates for inherited retina diseases were identified. The EyeSAGE database, combining three different gene-profiling platforms including the authors' multidonor-derived retina/RPE SAGE libraries and existing single-donor retina/RPE libraries, is a powerful resource for definition of the retina and RPE transcriptomes. It can be used to identify retina-specific genes, including alternatively spliced transcripts and to prioritize candidate genes within mapped retinal disease regions.

Prognostic impact of heart rate in elderly with systolic heart failure and concomitant atrial fibrillation.

PubMed

Barywani, Salim; Petzold, Max

2017-08-01

The present study aimed to investigate the impact of resting heart rate (HR) on 5-year all-cause mortality in patients ≥80 years with heart failure (HF) with reduced ejection fraction (HFrEF) and concomitant atrial fibrillation (AF) after optimal up-titration of beta-blockers (BBs). Patients (n = 185) aged ≥80 years with HF and left ventricular ejection fraction ≤40% were included between January 2000 and January 2008 from two university hospitals, Sahlgrenska and Östra and retrospectively studied from January 2 to May 30, 2013. Up-titrations of guideline recommended medications were performed at HF outpatient clinics. Of whole study population, 54% (n= 100) had AF. After optimal up-titration of BBs and angiotensin converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), mean HR in patients with AF was 73 ± 15 beats/minute (bpm), 36% had resting HR ≤65 bpm. Five-year all-cause mortality among patients with AF was significantly lower in patients with HR ≤65 bpm (63%) compared to HR >65 (80%). Cox proportional-hazard regression analysis adjusted for clinically important baseline variables and doses of ACEIs/ARBs and BBs demonstrated resting HR ≤65 bpm as an independent predictor of improved survival compared to resting HR >65 bpm (HR 0.3, 95%CI 0.1-0.7, P 0.005). In octogenarians with HFrEF and concomitant AF, lowering resting HR to levels as low as HR ≤65 bpm was still associated with improved survival from all-cause mortality. Our data indicate that mortality in AF became comparable to SR when patients were on maximally up-titrated beta-blocker doses with HR as low as 75 bpm.

Modeling trends from North American Breeding Bird Survey data: a spatially explicit approach

USGS Publications Warehouse

Bled, Florent; Sauer, John R.; Pardieck, Keith L.; Doherty, Paul; Royle, J. Andy

2013-01-01

Population trends, defined as interval-specific proportional changes in population size, are often used to help identify species of conservation interest. Efficient modeling of such trends depends on the consideration of the correlation of population changes with key spatial and environmental covariates. This can provide insights into causal mechanisms and allow spatially explicit summaries at scales that are of interest to management agencies. We expand the hierarchical modeling framework used in the North American Breeding Bird Survey (BBS) by developing a spatially explicit model of temporal trend using a conditional autoregressive (CAR) model. By adopting a formal spatial model for abundance, we produce spatially explicit abundance and trend estimates. Analyses based on large-scale geographic strata such as Bird Conservation Regions (BCR) can suffer from basic imbalances in spatial sampling. Our approach addresses this issue by providing an explicit weighting based on the fundamental sample allocation unit of the BBS. We applied the spatial model to three species from the BBS. Species have been chosen based upon their well-known population change patterns, which allows us to evaluate the quality of our model and the biological meaning of our estimates. We also compare our results with the ones obtained for BCRs using a nonspatial hierarchical model (Sauer and Link 2011). Globally, estimates for mean trends are consistent between the two approaches but spatial estimates provide much more precise trend estimates in regions on the edges of species ranges that were poorly estimated in non-spatial analyses. Incorporating a spatial component in the analysis not only allows us to obtain relevant and biologically meaningful estimates for population trends, but also enables us to provide a flexible framework in order to obtain trend estimates for any area.

Effective treatment of benign biliary strictures with a removable, fully covered, self-expandable metal stent: A prospective, multicenter European study

PubMed Central

Schmidt, Arthur; Pickartz, Tilman; Lerch, Markus M; Fanelli, Fabrizio; Fiocca, Fausto; Lucatelli, Pierleone; Cereatti, Fabrizio; Hoffmeister, Albrecht; van Steenbergen, Werner; Kraft, Matthias; Meier, Benjamin

2016-01-01

Background Temporary placement of removable, fully covered, self-expandable metal stents (fcSEMS) for treatment of benign biliary strictures (BBS) has been reported to be effective. However, the optimal extraction time point remains unclear and stent migration has been a major concern. Objective The objective of this study was to evaluate the efficacy and safety of this treatment modality using an fcSEMS with a special antimigration design and prolonged stent indwell time. Methods We performed a prospective, single-arm study at six tertiary care centers in Europe. Patients with BBS underwent endoscopic or percutaneous implantation of an fcSEMS (GORE® VIABIL® Biliary Endoprosthesis, W.L. Gore & Associates, Flagstaff, AZ, USA). The devices were scheduled to be removed nine months later, and patients were to return for follow-up for an additional 15 months. Results Forty-three patients were enrolled in the study. Stricture etiology was chronic pancreatitis in the majority of patients (57.5%). All fcSEMS were placed successfully, either endoscopically (76.7%) or percutaneously (23.3%). Stent migration was observed in two patients (5.2%). Primary patency of the SEMS prior to removal was 73.0%. All attempted stent removals were successful. At removal, stricture was resolved or significantly improved without need for further therapy in 78.9% of patients. Stricture recurrence during a follow-up of two years post-implant was observed in two patients. Conclusions Temporary placement of the fcSEMS is a feasible, safe and effective treatment for BBS. The design of the device used in this study accounts for very low migration rates and facilitates easy stent retrieval, even after it has been in place for up to 11 months. PMID:28507752

Long-term decline and short-term crash of the once abundant Rusty Blackbird

USGS Publications Warehouse

Greenberg, R.; Blancher, P.; Niven, D.; Droege, S.

2008-01-01

The Rusty Blackbird (Euphagus carolinus), a formerly common breeding species of boreal wetlands, has exhibited the most marked decline of any North American landbird. North American Breeding Bird Survey (BBS) trends in abundance are estimated to be -12.5% / yr over the last 40 years, which is tantamount to a >95% cumulative decline. Trends in abundance calculated from Christmas Bird Counts (CBC) for a similar period indicate a range-wide decline of -5.6% / yr. Qualitative analyses of ornithological accounts suggest the species has been declining for over a century before the period covered by the estimated declines. Several studies document range retraction in the southern boreal forest, whereas limited data suggest that abundance may be more stable in more northerly areas. This pattern is both supported and contradicted by winter declines based in CBC data. The lower estimates of decline in the CBC data compared to BBS is consistent with the idea that the coverage of BBS is biased towards the southern boreal whereas CBC covers the entire winter range. However, the CBC declines are similar between the South Atlantic coast (with populations derived from the southeastern boreal) and the Mississippi Valley (populations from the northwest boreal). The major hypotheses for the decline include degradation of boreal habitats from logging and agricultural agricultural development, mercury contamination, and wetland desiccation resulting from global warming. Other likely reasons for decline include loss or degradation of wooded wetlands of the southeastern U.S and mortality associated with abatement efforts targeting nuisance blackbirds. We present a matrix of hypotheses and predictions that test them based on the geography of decline and more detailed indicators of population health which should form the strategic basis of future research.

How well do route survey areas represent landscapes at larger spatial extents? An analysis of land cover composition along Breeding Bird Survey routes

USGS Publications Warehouse

Veech, Joseph A.; Pardieck, Keith L.; Ziolkowski, David

2017-01-01

The occurrence of birds in a survey unit is partly determined by the habitat present. Moreover, some bird species preferentially avoid some land cover types and are attracted to others. As such, land cover composition within the 400 m survey areas along a Breeding Bird Survey (BBS) route clearly influences the species available to be detected. Ideally, to extend survey results to the larger landscape, land cover composition within the survey area should be similar to that at larger spatial extents defining the landscape. Such representativeness helps minimize possible roadside effects (bias), here defined as differences in bird species composition and abundance along a roadside as compared to a larger surrounding landscape. We used land cover data from the 2011 National Land Cover Database to examine representativeness of land cover composition along routes. Using ArcGIS, the percentages of each of 15 land cover types within 400 m buffers along 2,696 U.S. BBS routes were calculated and compared to percentages in 2 km, 5 km, and 10 km buffers surrounding each route. This assessment revealed that aquatic cover types and highly urbanized land tend to be slightly underrepresented in the survey areas. Two anthropogenic cover types (pasture/hay and cropland) may be slightly overrepresented in the survey areas. Over all cover types, 92% of the 2,696 routes exhibited “good” representativeness, with <5 percentage points per cover type difference in proportional cover between the 400 m and 10 km buffers. This assessment further supports previous research indicating that any land-cover-based roadside bias in the bird data of the BBS is likely minimal.

Evidence for the decay B0→J/ψω and measurement of the relative branching fractions of Bs0 meson decays to J/ψη and J/ψη'

NASA Astrophysics Data System (ADS)

Aaij, R.; Abellan Beteta, C.; Adametz, A.; Adeva, B.; Adinolfi, M.; Adrover, C.; Affolder, A.; Ajaltouni, Z.; Albrecht, J.; Alessio, F.; Alexander, M.; Ali, S.; Alkhazov, G.; Alvarez Cartelle, P.; Alves, A. A.; Amato, S.; Amhis, Y.; Anderlini, L.; Anderson, J.; Appleby, R. B.; Aquines Gutierrez, O.; Archilli, F.; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Bachmann, S.; Back, J. J.; Baesso, C.; Balagura, V.; Baldini, W.; Barlow, R. J.; Barschel, C.; Barsuk, S.; Barter, W.; Bates, A.; Bauer, Th.; Bay, A.; Beddow, J.; Bediaga, I.; Belogurov, S.; Belous, K.; Belyaev, I.; Ben-Haim, E.; Benayoun, M.; Bencivenni, G.; Benson, S.; Benton, J.; Berezhnoy, A.; Bernet, R.; Bettler, M.-O.; van Beuzekom, M.; Bien, A.; Bifani, S.; Bird, T.; Bizzeti, A.; Bjørnstad, P. M.; Blake, T.; Blanc, F.; Blanks, C.; Blouw, J.; Blusk, S.; Bobrov, A.; Bocci, V.; Bondar, A.; Bondar, N.; Bonivento, W.; Borghi, S.; Borgia, A.; Bowcock, T. J. V.; Bozzi, C.; Brambach, T.; van den Brand, J.; Bressieux, J.; Brett, D.; Britsch, M.; Britton, T.; Brook, N. H.; Brown, H.; Büchler-Germann, A.; Burducea, I.; Bursche, A.; Buytaert, J.; Cadeddu, S.; Callot, O.; Calvi, M.; Calvo Gomez, M.; Camboni, A.; Campana, P.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carson, L.; Carvalho Akiba, K.; Casse, G.; Cattaneo, M.; Cauet, Ch.; Charles, M.; Charpentier, Ph.; Chen, P.; Chiapolini, N.; Chrzaszcz, M.; Ciba, K.; Cid Vidal, X.; Ciezarek, G.; Clarke, P. E. L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Coca, C.; Coco, V.; Cogan, J.; Cogneras, E.; Collins, P.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombes, M.; Corti, G.; Couturier, B.; Cowan, G. A.; Craik, D.; Cunliffe, S.; Currie, R.; D'Ambrosio, C.; David, P.; David, P. N. Y.; De Bonis, I.; De Bruyn, K.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Simone, P.; Decamp, D.; Deckenhoff, M.; Degaudenzi, H.; Del Buono, L.; Deplano, C.; Derkach, D.; Deschamps, O.; Dettori, F.; Dickens, J.; Dijkstra, H.; Diniz Batista, P.; Domingo Bonal, F.; Donleavy, S.; Dordei, F.; Dosil Suárez, A.; Dossett, D.; Dovbnya, A.; Dupertuis, F.; Dzhelyadin, R.; Dziurda, A.; Dzyuba, A.; Easo, S.; Egede, U.; Egorychev, V.; Eidelman, S.; van Eijk, D.; Eisele, F.; Eisenhardt, S.; Ekelhof, R.; Eklund, L.; El Rifai, I.; Elsasser, Ch.; Elsby, D.; Esperante Pereira, D.; Falabella, A.; Färber, C.; Fardell, G.; Farinelli, C.; Farry, S.; Fave, V.; Fernandez Albor, V.; Ferreira Rodrigues, F.; Ferro-Luzzi, M.; Filippov, S.; Fitzpatrick, C.; Fontana, M.; Fontanelli, F.; Forty, R.; Francisco, O.; Frank, M.; Frei, C.; Frosini, M.; Furcas, S.; Gallas Torreira, A.; Galli, D.; Gandelman, M.; Gandini, P.; Gao, Y.; Garnier, J.-C.; Garofoli, J.; Garra Tico, J.; Garrido, L.; Gaspar, C.; Gauld, R.; Gersabeck, E.; Gersabeck, M.; Gershon, T.; Ghez, Ph.; Gibson, V.; Gligorov, V. V.; Göbel, C.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gordon, H.; Grabalosa Gándara, M.; Graciani Diaz, R.; Granado Cardoso, L. A.; Graugés, E.; Graziani, G.; Grecu, A.; Greening, E.; Gregson, S.; Grünberg, O.; Gui, B.; Gushchin, E.; Guz, Yu.; Gys, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S. C.; Hall, S.; Hampson, T.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Harrison, J.; Harrison, P. F.; Hartmann, T.; He, J.; Heijne, V.; Hennessy, K.; Henrard, P.; Hernando Morata, J. A.; van Herwijnen, E.; Hicks, E.; Hill, D.; Hoballah, M.; Hopchev, P.; Hulsbergen, W.; Hunt, P.; Huse, T.; Hussain, N.; Huston, R. S.; Hutchcroft, D.; Hynds, D.; Iakovenko, V.; Ilten, P.; Imong, J.; Jacobsson, R.; Jaeger, A.; Jahjah Hussein, M.; Jans, E.; Jansen, F.; Jaton, P.; Jean-Marie, B.; Jing, F.; John, M.; Johnson, D.; Jones, C. R.; Jost, B.; Kaballo, M.; Kandybei, S.; Karacson, M.; Karbach, M.; Keaveney, J.; Kenyon, I. R.; Kerzel, U.; Ketel, T.; Keune, A.; Khanji, B.; Kim, Y. M.; Kochebina, O.; Komarov, I.; Komarov, V.; Koopman, R. F.; Koppenburg, P.; Korolev, M.; Kozlinskiy, A.; Kravchuk, L.; Kreplin, K.; Kreps, M.; Krocker, G.; Krokovny, P.; Kruse, F.; Kucharczyk, M.; Kudryavtsev, V.; Kvaratskheliya, T.; La Thi, V. N.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lambert, D.; Lambert, R. W.; Lanciotti, E.; Lanfranchi, G.; Langenbruch, C.; Latham, T.; Lazzeroni, C.; Le Gac, R.; van Leerdam, J.; Lees, J.-P.; Lefèvre, R.; Leflat, A.; Lefrançois, J.; Leroy, O.; Lesiak, T.; Li, L.; Li, Y.; Li Gioi, L.; Liles, M.; Lindner, R.; Linn, C.; Liu, B.; Liu, G.; von Loeben, J.; Lopes, J. H.; Lopez Asamar, E.; Lopez-March, N.; Lu, H.; Luisier, J.; Mac Raighne, A.; Machefert, F.; Machikhiliyan, I. V.; Maciuc, F.; Maev, O.; Magnin, J.; Maino, M.; Malde, S.; Manca, G.; Mancinelli, G.; Mangiafave, N.; Marconi, U.; Märki, R.; Marks, J.; Martellotti, G.; Martens, A.; Martin, L.; Martín Sánchez, A.; Martinelli, M.; Martinez Santos, D.; Massafferri, A.; Mathe, Z.; Matteuzzi, C.; Matveev, M.; Maurice, E.; Mazurov, A.; McCarthy, J.; McGregor, G.; McNulty, R.; Meissner, M.; Merk, M.; Merkel, J.; Milanes, D. A.; Minard, M.-N.; Molina Rodriguez, J.; Monteil, S.; Moran, D.; Morawski, P.; Mountain, R.; Mous, I.; Muheim, F.; Müller, K.; Muresan, R.; Muryn, B.; Muster, B.; Mylroie-Smith, J.; Naik, P.; Nakada, T.; Nandakumar, R.; Nasteva, I.; Needham, M.; Neufeld, N.; Nguyen, A. D.; Nguyen-Mau, C.; Nicol, M.; Niess, V.; Nikitin, N.; Nikodem, T.; Nomerotski, A.; Novoselov, A.; Oblakowska-Mucha, A.; Obraztsov, V.; Oggero, S.; Ogilvy, S.; Okhrimenko, O.; Oldeman, R.; Orlandea, M.; Otalora Goicochea, J. M.; Owen, P.; Pal, B. K.; Palano, A.; Palutan, M.; Panman, J.; Papanestis, A.; Pappagallo, M.; Parkes, C.; Parkinson, C. J.; Passaleva, G.; Patel, G. D.; Patel, M.; Patrick, G. N.; Patrignani, C.; Pavel-Nicorescu, C.; Pazos Alvarez, A.; Pellegrino, A.; Penso, G.; Pepe Altarelli, M.; Perazzini, S.; Perego, D. L.; Perez Trigo, E.; Pérez-Calero Yzquierdo, A.; Perret, P.; Perrin-Terrin, M.; Pessina, G.; Petridis, K.; Petrolini, A.; Phan, A.; Picatoste Olloqui, E.; Pie Valls, B.; Pietrzyk, B.; Pilař, T.; Pinci, D.; Playfer, S.; Plo Casasus, M.; Polci, F.; Polok, G.; Poluektov, A.; Polycarpo, E.; Popov, D.; Popovici, B.; Potterat, C.; Powell, A.; Prisciandaro, J.; Pugatch, V.; Puig Navarro, A.; Qian, W.; Rademacker, J. H.; Rakotomiaramanana, B.; Rangel, M. S.; Raniuk, I.; Rauschmayr, N.; Raven, G.; Redford, S.; Reid, M. M.; dos Reis, A. C.; Ricciardi, S.; Richards, A.; Rinnert, K.; Rives Molina, V.; Roa Romero, D. A.; Robbe, P.; Rodrigues, E.; Rodriguez Perez, P.; Rogers, G. J.; Roiser, S.; Romanovsky, V.; Romero Vidal, A.; Rouvinet, J.; Ruf, T.; Ruiz, H.; Sabatino, G.; Saborido Silva, J. J.; Sagidova, N.; Sail, P.; Saitta, B.; Salzmann, C.; Sanmartin Sedes, B.; Sannino, M.; Santacesaria, R.; Santamarina Rios, C.; Santinelli, R.; Santovetti, E.; Sapunov, M.; Sarti, A.; Satriano, C.; Satta, A.; Savrie, M.; Savrina, D.; Schaack, P.; Schiller, M.; Schindler, H.; Schleich, S.; Schlupp, M.; Schmelling, M.; Schmidt, B.; Schneider, O.; Schopper, A.; Schune, M.-H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Seco, M.; Semennikov, A.; Senderowska, K.; Sepp, I.; Serra, N.; Serrano, J.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shatalov, P.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, O.; Shevchenko, V.; Shires, A.; Silva Coutinho, R.; Skwarnicki, T.; Smith, N. A.; Smith, E.; Smith, M.; Sobczak, K.; Soler, F. J. P.; Solomin, A.; Soomro, F.; Souza, D.; Souza De Paula, B.; Spaan, B.; Sparkes, A.; Spradlin, P.; Stagni, F.; Stahl, S.; Steinkamp, O.; Stoica, S.; Stone, S.; Storaci, B.; Straticiuc, M.; Straumann, U.; Subbiah, V. K.; Swientek, S.; Szczekowski, M.; Szczypka, P.; Szumlak, T.; T'Jampens, S.; Teklishyn, M.; Teodorescu, E.; Teubert, F.; Thomas, C.; Thomas, E.; van Tilburg, J.; Tisserand, V.; Tobin, M.; Tolk, S.; Topp-Joergensen, S.; Torr, N.; Tournefier, E.; Tourneur, S.; Tran, M. T.; Tsaregorodtsev, A.; Tuning, N.; Ubeda Garcia, M.; Ukleja, A.; Urner, D.; Uwer, U.; Vagnoni, V.; Valenti, G.; Vazquez Gomez, R.; Vazquez Regueiro, P.; Vecchi, S.; Velthuis, J. J.; Veltri, M.; Veneziano, G.; Vesterinen, M.; Viaud, B.; Videau, I.; Vieira, D.; Vilasis-Cardona, X.; Visniakov, J.; Vollhardt, A.; Volyanskyy, D.; Voong, D.; Vorobyev, A.; Vorobyev, V.; Voss, H.; Voß, C.; Waldi, R.; Wallace, R.; Wandernoth, S.; Wang, J.; Ward, D. R.; Watson, N. K.; Webber, A. D.; Websdale, D.; Whitehead, M.; Wicht, J.; Wiedner, D.; Wiggers, L.; Wilkinson, G.; Williams, M. P.; Williams, M.; Wilson, F. F.; Wishahi, J.; Witek, M.; Witzeling, W.; Wotton, S. A.; Wright, S.; Wu, S.; Wyllie, K.; Xie, Y.; Xing, F.; Xing, Z.; Yang, Z.; Young, R.; Yuan, X.; Yushchenko, O.; Zangoli, M.; Zavertyaev, M.; Zhang, F.; Zhang, L.; Zhang, W. C.; Zhang, Y.; Zhelezov, A.; Zhong, L.; Zvyagin, A.; LHCb Collaboration

2013-02-01

First evidence of the B0→J/ψω decay is found and the Bs0→J/ψη and Bs0→J/ψη' decays are studied using a dataset corresponding to an integrated luminosity of 1.0 fb-1 collected by the LHCb experiment in proton-proton collisions at a centre-of-mass energy of √{s}=7 TeV. The branching fractions of these decays are measured relative to that of the B0→J/ψρ0 decay: {B(B0→J/ψω)}/{B(B0→J/ψρ0)}=0.89±0.19(stat)-0.13+0.07(syst), {B(B}/{s0→J/ψη)B(B0→J/ψρ0)}=14.0±1.2(stat)-1.5+1.1(syst)-1.0+1.1(fd/fs), {B(B}/{s0→J/ψη')B(B0→J/ψρ0)}=12.7±1.1(stat)-1.3+0.5(syst)-0.9+1.0(fd/fs), where the last uncertainty is due to the knowledge of fd/fs, the ratio of b-quark hadronization factors that accounts for the different production rate of B0 and Bs0 mesons. The ratio of the branching fractions of Bs0→J/ψη' and Bs0→J/ψη decays is measured to be {B(B}/{s0→J/ψη')B(Bs0→J/ψη)}=0.90±0.09(stat)-0.02+0.06(syst).

Effects of Virtual Reality Training using Xbox Kinect on Motor Function in Stroke Survivors: A Preliminary Study.

PubMed

Park, Dae-Sung; Lee, Do-Gyun; Lee, Kyeongbong; Lee, GyuChang

2017-10-01

Although the Kinect gaming system (Microsoft Corp, Redmond, WA) has been shown to be of therapeutic benefit in rehabilitation, the applicability of Kinect-based virtual reality (VR) training to improve motor function following a stroke has not been investigated. This study aimed to investigate the effects of VR training, using the Xbox Kinect-based game system, on the motor recovery of patients with chronic hemiplegic stroke. This was a randomized controlled trial. Twenty patients with hemiplegic stroke were randomly assigned to either the intervention group or the control group. Participants in the intervention group (n = 10) received 30 minutes of conventional physical therapy plus 30 minutes of VR training using Xbox Kinect-based games, and those in the control group (n = 10) received 30 minutes of conventional physical therapy only. All interventions consisted of daily sessions for a 6-week period. All measurements using Fugl-Meyer Assessment (FMA-LE), the Berg Balance Scale (BBS), the Timed Up and Go test (TUG), and the 10-meter Walk Test (10mWT) were performed at baseline and at the end of the 6 weeks. The scores on the FMA-LE, BBS, TUG, and 10mWT improved significantly from baseline to post intervention in both the intervention and the control groups after training. The pre-to-post difference scores on BBS, TUG, and 10mWT for the intervention group were significantly more improved than those for the control group (P <.05). Evidence from the present study supports the use of additional VR training with the Xbox Kinect gaming system as an effective therapeutic approach for improving motor function during stroke rehabilitation. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Effective treatment of benign biliary strictures with a removable, fully covered, self-expandable metal stent: A prospective, multicenter European study.

PubMed

Schmidt, Arthur; Pickartz, Tilman; Lerch, Markus M; Fanelli, Fabrizio; Fiocca, Fausto; Lucatelli, Pierleone; Cereatti, Fabrizio; Hoffmeister, Albrecht; van Steenbergen, Werner; Kraft, Matthias; Meier, Benjamin; Caca, Karel

2017-04-01

Temporary placement of removable, fully covered, self-expandable metal stents (fcSEMS) for treatment of benign biliary strictures (BBS) has been reported to be effective. However, the optimal extraction time point remains unclear and stent migration has been a major concern. The objective of this study was to evaluate the efficacy and safety of this treatment modality using an fcSEMS with a special antimigration design and prolonged stent indwell time. We performed a prospective, single-arm study at six tertiary care centers in Europe. Patients with BBS underwent endoscopic or percutaneous implantation of an fcSEMS (GORE® VIABIL® Biliary Endoprosthesis, W.L. Gore & Associates, Flagstaff, AZ, USA). The devices were scheduled to be removed nine months later, and patients were to return for follow-up for an additional 15 months. Forty-three patients were enrolled in the study. Stricture etiology was chronic pancreatitis in the majority of patients (57.5%). All fcSEMS were placed successfully, either endoscopically (76.7%) or percutaneously (23.3%). Stent migration was observed in two patients (5.2%). Primary patency of the SEMS prior to removal was 73.0%. All attempted stent removals were successful. At removal, stricture was resolved or significantly improved without need for further therapy in 78.9% of patients. Stricture recurrence during a follow-up of two years post-implant was observed in two patients. Temporary placement of the fcSEMS is a feasible, safe and effective treatment for BBS. The design of the device used in this study accounts for very low migration rates and facilitates easy stent retrieval, even after it has been in place for up to 11 months.

Total management of chronic obstructive pulmonary disease (COPD) as an independent risk factor for cardiovascular disease.

PubMed

Onishi, Katsuya

2017-08-01

Patients with cardiovascular disease (CVD) often have multiple comorbid conditions that may interact with each other, confound the choice of treatments, and reduce mortality. Chronic obstructive pulmonary disease (COPD) is one of the most important comorbidities of CVD, which causes serious consequences in patients with ischemic heart disease, stroke, arrhythmia, and heart failure. COPD shares common risk factors such as tobacco smoking and aging with CVD, is associated with less physical activity, and produces systemic inflammation and oxidative stress. Overall, patients with COPD have a 2-3-fold increased risk of CVD as compared to age-matched controls when adjusted for tobacco smoking. Chronic heart failure (HF) is a frequent and important comorbidity which has a significant impact on prognosis in COPD, and vice versa. HF overlaps in symptoms and signs and has a common comorbidity with COPD, so that diagnosis of COPD is difficult in patients with HF. The combination of HF and COPD presents many therapeutic challenges including beta-blockers (BBs) and beta-agonists. Inhaled long-acting bronchodilators including beta2-agonists and anticholinergics for COPD would not worsen HF. Diuretics are relatively safe, and angiotensin-converting enzyme inhibitors are preferred to treat HF accompanied with COPD. BBs are only relatively contraindicated in asthma, but not in COPD. Low doses of cardioselective BBs should be aggressively initiated in clinically stable patients with HF accompanied with COPD combined with close monitoring for signs of airway obstruction and gradually up-titrated to the maximum tolerated dose. Encouraging appropriate and aggressive treatment for both HF and COPD should be recommended to improve quality of life and mortality in HF patients with COPD. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Myristoylated alanine-rich C kinase substrate-mediated neurotensin release via protein kinase C-delta downstream of the Rho/ROK pathway.

PubMed

Li, Jing; O'Connor, Kathleen L; Greeley, George H; Blackshear, Perry J; Townsend, Courtney M; Evers, B Mark

2005-03-04

Myristoylated alanine-rich protein kinase C substrate (MARCKS) is a cellular substrate for protein kinase C (PKC). Recently, we have shown that PKC isoforms-alpha and -delta, as well as the Rho/Rho kinase (ROK) pathway, play a role in phorbol 12-myristate 13-acetate (PMA)-mediated secretion of the gut peptide neurotensin (NT) in the BON human endocrine cell line. Here, we demonstrate that activation of MARCKS protein is important for PMA- and bombesin (BBS)-mediated NT secretion in BON cells. Small interfering RNA (siRNA) to MARCKS significantly inhibited, whereas overexpression of wild-type MARCKS significantly increased PMA-mediated NT secretion. Endogenous MARCKS and green fluorescent protein-tagged wild-type MARCKS were translocated from membrane to cytosol upon PMA treatment, further confirming MARCKS activation. MARCKS phosphorylation was inhibited by PKC-delta siRNA, ROKalpha siRNA, and C3 toxin (a Rho protein inhibitor), suggesting that the PKC-delta and the Rho/ROK pathways are necessary for MARCKS activation. The phosphorylation of PKC-delta was inhibited by C3 toxin, demonstrating that the role of MARCKS in NT secretion was regulated by PKC-delta downstream of the Rho/ROK pathway. BON cell clones stably transfected with the receptor for gastrin releasing peptide, a physiologic stimulant of NT, and treated with BBS, the amphibian equivalent of gastrin releasing peptide, demonstrated a similar MARCKS phosphorylation as noted with PMA. BBS-mediated NT secretion was attenuated by MARCKS siRNA. Collectively, these findings provide evidence for novel signaling pathways, including the sequential regulation of MARCKS activity by Rho/ROK and PKC-delta proteins, in stimulated gut peptide secretion.

Falls prevention and balance rehabilitation in multiple sclerosis: a bi-centre randomised controlled trial.

PubMed

Cattaneo, Davide; Rasova, Kamila; Gervasoni, Elisa; Dobrovodská, Gabriela; Montesano, Angelo; Jonsdottir, Johanna

2018-03-01

People with Multiple Sclerosis (PwMS) have a high incidence of accidental falls that have a potentially detrimental effect on their daily life participation. The effect of balance specific rehabilitation on clinical balance measures and frequency of falls in PwMS was studied. A bi-centre randomised rater-blinded controlled trial. Participants in both groups received 20 treatment sessions. Participants in the intervention group received treatment aimed at improving balance and mobility. Participants in the control group received treatments to reduce limitations at activity and body function level. Primary measures were frequency of fallers (>1 fall in two months) and responders (>3 points improvement) at the Berg Balance Scale (BBS). Data was analysed according to an intention to treat approach. One hundred and nineteen participants were randomised. Following treatment frequency of fallers was 22% in the intervention group and 23% in the control group, odds ratio (OR) and (confidence limits): 1.05 (0.41 to 2.77). Responders on the BBS were 28% in the intervention group and 33% in the control group, OR = 0.75 (0.30 to 1.91). At follow up ORs for fallers and responders at BBS were 0.98 (0.48 to 2.01) and 0.79 (0.26 to 2.42), respectively. Twenty sessions 2-3 times/week of balance specific rehabilitation did not reduce fall frequency nor improve balance suggesting the need for more frequent and challenging interventions. Implications for Rehabilitation Programs for balance rehabilitation can improve balance but their effects in fall prevention are unclear. Twenty treatments sessions 2/3 times per week did not reduced frequency of falls in MS. The comparison with similar studies suggests that higher intensity of practice of highly challenging balance activities appears to be critical to maximizing effectiveness.

A small-group functional balance intervention for individuals with Alzheimer disease: a pilot study.

PubMed

Ries, Julie D; Drake, Jamie Michelle; Marino, Christopher

2010-03-01

Individuals with Alzheimer disease (AD) have a higher risk of falls than their cognitively intact peers. This pilot study was designed to assess the feasibility and effectiveness of a small-group balance exercise program for individuals with AD in a day center environment. Seven participants met the inclusion criteria: diagnosis of AD or probable AD, medical stability, and ability to walk (with or without assistive device). We used an exploratory pre- and post-test study design. Participants engaged in a functional balance exercise program in two 45-minute sessions each week for eight weeks. Balance activities were functional and concrete, and the intervention was organized into constant, blocked, massed practice. Outcome measures included Berg Balance Scale (BBS), Timed Up and Go (TUG), and gait speed (GS; self-selected and fast assessed by an instrumented walkway). Data were analyzed by comparing individual change scores with previously identified minimal detectable change scores at the 90% confidence level (MDC90). Pre- and post-test data were acquired for five participants (two participants withdrew). The BBS improved in all five participants, and improved > or = 6.4 points (the MDC90 for the BBS in three participants. Four participants improved their performance on the TUG, and three participants improved > or = 4.09 seconds (the MDC90 for the TUG). Self-selected GS increased > or = 9.44 cm/sec (the MDC90 for gait speed) in three participants. Two participants demonstrated post-test self-selected GS comparable with their pretest fast GS. This pilot study suggests that a small-group functional balance intervention for individuals with AD is feasible and effective. Although participants had no explicit memory of the program, four of five improved in at least two outcome measures. Larger scale functional balance intervention studies with individuals with AD are warranted.

Recovery of balance function among individuals with total knee arthroplasty: Comparison of responsiveness among four balance tests.

PubMed

Chan, Andy C M; Ouyang, Xi H; Jehu, Deborah A M; Chung, Raymond C K; Pang, Marco Y C

2018-01-01

Balance deficits are common after total knee arthroplasty (TKA); however the responsiveness of commonly used balance measurement tools has not been well defined. The objective of this prospective study was to compare the internal and external responsiveness of four measurement tools in assessing recovery of balance function following TKA. A total of 134 individuals with TKA (95 women; age: 66.3±6.6years) completed the Balance Evaluation Systems Test (BESTest), Mini-BESTest, Brief-BESTest, and Berg Balance Scale (BBS) at 2, 4, 8, 12, and 24 weeks post-TKA. The Functional Gait Assessment (FGA) served as the anchor measure, and was also measured across these time points. Internal responsiveness was indicated by the standardized response mean (SRM), while external responsiveness was reflected by the degree of association of the changes of balance scores with those of FGA. The SRM ranged from 0.60-1.14 for the BESTest, 0.40-0.94 for the Mini-BESTest, 0.27-0.91 for the Brief-BESTest, and 0.19-0.70 for the BBS, over time. The change in BESTest and Mini-BESTest scores predicted the change in the FGA scores across all time periods, except for the Mini-BESTest between weeks 12-24, accounting for 13-27%, and 12-24% of the variance, respectively. The Brief-BESTest scores only predicted FGA scores between the weeks 2-4 (R 2 =20%). The changes in BBS scores were not associated with the FGA. The BESTest is the most responsive in measuring recovery of balance among individuals with TKA. The Mini-BESTest is a reasonable option during time constraints. Copyright © 2017. Published by Elsevier B.V.

Feasibility study of short-term effects of chiropractic manipulation on older adults with impaired balance

PubMed Central

Hawk, Cheryl; Pfefer, Mark T.; Strunk, Richard; Ramcharan, Michael; Uhl, Nathan

2007-01-01

Abstract Objective The purpose of this study was to collect preliminary information on the effects of chiropractic spinal manipulation on reducing risk of falls in older adults with impaired balance, as assessed by the Berg Balance Scale (BBS). This information is necessary to develop a line of investigation into the role of chiropractic care on reduction of fall risk in this population. Methods Randomized, 2-group pretest/posttest design feasibility study with a target sample size of 10 (5 per group), conducted within the outpatient health center of a chiropractic college. Inclusion criteria were as follows: aged 60 years or older, able to stand on one leg <5 seconds, and able to attend all sessions. Patients were assigned to chiropractic care (CMT) or supervised exercise (EX) and scheduled for 2 visits per week for 8 weeks. Results A total of 26 people responded to recruitment; and 11 were enrolled: 6 in the CMT and 5 in the EX group. Two patients dropped out at the baseline visit when they were assigned to the EX group. One CMT patient dropped out in the seventh week because of a fall at home resulting in a leg fracture. All remaining patients were compliant with treatment protocols. Five of 6 CMT patients and 4 of 5 EX patients had baseline BBS scores <45, indicating increased risk of falls. At visit 16, 2 CMT and 1 of the 3 remaining EX patients had BBS scores <45. One mild and transient adverse event was noted. Conclusion Further investigation of the possible role of chiropractic care in reducing fall risk in this population appears feasible. PMID:19674706

A novel and simple test of gait adaptability predicts gold standard measures of functional mobility in stroke survivors.

PubMed

Hollands, K L; Pelton, T A; van der Veen, S; Alharbi, S; Hollands, M A

2016-01-01

Although there is evidence that stroke survivors have reduced gait adaptability, the underlying mechanisms and the relationship to functional recovery are largely unknown. We explored the relationships between walking adaptability and clinical measures of balance, motor recovery and functional ability in stroke survivors. Stroke survivors (n=42) stepped to targets, on a 6m walkway, placed to elicit step lengthening, shortening and narrowing on paretic and non-paretic sides. The number of targets missed during six walks and target stepping speed was recorded. Fugl-Meyer (FM), Berg Balance Scale (BBS), self-selected walking speed (SWWS) and single support (SS) and step length (SL) symmetry (using GaitRite when not walking to targets) were also assessed. Stepwise multiple-linear regression was used to model the relationships between: total targets missed, number missed with paretic and non-paretic legs, target stepping speed, and each clinical measure. Regression revealed a significant model for each outcome variable that included only one independent variable. Targets missed by the paretic limb, was a significant predictor of FM (F(1,40)=6.54, p=0.014,). Speed of target stepping was a significant predictor of each of BBS (F(1,40)=26.36, p<0.0001), SSWS (F(1,40)=37.00, p<0.0001). No variables were significant predictors of SL or SS asymmetry. Speed of target stepping was significantly predictive of BBS and SSWS and paretic targets missed predicted FM, suggesting that fast target stepping requires good balance and accurate stepping demands good paretic leg function. The relationships between these parameters indicate gait adaptability is a clinically meaningful target for measurement and treatment of functionally adaptive walking ability in stroke survivors. Copyright © 2015 Elsevier B.V. All rights reserved.

Reliability of the Balance Evaluation Systems Test (BESTest) and BESTest sections for adults with hemiparesis

PubMed Central

Rodrigues, Letícia C.; Marques, Aline P.; Barros, Paula B.; Michaelsen, Stella M.

2014-01-01

BACKGROUND: The Balance Evaluation Systems Test (BESTest) was recently created to allow the development of treatments according to the specific balance system affected in each patient. The Brazilian version of the BESTest has not been specifically tested after stroke. OBJECTIVE: To evaluate the intra- and inter-rater reliability and concurrent and convergent validity of the total score of the BESTest and BESTest sections for adults with hemiparesis after stroke. METHOD: The study included 16 subjects (61.1±7.5 years) with chronic hemiparesis (54.5±43.5 months after stroke). The BESTest was administered by two raters in the same week and one of the raters repeated the test after a one-week interval. Intraclass correlation coefficient (ICC) was calculated to assess intra- and interrater reliability. Concurrent validity with the Berg Balance Scale (BBS) and convergent validity with the Activities-specific Balance Confidence scale (ABC-Brazil) were assessed using Pearson's correlation coefficient. RESULTS: Both the BESTest total score (ICC=0.98) and the BESTest sections (ICC between 0.85 and 0.96) have excellent intrarater reliability. Interrater reliability for the total score was excellent (ICC=0.93) and, for the sections, it ranged between 0.71 and 0.94. The correlation coefficient between the BESTest and the BBS and ABC-Brazil were 0.78 and 0.59, respectively. CONCLUSIONS: The Brazilian version of the BESTest demonstrated adequate reliability when measured by sections and could identify what balance system was affected in patients after stroke. Concurrent validity was excellent with the BBS total score and good to excellent with the sections. The total scores but not the sections present adequate convergent validity with the ABC-Brazil. However, other psychometric properties should be further investigated. PMID:25003281

Effects on interaction kinetics of mutations at the VH-VL interface of Fabs depend on the structural context.

PubMed

Khalifa, M B; Weidenhaupt, M; Choulier, L; Chatellier, J; Rauffer-Bruyère, N; Altschuh, D; Vernet, T

2000-01-01

The influence of framework residues belonging to VH and VL modules of antibody molecules on antigen binding remains poorly understood. To investigate the functional role of such residues, we have performed semi-conservative amino acid replacements at the VH-VL interface. This work was carried out with (i) variants of the same antibody and (ii) with antibodies of different specificities (Fab fragments 145P and 1F1h), in order to check if functional effects are additive and/or similar for the two antibodies. Interaction kinetics of Fab mutants with peptide and protein antigens were measured using a BIACORE instrument. The substitutions introduced at the VH-VL interface had no significant effects on k(a) but showed small, significant effects on k(d). Mutations in the VH module affected k(d) not only for the two different antibodies but also for variants of the same antibody. These effects varied both in direction and in magnitude. In the VL module, the double mutation F(L37)L-Q(L38)L, alone or in combination with other mutations, consistently decreased k(d) about two-fold in Fab 145P. Other mutations in the VL module had no effect on k(d) in 145P, but always decreased k(d) in 1F1h. Moreover, in both systems, small-magnitude non-additive effects on k(d) were observed, but affinity variations seemed to be limited by a threshold. When comparing functional effects in antibodies of different specificity, no general rules could be established. In addition, no clear relationship could be pointed out between the nature of the amino acid change and the observed functional effect. Our results show that binding kinetics are affected by alteration of framework residues remote from the binding site, although these effects are unpredictable for most of the studied changes. Copyright 2000 John Wiley & Sons, Ltd.

Multiple Mutations Modulate the Function of Dihydrofolate Reductase in Trimethoprim-Resistant Streptococcus pneumoniae

PubMed Central

Maskell, Jeffrey P.; Sefton, Armine M.; Hall, Lucinda M. C.

2001-01-01

Trimethoprim resistance in Streptococcus pneumoniae can be conferred by a single amino acid substitution (I100-L) in dihydrofolate reductase (DHFR), but resistant clinical isolates usually carry multiple DHFR mutations. DHFR genes from five trimethoprim-resistant isolates from the United Kingdom were compared to susceptible isolates and used to transform a susceptible control strain (CP1015). All trimethoprim-resistant isolates and transformants contained the I100-L mutation. The properties of DHFRs from transformants with different combinations of mutations were compared. In a transformant with only the I100-L mutation (R12/T2) and a D92-A mutation also found in the DHFRs of susceptible isolates, the enzyme was much more resistant to trimethoprim inhibition (50% inhibitory concentration [IC50], 4.2 μM) than was the DHFR from strain CP1015 (IC50, 0.09 μM). However, Km values indicated a lower affinity for the enzyme's natural substrates (Km for dihydrofolate [DHF], 3.1 μM for CP1015 and 27.5 μM for R12/T2) and a twofold decrease in the specificity constant. In transformants with additional mutations in the C-terminal portion of the enzyme, Km values for DHF were reduced (9.2 to 15.2 μM), indicating compensation for the lower affinity generated by I100-L. Additional mutations in the N-terminal portion of the enzyme were associated with up to threefold-increased resistance to trimethoprim (IC50 of up to 13.7 μM). It is postulated that carriage of the mutation M53-I—which, like I100-L, corresponds to a trimethoprim binding site in the Escherichia coli DHFR—is responsible for this increase. This study demonstrates that although the I100-L mutation alone may give rise to trimethoprim resistance, additional mutations serve to enhance resistance and modulate the effects of existing mutations on the affinity of DHFR for its natural substrates. PMID:11257022

Mechanisms of viral mutation.

PubMed

Sanjuán, Rafael; Domingo-Calap, Pilar

2016-12-01

The remarkable capacity of some viruses to adapt to new hosts and environments is highly dependent on their ability to generate de novo diversity in a short period of time. Rates of spontaneous mutation vary amply among viruses. RNA viruses mutate faster than DNA viruses, single-stranded viruses mutate faster than double-strand virus, and genome size appears to correlate negatively with mutation rate. Viral mutation rates are modulated at different levels, including polymerase fidelity, sequence context, template secondary structure, cellular microenvironment, replication mechanisms, proofreading, and access to post-replicative repair. Additionally, massive numbers of mutations can be introduced by some virus-encoded diversity-generating elements, as well as by host-encoded cytidine/adenine deaminases. Our current knowledge of viral mutation rates indicates that viral genetic diversity is determined by multiple virus- and host-dependent processes, and that viral mutation rates can evolve in response to specific selective pressures.

PTPRS Regulates Colorectal Cancer RAS Pathway Activity by Inactivating Erk and Preventing Its Nuclear Translocation.

PubMed

Davis, Thomas B; Yang, Mingli; Schell, Michael J; Wang, Heiman; Ma, Le; Pledger, W Jack; Yeatman, Timothy J

2018-06-18

Colorectal cancer (CRC) growth and progression is frequently driven by RAS pathway activation through upstream growth factor receptor activation or through mutational activation of KRAS or BRAF. Here we describe an additional mechanism by which the RAS pathway may be modulated in CRC. PTPRS, a receptor-type protein tyrosine phosphatase, appears to regulate RAS pathway activation through ERK. PTPRS modulates ERK phosphorylation and subsequent translocation to the nucleus. Native mutations in PTPRS, present in ~10% of CRC, may reduce its phosphatase activity while increasing ERK activation and downstream transcriptional signaling.

DOE Office of Scientific and Technical Information (OSTI.GOV)

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Contents: a water quality highlight--environmental excellence awards in epa region vi; commentary--lakes conference brings exciting opportunities; news-notes editorial policy; noteworthy water quality happenings; news from the states; notes on the coastal environment; agricultural notes; notes on riparian and watershed management; notes on environmental education; nps electronic bulletin board (bbs) news.

Predicting falls in older adults using the four square step test.

PubMed

Cleary, Kimberly; Skornyakov, Elena

2017-10-01

The Four Square Step Test (FSST) is a performance-based balance tool involving stepping over four single-point canes placed on the floor in a cross configuration. The purpose of this study was to evaluate properties of the FSST in older adults who lived independently. Forty-five community dwelling older adults provided fall history and completed the FSST, Berg Balance Scale (BBS), Timed Up and Go (TUG), and Tinetti in random order. Future falls were recorded for 12 months following testing. The FSST accurately distinguished between non-fallers and multiple fallers, and the 15-second threshold score accurately distinguished multiple fallers from non-multiple fallers based on fall history. The FSST predicted future falls, and performance on the FSST was significantly correlated with performance on the BBS, TUG, and Tinetti. However, the test is not appropriate for older adults who use walkers. Overall, the FSST is a valid yet underutilized measure of balance performance and fall prediction tool that physical therapists should consider using in ambulatory community dwelling older adults.

[Exceptional production of leukocyte-free erythrocyte concentrates using filtration with the BPF 4 BBS leukocyte filter].

PubMed

Zimmermann, B; Hillringhaus, I; Diekamp, U

1994-01-01

Leukocyte depletion prevents some undesirable effects of red cell transfusions. We evaluated the blood filter system BPF 4 BBS (PALL) by filtering 26 units of buffy coat-free red cell concentrates, prepared from 500 ml of whole blood and suspended in SAG-M-additive solution, over 8 min within 48 h after donation at room temperature. Filtration reduced the leukocyte content by more than 99.99% in 25 of the 26 units examined. In 20 instances, no leukocyte was found in the Nageotte counting chamber (2 x 50 microliters) corresponding to a total leukocyte count below 2.38 x 10(4). In 5 instances a single leukocyte was seen, corresponding to a total leukocyte count of (2.35 +/- 0.01) x 10(4). One unit contained 2.93 x 10(5) leukocytes after filtration, corresponding to a 99.98% leukocyte reduction. Red cell recovery was 92.5 +/- 3.8%. This system is well suited for routine use.

The Effect of Balance Training by Tetraks Interactive Balance System on Balance and Fall Risk in Parkinson's Patients: A Report of Four Cases.

PubMed

Balci, Nilay Çömük; Tonga, Eda; Gülşen, Mustafa

2013-09-01

This pilot study aimed to investigate the effect of balance training by Tetraks Interactive Balance System (TIBS) on balance and fall risk in patients with mild to moderate Parkinson's disease. Four patients with Parkinson's disease between the ages of 56 and 70 years (61.25±6.70) were applied balance training for 3 weeks by TIBS. Sociodemographic features and physical properties of the subjects were recorded. Their motor performance was evaluated by the Unified Parkinson's Disease Rating Scale (UPDRS), balance was measured using the Berg Balance Scale (BBS), Functional Reach Test (FRT), Timed Up and Go Test (TUG), and the Standing on One Leg Balance Test (SOL) and, their fall risks were evaluated by TIBS. Evaluations were performed twice, before and after treatment. Following training, Parkinson's patients showed improvements in UPDRS, TUG, BBS, FRT, SOL and fall risk. Balance training by TIBS has positive effects on balance and decreases fall risk in Parkinson's disease patients.

Search for the Decays B_{s}^{0}→τ^{+}τ^{-} and B^{0}→τ^{+}τ^{-}.

PubMed

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Redi, F; Reichert, S; Dos Reis, A C; Remon Alepuz, C; Renaudin, V; Ricciardi, S; Richards, S; Rihl, M; Rinnert, K; Rives Molina, V; Robbe, P; Rodrigues, A B; Rodrigues, E; Rodriguez Lopez, J A; Rodriguez Perez, P; Rogozhnikov, A; Roiser, S; Rollings, A; Romanovskiy, V; Romero Vidal, A; Ronayne, J W; Rotondo, M; Rudolph, M S; Ruf, T; Ruiz Valls, P; Saborido Silva, J J; Sadykhov, E; Sagidova, N; Saitta, B; Salustino Guimaraes, V; Sanchez Gonzalo, D; Sanchez Mayordomo, C; Sanmartin Sedes, B; Santacesaria, R; Santamarina Rios, C; Santimaria, M; Santovetti, E; Sarti, A; Satriano, C; Satta, A; Saunders, D M; Savrina, D; Schael, S; Schellenberg, M; Schiller, M; Schindler, H; Schlupp, M; Schmelling, M; Schmelzer, T; Schmidt, B; Schneider, O; Schopper, A; Schreiner, H F; Schubert, K; Schubiger, M; Schune, M-H; Schwemmer, R; Sciascia, B; Sciubba, A; Semennikov, A; Sergi, A; Serra, N; Serrano, J; Sestini, L; Seyfert, P; Shapkin, M; Shapoval, I; Shcheglov, Y; Shears, T; Shekhtman, L; Shevchenko, V; Siddi, B G; Silva Coutinho, R; Silva de Oliveira, L; Simi, G; Simone, S; Sirendi, M; Skidmore, N; Skwarnicki, T; Smith, E; Smith, I T; Smith, J; Smith, M; Soares Lavra, L; Sokoloff, M D; Soler, F J P; Souza De Paula, B; Spaan, B; Spradlin, P; Sridharan, S; Stagni, F; Stahl, M; Stahl, S; Stefko, P; Stefkova, S; Steinkamp, O; Stemmle, S; Stenyakin, O; Stevens, H; Stoica, S; Stone, S; Storaci, B; Stracka, S; Stramaglia, M E; Straticiuc, M; Straumann, U; Sun, L; Sutcliffe, W; Swientek, K; Syropoulos, V; Szczekowski, M; Szumlak, T; T'Jampens, S; Tayduganov, A; Tekampe, T; Tellarini, G; Teubert, F; Thomas, E; van Tilburg, J; Tilley, M J; Tisserand, V; Tobin, M; Tolk, S; Tomassetti, L; Tonelli, D; Topp-Joergensen, S; Toriello, F; Tourinho Jadallah Aoude, R; Tournefier, E; Tourneur, S; Trabelsi, K; Traill, M; Tran, M T; Tresch, M; Trisovic, A; Tsaregorodtsev, A; Tsopelas, P; Tully, A; Tuning, N; Ukleja, A; Ustyuzhanin, A; Uwer, U; Vacca, C; Vagnoni, V; Valassi, A; Valat, S; Valenti, G; Vazquez Gomez, R; Vazquez Regueiro, P; Vecchi, S; van Veghel, M; Velthuis, J J; Veltri, M; Veneziano, G; Venkateswaran, A; Verlage, T A; Vernet, M; Vesterinen, M; Viana Barbosa, J V; Viaud, B; Vieira, D; Vieites Diaz, M; Viemann, H; Vilasis-Cardona, X; Vitti, M; Volkov, V; Vollhardt, A; Voneki, B; Vorobyev, A; Vorobyev, V; Voß, C; de Vries, J A; Vázquez Sierra, C; Waldi, R; Wallace, C; Wallace, R; Walsh, J; Wang, J; Ward, D R; Wark, H M; Watson, N K; Websdale, D; Weiden, A; Whitehead, M; Wicht, J; Wilkinson, G; Wilkinson, M; Williams, M; Williams, M P; Williams, M; Williams, T; Wilson, F F; Wimberley, J; Winn, M A; Wishahi, J; Wislicki, W; Witek, M; Wormser, G; Wotton, S A; Wraight, K; Wyllie, K; Xie, Y; Xing, Z; Xu, Z; Yang, Z; Yang, Z; Yao, Y; Yin, H; Yu, J; Yuan, X; Yushchenko, O; Zarebski, K A; Zavertyaev, M; Zhang, L; Zhang, Y; Zhelezov, A; Zheng, Y; Zhu, X; Zhukov, V; Zucchelli, S

2017-06-23

A search for the rare decays B_{s}^{0}→τ^{+}τ^{-} and B^{0}→τ^{+}τ^{-} is performed using proton-proton collision data collected with the LHCb detector. The data sample corresponds to an integrated luminosity of 3  fb^{-1} collected in 2011 and 2012. The τ leptons are reconstructed through the decay τ^{-}→π^{-}π^{+}π^{-}ν_{τ}. Assuming no contribution from B^{0}→τ^{+}τ^{-} decays, an upper limit is set on the branching fraction B(B_{s}^{0}→τ^{+}τ^{-})<6.8×10^{-3} at the 95% confidence level. If instead no contribution from B_{s}^{0}→τ^{+}τ^{-} decays is assumed, the limit is B(B^{0}→τ^{+}τ^{-})<2.1×10^{-3} at the 95% confidence level. These results correspond to the first direct limit on B(B_{s}^{0}→τ^{+}τ^{-}) and the world's best limit on B(B^{0}→τ^{+}τ^{-}).

[Bardet-Biedl syndrome: cilia and obesity - from genes to integrative approaches].

PubMed

Chennen, Kirsley; Scerbo, Maria Julia; Dollfus, Hélène; Poch, Olivier; Marion, Vincent

2014-11-01

The primary cilium is a specialized organelle, present at the surface of most eukaryotic cells, whose main function is to detect, integrate and transmit intra- and extra-cellular signals. Its dysfunction usually results in a group of severe clinical manifestations nowadays termed ciliopathies. The latter can be of syndromic nature with multi-organ dysfunctions and can also be associated with a morbid obese phenotype, like it is the case in the iconic ciliopathy, the Bardet Biedl syndrome (BBS). This review will discuss the contribution of the unique context offered by the emblematic BBS for understanding the mechanisms leading to obesity via the involvement of the primary cilium together with identification of novel molecular players and signaling pathways it has helped to highlight. In the current context of translational medicine and system biology, this article will also discuss the potential benefits and challenges posed by these techniques via multi-level approaches to better dissect the underlying mechanisms leading to the complex condition of obesity. © 2014 médecine/sciences – Inserm.

Ranges of North American breeding birds: visualizing long-term population changes in North American breeding birds

USGS Publications Warehouse

Price, Jeff

1995-01-01

These maps show changes in the distribution and abundance patterns of some North American birds for the last 20 years. For each species there are four maps, each representing the average distribution and abundance pattern over the five-year periods 1970-1974, 1975-1979, 1980-1984, and 1985-1989. The maps are based on data collected by the USFWS/CWS Breeding Bird Survey (BBS). Only BBS routes that were run at least once during each of the five-year periods were used (about 1300 routes). The maps were created in the software package Surfer using a kriging technique to interpolate mean relative abundances for areas where no routes were run. On each map, a portion of northeast Canada was blanked out because there were not enough routes to allow for adequate interpolation. All of the maps in this presentation use the same color scale (shown below). The minimum value mapped was 0.5 birds per route, which represents the edge of the species range.

Trade-offs with stability modulate innate and mutationally acquired drug-resistance in bacterial dihydrofolate reductase enzymes.

PubMed

Matange, Nishad; Bodkhe, Swapnil; Patel, Maitri; Shah, Pooja

2018-06-05

Structural stability is a major constraint on the evolution of protein sequences. However, under strong directional selection, mutations that confer novel phenotypes but compromise structural stability of proteins may be permissible. During the evolution of antibiotic resistance, mutations that confer drug resistance often have pleiotropic effects on the structure and function of antibiotic-target proteins, usually essential metabolic enzymes. In this study, we show that trimethoprim-resistant alleles of dihydrofolate reductase from Escherichia coli (EcDHFR) harbouring the Trp30Gly, Trp30Arg or Trp30Cys mutations are significantly less stable than the wild type making them prone to aggregation and proteolysis. This destabilization is associated with lower expression level resulting in a fitness cost and negative epistasis with other TMP-resistant mutations in EcDHFR. Using structure-based mutational analysis we show that perturbation of critical stabilizing hydrophobic interactions in wild type EcDHFR enzyme explains the phenotypes of Trp30 mutants. Surprisingly, though crucial for the stability of EcDHFR, significant sequence variation is found at this site among bacterial DHFRs. Mutational and computational analyses in EcDHFR as well as in DHFR enzymes from Staphylococcus aureus and Mycobacterium tuberculosis demonstrate that natural variation at this site and its interacting hydrophobic residues, modulates TMP-resistance in other bacterial DHFRs as well, and may explain the different susceptibilities of bacterial pathogens to trimethoprim. Our study demonstrates that trade-offs between structural stability and function can influence innate drug resistance as well as the potential for mutationally acquired drug resistance of an enzyme. ©2018 The Author(s).

Mutations in epigenetic regulators including SETD2 are gained during relapse in paediatric acute lymphoblastic leukaemia.

PubMed

Mar, Brenton G; Bullinger, Lars B; McLean, Kathleen M; Grauman, Peter V; Harris, Marian H; Stevenson, Kristen; Neuberg, Donna S; Sinha, Amit U; Sallan, Stephen E; Silverman, Lewis B; Kung, Andrew L; Lo Nigro, Luca; Ebert, Benjamin L; Armstrong, Scott A

2014-03-24

Relapsed paediatric acute lymphoblastic leukaemia (ALL) has high rates of treatment failure. Epigenetic regulators have been proposed as modulators of chemoresistance, here, we sequence genes encoding epigenetic regulators in matched diagnosis-remission-relapse ALL samples. We find significant enrichment of mutations in epigenetic regulators at relapse with recurrent somatic mutations in SETD2, CREBBP, MSH6, KDM6A and MLL2, mutations in signalling factors are not enriched. Somatic alterations in SETD2, including frameshift and nonsense mutations, are present at 12% in a large de novo ALL patient cohort. We conclude that the enrichment of mutations in epigenetic regulators at relapse is consistent with a role in mediating therapy resistance.

The Evolution of DNA-Templated Synthesis as a Tool for Materials Discovery.

PubMed

O'Reilly, Rachel K; Turberfield, Andrew J; Wilks, Thomas R

2017-10-17

Precise control over reactivity and molecular structure is a fundamental goal of the chemical sciences. Billions of years of evolution by natural selection have resulted in chemical systems capable of information storage, self-replication, catalysis, capture and production of light, and even cognition. In all these cases, control over molecular structure is required to achieve a particular function: without structural control, function may be impaired, unpredictable, or impossible. The search for molecules with a desired function is often achieved by synthesizing a combinatorial library, which contains many or all possible combinations of a set of chemical building blocks (BBs), and then screening this library to identify "successful" structures. The largest libraries made by conventional synthesis are currently of the order of 10 8 distinct molecules. To put this in context, there are 10 13 ways of arranging the 21 proteinogenic amino acids in chains up to 10 units long. Given that we know that a number of these compounds have potent biological activity, it would be highly desirable to be able to search them all to identify leads for new drug molecules. Large libraries of oligonucleotides can be synthesized combinatorially and translated into peptides using systems based on biological replication such as mRNA display, with selected molecules identified by DNA sequencing; but these methods are limited to BBs that are compatible with cellular machinery. In order to search the vast tracts of chemical space beyond nucleic acids and natural peptides, an alternative approach is required. DNA-templated synthesis (DTS) could enable us to meet this challenge. DTS controls chemical product formation by using the specificity of DNA hybridization to bring selected reactants into close proximity, and is capable of the programmed synthesis of many distinct products in the same reaction vessel. By making use of dynamic, programmable DNA processes, it is possible to engineer a system that can translate instructions coded as a sequence of DNA bases into a chemical structure-a process analogous to the action of the ribosome in living organisms but with the potential to create a much more chemically diverse set of products. It is also possible to ensure that each product molecule is tagged with its identifying DNA sequence. Compound libraries synthesized in this way can be exposed to selection against suitable targets, enriching successful molecules. The encoding DNA can then be amplified using the polymerase chain reaction and decoded by DNA sequencing. More importantly, the DNA instruction sequences can be mutated and reused during multiple rounds of amplification, translation, and selection. In other words, DTS could be used as the foundation for a system of synthetic molecular evolution, which could allow us to efficiently search a vast chemical space. This has huge potential to revolutionize materials discovery-imagine being able to evolve molecules for light harvesting, or catalysts for CO 2 fixation. The field of DTS has developed to the point where a wide variety of reactions can be performed on a DNA template. Complex architectures and autonomous "DNA robots" have been implemented for the controlled assembly of BBs, and these mechanisms have in turn enabled the one-pot synthesis of large combinatorial libraries. Indeed, DTS libraries are being exploited by pharmaceutical companies and have already found their way into drug lead discovery programs. This Account explores the processes involved in DTS and highlights the challenges that remain in creating a general system for molecular discovery by evolution.

The Evolution of DNA-Templated Synthesis as a Tool for Materials Discovery

PubMed Central

2017-01-01

Conspectus Precise control over reactivity and molecular structure is a fundamental goal of the chemical sciences. Billions of years of evolution by natural selection have resulted in chemical systems capable of information storage, self-replication, catalysis, capture and production of light, and even cognition. In all these cases, control over molecular structure is required to achieve a particular function: without structural control, function may be impaired, unpredictable, or impossible. The search for molecules with a desired function is often achieved by synthesizing a combinatorial library, which contains many or all possible combinations of a set of chemical building blocks (BBs), and then screening this library to identify “successful” structures. The largest libraries made by conventional synthesis are currently of the order of 108 distinct molecules. To put this in context, there are 1013 ways of arranging the 21 proteinogenic amino acids in chains up to 10 units long. Given that we know that a number of these compounds have potent biological activity, it would be highly desirable to be able to search them all to identify leads for new drug molecules. Large libraries of oligonucleotides can be synthesized combinatorially and translated into peptides using systems based on biological replication such as mRNA display, with selected molecules identified by DNA sequencing; but these methods are limited to BBs that are compatible with cellular machinery. In order to search the vast tracts of chemical space beyond nucleic acids and natural peptides, an alternative approach is required. DNA-templated synthesis (DTS) could enable us to meet this challenge. DTS controls chemical product formation by using the specificity of DNA hybridization to bring selected reactants into close proximity, and is capable of the programmed synthesis of many distinct products in the same reaction vessel. By making use of dynamic, programmable DNA processes, it is possible to engineer a system that can translate instructions coded as a sequence of DNA bases into a chemical structure—a process analogous to the action of the ribosome in living organisms but with the potential to create a much more chemically diverse set of products. It is also possible to ensure that each product molecule is tagged with its identifying DNA sequence. Compound libraries synthesized in this way can be exposed to selection against suitable targets, enriching successful molecules. The encoding DNA can then be amplified using the polymerase chain reaction and decoded by DNA sequencing. More importantly, the DNA instruction sequences can be mutated and reused during multiple rounds of amplification, translation, and selection. In other words, DTS could be used as the foundation for a system of synthetic molecular evolution, which could allow us to efficiently search a vast chemical space. This has huge potential to revolutionize materials discovery—imagine being able to evolve molecules for light harvesting, or catalysts for CO2 fixation. The field of DTS has developed to the point where a wide variety of reactions can be performed on a DNA template. Complex architectures and autonomous “DNA robots” have been implemented for the controlled assembly of BBs, and these mechanisms have in turn enabled the one-pot synthesis of large combinatorial libraries. Indeed, DTS libraries are being exploited by pharmaceutical companies and have already found their way into drug lead discovery programs. This Account explores the processes involved in DTS and highlights the challenges that remain in creating a general system for molecular discovery by evolution. PMID:28915003

α2-containing GABAA receptors expressed in hippocampal region CA3 control fast network oscillations

PubMed Central

Heistek, Tim S; Ruiperez-Alonso, Marta; Timmerman, A Jaap; Brussaard, Arjen B; Mansvelder, Huibert D

2013-01-01

GABAA receptors are critically involved in hippocampal oscillations. GABAA receptor α1 and α2 subunits are differentially expressed throughout the hippocampal circuitry and thereby may have distinct contributions to oscillations. It is unknown which GABAA receptor α subunit controls hippocampal oscillations and where these receptors are expressed. To address these questions we used transgenic mice expressing GABAA receptor α1 and/or α2 subunits with point mutations (H101R) that render these receptors insensitive to allosteric modulation at the benzodiazepine binding site, and tested how increased or decreased function of α subunits affects hippocampal oscillations. Positive allosteric modulation by zolpidem prolonged decay kinetics of hippocampal GABAergic synaptic transmission and reduced the frequency of cholinergically induced oscillations. Allosteric modulation of GABAergic receptors in CA3 altered oscillation frequency in CA1, while modulation of GABA receptors in CA1 did not affect oscillations. In mice having a point mutation (H101R) at the GABAA receptor α2 subunit, zolpidem effects on cholinergically induced oscillations were strongly reduced compared to wild-type animals, while zolpidem modulation was still present in mice with the H101R mutation at the α1 subunit. Furthermore, genetic knockout of α2 subunits strongly reduced oscillations, whereas knockout of α1 subunits had no effect. Allosteric modulation of GABAergic receptors was strongly reduced in unitary connections between fast spiking interneurons and pyramidal neurons in CA3 of α2H101R mice, but not of α1H101R mice, suggesting that fast spiking interneuron to pyramidal neuron synapses in CA3 contain α2 subunits. These findings suggest that α2-containing GABAA receptors expressed in the CA3 region provide the inhibition that controls hippocampal rhythm during cholinergically induced oscillations. PMID:23109109

Identifying candidate driver genes by integrative ovarian cancer genomics data

NASA Astrophysics Data System (ADS)

Lu, Xinguo; Lu, Jibo

2017-08-01

Integrative analysis of molecular mechanics underlying cancer can distinguish interactions that cannot be revealed based on one kind of data for the appropriate diagnosis and treatment of cancer patients. Tumor samples exhibit heterogeneity in omics data, such as somatic mutations, Copy Number Variations CNVs), gene expression profiles and so on. In this paper we combined gene co-expression modules and mutation modulators separately in tumor patients to obtain the candidate driver genes for resistant and sensitive tumor from the heterogeneous data. The final list of modulators identified are well known in biological processes associated with ovarian cancer, such as CCL17, CACTIN, CCL16, CCL22, APOB, KDF1, CCL11, HNF1B, LRG1, MED1 and so on, which can help to facilitate the discovery of biomarkers, molecular diagnostics, and drug discovery.

Structural and functional characterization of the product of disease-related factor H gene conversion.

PubMed

Herbert, Andrew P; Kavanagh, David; Johansson, Conny; Morgan, Hugh P; Blaum, Bärbel S; Hannan, Jonathan P; Barlow, Paul N; Uhrín, Dušan

2012-03-06

Numerous complement factor H (FH) mutations predispose patients to atypical hemolytic uremic syndrome (aHUS) and other disorders arising from inadequately regulated complement activation. No unifying structural or mechanistic consequences have been ascribed to these mutants beyond impaired self-cell protection. The S1191L and V1197A mutations toward the C-terminus of FH, which occur in patients singly or together, arose from gene conversion between CFH encoding FH and CFHR1 encoding FH-related 1. We show that neither single nor double mutations structurally perturbed recombinant proteins consisting of the FH C-terminal modules, 19 and 20 (FH19-20), although all three FH19-20 mutants were poor, compared to wild-type FH19-20, at promoting hemolysis of C3b-coated erythrocytes through competition with full-length FH. Indeed, our new crystal structure of the S1191L mutant of FH19-20 complexed with an activation-specific complement fragment, C3d, was nearly identical to that of the wild-type FH19-20:C3d complex, consistent with mutants binding to C3b with wild-type-like affinity. The S1191L mutation enhanced thermal stability of module 20, whereas the V1197A mutation dramatically decreased it. Thus, although mutant proteins were folded at 37 °C, they differ in conformational rigidity. Neither single substitutions nor double substitutions increased measurably the extent of FH19-20 self-association, nor did these mutations significantly affect the affinity of FH19-20 for three glycosaminoglycans, despite critical roles of module 20 in recognizing polyanionic self-surface markers. Unexpectedly, FH19-20 mutants containing Leu1191 self-associated on a heparin-coated surface to a higher degree than on surfaces coated with dermatan or chondroitin sulfates. Thus, potentially disease-related functional distinctions between mutants, and between FH and FH-related 1, may manifest in the presence of specific glycosaminoglycans.

Mediator Tail Module Is Required for Tac1-Activated CDR1 Expression and Azole Resistance in Candida albicans.

PubMed

Liu, Zhongle; Myers, Lawrence C

2017-11-01

The human fungal pathogen Candida albicans develops drug resistance after long-term exposure to azole drugs in the treatment of chronic candidiasis. Gain-of-function (GOF) mutations in the transcription factor Tac1 and the consequent expression of its targets, drug efflux pumps Cdr1 and Cdr2, are a common mechanism by which C. albicans acquires fluconazole resistance. The mechanism by which GOF mutations hyperactivate Tac1 is currently unknown. Here, we define a transcriptional activation domain (TAD) at the C terminus of Tac1. GOF mutations within the Tac1 TAD, outside the context of full-length Tac1, generally do not enhance its absolute potential as a transcriptional activator. Negative regulation of the Tac1 TAD by the Tac1 middle region is necessary for the activating effect of GOF mutations or fluphenazine to be realized. We have found that full-length Tac1, when hyperactivated by xenobiotics or GOF mutations, facilitates the recruitment of the Mediator coactivator complex to the CDR1 promoter. Azole resistance and the activation of Tac1 target genes, such as CDR1 , are dependent on the Tac1 TAD and subunits of the Mediator tail module. The dependence of different Tac1 target promoters on the Mediator tail module, however, varies widely. Lastly, we show that hyperactivation of Tac1 is correlated with its Mediator-dependent phosphorylation, a potentially useful biomarker for Tac1 hyperactivation. The role of Mediator in events downstream of Tac1 hyperactivation in fluconazole-resistant clinical isolates is complex and provides opportunities and challenges for therapeutic intervention. Copyright © 2017 American Society for Microbiology.

Blueberries affect neuroinflammation and cognition differentially depending on individual cognitive baseline status

USDA-ARS?s Scientific Manuscript database

Aging and neurodegenerative diseases are thought to be the results of prolonged effects of oxidative stress and inflammation. Previously, we have shown that daily supplementation of blueberries (BBs) was able to reverse age-related deficits in behavioral and neuronal function in aged rats. However, ...

A Study of Taiwanese Teens' Traditional and Cyberbullying Behaviors

ERIC Educational Resources Information Center

Yang, Shu Ching; Lin, Chia-Ying; Chen, An-Sing

2014-01-01

This study examined several types of teen behaviors, specifically bullying, being bullied, and witnessing bullying, and analyzed teens' judgments of the seriousness of the bullying. A Bullying Behaviors Scale (BBS) was designed to investigate both traditional bullying (TB) and cyberbullying (CB) behaviors among teens in grades 5 through 11. The…

Behavior-Based Safety and Occupational Risk Management

ERIC Educational Resources Information Center

Geller, E. Scott

2005-01-01

The behavior-based approach to managing occupational risk and preventing workplace injuries is reviewed. Unlike the typical top-down control approach to industrial safety, behavior-based safety (BBS) provides tools and procedures workers can use to take personal control of occupational risks. Strategies the author and his colleagues have been…

HBV subgenotypes F1b and F4 replication induces an incomplete autophagic process in hepatocytes: Role of BCP and preCore mutations.

PubMed

Elizalde, María Mercedes; Pérez, Paula Soledad; Sevic, Ina; Grasso, Daniel; Ropolo, Alejandro; Barbini, Luciana; Campos, Rodolfo Héctor; Vaccaro, María Inés; Flichman, Diego Martín

2018-01-01

Hepatitis B virus (HBV) genotypes and mutants have been associated with differences in clinical and virological characteristics. Autophagy is a cellular process that degrades long-lived proteins and damaged organelles. Viruses have evolved mechanisms to alter this process to survive in host cells. In this work, we studied the modulation of autophagy by the replication of HBV subgenotypes F1b and F4, and the naturally occurring mutants BCP and preCore. HBV subgenotypes F1b and F4 replication induced accumulation of autophagosomes in hepatoma cells. However, no autophagic protein degradation was observed, indicating a blockage of autophagic flux at later stages. This inhibition of autophagy flux might be due to an impairment of lysosomal acidification in hepatoma cells. Moreover, HBV-mediated autophagy modulation was independent of the viral subgenotypes and enhanced in viruses with BCP and preCore naturally occurring mutations. These results contribute to understand the mechanisms by which different HBV variants contribute to the pathogenesis of HBV infections. In addition, this study is the first to describe the role that two highly prevalent naturally occurring mutations exert on the modulation of HBV-induced autophagy.

HBV subgenotypes F1b and F4 replication induces an incomplete autophagic process in hepatocytes: Role of BCP and preCore mutations

PubMed Central

Pérez, Paula Soledad; Sevic, Ina; Ropolo, Alejandro; Barbini, Luciana; Campos, Rodolfo Héctor; Vaccaro, María Inés; Flichman, Diego Martín

2018-01-01

Hepatitis B virus (HBV) genotypes and mutants have been associated with differences in clinical and virological characteristics. Autophagy is a cellular process that degrades long-lived proteins and damaged organelles. Viruses have evolved mechanisms to alter this process to survive in host cells. In this work, we studied the modulation of autophagy by the replication of HBV subgenotypes F1b and F4, and the naturally occurring mutants BCP and preCore. HBV subgenotypes F1b and F4 replication induced accumulation of autophagosomes in hepatoma cells. However, no autophagic protein degradation was observed, indicating a blockage of autophagic flux at later stages. This inhibition of autophagy flux might be due to an impairment of lysosomal acidification in hepatoma cells. Moreover, HBV-mediated autophagy modulation was independent of the viral subgenotypes and enhanced in viruses with BCP and preCore naturally occurring mutations. These results contribute to understand the mechanisms by which different HBV variants contribute to the pathogenesis of HBV infections. In addition, this study is the first to describe the role that two highly prevalent naturally occurring mutations exert on the modulation of HBV-induced autophagy. PMID:29738548

Detailed Analysis of the Binding Mode of Vanilloids to Transient Receptor Potential Vanilloid Type I (TRPV1) by a Mutational and Computational Study

PubMed Central

Mori, Yoshikazu; Ogawa, Kazuo; Warabi, Eiji; Yamamoto, Masahiro; Hirokawa, Takatsugu

2016-01-01

Transient receptor potential vanilloid type 1 (TRPV1) is a non-selective cation channel and a multimodal sensor protein. Since the precise structure of TRPV1 was obtained by electron cryo-microscopy, the binding mode of representative agonists such as capsaicin and resiniferatoxin (RTX) has been extensively characterized; however, detailed information on the binding mode of other vanilloids remains lacking. In this study, mutational analysis of human TRPV1 was performed, and four agonists (capsaicin, RTX, [6]-shogaol and [6]-gingerol) were used to identify amino acid residues involved in ligand binding and/or modulation of proton sensitivity. The detailed binding mode of each ligand was then simulated by computational analysis. As a result, three amino acids (L518, F591 and L670) were newly identified as being involved in ligand binding and/or modulation of proton sensitivity. In addition, in silico docking simulation and a subsequent mutational study suggested that [6]-gingerol might bind to and activate TRPV1 in a unique manner. These results provide novel insights into the binding mode of various vanilloids to the channel and will be helpful in developing a TRPV1 modulator. PMID:27606946

Ion Channel Modulators in Cystic Fibrosis.

PubMed

Gentzsch, Martina; Mall, Marcus A

2018-05-08

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and remains one of the most common life-shortening genetic diseases affecting the lung and other organs. CFTR functions as a cAMP-dependent anion channel that transports chloride and bicarbonate across epithelial surfaces and disruption of these ion transport processes plays a central role in the pathogenesis of CF. These findings provided the rationale for pharmacological modulation of ion transport, either by targeting mutant CFTR or alternative ion channels that can compensate for CFTR dysfunction, as a promising therapeutic approach. High throughput screening has supported the development of CFTR modulator compounds. CFTR correctors are designed to improve defective protein processing, trafficking and cell surface expression, whereas potentiators increase the activity of mutant CFTR at the cell surface. The approval of the first potentiator ivacaftor for the treatment of patients with specific CFTR mutations and, more recently the corrector lumacaftor in combination with ivacaftor for patients homozygous for the common F508del mutation, were major breakthroughs on the path to causal therapies for all patients with CF. In this review, we focus on recent developments and remaining challenges of CFTR-directed therapies, as well as modulators of other ion channels such as alternative chloride channels and the epithelial sodium channel (ENaC) as additional targets in CF lung disease. Further, we discuss how patient-derived precision medicine models may aid the translation of emerging next generation ion channel modulators from the laboratory to the clinic and tailor their use for optimal therapeutic benefits in individual patients with CF. Copyright © 2018. Published by Elsevier Inc.

Amelogenesis imperfecta caused by N-terminal enamelin point mutations in mice and men is driven by endoplasmic reticulum stress

PubMed Central

Barron, Martin J.; Smith, Claire E.L.; Poulter, James A.; Mighell, Alan J.; Inglehearn, Chris F.; Brown, Catriona J.; Rodd, Helen; Kirkham, Jennifer; Dixon, Michael J.

2017-01-01

Abstract ‘Amelogenesis imperfecta’ (AI) describes a group of inherited diseases of dental enamel that have major clinical impact. Here, we identify the aetiology driving AI in mice carrying a p.S55I mutation in enamelin; one of the most commonly mutated proteins underlying AI in humans. Our data indicate that the mutation inhibits the ameloblast secretory pathway leading to ER stress and an activated unfolded protein response (UPR). Initially, with the support of the UPR acting in pro-survival mode, Enamp.S55I heterozygous mice secreted structurally normal enamel. However, enamel secreted thereafter was structurally abnormal; presumably due to the UPR modulating ameloblast behaviour and function in an attempt to relieve ER stress. Homozygous mutant mice failed to produce enamel. We also identified a novel heterozygous ENAMp.L31R mutation causing AI in humans. We hypothesize that ER stress is the aetiological factor in this case of human AI as it shared the characteristic phenotype described above for the Enamp.S55I mouse. We previously demonstrated that AI in mice carrying the Amelxp.Y64H mutation is a proteinopathy. The current data indicate that AI in Enamp.S55I mice is also a proteinopathy, and based on comparative phenotypic analysis, we suggest that human AI resulting from the ENAMp.L31R mutation is another proteinopathic disease. Identifying a common aetiology for AI resulting from mutations in two different genes opens the way for developing pharmaceutical interventions designed to relieve ER stress or modulate the UPR during enamel development to ameliorate the clinical phenotype. PMID:28334996

Amelogenesis imperfecta caused by N-terminal enamelin point mutations in mice and men is driven by endoplasmic reticulum stress.

PubMed

Brookes, Steven J; Barron, Martin J; Smith, Claire E L; Poulter, James A; Mighell, Alan J; Inglehearn, Chris F; Brown, Catriona J; Rodd, Helen; Kirkham, Jennifer; Dixon, Michael J

2017-05-15

'Amelogenesis imperfecta' (AI) describes a group of inherited diseases of dental enamel that have major clinical impact. Here, we identify the aetiology driving AI in mice carrying a p.S55I mutation in enamelin; one of the most commonly mutated proteins underlying AI in humans. Our data indicate that the mutation inhibits the ameloblast secretory pathway leading to ER stress and an activated unfolded protein response (UPR). Initially, with the support of the UPR acting in pro-survival mode, Enamp.S55I heterozygous mice secreted structurally normal enamel. However, enamel secreted thereafter was structurally abnormal; presumably due to the UPR modulating ameloblast behaviour and function in an attempt to relieve ER stress. Homozygous mutant mice failed to produce enamel. We also identified a novel heterozygous ENAMp.L31R mutation causing AI in humans. We hypothesize that ER stress is the aetiological factor in this case of human AI as it shared the characteristic phenotype described above for the Enamp.S55I mouse. We previously demonstrated that AI in mice carrying the Amelxp.Y64H mutation is a proteinopathy. The current data indicate that AI in Enamp.S55I mice is also a proteinopathy, and based on comparative phenotypic analysis, we suggest that human AI resulting from the ENAMp.L31R mutation is another proteinopathic disease. Identifying a common aetiology for AI resulting from mutations in two different genes opens the way for developing pharmaceutical interventions designed to relieve ER stress or modulate the UPR during enamel development to ameliorate the clinical phenotype. © The Author 2017. Published by Oxford University Press.

Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers.

PubMed

Blanco, Ignacio; Kuchenbaecker, Karoline; Cuadras, Daniel; Wang, Xianshu; Barrowdale, Daniel; de Garibay, Gorka Ruiz; Librado, Pablo; Sánchez-Gracia, Alejandro; Rozas, Julio; Bonifaci, Núria; McGuffog, Lesley; Pankratz, Vernon S; Islam, Abul; Mateo, Francesca; Berenguer, Antoni; Petit, Anna; Català, Isabel; Brunet, Joan; Feliubadaló, Lidia; Tornero, Eva; Benítez, Javier; Osorio, Ana; Ramón y Cajal, Teresa; Nevanlinna, Heli; Aittomäki, Kristiina; Arun, Banu K; Toland, Amanda E; Karlan, Beth Y; Walsh, Christine; Lester, Jenny; Greene, Mark H; Mai, Phuong L; Nussbaum, Robert L; Andrulis, Irene L; Domchek, Susan M; Nathanson, Katherine L; Rebbeck, Timothy R; Barkardottir, Rosa B; Jakubowska, Anna; Lubinski, Jan; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Claes, Kathleen; Van Maerken, Tom; Díez, Orland; Hansen, Thomas V; Jønson, Lars; Gerdes, Anne-Marie; Ejlertsen, Bent; de la Hoya, Miguel; Caldés, Trinidad; Dunning, Alison M; Oliver, Clare; Fineberg, Elena; Cook, Margaret; Peock, Susan; McCann, Emma; Murray, Alex; Jacobs, Chris; Pichert, Gabriella; Lalloo, Fiona; Chu, Carol; Dorkins, Huw; Paterson, Joan; Ong, Kai-Ren; Teixeira, Manuel R; Hogervorst, Frans B L; van der Hout, Annemarie H; Seynaeve, Caroline; van der Luijt, Rob B; Ligtenberg, Marjolijn J L; Devilee, Peter; Wijnen, Juul T; Rookus, Matti A; Meijers-Heijboer, Hanne E J; Blok, Marinus J; van den Ouweland, Ans M W; Aalfs, Cora M; Rodriguez, Gustavo C; Phillips, Kelly-Anne A; Piedmonte, Marion; Nerenstone, Stacy R; Bae-Jump, Victoria L; O'Malley, David M; Ratner, Elena S; Schmutzler, Rita K; Wappenschmidt, Barbara; Rhiem, Kerstin; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Plendl, Hansjoerg J; Niederacher, Dieter; Sutter, Christian; Wang-Gohrke, Shan; Steinemann, Doris; Preisler-Adams, Sabine; Kast, Karin; Varon-Mateeva, Raymonda; Gehrig, Andrea; Bojesen, Anders; Pedersen, Inge Sokilde; Sunde, Lone; Jensen, Uffe Birk; Thomassen, Mads; Kruse, Torben A; Foretova, Lenka; Peterlongo, Paolo; Bernard, Loris; Peissel, Bernard; Scuvera, Giulietta; Manoukian, Siranoush; Radice, Paolo; Ottini, Laura; Montagna, Marco; Agata, Simona; Maugard, Christine; Simard, Jacques; Soucy, Penny; Berger, Andreas; Fink-Retter, Anneliese; Singer, Christian F; Rappaport, Christine; Geschwantler-Kaulich, Daphne; Tea, Muy-Kheng; Pfeiler, Georg; John, Esther M; Miron, Alex; Neuhausen, Susan L; Terry, Mary Beth; Chung, Wendy K; Daly, Mary B; Goldgar, David E; Janavicius, Ramunas; Dorfling, Cecilia M; van Rensburg, Elisabeth J; Fostira, Florentia; Konstantopoulou, Irene; Garber, Judy; Godwin, Andrew K; Olah, Edith; Narod, Steven A; Rennert, Gad; Paluch, Shani Shimon; Laitman, Yael; Friedman, Eitan; Liljegren, Annelie; Rantala, Johanna; Stenmark-Askmalm, Marie; Loman, Niklas; Imyanitov, Evgeny N; Hamann, Ute; Spurdle, Amanda B; Healey, Sue; Weitzel, Jeffrey N; Herzog, Josef; Margileth, David; Gorrini, Chiara; Esteller, Manel; Gómez, Antonio; Sayols, Sergi; Vidal, Enrique; Heyn, Holger; Stoppa-Lyonnet, Dominique; Léoné, Melanie; Barjhoux, Laure; Fassy-Colcombet, Marion; de Pauw, Antoine; Lasset, Christine; Ferrer, Sandra Fert; Castera, Laurent; Berthet, Pascaline; Cornelis, François; Bignon, Yves-Jean; Damiola, Francesca; Mazoyer, Sylvie; Sinilnikova, Olga M; Maxwell, Christopher A; Vijai, Joseph; Robson, Mark; Kauff, Noah; Corines, Marina J; Villano, Danylko; Cunningham, Julie; Lee, Adam; Lindor, Noralane; Lázaro, Conxi; Easton, Douglas F; Offit, Kenneth; Chenevix-Trench, Georgia; Couch, Fergus J; Antoniou, Antonis C; Pujana, Miguel Angel

2015-01-01

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04-1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03-1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.

Ion Channel Genes and Epilepsy: Functional Alteration, Pathogenic Potential, and Mechanism of Epilepsy.

PubMed

Wei, Feng; Yan, Li-Min; Su, Tao; He, Na; Lin, Zhi-Jian; Wang, Jie; Shi, Yi-Wu; Yi, Yong-Hong; Liao, Wei-Ping

2017-08-01

Ion channels are crucial in the generation and modulation of excitability in the nervous system and have been implicated in human epilepsy. Forty-one epilepsy-associated ion channel genes and their mutations are systematically reviewed. In this paper, we analyzed the genotypes, functional alterations (funotypes), and phenotypes of these mutations. Eleven genes featured loss-of-function mutations and six had gain-of-function mutations. Nine genes displayed diversified funotypes, among which a distinct funotype-phenotype correlation was found in SCN1A. These data suggest that the funotype is an essential consideration in evaluating the pathogenicity of mutations and a distinct funotype or funotype-phenotype correlation helps to define the pathogenic potential of a gene.

AMPA receptor flip/flop mutants affecting deactivation, desensitization, and modulation by cyclothiazide, aniracetam, and thiocyanate.

PubMed

Partin, K M; Fleck, M W; Mayer, M L

1996-11-01

AMPA receptor GluRA subunits with mutations at position 750, a residue shown previously to control allosteric regulation by cyclothiazide, were analyzed for modulation of deactivation and desensitization by cyclothiazide, aniracetam, and thiocyanate. Point mutations from Ser to Asn, Ala, Asp, Gly, Gln, Met, Cys, Thr, Leu, Val, and Tyr were constructed in GluRAflip. The last four of these mutants were not functional; S750D was active only in the presence of cyclothiazide, and the remaining mutants exhibited altered rates of deactivation and desensitization for control responses to glutamate, and showed differential modulation by cyclothiazide and aniracetam. Results from kinetic analysis are consistent with aniracetam and cyclothiazide acting via distinct mechanisms. Our experiments demonstrate for the first time the functional importance of residue 750 in regulating intrinsic channel-gating kinetics and emphasize the biological significance of alternative splicing in the M3-M4 extracellular loop.

Imparting albumin-binding affinity to a human protein by mimicking the contact surface of a bacterial binding protein.

PubMed

Oshiro, Satoshi; Honda, Shinya

2014-04-18

Attachment of a bacterial albumin-binding protein module is an attractive strategy for extending the plasma residence time of protein therapeutics. However, a protein fused with such a bacterial module could induce unfavorable immune reactions. To address this, we designed an alternative binding protein by imparting albumin-binding affinity to a human protein using molecular surface grafting. The result was a series of human-derived 6 helix-bundle proteins, one of which specifically binds to human serum albumin (HSA) with adequate affinity (KD = 100 nM). The proteins were designed by transferring key binding residues of a bacterial albumin-binding module, Finegoldia magna protein G-related albumin-binding domain (GA) module, onto the human protein scaffold. Despite 13-15 mutations, the designed proteins maintain the original secondary structure by virtue of careful grafting based on structural informatics. Competitive binding assays and thermodynamic analyses of the best binders show that the binding mode resembles that of the GA module, suggesting that the contacting surface of the GA module is mimicked well on the designed protein. These results indicate that the designed protein may act as an alternative low-risk binding module to HSA. Furthermore, molecular surface grafting in combination with structural informatics is an effective approach for avoiding deleterious mutations on a target protein and for imparting the binding function of one protein onto another.

Towards Community-Based Communication Intervention for Severely Handicapped Children. Report ASS/BBS-48.

ERIC Educational Resources Information Center

Alant, Erna

This report describes the development of a community-based service for the implementation of augmentative and alternative communication strategies with regard to children with severe disabilities in South Africa. The intervention process was developed by the Centre for Augmentative and Alternative Communication of the University of Pretoria. The…

A Poverty of Riches. New Challenges and Opportunities in PLA Research

DTIC Science & Technology

2003-01-01

Press ( Beijing Daxue Chubanshe ). This guide provides listings and rankings of “core” Chinese journals in numerous categories, including military...178 - vii - Martial Law in Beijing , 1989...............................................................................182 Phony...Administrative Control AMS Academy of Military Science BADCC Beijing Aerospace Directing and Controlling Center BBS Bulletin Board Systems BNS Beidou

Telecommunications Handbook: Connecting to NEWTON. Version 1.4.

ERIC Educational Resources Information Center

Baker, Christopher; And Others

This handbook was written for use with the Argonne National Laboratory's electronic bulletin board system (BBS) called NEWTON, which is designed to create an electronic network that will link scientists, teachers, and students with the many diversified resources of the Argonne National Laboratory. The link to Argonne will include such resources as…

The Effect of Balance Training by Tetraks Interactive Balance System on Balance and Fall Risk in Parkinson’s Patients: A Report of Four Cases

PubMed Central

BALCI, Nilay Çömük; TONGA, Eda; GÜLŞEN, Mustafa

2013-01-01

This pilot study aimed to investigate the effect of balance training by Tetraks Interactive Balance System (TIBS) on balance and fall risk in patients with mild to moderate Parkinson’s disease. Four patients with Parkinson’s disease between the ages of 56 and 70 years (61.25±6.70) were applied balance training for 3 weeks by TIBS. Sociodemographic features and physical properties of the subjects were recorded. Their motor performance was evaluated by the Unified Parkinson’s Disease Rating Scale (UPDRS), balance was measured using the Berg Balance Scale (BBS), Functional Reach Test (FRT), Timed Up and Go Test (TUG), and the Standing on One Leg Balance Test (SOL) and, their fall risks were evaluated by TIBS. Evaluations were performed twice, before and after treatment. Following training, Parkinson’s patients showed improvements in UPDRS, TUG, BBS, FRT, SOL and fall risk. Balance training by TIBS has positive effects on balance and decreases fall risk in Parkinson’s disease patients. PMID:28360557

Predicting home and community walking activity in people with stroke.

PubMed

Fulk, George D; Reynolds, Chelsea; Mondal, Sumona; Deutsch, Judith E

2010-10-01

To determine the ability of the 6-minute walk test (6MWT) and other commonly used clinical outcome measures to predict home and community walking activity in high-functioning people with stroke. Cross-sectional. Outpatient physical therapy clinic. Participants (N=32) with chronic stroke (n=19; >6mo poststroke) with self-selected gait speed (GS) faster than .40m/s and age-matched healthy participants (n=13). Not applicable. 6MWT, self-selected GS, Berg Balance Scale (BBS), lower extremity motor section of the Fugl-Meyer Assessment, and Stroke Impact Scale. Dependent variable: average steps taken per day during a 7-day period, measured using an accelerometer. 6MWT, self-selected GS, and BBS were moderately related to home and community walking activity. The 6MWT was the only predictor of average steps taken per day; it explained 46% of the variance in steps per day. The 6MWT is a useful outcome measure in higher functioning people with stroke to guide intervention and assess community walking activity. Copyright © 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Pig Organ Energy Loss Comparison Experiments Using BBs.

PubMed

Maiden, Nicholas R; Musgrave, Ian; Fisk, Wesley; Byard, Roger W

2016-05-01

Torso models for ballistics research require that the mechanical properties of simulant materials must match the heterogeneous nature of tissues/organs within the human thorax/abdomen. A series of energy loss experiments were conducted on fresh porcine organs/tissues at room temperature and 37°C, using steel 4.5 mm BBs fired from a Daisy(®) brand air rifle. They were compared to FBI and NATO specification ordnance gelatin and a candidate surrogate material called Simulant "A". Two CED M2 chronographs measured BB velocity. The resulting energy loss was established using KE = 1/2 mv² before and after target perforation. The combined results at room temperature and 37°C were as follows: FBI specification gelatin was similar (p > 0.05) to heart and lung, spleen was similar to NATO specification gelatin, Simulant "A" was similar to hindquarter muscle, and hindquarter muscle, kidney, and spleen were similar to each other regarding energy retardation. These results can be used as a basis for the development of simulant materials to create an anatomically correct heterogeneous model. © 2016 American Academy of Forensic Sciences.

The Effects of Augmented Reality-based Otago Exercise on Balance, Gait, and Falls Efficacy of Elderly Women.

PubMed

Yoo, Ha-Na; Chung, Eunjung; Lee, Byoung-Hee

2013-07-01

[Purpose] The purpose of this study was to determine the effects of augmented reality-based Otago exercise on balance, gait, and falls efficacy of elderly women. [Subjects] The subjects were 21 elderly women, who were randomly divided into two groups: an augmented reality-based Otago exercise group of 10 subjects and an Otago exercise group of 11 subjects. [Methods] All subjects were evaluated for balance (Berg Balance Scale, BBS), gait parameters (velocity, cadence, step length, and stride length), and falls efficacy. Within 12 weeks, Otago exercise for muscle strengthening and balance training was conducted three times, for a period of 60 minutes each, and subjects in the experimental group performed augmented reality-based Otago exercise. [Results] Following intervention, the augmented reality-based Otago exercise group showed significant increases in BBS, velocity, cadence, step length (right side), stride length (right side and left side) and falls efficacy. [Conclusion] The results of this study suggest the feasibility and suitability of this augmented reality-based Otago exercise for elderly women.

Ciliopathy proteins establish a bipartite signaling compartment in a C. elegans thermosensory neuron

PubMed Central

Nguyen, Phuong Anh T.; Liou, Willisa; Hall, David H.; Leroux, Michel R.

2014-01-01

ABSTRACT How signaling domains form is an important, yet largely unexplored question. Here, we show that ciliary proteins help establish two contiguous, yet distinct cyclic GMP (cGMP) signaling compartments in Caenorhabditis elegans thermosensory AFD neurons. One compartment, a bona fide cilium, is delineated by proteins associated with Bardet–Biedl syndrome (BBS), Meckel syndrome and nephronophthisis at its base, and requires NPHP-2 (known as inversin in mammals) to anchor a cGMP-gated ion channel within the proximal ciliary region. The other, a subcompartment with profuse microvilli and a different lipid environment, is separated from the dendrite by a cellular junction and requires BBS-8 and DAF-25 (known as Ankmy2 in mammals) for correct localization of guanylyl cyclases needed for thermosensation. Consistent with a requirement for a membrane diffusion barrier at the subcompartment base, we reveal the unexpected presence of ciliary transition zone proteins where no canonical transition zone ultrastructure exists. We propose that differential compartmentalization of signal transduction components by ciliary proteins is important for the functions of ciliated sensory neurons. PMID:25335890

Control of Wnt Receptor Turnover by R-spondin-ZNRF3/RNF43 Signaling Module and Its Dysregulation in Cancer.

PubMed

Hao, Huai-Xiang; Jiang, Xiaomo; Cong, Feng

2016-06-08

Aberrant activation of the Wnt/β-catenin pathway is frequently found in various cancers, often through mutations of downstream components. Inhibiting β-catenin signaling in tumors with downstream pathway mutations remains challenging, due to a lack of favorable targets. On the other hand, targeting upstream components of the Wnt pathway is rather straightforward. However, it is difficult to identify tumors addicted to autocrine or paracrine Wnt signaling. Discovery of the R-spondin-ZNRF3/RNF43 signaling module and its genetic alterations in cancers represents a breakthrough in this area. Membrane E3 ligase ZNRF3 and RNF43 are critical negative feedback regulators of the Wnt pathway, which function through promoting ubiquitination and degradation of Wnt receptors. R-spondin proteins (RSPO1-4) serve as natural antagonists of ZNRF3/RNF43. To maintain strong and sustained Wnt/β-catenin signaling, cancers need to overcome ZNRF3/RNF43-mediated feedback inhibition. Indeed, mutations of RNF43/ZNRF3 and recurrent translocations of RSPO2/RSPO3 have recently been identified in various cancers. Significantly, genetic alterations in RNF43/ZNRF3/RSPO2/RSPO3 have shown promise as predictive biomarkers in pre-clinical models for the efficacy of upstream Wnt inhibitors. In this review, we will discuss the biology of the R-spondin-ZNRF3/RNF43 signaling module, cancer-associated alterations of this signaling module, and their value as biomarkers to identify Wnt-addicted tumors.

Control of Wnt Receptor Turnover by R-spondin-ZNRF3/RNF43 Signaling Module and Its Dysregulation in Cancer

PubMed Central

Hao, Huai-Xiang; Jiang, Xiaomo; Cong, Feng

2016-01-01

Aberrant activation of the Wnt/β-catenin pathway is frequently found in various cancers, often through mutations of downstream components. Inhibiting β-catenin signaling in tumors with downstream pathway mutations remains challenging, due to a lack of favorable targets. On the other hand, targeting upstream components of the Wnt pathway is rather straightforward. However, it is difficult to identify tumors addicted to autocrine or paracrine Wnt signaling. Discovery of the R-spondin-ZNRF3/RNF43 signaling module and its genetic alterations in cancers represents a breakthrough in this area. Membrane E3 ligase ZNRF3 and RNF43 are critical negative feedback regulators of the Wnt pathway, which function through promoting ubiquitination and degradation of Wnt receptors. R-spondin proteins (RSPO1-4) serve as natural antagonists of ZNRF3/RNF43. To maintain strong and sustained Wnt/β-catenin signaling, cancers need to overcome ZNRF3/RNF43-mediated feedback inhibition. Indeed, mutations of RNF43/ZNRF3 and recurrent translocations of RSPO2/RSPO3 have recently been identified in various cancers. Significantly, genetic alterations in RNF43/ZNRF3/RSPO2/RSPO3 have shown promise as predictive biomarkers in pre-clinical models for the efficacy of upstream Wnt inhibitors. In this review, we will discuss the biology of the R-spondin-ZNRF3/RNF43 signaling module, cancer-associated alterations of this signaling module, and their value as biomarkers to identify Wnt-addicted tumors. PMID:27338477

dNTP pool levels modulate mutator phenotypes of error-prone DNA polymerase ε variants.

PubMed

Williams, Lindsey N; Marjavaara, Lisette; Knowels, Gary M; Schultz, Eric M; Fox, Edward J; Chabes, Andrei; Herr, Alan J

2015-05-12

Mutator phenotypes create genetic diversity that fuels tumor evolution. DNA polymerase (Pol) ε mediates leading strand DNA replication. Proofreading defects in this enzyme drive a number of human malignancies. Here, using budding yeast, we show that mutator variants of Pol ε depend on damage uninducible (Dun)1, an S-phase checkpoint kinase that maintains dNTP levels during a normal cell cycle and up-regulates dNTP synthesis upon checkpoint activation. Deletion of DUN1 (dun1Δ) suppresses the mutator phenotype of pol2-4 (encoding Pol ε proofreading deficiency) and is synthetically lethal with pol2-M644G (encoding altered Pol ε base selectivity). Although pol2-4 cells cycle normally, pol2-M644G cells progress slowly through S-phase. The pol2-M644G cells tolerate deletions of mediator of the replication checkpoint (MRC) 1 (mrc1Δ) and radiation sensitive (Rad) 9 (rad9Δ), which encode mediators of checkpoint responses to replication stress and DNA damage, respectively. The pol2-M644G mutator phenotype is partially suppressed by mrc1Δ but not rad9Δ; neither deletion suppresses the pol2-4 mutator phenotype. Thus, checkpoint activation augments the Dun1 effect on replication fidelity but is not required for it. Deletions of genes encoding key Dun1 targets that negatively regulate dNTP synthesis, suppress the dun1Δ pol2-M644G synthetic lethality and restore the mutator phenotype of pol2-4 in dun1Δ cells. DUN1 pol2-M644G cells have constitutively high dNTP levels, consistent with checkpoint activation. In contrast, pol2-4 and POL2 cells have similar dNTP levels, which decline in the absence of Dun1 and rise in the absence of the negative regulators of dNTP synthesis. Thus, dNTP pool levels correlate with Pol ε mutator severity, suggesting that treatments targeting dNTP pools could modulate mutator phenotypes for therapy.

Splicing Modulation as a Potential Treatment for Vemurafenib-Resistant Melanoma | Center for Cancer Research

Cancer.gov

Over half of melanomas contain mutations in the serine/threonine kinase BRAF. The most common mutation, BRAF(V600E), leads to excessive activation of the MAPK proliferation pathway. Vemurafenib is a potent kinase inhibitor with remarkable clinical activity in BRAF(V600E)-positive melanoma tumors. Patients initially respond to treatment with vemurafenib, but inevitably develop

Relevance of nerve conduction velocity in the assessment of balance performance in older adults with diabetes mellitus.

PubMed

Wang, Ting-Yun; Chen, Shih-Ching; Peng, Chih-Wei; Kang, Chun-Wei; Chen, Yu-Luen; Chen, Chun-Lung; Chou, Yi-Lin; Lai, Chien-Hung

2017-03-01

Purpose This study investigated the relationship between peripheral nerve conduction velocity (NCV) and balance performance in older adults with diabetes. Methods Twenty older adults with diabetes were recruited to evaluate the NCV of their lower limbs and balance performance. The balance assessments comprised the timed up and go (TUG) test, Berg balance scale (BBS), unipedal stance test (UST), multidirectional reach test (MDRT), maximum step length (MSL) test and quiet standing with eyes open and closed. The relationship between NCV and balance performance was evaluated by Pearson's correlation coefficients, and the balance performances of the diabetic patients with and without peripheral neuropathy were compared by using Mann-Whitney U tests. Results The NCV in the lower limbs exhibited a moderate to strong correlation with most of the balance tests including the TUG (r = -0.435 to -0.520, p < 0.05), BBS (r = 0.406-0.554, p < 0.05), UST (r = 0.409-0.647, p < 0.05) and MSL (r = 0.399-0.585, P < 0.05). In addition, patients with diabetic peripheral neuropathy had a poorer TUG (p < 0.05), BBS (p < 0.01), UST (p < 0.05) and MSL performance (p < 0.05) compared with those without peripheral neuropathy (p < 0.05). Conclusion Our findings revealed that a decline in peripheral nerve conduction in the lower limb is not only an indication of nerve dysfunction, but may also be related to the impairment of balance performance in patients with diabetes. Implications for Rehabilitation Nerve conduction velocity in the lower limbs of diabetic older adults showed moderate to strong correlations with most of the results of balance tests, which are commonly used in clinics. Decline in nerve conduction velocity of the lower limbs may be related to the impairment of balance control in patients with diabetes. Diabetic older adults with peripheral neuropathy exhibited greater postural instability than those without peripheral neuropathy.

Benign biliary strictures refractory to standard bilioplasty treated using polydoxanone biodegradable biliary stents: retrospective multicentric data analysis on 107 patients.

PubMed

Mauri, Giovanni; Michelozzi, Caterina; Melchiorre, Fabio; Poretti, Dario; Pedicini, Vittorio; Salvetti, Monica; Criado, Eva; Falcò Fages, Joan; De Gregorio, Miguel Ángel; Laborda, Alicia; Sonfienza, Luca Maria; Cornalba, Gianpaolo; Monfardini, Lorenzo; Panek, Jiri; Andrasina, Tomas; Gimenez, Mariano

2016-11-01

To assess mid-term outcome of biodegradable biliary stents (BBSs) to treat benign biliary strictures refractory to standard bilioplasty. Institutional review board approval was obtained and patient consent was waived. 107 patients (61 males, 46 females, mean age 59 ± 16 years), were treated. Technical success and complications were recorded. Ninety-seven patients (55 males, 42 females, aged 57 ± 17 years) were considered for follow-up analysis (mean follow-up 23 ± 12 months). Fisher's exact test and Mann-Whitney U tests were used and a Kaplan-Meier curve was calculated. The procedure was always feasible. In 2/107 cases (2 %), stent migration occurred (technical success 98 %). 4/107 patients (4 %) experienced mild haemobilia. No major complications occurred. In 19/97 patients (18 %), stricture recurrence occurred. In this group, higher rate of subsequent cholangitis (84.2 % vs. 12.8 %, p = 0.001) and biliary stones (26.3 % vs. 2.5 %, p = 0.003) was noted. Estimated mean time to stricture recurrence was 38 months (95 % C.I 34-42 months). Estimated stricture recurrence rate at 1, 2, and 3 years was respectively 7.2 %, 26.4 %, and 29.4 %. Percutaneous placement of a BBS is a feasible and safe strategy to treat benign biliary strictures refractory to standard bilioplasty, with promising results in the mid-term period. • Percutaneous placement of a BBS is 100 % feasible. • The procedure appears free from major complications, with few minor complications. • BBSs offer promising results in the mid-term period. • With a BBS, external catheter/drainage can be removed early. • BBSs represent a new option in treating benign biliary stenosis.

A New Fully Covered Self-Expandable Metal Stent for the Treatment of Postsurgical Benign Biliary Strictures.

PubMed

Wu, Jun; Zhou, Dong-Xun; Wang, Tian-Tian; Gao, Dao-Jian; Hu, Bing

2017-09-01

Endotherapy with plastic stent (PS) placement is the main modality for treating benign biliary strictures (BBSs). Fully covered self-expandable metal stents (FCSEMSs) are being increasingly used for BBS management, with high stricture resolution. However, traditional metal tents are associated with high migration, causing treatment failure. We investigated the efficacy and safety of a new FCSEMS for postsurgical BBS treatment and compared these parameters between the FCSEMS and PS treatment through retrospective analysis. The primary outcome measurements included stricture resolution, stricture recurrence, and complications. In total, 69 patients were included, of whom 32 underwent FCSEMS treatment and 37 underwent PS treatment. The technical success rate and the number of endoscopic retrograde cholangiopancreatography procedures were similar between the groups. The median stenting duration was 5.2 months (range 1.5-15.3) in the FCSEMS group and 10.7 months (range 2.5-22.6) in the PS group (P < 0.01). The stents removal rate was 96.9% in the FCSEMS group and 94.6% in the PS group. The stricture resolution rate based on intention-to-treat analysis was 83.8% in the PS group and 84.4% (27/32) in the FCSEMS group (P = 0.947), whereas the rates from per-protocol analysis were 88.6% (31/35) and 87.1% (27/31), respectively (P = 0.574). Early and late complications were similar between the groups. The median follow-up time was 43 months (range 13-71). The stricture recurrence rate was 11.1% (3/27) in the FCSEMS group and 16.1% (5/31) in the PS group (P = 0.435). The new FCSEMS and the PS approach showed similar efficacy and safety in postsurgical BBS treatment. However, the FCSEMS required fewer procedural steps and shorter stenting time, making it an effective alternative modality.

Combined analysis of roadside and off-road breeding bird survey data to assess population change in Alaska

USGS Publications Warehouse

Handel, Colleen M.; Sauer, John

2017-01-01

Management interest in North American birds has increasingly focused on species that breed in Alaska, USA, and Canada, where habitats are changing rapidly in response to climatic and anthropogenic factors. We used a series of hierarchical models to estimate rates of population change in 2 forested Bird Conservation Regions (BCRs) in Alaska based on data from the roadside North American Breeding Bird Survey (BBS) and the Alaska Landbird Monitoring Survey, which samples off-road areas on public resource lands. We estimated long-term (1993–2015) population trends for 84 bird species from the BBS and short-term (2003–2015) trends for 31 species from both surveys. Among the 84 species with long-term estimates, 11 had positive trends and 17 had negative trends in 1 or both BCRs; negative trends were primarily found among aerial insectivores and wetland-associated species, confirming range-wide negative continental trends for many of these birds. Three species with negative trends in the contiguous United States and southern Canada had positive trends in Alaska, suggesting different population dynamics at the northern edges of their ranges. Regional population trends within Alaska differed for several species, particularly those represented by different subspecies in the 2 BCRs, which are separated by rugged, glaciated mountain ranges. Analysis of the roadside and off-road data in a joint hierarchical model with shared parameters resulted in improved precision of trend estimates and suggested a roadside-related difference in underlying population trends for several species, particularly within the Northwestern Interior Forest BCR. The combined analysis highlights the importance of considering population structure, physiographic barriers, and spatial heterogeneity in habitat change when assessing patterns of population change across a landscape as broad as Alaska. Combined analysis of roadside and off-road survey data in a hierarchical framework may be particularly useful for evaluating patterns of population change in relatively undeveloped regions with sparse roadside BBS coverage.

Angiogenic axis angiopoietin-1 and angiopoietin-2/Tie-2 in non-small cell lung cancer: a bronchoalveolar lavage and serum study.

PubMed

Naumnik, W; Naumnik, B; Niewiarowska, K; Ossolinska, M; Chyczewska, E

2013-01-01

Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), ligands for the Tie-2 receptor expressed on endothelial cells, play a critical role in angiogenesis, in concert with vascular endothelial growth factor (VEGF). Angiogenesis is important for tumor growth and development and also is implicated in the pathogenesis of interstitial lung diseases. The aim of this study was to evaluate the concentration of Ang-1, Ang-2, Tie-2, interleukin-18 (IL-18), transforming growth factor beta-1 (TGF β1), and VEGF domain in both serum and bronchoalveolar lavage fluid (BALF) of lung cancer patients before chemotherapy. We studied 45 non-small cell lung cancer (NSCLC) patients (M/F; 38/7; mean age 62 ± 4 years). The age-matched control groups consisted of 15 sarcoidosis (BBS), 15 hypersensivity pneumonitis (HP), and 15 healthy subjects. The patients with NSCLC had a significantly higher level of Ang-1 compared with the BBS and healthy subjects, and a higher level of Ang-2 compared with the healthy subjects in both serum and BALF. BALF level of IL-18 was lower in the NSCLC than that in the HP group, but higher than that in the BBS patients. Serum level of IL-18 was higher in the NSCLC than in the healthy subjects. The NSCLC group had lower VEGF in BALF than that in healthy subjects. Receiver-operating characteristics (ROC) curves were applied to find the cut-off the serum levels of Ang-1 and Ang-2 levels in BALF. We did not find any correlation between the levels of Ang-1, Ang-2, Tie-2, and the stage of tumor or treatment response (prospectively). We conclude that the angiogenic axis Ang-1 and Ang-2/Tie-2 may play an important role in lung cancer development and their concentrations may be a useful marker at the time of initial diagnosis of lung cancer.

[Effects of Acupuncture Intervention Combined with Rehabilitation on Standing-balance-walking Ability in Stroke Patients].

PubMed

Chu, Jia-mei; Bao, Ye-hua; Zhu, Min

2015-12-01

To observe the influence of acupuncture stimulation of lateral side of Tianzhu (para-BL 10), electroacupuncture (EA) stimulation of scalp-point Balance Area (MS 14), Motor Area (MS 6) and body acupoints combined with rehabilitation training on standing-balance and walking ability in stroke patients. A total of 145 stroke inpatients were randomly assigned to rehabilitation group (n=48), routine acupuncture group (n=49) and para-BL10 group (n = 48). Patients of the rehabilitation group received balance training and routine rehabilitation training treatment, those of the routine acupuncture group received acupuncture stimulation of scalp-points (MS 14, MS 6), body acupoints, balance training and routine rehabilitation training,and those of the para-BL10 group received acupuncture stimulation of lateral side of BL 10 combined with scalp-points of MS 14 and MS 6 and body acupoints, and balance training and routine rehabilitation training. The treatment was conducted once daily, 5 times per week, 8 weeks altogether. The patients' balancing function, lower-limb motor function and walking ability were assessed using Berg Balance Scale (BBS), Sheikh Trunk Control Ability Scale(STCAS), Fugl-Meyer Assessment Scale (FMAS), and Holden Functional Ambulation Classification (FAC), respectively. After 4 and 8 weeks' treatment, the scores of BBS, STCAS, FMAS and FAC in patients of the rehabilitation, routine acupuncture and para-BL10 groups were significantly increased and 10 meters-walking time obviously reduced in comparison with pre-treatment in the same one group (P<0.01). The effects of acupuncture stimulation of para-BL 10 were considerably better than both rehabilitation and routine acupuncture groups in raising BBS, STCAS, FMAS and FAC scores and in reducing 10 m-walking time (P<0.05). Acupuncture stimulation of lateral side of BL 10 combined with scalp-points has a significant benefit for stroke patients in standing-balance ability and walking ability.

A line fiducial method for geometric calibration of cone-beam CT systems with diverse scan trajectories

NASA Astrophysics Data System (ADS)

Jacobson, M. W.; Ketcha, M. D.; Capostagno, S.; Martin, A.; Uneri, A.; Goerres, J.; De Silva, T.; Reaungamornrat, S.; Han, R.; Manbachi, A.; Stayman, J. W.; Vogt, S.; Kleinszig, G.; Siewerdsen, J. H.

2018-01-01

Modern cone-beam CT systems, especially C-arms, are capable of diverse source-detector orbits. However, geometric calibration of these systems using conventional configurations of spherical fiducials (BBs) may be challenged for novel source-detector orbits and system geometries. In part, this is because the BB configurations are designed with careful forethought regarding the intended orbit so that BB marker projections do not overlap in projection views. Examples include helical arrangements of BBs (Rougee et al 1993 Proc. SPIE 1897 161-9) such that markers do not overlap in projections acquired from a circular orbit and circular arrangements of BBs (Cho et al 2005 Med. Phys. 32 968-83). As a more general alternative, this work proposes a calibration method based on an array of line-shaped, radio-opaque wire segments. With this method, geometric parameter estimation is accomplished by relating the 3D line equations representing the wires to the 2D line equations of their projections. The use of line fiducials simplifies many challenges with fiducial recognition and extraction in an orbit-independent manner. For example, their projections can overlap only mildly, for any gantry pose, as long as the wires are mutually non-coplanar in 3D. The method was tested in application to circular and non-circular trajectories in simulation and in real orbits executed using a mobile C-arm prototype for cone-beam CT. Results indicated high calibration accuracy, as measured by forward and backprojection/triangulation error metrics. Triangulation errors on the order of microns and backprojected ray deviations uniformly less than 0.2 mm were observed in both real and simulated orbits. Mean forward projection errors less than 0.1 mm were observed in a comprehensive sweep of different C-arm gantry angulations. Finally, successful integration of the method into a CT imaging chain was demonstrated in head phantom scans.

Bone breaking strength and apparent metabolisability of calcium and phosphorus in selected and unselected broiler chicken genotypes.

PubMed

McDevitt, R M; McEntee, G M; Rance, K A

2006-10-01

1. The present study examined the bone strength and apparent mineral metabolisability of a selected broiler chicken compared with those of a relatively unselected genotype. 2. Selected (SB) and unselected genotypes (UB) were reared under standard conditions and were fed on either a high quality (HQ) or a low quality (LQ) diet. Tibiotarsi samples were collected at 42 d from SB and compared to tibiotarsi from UB of the same age and the same body mass (BM). 3. Bones were assessed for: bone breaking strength (BBS), morphology (weight and length), and both organic (OM) and inorganic content (ASH). Apparent dry matter digestibility and the coefficient of apparent metabolisability of calcium and phosphorus were determined at the same BM. 4. The BBS of SB (214 +/- 9 N) was greater than that of same-age UB (119 +/- 8 N) but the same as that of same-BM UB (218 +/- 10 N). At the same age, the SB had stronger, heavier bones with more ash and organic matter per unit length of tibiotarsus than UB. At the same BM, the tibiotarsi of the SB were shorter and lighter, with a higher ash and a similar organic content than the bones of the UB. At the same BM, BBS was about 15% lower in both genotypes fed on the LQ compared to the HQ diet. 5. The coefficients of apparent metabolisability of calcium and phosphorus were the same in both genotypes when fed on the HQ diet, but were lower in the SB than in the UB genotype when the birds were given the LQ diet. 6. The tibiotarsi of the selected broilers were stronger, or at least as strong, as those of the unselected broiler genotype, which may be due to similar levels of apparent calcium metabolisability of the selected chickens.

Effects of a High-Intensity Functional Exercise Program on Dependence in Activities of Daily Living and Balance in Older Adults with Dementia

PubMed Central

Toots, Annika; Littbrand, Håkan; Lindelöf, Nina; Wiklund, Robert; Holmberg, Henrik; Nordström, Peter; Lundin-Olsson, Lillemor; Gustafson, Yngve; Rosendahl, Erik

2016-01-01

Objectives To investigate the effects of a high-intensity functional exercise program on independence in activities of  daily living (ADLs) and balance in older people with dementia and whether exercise effects differed between dementia types. Design Cluster-randomized controlled trial: Umeå Dementia and Exercise (UMDEX) study. Setting Residential care facilities, Umeå, Sweden. Participants Individuals aged 65 and older with a dementia diagnosis, a Mini-Mental State Examination score of 10 or greater, and dependence in ADLs (N = 186). Intervention Ninety-three participants each were allocated to the high-intensity functional exercise program, comprising lower limb strength and balance exercises, and 93 to a seated control activity. Measurements Blinded assessors measured ADL independence using the Functional Independence Measure (FIM) and Barthel Index (BI) and balance using the Berg Balance Scale (BBS) at baseline and 4 (directly after intervention completion) and 7 months. Results Linear mixed models showed no between-group effect on ADL independence at 4 (FIM=1.3, 95% confidence interval (CI)=−1.6–4.3; BI=0.6, 95% CI=−0.2–1.4) or 7 (FIM=0.8, 95% CI=−2.2–3.8; BI=0.6, 95% CI=−0.3–1.4) months. A significant between-group effect on balance favoring exercise was observed at 4 months (BBS=4.2, 95% CI=1.8–6.6). In interaction analyses, exercise effects differed significantly between dementia types. Positive between-group exercise effects were found in participants with non-Alzheimer's dementia according to the FIM at 7 months and BI and BBS at 4 and 7 months. Conclusion In older people with mild to moderate dementia living in residential care facilities, a 4-month high-intensity functional exercise program appears to slow decline in ADL independence and improve balance, albeit only in participants with non-Alzheimer's dementia. PMID:26782852

Randomized Controlled Trial to Examine the Impact of Aquatic Exercise Training on Functional Capacity, Balance, and Perceptions of Fatigue in Female Patients With Multiple Sclerosis.

PubMed

Kargarfard, Mehdi; Shariat, Ardalan; Ingle, Lee; Cleland, Joshua A; Kargarfard, Mina

2018-02-01

To assess the effects of an 8-week aquatic exercise training program on functional capacity, balance, and perceptions of fatigue in women with multiple sclerosis (MS). Randomized controlled design. Referral center of an MS society. Women (N=32; mean age ± SD, 36.4±8.2y) with diagnosed relapsing-remitting MS. After undergoing baseline testing by a neurologist, participants were allocated to either an intervention (aquatic training program, n=17) or a control group (n=15). The intervention consisted of an 8-week aquatic training program (3 supervised training sessions per week; session duration, 45-60min; 50%-75% estimated maximum heart rate). Six-minute walk test (6-MWT), balance (Berg Balance Scale [BBS]), and perceptions of fatigue (Modified Fatigue Impact Scale; [MFIS]) at baseline and after the 8-week intervention. Differences over time between the experimental and control groups were assessed by a 2×2 (group by time) repeated-measures analysis of variance. Thirty-two women completed the 8-week aquatic training intervention (experimental group, n=17; control group, n=15). All outcome measures improved in the experimental group: 6-MWT performance (pretest mean ± SD, 451±58m; posttest mean ± SD, 503±57m; P<.001); BBS (pretest mean ± SD, 53.59±1.70; posttest mean ± SD, 55.18±1.18; P<.001), and MFIS (pretest mean ± SD, 43.1±14.6; posttest mean ± SD, 32.8±5.9; P<.01). A significant group-by-time interaction was evident between the experimental and control groups for 6-MWT (P<.001, partial eta 2 [η p 2 ]=.551), BBS (P<.001, η p 2 =.423), and MFIS (P<.001, η p 2 =.679). Aquatic exercise training improved functional capacity, balance, and perceptions of fatigue in women with MS. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Does Cognitive Impairment Affect Rehabilitation Outcome in Parkinson’s Disease?

PubMed Central

Ferrazzoli, Davide; Ortelli, Paola; Maestri, Roberto; Bera, Rossana; Giladi, Nir; Ghilardi, Maria Felice; Pezzoli, Gianni; Frazzitta, Giuseppe

2016-01-01

Background: The cognitive status is generally considered as a major determinant of rehabilitation outcome in Parkinson’s disease (PD). No studies about the effect of cognitive impairment on motor rehabilitation outcomes in PD have been performed before. Objective: This study is aimed to evaluate the impact of cognitive decline on rehabilitation outcomes in patients with PD. Methods: We retrospectively identified 485 patients with PD hospitalized for a 4-week Multidisciplinary Intensive Rehabilitation Treatment (MIRT) between January 2014 and September 2015. According to Mini Mental State Examination (MMSE), patients were divided into: group 1—normal cognition (score 27–30), group 2—mild cognitive impairment (score 21–26), group 3—moderate or severe cognitive impairment (score ≤ 20). According to Frontal Assessment Battery (FAB), subjects were divided into patients with normal (score ≥13.8) and pathological (score <13.8) executive functions. The outcome measures were: Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Disability Scale (PDDS), Six Minutes Walking Test (6MWT), Timed Up and Go Test (TUG) and Berg Balance Scale (BBS). Results: All scales had worse values with the increase of cognitive impairment and passing from normal to pathological executive functions. After rehabilitation, all the outcome measures improved in all groups (p < 0.0001). Between groups, the percentage of improvement was significantly different for total UPDRS (p = 0.0009, best improvement in normal MMSE group; p = 0.019, best improvement in normal FAB group), and BBS (p < 0.0001, all pairwise comparisons significant, best improvement in patients with worse MMSE score; p < 0.0001, best improvement in patients with pathological FAB). TUG (p = 0.006) and BBS (p < 0.0001) improved in patients with pathological FAB score, more than in those with normal FAB score. Conclusions: Patients gain benefit in the rehabilitative outcomes, regardless of cognition. Our data suggest that rehabilitation could be effective also in Parkinsonian subjects with cognitive impairment, as well as with dysexecutive syndrome. PMID:27563290

Dinosaur bone beds and mass mortality: Implications for the K-T extinction

NASA Technical Reports Server (NTRS)

Carpenter, Kenneth

1988-01-01

Mass accumulations of fossilized large terrestrial vertebrate skeletons (bone beds: BB) provide a test for K-T catastrophic extinction hypotheses. The two major factors contributing to BB formation are mode of death and sedimentation rate. Catastrophic mass mortality (CMM) is the sudden death of numerous individuals where species, age, health, gender, or social ranking offer no survivorship advantage. Noncatastrophic mass mortality (NCMM) occurs over time and is strongly influenced by species, age, or gender. In addition to cause of death, sedimentation rate is also important in BB formation. Models of BBs can be made. The CMM drops all individuals in their tracks, therefore, the BB should reflect the living population with respect to species, age, or gender. The NCMM results in monospecific BBs skewed in the direction of the less fit, usually the very young or very old, or towards a specific gender. The NCMM and AM BBs may become more similar the more spread out over time NCMM deaths occur because carcasses are widely scattered requiring hydraulic accumulation, and the greater time allows for more disarticulation and weathering. The CMM and NCMM BB appear to be dominated by social animals. Applying this and the characteristics of mortality patterns to the uppermost Cretaceous Hell Creek Formation indicates that only NCMM and AM BB occur. Furthermore, NCMM BB are rare in the upper third of the Hell Creek. Near the K-T boundary, only AM BB are known. The absence of CMM and NCMM BB appears to be real reflecting a decrease in population levels of some dinosaurs prior to the K-T event. The absence of CMM suggests that the K-T event did not lead to an instantaneous extinction of dinosaurs. Nor was there a protracted die-off due to an asteroid impact winter, because no NCMM BB are known at or near the K-T boundary.

New Approach in Fibromyalgia Exercise Program: A Preliminary Study Regarding the Effectiveness of Balance Training.

PubMed

Kibar, Sibel; Yıldız, Hatice Ecem; Ay, Saime; Evcik, Deniz; Ergin, Emine Süreyya

2015-09-01

To determine the effectiveness of balance exercises on the functional level and quality of life (QOL) of patients with fibromyalgia syndrome (FMS) and to investigate the circumstances associated with balance disorders in FMS. Randomized controlled trial. Physical medicine and rehabilitation clinic. Patients (N=57) (age range, 18-65y) with FMS were randomly assigned into 2 groups. Group 1 was given flexibility and balance exercises for 6 weeks, whereas group 2 received only a flexibility program as the control group. Functional balance was measured by the Berg Balance Scale (BBS), and dynamic and static balance were evaluated by a kinesthetic ability trainer (KAT) device. Fall risk was assessed with the Hendrich II fall risk model. The Nottingham Health Profile, Fibromyalgia Impact Questionnaire (FIQ), and Beck Depression Inventory (BDI) were used to determine QOL and functional and depression levels, respectively. Assessments were performed at baseline and after the 6-week program. In group 1, statistically significant improvements were observed in all parameters (P<.05), but no improvement was seen in group 2 (P>.05). When comparing the 2 groups, there were significant differences in group 1 concerning the KAT static balance test (P=.017) and FIQ measurements (P=.005). In the correlation analysis, the BDI was correlated with the BBS (r=-.434) and Hendrich II results (r=.357), whereas body mass index (BMI) was correlated with the KAT static balance measurements (r=.433), BBS (r=-.285), and fall frequency (r=.328). A 6-week balance training program had a beneficial effect on the static balance and functional levels of patients with FMS. We also observed that depression deterioration was related to balance deficit and fall risk. Higher BMI was associated with balance deficit and fall frequency. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Effects of a High-Intensity Functional Exercise Program on Dependence in Activities of Daily Living and Balance in Older Adults with Dementia.

PubMed

Toots, Annika; Littbrand, Håkan; Lindelöf, Nina; Wiklund, Robert; Holmberg, Henrik; Nordström, Peter; Lundin-Olsson, Lillemor; Gustafson, Yngve; Rosendahl, Erik

2016-01-01

To investigate the effects of a high-intensity functional exercise program on independence in activities of daily living (ADLs) and balance in older people with dementia and whether exercise effects differed between dementia types. Cluster-randomized controlled trial: Umeå Dementia and Exercise (UMDEX) study. Residential care facilities, Umeå, Sweden. Individuals aged 65 and older with a dementia diagnosis, a Mini-Mental State Examination score of 10 or greater, and dependence in ADLs (N=186). Ninety-three participants each were allocated to the high-intensity functional exercise program, comprising lower limb strength and balance exercises, and 93 to a seated control activity. Blinded assessors measured ADL independence using the Functional Independence Measure (FIM) and Barthel Index (BI) and balance using the Berg Balance Scale (BBS) at baseline and 4 (directly after intervention completion) and 7 months. Linear mixed models showed no between-group effect on ADL independence at 4 (FIM=1.3, 95% confidence interval (CI)=-1.6-4.3; BI=0.6, 95% CI=-0.2-1.4) or 7 (FIM=0.8, 95% CI=-2.2-3.8; BI=0.6, 95% CI=-0.3-1.4) months. A significant between-group effect on balance favoring exercise was observed at 4 months (BBS=4.2, 95% CI=1.8-6.6). In interaction analyses, exercise effects differed significantly between dementia types. Positive between-group exercise effects were found in participants with non-Alzheimer's dementia according to the FIM at 7 months and BI and BBS at 4 and 7 months. In older people with mild to moderate dementia living in residential care facilities, a 4-month high-intensity functional exercise program appears to slow decline in ADL independence and improve balance, albeit only in participants with non-Alzheimer's dementia. © 2016 The Authors. The Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society.

The hepcidin gene promoter nc.-1010C > T; -582A > G haplotype modulates serum ferritin in individuals carrying the common H63D mutation in HFE gene.

PubMed

Silva, Bruno; Pita, Lina; Gomes, Susana; Gonçalves, João; Faustino, Paula

2014-12-01

Hereditary hemochromatosis is an autosomal recessive disorder characterized by severe iron overload. It is usually associated with homozygosity for the HFE gene mutation c.845G > A; p.C282Y. However, in some cases, another HFE mutation (c.187C > G; p.H63D) seems to be associated with the disease. Its penetrance is very low, suggesting the possibility of other iron genetic modulators being involved. In this work, we have screened for HAMP promoter polymorphisms in 409 individuals presenting normal or increased serum ferritin levels together with normal or H63D-mutated HFE genotypes. Our results show that the hepcidin gene promoter TG haplotype, originated by linkage of the nc.-1010C > T and nc.-582A > G polymorphisms, is more frequent in the HFE_H63D individuals presenting serum ferritin levels higher than 300 μg/L than in those presenting the HFE_H63D mutation but with normal serum ferritin levels or in the normal control group.Moreover, it was observed that the TG haplotype was associated to increased serum ferritin levels in the overall pool of HFE_H63D individuals. Thus, our data suggest that screening for these polymorphisms could be of interest in order to explain the phenotype. However, this genetic condition seems to have no clinical significance.

The influence of allosteric modulators and transmembrane mutations on desensitisation and activation of α7 nicotinic acetylcholine receptors

PubMed Central

Chatzidaki, Anna; D'Oyley, Jarryl M.; Gill-Thind, JasKiran K.; Sheppard, Tom D.; Millar, Neil S.

2015-01-01

Acetylcholine activates nicotinic acetylcholine receptors (nAChRs) by binding at an extracellular orthosteric site. Previous studies have described several positive allosteric modulators (PAMs) that are selective for homomeric α7 nAChRs. These include type I PAMs, which exert little or no effect on the rate of receptor desensitisation, and type II PAMs, which cause a dramatic loss of agonist-induced desensitisation. Here we report evidence that transmembrane mutations in α7 nAChRs have diverse effects on receptor activation and desensitisation by allosteric ligands. It has been reported previously that the L247T mutation, located toward the middle of the second transmembrane domain (at the 9′ position), confers reduced levels of desensitisation. In contrast, the M260L mutation, located higher up in the TM2 domain (at the 22′ position), does not show any difference in desensitisation compared to wild-type receptors. We have found that in receptors containing the L247T mutation, both type I PAMs and type II PAMs are converted into non-desensitising agonists. In contrast, in receptors containing the M260L mutation, this effect is seen only with type II PAMs. These findings, indicating that the M260L mutation has a selective effect on type II PAMs, have been confirmed both with previously described PAMs and also with a series of novel α7-selective PAMs. The novel PAMs examined in this study have close chemical similarity but diverse pharmacological properties. For example, they include compounds displaying effects on receptor desensitisation that are typical of classical type I and type II PAMs but, in addition, they include compounds with intermediate properties. PMID:25998276

The influence of allosteric modulators and transmembrane mutations on desensitisation and activation of α7 nicotinic acetylcholine receptors.

PubMed

Chatzidaki, Anna; D'Oyley, Jarryl M; Gill-Thind, JasKiran K; Sheppard, Tom D; Millar, Neil S

2015-10-01

Acetylcholine activates nicotinic acetylcholine receptors (nAChRs) by binding at an extracellular orthosteric site. Previous studies have described several positive allosteric modulators (PAMs) that are selective for homomeric α7 nAChRs. These include type I PAMs, which exert little or no effect on the rate of receptor desensitisation, and type II PAMs, which cause a dramatic loss of agonist-induced desensitisation. Here we report evidence that transmembrane mutations in α7 nAChRs have diverse effects on receptor activation and desensitisation by allosteric ligands. It has been reported previously that the L247T mutation, located toward the middle of the second transmembrane domain (at the 9' position), confers reduced levels of desensitisation. In contrast, the M260L mutation, located higher up in the TM2 domain (at the 22' position), does not show any difference in desensitisation compared to wild-type receptors. We have found that in receptors containing the L247T mutation, both type I PAMs and type II PAMs are converted into non-desensitising agonists. In contrast, in receptors containing the M260L mutation, this effect is seen only with type II PAMs. These findings, indicating that the M260L mutation has a selective effect on type II PAMs, have been confirmed both with previously described PAMs and also with a series of novel α7-selective PAMs. The novel PAMs examined in this study have close chemical similarity but diverse pharmacological properties. For example, they include compounds displaying effects on receptor desensitisation that are typical of classical type I and type II PAMs but, in addition, they include compounds with intermediate properties. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Nuclear modifier MTO2 modulates the aminoglycoside-sensitivity of mitochondrial 15S rRNA C1477G mutation in Saccharomyces cerevisiae.

PubMed

He, Xiangyu; Zhu, Xiaoyu; Wang, Xuexiang; Wang, Wei; Dai, Yu; Yan, Qingfeng

2013-01-01

The phenotypic manifestations of mitochondrial DNA (mtDNA) mutations are modulated by mitochondrial DNA haplotypes, nuclear modifier genes and environmental factors. The yeast mitochondrial 15S rRNA C1477G (P(R) or P(R) 454) mutation corresponds to the human 12S rRNA C1494T and A1555G mutations, which are well known as primary factors for aminoglycoside-induced nonsyndromic deafness. Here we report that the deletion of the nuclear modifier gene MTO2 suppressed the aminoglycoside-sensitivity of mitochondrial 15S rRNA C1477G mutation in Saccharomyces cerevisiae. First, the strain with a single mtDNA C1477G mutation exhibited hypersensitivity to neomycin. Functional assays indicated that the steady-state transcription level of mitochondrial DNA, the mitochondrial respiratory rate, and the membrane potential decreased significantly after neomycin treatment. The impaired mitochondria could not produce sufficient energy to maintain cell viability. Second, when the mto2 null and the mitochondrial C1477G mutations co-existed (mto2(P(R))), the oxygen consumption rate in the double mutant decreased markedly compared to that of the control strains (MTO2(P(S)), mto2(P(S)) and MTO2(P(R))). The expression levels of the key glycolytic genes HXK2, PFK1 and PYK1 in the mto2(P(R)) strain were stimulated by neomycin and up-regulated by 89%, 112% and 55%, respectively. The enhanced glycolysis compensated for the respiratory energy deficits, and could be inhibited by the glycolytic enzyme inhibitor. Our findings in yeast will provide a new insight into the pathogenesis of human deafness.

A network system of medical and welfare information service for the patients, their families, hospitals, local governments, and commercial companies in a medical service area.

PubMed

Matsumura, Kouji; Antoku, Yasuaki; Inoue, Reika; Kobayashi, Mariko; Hanada, Eisuke; Iwasaki, Yasutaka; Kumagai, Yasushi; Iwamoto, Haruya; Tsuchihashi, Saburo; Iwaki, Miho; Kira, Jun-ichi; Nose, Yoshiaki

2002-06-01

A service information system using the Internet, which connected the various people who are related to medical treatment and nursing welfare, was constructed. An intractable neurological disease patient who lives in the Onga district, Fukuoka, Japan, and the people who are related to the service were chosen as test users in an experimental model. The communicated service information was divided into open-use data (electronic bulletin board, welfare service, medical care service, and link to private company service home page) and closed-use data (the individual patient's hysterics). The open data server was installed in an Internet service provider The open data could be accessed not only by the patient, but also by the family, information center, companies, hospitals, and nursing commodity store related to patient's nursing and medical treatment. Closed data server was installed in an information center (public health center). Only patient and information center staff can access the closed data. Patients should search and collect the service information of various medical and welfare services by themselves. Therefore, services prepared for the patient are difficult to know, and they cannot be sufficiently utilized. With the use of this information system, all usable service information became accessible, and patients could easily use it. The electronic bulletin board system (BBS) was used by patients for knowing each other or each others' family, and was used as a device for exchange of wisdom. Also, the questions for the specialist, such as doctor, dentist, teacher, physical therapist, care manager, welfare office staff member, and public health nurse, and the answers were shown on the BBS. By arranging data file, a reference of various patients in question and answer, which appeared in this BBS, was made as "advisory hints" and was added to the open data. The advisory hints became the new service information for the patients and their family. This BBS discovered the possibility of becoming an important information source for companies, hospital and, administration to know the requirements of patients and their families and the kind of services to be served. Although suppliers provide medical and welfare services for the patient, there is a tendency that the service information is sent by the suppliers at their own convenience. The information system in which various people participated was constructed in order to collect information for the patient, taking a patient-oriented approach. The result of the model test showed that this information system using Internet technology is a good system for both the service supplier and its receiver.

SPOP mutation leads to genomic instability in prostate cancer

PubMed Central

Boysen, Gunther; Barbieri, Christopher E; Prandi, Davide; Blattner, Mirjam; Chae, Sung-Suk; Dahija, Arun; Nataraj, Srilakshmi; Huang, Dennis; Marotz, Clarisse; Xu, Limei; Huang, Julie; Lecca, Paola; Chhangawala, Sagar; Liu, Deli; Zhou, Pengbo; Sboner, Andrea; de Bono, Johann S

2015-01-01

Genomic instability is a fundamental feature of human cancer often resulting from impaired genome maintenance. In prostate cancer, structural genomic rearrangements are a common mechanism driving tumorigenesis. However, somatic alterations predisposing to chromosomal rearrangements in prostate cancer remain largely undefined. Here, we show that SPOP, the most commonly mutated gene in primary prostate cancer modulates DNA double strand break (DSB) repair, and that SPOP mutation is associated with genomic instability. In vivo, SPOP mutation results in a transcriptional response consistent with BRCA1 inactivation resulting in impaired homology-directed repair (HDR) of DSB. Furthermore, we found that SPOP mutation sensitizes to DNA damaging therapeutic agents such as PARP inhibitors. These results implicate SPOP as a novel participant in DSB repair, suggest that SPOP mutation drives prostate tumorigenesis in part through genomic instability, and indicate that mutant SPOP may increase response to DNA-damaging therapeutics. DOI: http://dx.doi.org/10.7554/eLife.09207.001 PMID:26374986

Glutamate receptor mutations in psychiatric and neurodevelopmental disorders

PubMed Central

Soto, David; Altafaj, Xavier; Sindreu, Carlos; Bayés, Àlex

2014-01-01

Alterations in glutamatergic neurotransmission have long been associated with psychiatric and neurodevelopmental disorders (PNDD), but only recent advances in high-throughput DNA sequencing have allowed interrogation of the prevalence of mutations in glutamate receptors (GluR) among afflicted individuals. In this review we discuss recent work describing GluR mutations in the context of PNDDs. Although there are no strict relationships between receptor subunit or type and disease, some interesting preliminary conclusions have arisen. Mutations in genes coding for ionotropic glutamate receptor subunits, which are central to synaptic transmission and plasticity, are mostly associated with intellectual disability and autism spectrum disorders. In contrast, mutations of metabotropic GluRs, having a role on modulating neural transmission, are preferentially associated with psychiatric disorders. Also, the prevalence of mutations among GluRs is highly heterogeneous, suggesting a critical role of certain subunits in PNDD pathophysiology. The emerging bias between GluR subtypes and specific PNDDs may have clinical implications. PMID:24605182

Glutamate receptor mutations in psychiatric and neurodevelopmental disorders.

PubMed

Soto, David; Altafaj, Xavier; Sindreu, Carlos; Bayés, Alex

2014-01-01

Alterations in glutamatergic neurotransmission have long been associated with psychiatric and neurodevelopmental disorders (PNDD), but only recent advances in high-throughput DNA sequencing have allowed interrogation of the prevalence of mutations in glutamate receptors (GluR) among afflicted individuals. In this review we discuss recent work describing GluR mutations in the context of PNDDs. Although there are no strict relationships between receptor subunit or type and disease, some interesting preliminary conclusions have arisen. Mutations in genes coding for ionotropic glutamate receptor subunits, which are central to synaptic transmission and plasticity, are mostly associated with intellectual disability and autism spectrum disorders. In contrast, mutations of metabotropic GluRs, having a role on modulating neural transmission, are preferentially associated with psychiatric disorders. Also, the prevalence of mutations among GluRs is highly heterogeneous, suggesting a critical role of certain subunits in PNDD pathophysiology. The emerging bias between GluR subtypes and specific PNDDs may have clinical implications.

Synaptic vesicle glycoprotein 2A (SV2A) regulates kindling epileptogenesis via GABAergic neurotransmission

PubMed Central

Tokudome, Kentaro; Okumura, Takahiro; Shimizu, Saki; Mashimo, Tomoji; Takizawa, Akiko; Serikawa, Tadao; Terada, Ryo; Ishihara, Shizuka; Kunisawa, Naofumi; Sasa, Masashi; Ohno, Yukihiro

2016-01-01

Synaptic vesicle glycoprotein 2A (SV2A) is a prototype synaptic vesicle protein regulating action potential-dependent neurotransmitters release. SV2A also serves as a specific binding site for certain antiepileptics and is implicated in the treatment of epilepsy. Here, to elucidate the role of SV2A in modulating epileptogenesis, we generated a novel rat model (Sv2aL174Q rat) carrying a Sv2a-targeted missense mutation (L174Q) and analyzed its susceptibilities to kindling development. Although animals homozygous for the Sv2aL174Q mutation exhibited normal appearance and development, they are susceptible to pentylenetetrazole (PTZ) seizures. In addition, development of kindling associated with repeated PTZ treatments or focal stimulation of the amygdala was markedly facilitated by the Sv2aL174Q mutation. Neurochemical studies revealed that the Sv2aL174Q mutation specifically reduced depolarization-induced GABA, but not glutamate, release in the hippocampus without affecting basal release or the SV2A expression level in GABAergic neurons. In addition, the Sv2aL174Q mutation selectively reduced the synaptotagmin1 (Syt1) level among the exocytosis-related proteins examined. The present results demonstrate that dysfunction of SV2A due to the Sv2aL174Q mutation impairs the synaptic GABA release by reducing the Syt1 level and facilitates the kindling development, illustrating the crucial role of SV2A-GABA system in modulating kindling epileptogenesis. PMID:27265781

Epilepsy-causing mutations in Kv7.2 C-terminus affect binding and functional modulation by calmodulin.

PubMed

Ambrosino, Paolo; Alaimo, Alessandro; Bartollino, Silvia; Manocchio, Laura; De Maria, Michela; Mosca, Ilaria; Gomis-Perez, Carolina; Alberdi, Araitz; Scambia, Giovanni; Lesca, Gaetan; Villarroel, Alvaro; Taglialatela, Maurizio; Soldovieri, Maria Virginia

2015-09-01

Mutations in the KCNQ2 gene, encoding for voltage-gated Kv7.2K(+) channel subunits, are responsible for early-onset epileptic diseases with widely-diverging phenotypic presentation, ranging from Benign Familial Neonatal Seizures (BFNS) to epileptic encephalopathy. In the present study, Kv7.2 BFNS-causing mutations (W344R, L351F, L351V, Y362C, and R553Q) have been investigated for their ability to interfere with calmodulin (CaM) binding and CaM-induced channel regulation. To this aim, semi-quantitative (Far-Western blotting) and quantitative (Surface Plasmon Resonance and dansylated CaM fluorescence) biochemical assays have been performed to investigate the interaction of CaM with wild-type or mutant Kv7.2 C-terminal fragments encompassing the CaM-binding domain; in parallel, mutation-induced changes in CaM-dependent Kv7.2 or Kv7.2/Kv7.3 current regulation were investigated by patch-clamp recordings in Chinese Hamster Ovary (CHO) cells co-expressing Kv7.2 or Kv7.2/Kv7.3 channels and CaM or CaM1234 (a CaM isoform unable to bind Ca(2+)). The results obtained suggest that each BFNS-causing mutation prompts specific biochemical and/or functional consequences; these range from slight alterations in CaM affinity which did not translate into functional changes (L351V), to a significant reduction in the affinity and functional modulation by CaM (L351F, Y362C or R553Q), to a complete functional loss without significant alteration in CaM affinity (W344R). CaM overexpression increased Kv7.2 and Kv7.2/Kv7.3 current levels, and partially (R553Q) or fully (L351F) restored normal channel function, providing a rationale pathogenetic mechanism for mutation-induced channel dysfunction in BFNS, and highlighting the potentiation of CaM-dependent Kv7.2 modulation as a potential therapeutic approach for Kv7.2-related epilepsies. Copyright © 2015 Elsevier B.V. All rights reserved.

An Apple a Day and at Night: A Distance Tutoring Program for At-Risk Students.

ERIC Educational Resources Information Center

Ross, Steven M.; And Others

1989-01-01

Describes a program of distance tutoring developed by Apple Computer, Inc., Memphis City Schools, and Memphis State University for at-risk minority students. The electronic bulletin board system (BBS) used is described; types of distance learning systems are explained; and research outcomes are discussed, including tutor roles and writing skills.…

Assessing ecoregional-scale habitat suitability index models for priority landbirds

Treesearch

John M. Tirpak; D. Todd Jones-Farrand; Frank R. Thompson; Daniel J. Twedt; Charles K. Baxter; Jane A. Fitzgerald; William B. Uihlein

2009-01-01

Emerging methods in habitat and wildlife population modeling promise new horizons in conservation but only if these methods provide robust population-habitat linkages. We used Breeding Bird Survey (BBS) data to verify and validate newly developed habitat suitability index (HSI) models for 40 priority landbird species in the Central Hardwoods and West Gulf Coastal Plain...

Measuring Bystander Attitudes and Behavior to Prevent Sexual Violence

ERIC Educational Resources Information Center

McMahon, Sarah; Allen, Christopher T.; Postmus, Judy L.; McMahon, Sheila M.; Peterson, N. Andrew; Lowe Hoffman, Melanie

2014-01-01

Objective: The purpose of this study is to further investigate the factor structure and strength of the Bystander Attitude Scale-Revised and Bystander Behavior Scale-Revised (BAS-R and BBS-R). Participants: First-year students (N = 4,054) at a large public university in the Northeast completed a survey in 2010 as part of a larger longitudinal…

Effects of long-term forest management on a regional avifauna

Treesearch

John C. Kilgo; Kathleen E. Franzreb; Sidney A. Gauthreaux; Karl V. Miller; Brian R. Chapman

2000-01-01

We compared breeding bird populations on and off of the Savannah River Site, SC, to determine whether management practices have affected abundance and composition of the resident avifauna. We assessed relative abundance by comparing Breeding Bird Survey (BBS) data from six routes off the Savannah River Site with three surrogate routes generated using point-count data...

Review on "BBS Are Our Kids Tough Enough: Chinese Schools" Based on History, Literature and Personal Experience

ERIC Educational Resources Information Center

Zhao, Yiran

2015-01-01

The aim behind this article is to clear up some misunderstandings about British and Chinese education approaches in the popular BBC documentary "Are our kids tough enough: Chinese Schools". The article evaluates the differences in academic performance, class disciplines and education values of two education practices that have caused…

A Review of MS-DOS Bulletin Board Software Suitable for Long Distance Learning.

ERIC Educational Resources Information Center

Sessa, Anneliese

This paper describes the advantages of using computer bulletin boards systems (BBS) for distance learning, including the use of the New York City Education Network (NYCENET) to access various databases and to communicate with individuals or the public. Questions to be answered in order to determine the most appropriate software for running a BBS…

Non-essential role for cilia in coordinating precise alignment of lens fibres

PubMed Central

Sugiyama, Yuki; Shelley, Elizabeth J.; Yoder, Bradley K.; Kozmik, Zbynek; May-Simera, Helen L.; Beales, Philip L.; Lovicu, Frank J.; McAvoy, John W.

2016-01-01

The primary cilium, a microtubule-based organelle found in most cells, is a centre for mechano-sensing fluid movement and cellular signalling, notably through the Hedgehog pathway. We recently found that each lens fibre cell has an apically situated primary cilium that is polarised to the side of the cell facing the anterior pole of the lens. The direction of polarity is similar in neighbouring cells so that in the global view, lens fibres exhibit planar cell polarity (PCP) along the equatorial-anterior polar axis. Ciliogenesis has been associated with the establishment of PCP, although the exact relationship between PCP and the role of cilia is still controversial. To test the hypothesis that the primary cilia have a role in coordinating the precise alignment/orientation of the fibre cells, IFT88, a key component of the intraflagellar transport (IFT) complex, was removed specifically from the lens at different developmental stages using several lens-specific Cre-expressing mouse lines (MLR10- and LR-Cre). Irrespective of which Cre-line was adopted, both demonstrated that in IFT88-depleted cells, the ciliary axoneme was absent or substantially shortened, confirming the disruption of primary cilia formation. However no obvious histological defects were detected even when IFT88 was removed from the lens placode as early as E9.5. Specifically, the lens fibres aligned/oriented towards the poles to form the characteristic Y-shaped sutures as normal. Consistent with this, in primary lens epithelial explants prepared from these conditional knockout mouse lenses, the basal bodies still showed polarised localisation at the apical surface of elongating cells upon FGF-induced fibre differentiation. We further investigated the lens phenotype in knockouts of Bardet–Biedl Syndrome (BBS) proteins 4 and 8, the components of the BBSome complex which modulate ciliary function. In these BBS4 and 8 knockout lenses, again we found the pattern of the anterior sutures formed by the apical tips of elongating/migrating fibres were comparable to the control lenses. Taken together, these results indicate that primary cilia do not play an essential role in the precise cellular alignment/orientation of fibre cells. Thus, it appears that in the lens cilia are not required to establish PCP. PMID:26825015

Assessing Associations between the AURKA-HMMR-TPX2-TUBG1 Functional Module and Breast Cancer Risk in BRCA1/2 Mutation Carriers

PubMed Central

Blanco, Ignacio; Kuchenbaecker, Karoline; Cuadras, Daniel; Wang, Xianshu; Barrowdale, Daniel; de Garibay, Gorka Ruiz; Librado, Pablo; Sánchez-Gracia, Alejandro; Rozas, Julio; Bonifaci, Núria; McGuffog, Lesley; Pankratz, Vernon S.; Islam, Abul; Mateo, Francesca; Berenguer, Antoni; Petit, Anna; Català, Isabel; Brunet, Joan; Feliubadaló, Lidia; Tornero, Eva; Benítez, Javier; Osorio, Ana; Cajal, Teresa Ramón y; Nevanlinna, Heli; Aittomäki, Kristiina; Arun, Banu K.; Toland, Amanda E.; Karlan, Beth Y.; Walsh, Christine; Lester, Jenny; Greene, Mark H.; Mai, Phuong L.; Nussbaum, Robert L.; Andrulis, Irene L.; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Barkardottir, Rosa B.; Jakubowska, Anna; Lubinski, Jan; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Claes, Kathleen; Van Maerken, Tom; Díez, Orland; Hansen, Thomas V.; Jønson, Lars; Gerdes, Anne-Marie; Ejlertsen, Bent; de la Hoya, Miguel; Caldés, Trinidad; Dunning, Alison M.; Oliver, Clare; Fineberg, Elena; Cook, Margaret; Peock, Susan; McCann, Emma; Murray, Alex; Jacobs, Chris; Pichert, Gabriella; Lalloo, Fiona; Chu, Carol; Dorkins, Huw; Paterson, Joan; Ong, Kai-Ren; Teixeira, Manuel R.; Hogervorst, Frans B. L.; van der Hout, Annemarie H.; Seynaeve, Caroline; van der Luijt, Rob B.; Ligtenberg, Marjolijn J. L.; Devilee, Peter; Wijnen, Juul T.; Rookus, Matti A.; Meijers-Heijboer, Hanne E. J.; Blok, Marinus J.; van den Ouweland, Ans M. W.; Aalfs, Cora M.; Rodriguez, Gustavo C.; Phillips, Kelly-Anne A.; Piedmonte, Marion; Nerenstone, Stacy R.; Bae-Jump, Victoria L.; O'Malley, David M.; Ratner, Elena S.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Rhiem, Kerstin; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Plendl, Hansjoerg J.; Niederacher, Dieter; Sutter, Christian; Wang-Gohrke, Shan; Steinemann, Doris; Preisler-Adams, Sabine; Kast, Karin; Varon-Mateeva, Raymonda; Gehrig, Andrea; Bojesen, Anders; Pedersen, Inge Sokilde; Sunde, Lone; Jensen, Uffe Birk; Thomassen, Mads; Kruse, Torben A.; Foretova, Lenka; Peterlongo, Paolo; Bernard, Loris; Peissel, Bernard; Scuvera, Giulietta; Manoukian, Siranoush; Radice, Paolo; Ottini, Laura; Montagna, Marco; Agata, Simona; Maugard, Christine; Simard, Jacques; Soucy, Penny; Berger, Andreas; Fink-Retter, Anneliese; Singer, Christian F.; Rappaport, Christine; Geschwantler-Kaulich, Daphne; Tea, Muy-Kheng; Pfeiler, Georg; John, Esther M.; Miron, Alex; Neuhausen, Susan L.; Terry, Mary Beth; Chung, Wendy K.; Daly, Mary B.; Goldgar, David E.; Janavicius, Ramunas; Dorfling, Cecilia M.; van Rensburg, Elisabeth J.; Fostira, Florentia; Konstantopoulou, Irene; Garber, Judy; Godwin, Andrew K.; Olah, Edith; Narod, Steven A.; Rennert, Gad; Paluch, Shani Shimon; Laitman, Yael; Friedman, Eitan; Liljegren, Annelie; Rantala, Johanna; Stenmark-Askmalm, Marie; Loman, Niklas; Imyanitov, Evgeny N.; Hamann, Ute; Spurdle, Amanda B.; Healey, Sue; Weitzel, Jeffrey N.; Herzog, Josef; Margileth, David; Gorrini, Chiara; Esteller, Manel; Gómez, Antonio; Sayols, Sergi; Vidal, Enrique; Heyn, Holger; Stoppa-Lyonnet, Dominique; Léoné, Melanie; Barjhoux, Laure; Fassy-Colcombet, Marion; de Pauw, Antoine; Lasset, Christine; Ferrer, Sandra Fert; Castera, Laurent; Berthet, Pascaline; Cornelis, François; Bignon, Yves-Jean; Damiola, Francesca; Mazoyer, Sylvie; Maxwell, Christopher A.; Vijai, Joseph; Robson, Mark; Kauff, Noah; Corines, Marina J.; Villano, Danylko; Cunningham, Julie; Lee, Adam; Lindor, Noralane; Lázaro, Conxi; Easton, Douglas F.; Offit, Kenneth; Chenevix-Trench, Georgia; Couch, Fergus J.; Antoniou, Antonis C.; Pujana, Miguel Angel

2015-01-01

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 – 1.15, p = 1.9 x 10−4 (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 – 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients’ survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers. PMID:25830658

Computational Model of the Modulation of Gene Expression Following DNA Damage

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Dicello, J. F.; Nikjoo, H.; Cherubini, R.

2002-01-01

High linear energy transfer (LET) radiation, such as heavy ions or neutrons, has an increased biological effectiveness compared to X rays for gene mutation, genomic instability, and carcinogenesis. In the traditional paradigm, mutations or chromosomal aberrations are causative of late effects. However, in recent years experimental evidence has demonstrated the important role of the description of the modification of gene expression by radiation in understanding the mechanisms of radiation action. In this report, approaches are discussed to the mathematical description of mRNA and protein expression kinetics following DNA damage. Several hypotheses for models of radiation modulation of protein expression are discussed including possible non-linear processes that evolve from the linear dose responses that follow the initial DNA damage produced by radiation.

Significance of duon mutations in cancer genomes

NASA Astrophysics Data System (ADS)

Yadav, Vinod Kumar; Smith, Kyle S.; Flinders, Colin; Mumenthaler, Shannon M.; de, Subhajyoti

2016-06-01

Functional mutations in coding regions not only affect the structure and function of the protein products, but may also modulate their expression in some cases. This class of mutations, recently dubbed “duon mutations” due to their dual roles, can potentially have major impacts on downstream pathways. However their significance in diseases such as cancer remain unclear. In a survey covering 4606 samples from 19 cancer types, and integrating allelic expression, overall mRNA expression, regulatory motif perturbation, and chromatin signatures in one composite index called REDACT score, we identified potential duon mutations. Several such mutations are detected in known cancer genes in multiple cancer types. For instance a potential duon mutation in TP53 is associated with increased expression of the mutant allelic gene copy, thereby possibly amplifying the functional effects on the downstream pathways. Another potential duon mutation in SF3B1 is associated with abnormal splicing and changes in angiogenesis and matrix degradation related pathways. Our findings emphasize the need to interrogate the mutations in coding regions beyond their obvious effects on protein structures.

Splicing factor gene mutations in the myelodysplastic syndromes: impact on disease phenotype and therapeutic applications.

PubMed

Pellagatti, Andrea; Boultwood, Jacqueline

2017-01-01

Splicing factor gene mutations are the most frequent mutations found in patients with the myeloid malignancy myelodysplastic syndrome (MDS), suggesting that spliceosomal dysfunction plays a major role in disease pathogenesis. The aberrantly spliced target genes and deregulated cellular pathways associated with the commonly mutated splicing factor genes in MDS (SF3B1, SRSF2 and U2AF1) are being identified, illuminating the molecular mechanisms underlying MDS. Emerging data from mouse modeling studies indicate that the presence of splicing factor gene mutations can lead to bone marrow hematopoietic stem/myeloid progenitor cell expansion, impaired hematopoiesis and dysplastic differentiation that are hallmarks of MDS. Importantly, recent evidence suggests that spliceosome inhibitors and splicing modulators may have therapeutic value in the treatment of splicing factor mutant myeloid malignancies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antiandrogens act as selective androgen receptor modulators at the proteome level in prostate cancer cells.

PubMed

Brooke, Greg N; Gamble, Simon C; Hough, Michael A; Begum, Shajna; Dart, D Alwyn; Odontiadis, Michael; Powell, Sue M; Fioretti, Flavia M; Bryan, Rosie A; Waxman, Jonathan; Wait, Robin; Bevan, Charlotte L

2015-05-01

Current therapies for prostate cancer include antiandrogens, inhibitory ligands of the androgen receptor, which repress androgen-stimulated growth. These include the selective androgen receptor modulators cyproterone acetate and hydroxyflutamide and the complete antagonist bicalutamide. Their activity is partly dictated by the presence of androgen receptor mutations, which are commonly detected in patients who relapse while receiving antiandrogens, i.e. in castrate-resistant prostate cancer. To characterize the early proteomic response to these antiandrogens we used the LNCaP prostate cancer cell line, which harbors the androgen receptor mutation most commonly detected in castrate-resistant tumors (T877A), analyzing alterations in the proteome, and comparing these to the effect of these therapeutics upon androgen receptor activity and cell proliferation. The majority are regulated post-transcriptionally, possibly via nongenomic androgen receptor signaling. Differences detected between the exposure groups demonstrate subtle changes in the biological response to each specific ligand, suggesting a spectrum of agonistic and antagonistic effects dependent on the ligand used. Analysis of the crystal structures of the AR in the presence of cyproterone acetate, hydroxyflutamide, and DHT identified important differences in the orientation of key residues located in the AF-2 and BF-3 protein interaction surfaces. This further implies that although there is commonality in the growth responses between androgens and those antiandrogens that stimulate growth in the presence of a mutation, there may also be influential differences in the growth pathways stimulated by the different ligands. This therefore has implications for prostate cancer treatment because tumors may respond differently dependent upon which mutation is present and which ligand is activating growth, also for the design of selective androgen receptor modulators, which aim to elicit differential proteomic responses dependent upon cellular context. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Antiandrogens Act as Selective Androgen Receptor Modulators at the Proteome Level in Prostate Cancer Cells*

PubMed Central

Brooke, Greg N.; Gamble, Simon C.; Hough, Michael A.; Begum, Shajna; Dart, D. Alwyn; Odontiadis, Michael; Powell, Sue M.; Fioretti, Flavia M.; Bryan, Rosie A.; Waxman, Jonathan; Wait, Robin; Bevan, Charlotte L.

2015-01-01

Current therapies for prostate cancer include antiandrogens, inhibitory ligands of the androgen receptor, which repress androgen-stimulated growth. These include the selective androgen receptor modulators cyproterone acetate and hydroxyflutamide and the complete antagonist bicalutamide. Their activity is partly dictated by the presence of androgen receptor mutations, which are commonly detected in patients who relapse while receiving antiandrogens, i.e. in castrate-resistant prostate cancer. To characterize the early proteomic response to these antiandrogens we used the LNCaP prostate cancer cell line, which harbors the androgen receptor mutation most commonly detected in castrate-resistant tumors (T877A), analyzing alterations in the proteome, and comparing these to the effect of these therapeutics upon androgen receptor activity and cell proliferation. The majority are regulated post-transcriptionally, possibly via nongenomic androgen receptor signaling. Differences detected between the exposure groups demonstrate subtle changes in the biological response to each specific ligand, suggesting a spectrum of agonistic and antagonistic effects dependent on the ligand used. Analysis of the crystal structures of the AR in the presence of cyproterone acetate, hydroxyflutamide, and DHT identified important differences in the orientation of key residues located in the AF-2 and BF-3 protein interaction surfaces. This further implies that although there is commonality in the growth responses between androgens and those antiandrogens that stimulate growth in the presence of a mutation, there may also be influential differences in the growth pathways stimulated by the different ligands. This therefore has implications for prostate cancer treatment because tumors may respond differently dependent upon which mutation is present and which ligand is activating growth, also for the design of selective androgen receptor modulators, which aim to elicit differential proteomic responses dependent upon cellular context. PMID:25693800

Forskolin-induced Swelling in Intestinal Organoids: An In Vitro Assay for Assessing Drug Response in Cystic Fibrosis Patients.

PubMed

Boj, Sylvia F; Vonk, Annelotte M; Statia, Marvin; Su, Jinyi; Vries, Robert R G; Beekman, Jeffrey M; Clevers, Hans

2017-02-11

Recently-developed cystic fibrosis transmembrane conductance regulator (CFTR)-modulating drugs correct surface expression and/or function of the mutant CFTR channel in subjects with cystic fibrosis (CF). Identification of subjects that may benefit from these drugs is challenging because of the extensive heterogeneity of CFTR mutations, as well as other unknown factors that contribute to individual drug efficacy. Here, we describe a simple and relatively rapid assay for measuring individual CFTR function and response to CFTR modulators in vitro. Three dimensional (3D) epithelial organoids are grown from rectal biopsies in standard organoid medium. Once established, the organoids can be bio-banked for future analysis. For the assay, 30-80 organoids are seeded in 96-well plates in basement membrane matrix and are then exposed to drugs. One day later, the organoids are stained with calcein green, and forskolin-induced swelling is monitored by confocal live cell microscopy at 37 °C. Forskolin-induced swelling is fully CFTR-dependent and is sufficiently sensitive and precise to allow for discrimination between the drug responses of individuals with different and even identical CFTR mutations. In vitro swell responses correlate with the clinical response to therapy. This assay provides a cost-effective approach for the identification of drug-responsive individuals, independent of their CFTR mutations. It may also be instrumental in the development of future CFTR modulators.

Evaluation of Downstream Regulatory Element Antagonistic Modulator Gene in Human Multinodular Goiter

PubMed Central

Shinzato, Amanda; Lerario, Antonio M.; Lin, Chin J.; Danilovic, Debora S.; Marui, Suemi; Trarbach, Ericka B.

2015-01-01

Background DREAM (Downstream Regulatory Element Antagonistic Modulator) is a neuronal calcium sensor that was suggested to modulate TSH receptor activity and whose overexpression provokes an enlargement of the thyroid gland in transgenic mice. The aim of this study was to investigate somatic mutations and DREAM gene expression in human multinodular goiter (MNG). Material/Methods DNA and RNA samples were obtained from hyperplastic thyroid glands of 60 patients (54 females) with benign MNG. DREAM mutations were evaluated by PCR and direct automatic sequencing, whereas relative quantification of mRNA was performed by real-time PCR. Over- and under-expression were defined as a 2-fold increase and decrease in comparison to normal thyroid tissue, respectively. RQ M (relative quantification mean); SD (standard deviation). Results DREAM expression was detected in all nodules evaluated. DREAM mRNA was overexpressed in 31.7% of MNG (RQ M=6.26; SD=5.08), whereas 53.3% and 15% had either normal (RQ M=1.16; SD=0.46) or underexpression (RQ M=0.30; SD=0.10), respectively. Regarding DREAM mutations analysis, only previously described intronic polymorphisms were observed. Conclusions We report DREAM gene expression in the hyperplastic thyroid gland of MNG patients. However, DREAM expression did not vary significantly, and was somewhat underexpressed in most patients, suggesting that DREAM upregulation does not significantly affect nodular development in human goiter. PMID:26319784

Cohort Differences in the Availability of Informal Caregivers: Are the Boomers at Risk?

ERIC Educational Resources Information Center

Ryan, Lindsay H.; Smith, Jacqui; Antonucci, Toni C.; Jackson, James S.

2012-01-01

Purpose of the Study: We compare the close family resources of Baby Boomers (BBs) to previous cohorts of older adults at population level and then examine individual-level cohort comparisons of age-related trajectories of informal care availability from midlife into old age. Design and Methods: Population data from the U.S. Census and from the…

Developing Spatially Explicit Habitat Models for Grassland Bird Conservation Planning in the Prairie Pothole Region of North Dakota

Treesearch

Neal D. Niemuth; Michael E. Estey; Charles R. Loesch

2005-01-01

Conservation planning for birds is increasingly focused on landscapes. However, little spatially explicit information is available to guide landscape-level conservation planning for many species of birds. We used georeferenced 1995 Breeding Bird Survey (BBS) data in conjunction with land-cover information to develop a spatially explicit habitat model predicting the...

From Sea to Cyberspace: Women's Leadership and Learning around Information and Communication Technologies in Coastal Newfoundland

ERIC Educational Resources Information Center

Clover, Darlene E.

2007-01-01

Due to a moratorium on the cod fishery in 1992, small, isolated coastal villages in Newfoundland suffer increasing unemployment, health problems and threats of re-location by the government. In the hopes of addressing some of these problems, the Burgeo Broadcasting System (BBS) placed video-conferencing and broad-band internet into five small…

Feasibility and Reliability of the Modified Berg Balance Scale in Persons with Severe Intellectual and Visual Disabilities

ERIC Educational Resources Information Center

Waninge, A.; van Wijck, R.; Steenbergen, B.; van der Schans, C. P.

2011-01-01

Background: The purpose of this study was to determine the feasibility and reliability of the modified Berg Balance Scale (mBBS) in persons with severe intellectual and visual disabilities (severe multiple disabilities, SMD) assigned Gross Motor Function Classification System (GMFCS) grades I and II. Method: Thirty-nine participants with SMD and…

Connection between the membrane electron transport system and Hyn hydrogenase in the purple sulfur bacterium, Thiocapsa roseopersicina BBS.

PubMed

Tengölics, Roland; Mészáros, Lívia; Győri, E; Doffkay, Zsolt; Kovács, Kornél L; Rákhely, Gábor

2014-10-01

Thiocapsa. roseopersicina BBS has four active [NiFe] hydrogenases, providing an excellent opportunity to examine their metabolic linkages to the cellular redox processes. Hyn is a periplasmic membrane-associated hydrogenase harboring two additional electron transfer subunits: Isp1 is a transmembrane protein, while Isp2 is located on the cytoplasmic side of the membrane. In this work, the connection of HynSL to various electron transport pathways is studied. During photoautotrophic growth, electrons, generated from the oxidation of thiosulfate and sulfur, are donated to the photosynthetic electron transport chain via cytochromes. Electrons formed from thiosulfate and sulfur oxidation might also be also used for Hyn-dependent hydrogen evolution which was shown to be light and proton motive force driven. Hyn-linked hydrogen uptake can be promoted by both sulfur and nitrate. The electron flow from/to HynSL requires the presence of Isp2 in both directions. Hydrogenase-linked sulfur reduction could be inhibited by a QB site competitive inhibitor, terbutryne, suggesting a redox coupling between the Hyn hydrogenase and the photosynthetic electron transport chain. Based on these findings, redox linkages of Hyn hydrogenase are modeled. Copyright © 2014 Elsevier B.V. All rights reserved.

Blue emitting undecaplatinum clusters

NASA Astrophysics Data System (ADS)

Chakraborty, Indranath; Bhuin, Radha Gobinda; Bhat, Shridevi; Pradeep, T.

2014-07-01

A blue luminescent 11-atom platinum cluster showing step-like optical features and the absence of plasmon absorption was synthesized. The cluster was purified using high performance liquid chromatography (HPLC). Electrospray ionization (ESI) and matrix assisted laser desorption ionization (MALDI) mass spectrometry (MS) suggest a composition, Pt11(BBS)8, which was confirmed by a range of other experimental tools. The cluster is highly stable and compatible with many organic solvents.A blue luminescent 11-atom platinum cluster showing step-like optical features and the absence of plasmon absorption was synthesized. The cluster was purified using high performance liquid chromatography (HPLC). Electrospray ionization (ESI) and matrix assisted laser desorption ionization (MALDI) mass spectrometry (MS) suggest a composition, Pt11(BBS)8, which was confirmed by a range of other experimental tools. The cluster is highly stable and compatible with many organic solvents. Electronic supplementary information (ESI) available: Details of experimental procedures, instrumentation, chromatogram of the crude cluster; SEM/EDAX, DLS, PXRD, TEM, FT-IR, and XPS of the isolated Pt11 cluster; UV/Vis, MALDI MS and SEM/EDAX of isolated 2 and 3; and 195Pt NMR of the K2PtCl6 standard. See DOI: 10.1039/c4nr02778g

Automated image analysis reveals the dynamic 3-dimensional organization of multi-ciliary arrays

PubMed Central

Galati, Domenico F.; Abuin, David S.; Tauber, Gabriel A.; Pham, Andrew T.; Pearson, Chad G.

2016-01-01

ABSTRACT Multi-ciliated cells (MCCs) use polarized fields of undulating cilia (ciliary array) to produce fluid flow that is essential for many biological processes. Cilia are positioned by microtubule scaffolds called basal bodies (BBs) that are arranged within a spatially complex 3-dimensional geometry (3D). Here, we develop a robust and automated computational image analysis routine to quantify 3D BB organization in the ciliate, Tetrahymena thermophila. Using this routine, we generate the first morphologically constrained 3D reconstructions of Tetrahymena cells and elucidate rules that govern the kinetics of MCC organization. We demonstrate the interplay between BB duplication and cell size expansion through the cell cycle. In mutant cells, we identify a potential BB surveillance mechanism that balances large gaps in BB spacing by increasing the frequency of closely spaced BBs in other regions of the cell. Finally, by taking advantage of a mutant predisposed to BB disorganization, we locate the spatial domains that are most prone to disorganization by environmental stimuli. Collectively, our analyses reveal the importance of quantitative image analysis to understand the principles that guide the 3D organization of MCCs. PMID:26700722

Comparing routine neurorehabilitation program with trunk exercises based on Bobath concept in multiple sclerosis: pilot study.

PubMed

Keser, Ilke; Kirdi, Nuray; Meric, Aydin; Kurne, Asli Tuncer; Karabudak, Rana

2013-01-01

This study compared trunk exercises based on the Bobath concept with routine neurorehabilitation approaches in multiple sclerosis (MS). Bobath and routine neurorehabilitation exercises groups were evaluated. MS cases were divided into two groups. Both groups joined a 3 d/wk rehabilitation program for 8 wk. The experimental group performed trunk exercises based on the Bobath concept, and the control group performed routine neurorehabilitation exercises. Additionally, both groups performed balance and coordination exercises. All patients were evaluated with the Trunk Impairment Scale (TIS), Berg Balance Scale (BBS), International Cooperative Ataxia Rating Scale (ICARS), and Multiple Sclerosis Functional Composite (MSFC) before and after the physiotherapy program. In group analysis, TIS, BBS, ICARS, and MSFC scores and strength of abdominal muscles were significantly different after treatment in both groups (p < 0.05). When the groups were compared, no significant differences were found in any parameters (p > 0.05). Although trunk exercises based on the Bobath concept are rarely applied in MS rehabilitation, the results of this study show that they are as effective as routine neurorehabilitation exercises. Therefore, trunk exercises based on the Bobath concept can be beneficial in MS rehabilitation programs.

Feasibility of Rehabilitation Training With a Newly Developed, Portable, Gait Assistive Robot for Balance Function in Hemiplegic Patients

PubMed Central

2017-01-01

Objective To investigate the clinical feasibility of a newly developed, portable, gait assistive robot (WA-H, ‘walking assist for hemiplegia’) for improving the balance function of patients with stroke-induced hemiplegia. Methods Thirteen patients underwent 12 weeks of gait training on the treadmill while wearing WA-H for 30 minutes per day, 4 days a week. Patients' balance function was evaluated by the Berg Balance Scale (BBS), Fugl-Meyer Assessment Scale (FMAS), Timed Up and Go Test (TUGT), and Short Physical Performance Battery (SPPB) before and after 6 and 12 weeks of training. Results There were no serious complications or clinical difficulties during gait training with WA-H. In three categories of BBS, TUGT, and the balance scale of SPPB, there was a statistically significant improvement at the 6th week and 12th week of gait training with WA-H. In the subscale of balance function of FMAS, there was statistically significant improvement only at the 12th week. Conclusion Gait training using WA-H demonstrated a beneficial effect on balance function in patients with hemiplegia without a safety issue. PMID:28503449

[The preliminary assessment in the B-BS protocol as a tool for the discovery of job stress symptoms and contingencies: a method under experimentation by INAIL].

PubMed

Clerici, P; Guercio, A

2010-01-01

The proposed model is aimed at assessing work-related stress and consists of a preliminary phase during which the Organization is monitored, Indexes and stressors are defined, characterized and then weighted; existing symptoms (if any) are also identified. A 'Probability vs. Severity' Matrix is then built up as a result: these tasks can profitably be performed by a technical professional, typically the Responsible of the Safety and Health Committee. According to found evidences, a second phase, strictly based upon the application of psychosocial research tools, might be needed to investigate group of workers that resulted troublesome during the preliminary phase. The preliminary phase of investigation on organizational stressors and indexes can be easily and successfully integrated with the 'Safety Assessment' steps provided for the B-BS protocol, also aimed at monitoring the organizational wellbeing and consequently acting on the workers' behavior. The model has been specifically designed for Small and Medium Enterprises, with the global objective of preventing accidents at work due to misbehavior and distraction, by correctly and safely applying operational procedures and mutual relationships.

De novo mutations in MED13, a component of the Mediator complex, are associated with a novel neurodevelopmental disorder.

PubMed

Snijders Blok, Lot; Hiatt, Susan M; Bowling, Kevin M; Prokop, Jeremy W; Engel, Krysta L; Cochran, J Nicholas; Bebin, E Martina; Bijlsma, Emilia K; Ruivenkamp, Claudia A L; Terhal, Paulien; Simon, Marleen E H; Smith, Rosemarie; Hurst, Jane A; McLaughlin, Heather; Person, Richard; Crunk, Amy; Wangler, Michael F; Streff, Haley; Symonds, Joseph D; Zuberi, Sameer M; Elliott, Katherine S; Sanders, Victoria R; Masunga, Abigail; Hopkin, Robert J; Dubbs, Holly A; Ortiz-Gonzalez, Xilma R; Pfundt, Rolph; Brunner, Han G; Fisher, Simon E; Kleefstra, Tjitske; Cooper, Gregory M

2018-05-08

Many genetic causes of developmental delay and/or intellectual disability (DD/ID) are extremely rare, and robust discovery of these requires both large-scale DNA sequencing and data sharing. Here we describe a GeneMatcher collaboration which led to a cohort of 13 affected individuals harboring protein-altering variants, 11 of which are de novo, in MED13; the only inherited variant was transmitted to an affected child from an affected mother. All patients had intellectual disability and/or developmental delays, including speech delays or disorders. Other features that were reported in two or more patients include autism spectrum disorder, attention deficit hyperactivity disorder, optic nerve abnormalities, Duane anomaly, hypotonia, mild congenital heart abnormalities, and dysmorphisms. Six affected individuals had mutations that are predicted to truncate the MED13 protein, six had missense mutations, and one had an in-frame-deletion of one amino acid. Out of the seven non-truncating mutations, six clustered in two specific locations of the MED13 protein: an N-terminal and C-terminal region. The four N-terminal clustering mutations affect two adjacent amino acids that are known to be involved in MED13 ubiquitination and degradation, p.Thr326 and p.Pro327. MED13 is a component of the CDK8-kinase module that can reversibly bind Mediator, a multi-protein complex that is required for Polymerase II transcription initiation. Mutations in several other genes encoding subunits of Mediator have been previously shown to associate with DD/ID, including MED13L, a paralog of MED13. Thus, our findings add MED13 to the group of CDK8-kinase module-associated disease genes.

Systematic reconstruction of autism biology from massive genetic mutation profiles

PubMed Central

Zhang, Chaolin; Jiang, Yong-hui

2018-01-01

Autism spectrum disorder (ASD) affects 1% of world population and has become a pressing medical and social problem worldwide. As a paradigmatic complex genetic disease, ASD has been intensively studied and thousands of gene mutations have been reported. Because these mutations rarely recur, it is difficult to (i) pinpoint the fewer disease-causing versus majority random events and (ii) replicate or verify independent studies. A coherent and systematic understanding of autism biology has not been achieved. We analyzed 3392 and 4792 autism-related mutations from two large-scale whole-exome studies across multiple resolution levels, that is, variants (single-nucleotide), genes (protein-coding unit), and pathways (molecular module). These mutations do not recur or replicate at the variant level, but significantly and increasingly do so at gene and pathway levels. Genetic association reveals a novel gene + pathway dual-hit model, where the mutation burden becomes less relevant. In multiple independent analyses, hundreds of variants or genes repeatedly converge to several canonical pathways, either novel or literature-supported. These pathways define recurrent and systematic ASD biology, distinct from previously reported gene groups or networks. They also present a catalog of novel ASD risk factors including 118 variants and 72 genes. At a subpathway level, most variants disrupt the pathway-related gene functions, and in the same gene, they tend to hit residues extremely close to each other and in the same domain. Multiple interacting variants spotlight key modules, including the cAMP (adenosine 3′,5′-monophosphate) second-messenger system and mGluR (metabotropic glutamate receptor) signaling regulation by GRKs (G protein–coupled receptor kinases). At a superpathway level, distinct pathways further interconnect and converge to three biology themes: synaptic function, morphology, and plasticity. PMID:29651456

Systematic reconstruction of autism biology from massive genetic mutation profiles.

PubMed

Luo, Weijun; Zhang, Chaolin; Jiang, Yong-Hui; Brouwer, Cory R

2018-04-01

Autism spectrum disorder (ASD) affects 1% of world population and has become a pressing medical and social problem worldwide. As a paradigmatic complex genetic disease, ASD has been intensively studied and thousands of gene mutations have been reported. Because these mutations rarely recur, it is difficult to (i) pinpoint the fewer disease-causing versus majority random events and (ii) replicate or verify independent studies. A coherent and systematic understanding of autism biology has not been achieved. We analyzed 3392 and 4792 autism-related mutations from two large-scale whole-exome studies across multiple resolution levels, that is, variants (single-nucleotide), genes (protein-coding unit), and pathways (molecular module). These mutations do not recur or replicate at the variant level, but significantly and increasingly do so at gene and pathway levels. Genetic association reveals a novel gene + pathway dual-hit model, where the mutation burden becomes less relevant. In multiple independent analyses, hundreds of variants or genes repeatedly converge to several canonical pathways, either novel or literature-supported. These pathways define recurrent and systematic ASD biology, distinct from previously reported gene groups or networks. They also present a catalog of novel ASD risk factors including 118 variants and 72 genes. At a subpathway level, most variants disrupt the pathway-related gene functions, and in the same gene, they tend to hit residues extremely close to each other and in the same domain. Multiple interacting variants spotlight key modules, including the cAMP (adenosine 3',5'-monophosphate) second-messenger system and mGluR (metabotropic glutamate receptor) signaling regulation by GRKs (G protein-coupled receptor kinases). At a superpathway level, distinct pathways further interconnect and converge to three biology themes: synaptic function, morphology, and plasticity.

The N-terminal strand modulates immunoglobulin light chain fibrillogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pozo-Yauner, Luis del, E-mail: ldelpozo@inmegen.gob.mx; Wall, Jonathan S.; González Andrade, Martín

2014-01-10

Highlights: •We evaluated the impact of mutations in the N-terminal strand of 6aJL2 protein. •Mutations destabilized the protein in a position-dependent manner. •Destabilizing mutations accelerated the fibrillogenesis by shortening the lag time. •The effect on the kinetic of fibril elongation by seeding was of different nature. •The N-terminal strand is buried in the fibrillar state of 6aJL2 protein. -- Abstract: It has been suggested that the N-terminal strand of the light chain variable domain (V{sub L}) protects the molecule from aggregation by hindering spurious intermolecular contacts. We evaluated the impact of mutations in the N-terminal strand on the thermodynamic stabilitymore » and kinetic of fibrillogenesis of the V{sub L} protein 6aJL2. Mutations in this strand destabilized the protein in a position-dependent manner, accelerating the fibrillogenesis by shortening the lag time; an effect that correlated with the extent of destabilization. In contrast, the effect on the kinetics of fibril elongation, as assessed in seeding experiments was of different nature, as it was not directly dependant on the degree of destabilization. This finding suggests different factors drive the nucleation-dependent and elongation phases of light chain fibrillogenesis. Finally, taking advantage of the dependence of the Trp fluorescence upon environment, four single Trp substitutions were made in the N-terminal strand, and changes in solvent exposure during aggregation were evaluated by acrylamide-quenching. The results suggest that the N-terminal strand is buried in the fibrillar state of 6aJL2 protein. This finding suggest a possible explanation for the modulating effect exerted by the mutations in this strand on the aggregation behavior of 6aJL2 protein.« less

The Breeding Bird Survey: Its first fifteen years, 1965-1979

USGS Publications Warehouse

Robbins, C.S.; Bystrak, D.; Geissler, P.H.

1986-01-01

The Breeding Bird Survey (BBS) is an ongoing cooperative program sponsored jointly by the U.S. Fish and Wildife Service and the Canadian Wildlife Service. Its main purpose is to estimate population trends of the many species of birds that nest in North America north of Mexico and that migrate across international boundaries. This survey provides information, both locally by ecological or political regions and on a continental scale, on (1) short-term population changes that can be correlated with specific weather incidents, (2) recovery periods following catastrophic declines, (3) normal year-to-year variations, (4) long-term population trends, and (5) invasions of exotics. The BBS also permits detailed computer mapping of relative abundance of each species, either year by year to show changes in distribution and relative abundance, or the average over a period of years. It provides base-line data with which more intensive local studies can be compared. For biogeographic studies it provides uniform sampling of bird populations by major physiographic regions across the continent. In conjunction with the Audubon Christmas Bird Count, it permits comparison of summer and winter distribution of species that winter in the United States. Most species of North American birds migrate across international boundaries, especially those shared with Canada, Mexico, and the Soviet Union. As part of our responsibility under treaties with these nations, the U.S. Fish and Wildlife Service has developed the BBS to monitor avian population changes so that any adverse trends can be detected early. This provides the opportunity to determine the reasons for any increase or decrease, to define geographic areas in which changes are greatest, to study correlations between avian population changes and land-use changes, and to make recommendations for controlling undesirable bird population trends. For example, the BBS can be used to detect and estimate the extent of losses resulting from widespread use of pesticides, and to reveal whether major population changes of a given species (e.g., Dickcissel) in certain States are related to a continental decline or are merely a result of population shifts within the breeding range. Effects of urban and suburban expansion are often reflected in the loss of forest interior birds. Population trends for 230 species as well as several avian genera and families are discussed and graphed in this report. For most of these species, regional and well as continental trends are shown. The three major regions discussed are the Eastern, Central, and Western, bounded by the Mississippi River and the eastern base of the Rocky Mountains. Additional graphs for certain States or physiographic regions are included for selected species of special interest. The following paragraphs summarize general trends in the major bird families. The native herons in general are maintaining their populations, whereas the exotic Cattle Egret continues its geographic spread and its steady increase. Waterfowl as a group are stable or increasing. Although most widespread species of hawks are on the increase, the rarer species show evidence of decline. Among the gallinaceous birds, the greatest change was a sharp drop in Northern Bobwhite as a result of the exceptionally cold winters of 1976-77 and 1977-78 in the Ohio Valley and the Middle Atlantic States. Killdeer populations, except for a minor decline during these two winters, showed strong increases except in the West. American Woodcock were poorly sampled by the BBS because they were relatively inactive during daylight. Common Snipe and the other common shorebirds that nest in the United States and southern Canada exhibited stable or increasing populations, especially in the Eastern and Central regions. Herring Gull counts varied dramatically and irregularly from year to year. Laughing Gulls increased along the Atlantic coast and Franklin's Gulls declined in the interior of the continen

Effects of Mutations on Structure-Function Relationships of Matrix Metalloproteinase-1.

PubMed

Singh, Warispreet; Fields, Gregg B; Christov, Christo Z; Karabencheva-Christova, Tatyana G

2016-10-14

Matrix metalloproteinase-1 (MMP-1) is one of the most widely studied enzymes involved in collagen degradation. Mutations of specific residues in the MMP-1 hemopexin-like (HPX) domain have been shown to modulate activity of the MMP-1 catalytic (CAT) domain. In order to reveal the structural and conformational effects of such mutations, a molecular dynamics (MD) study was performed of in silico mutated residues in the X-ray crystallographic structure of MMP-1 complexed with a collagen-model triple-helical peptide (THP). The results indicate an important role of the mutated residues in MMP-1 interactions with the THP and communication between the CAT and the HPX domains. Each mutation has a distinct impact on the correlated motions in the MMP-1•THP. An increased collagenase activity corresponded to the appearance of a unique anti-correlated motion and decreased correlated motions, while decreased collagenase activity corresponded both to increased and decreased anti-correlated motions.

A novel autosomal partially dominant mutation designated G476D in the keratin 5 gene causing epidermolysis bullosa simplex Weber-Cockayne type: a family study with a genetic twist.

PubMed

Kowalewski, Cezary; Hamada, Takahiro; Wozniak, Katarzyna; Kawano, Yuko; Szczecinska, Weronika; Yasumoto, Shinichiro; Schwartz, Robert A; Hashimoto, Takashi

2007-07-01

Epidermolysis bullosa simplex Weber-Cockayne type (EBS-WC) is a genetically inherited skin disease characterized by blistering restricted to the palms and soles. Its inheritance in nearly all kindreds is caused by a dominant-negative mutation in either KRT5 or KRT14, the genes encoding keratin 5 and keratin 14 proteins, respectively. Rarely, recessive mutations have also been found. We described a family with EBS-WC caused by a novel autosomal dominant mutation (G476D) in the keratin 5 gene. One family member was first seen with mucosal erosions and generalized blisters localized on the anogenital area, trunk, face and sites of mechanical trauma. Molecular analysis in this patient showed the presence of an additional mutation, an autosomal recessive (G183E) one, in the same gene. This observation suggests an additional effect of a recessively inherited mutation modulating the phenotypic expression of EBS caused by a partially dominant mutation and is important for accurate genetic counseling.

Whole genome re-sequencing identifies a mutation in an ABC transporter (mdr2) in a Plasmodium chabaudi clone with altered susceptibility to antifolate drugs☆

PubMed Central

Martinelli, Axel; Henriques, Gisela; Cravo, Pedro; Hunt, Paul

2011-01-01

In malaria parasites, mutations in two genes of folate biosynthesis encoding dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) modify responses to antifolate therapies which target these enzymes. However, the involvement of other genes which modify the availability of exogenous folate, for example, has been proposed. Here, we used short-read whole-genome re-sequencing to determine the mutations in a clone of the rodent malaria parasite, Plasmodium chabaudi, which has altered susceptibility to both sulphadoxine and pyrimethamine. This clone bears a previously identified S106N mutation in dhfr and no mutation in dhps. Instead, three additional point mutations in genes on chromosomes 2, 13 and 14 were identified. The mutated gene on chromosome 13 (mdr2 K392Q) encodes an ABC transporter. Because Quantitative Trait Locus analysis previously indicated an association of genetic markers on chromosome 13 with responses to individual and combined antifolates, MDR2 is proposed to modulate antifolate responses, possibly mediated by the transport of folate intermediates. PMID:20858498

An isokinetic training program for reducing falls in a community-dwelling older adult: a case report.

PubMed

Beebe, Justin A; Hines, Roger W; McDaniel, Laura T; Shelden, Brenda L

2013-01-01

With the population older than 65 years, projected to double by the year 2030, falls in older adults are a substantial health concern. Muscle strength deficits are one of the multifactorial components linked to increased fall risk, and decreasing these deficits has been one of the goals of interventions designed to decrease fall risk. These interventions have traditionally focused on improving peak torque; however, recent research suggests that exercise protocols that focus on the rate of torque development (RTD) may be more effective in decreasing fall risk. This case report examines clinical outcomes following implementation of an isokinetic strengthening protocol coupled with a balance program designed to reduce fall risk in a community-dwelling older adult. The individual was a 70-year-old woman with a history of 3 falls over the past 8 months and no related medical etiology who had self-limited her activities because of fear of another fall. She was classified as having substantial risk for future falls because of fall history, increased fear of falling, and below age norms on the Berg Balance Scale (BBS), and the Timed Up and Go (TUG). The treatment program consisted of 12 weeks of high-intensity isokinetic knee extensor training, high challenge dynamic gait and balance activities, and core strengthening. The isokinetic protocol consisted of 4 sets of 10 concentric-only repetitions at speeds of 240°/sec and 300°/sec for a total of 8 work sets. Dynamic gait activities incorporating directional and obstacle drills, and rocker and balance boards were used for balance training activities. Progressive theraband exercises were used for core strengthening. As her home program, the participant was encouraged to return to line dancing twice per week. During the 12-week protocol, the participant completed two 90-minute therapy sessions and two 90-minute dance classes per week. After the 12 weeks of treatment, knee extensor peak torque at 150 ms improved on the right from 67.8 N to 107.1 N (57.9% increase), and on the left from 65.1 N to 97.6 N (49.9% increase). The BBS score improved from 45 to 52; and the TUG improved from 14.0 to 8.6 seconds. Both final scores exceeded fall risk cutoffs (BBS = 48; TUG = 13.5 seconds) and the change score exceeded minimal detectable change (BBS = 7; TUG 5.4 seconds). The treatment program produced improvements in knee extensor peak torque and RTD, but more importantly, the final scores on the clinical outcome measures placed the participant above established fall-risk cutoff scores. Although future research with increased numbers of participants and a control group should be conducted to confirm this study's results, these findings support the use of isokinetic training to reduce fall risk in older adults.

Use of miniroutes and Breeding Bird Survey data to estimate abundance

USGS Publications Warehouse

Robbins, C.S.; Dowell, B.A.

1986-01-01

1. Information on relative abundance is easily obtained and adds greatly to the value of an atlas project. 2. The Breeding Bird Survey (BBS) provides annual counts (birds per 50 roadside stops) that can be used to: (1) map relative abundance by physiographic region within a state or province, (2) map relative abundance on a more local scale by using results from individual routes, or (3) compute estimates of total state populations of a species. Where BBS coverage is too scanty to permit mapping, extra temporary routes may be established to provide additional information for the atlas. Or, if continuing coverage is anticipated, additional permanent random routes can be assigned by the U. S. Fish and Wildlife Service. 3. Miniroutes of 15 or more stops can be established in individual atlas blocks to serve the dual purposes of providing efficient uniform coverage and providing information on relative abundance. Miniroutes can also be extracted from BBS routes to supplement special atlas coverage, or vice versa; but the data from the BBS will not be confined to individual atlas blocks. 4. Advantages of 15- or 20-stop Miniroutes over 25-stop Miniroutes are several: the ability to do two per morning and the lower variability among M1niroute results. Also, many 5-km atlas blocks do not have enough secondary roads to accommodate 25 stops at one-half mile intervals. Disadvantages of 15-stop Miniroutes starting at sunrise are the smaller numbers of birds recorded, missing of the very productive dawn chorus period (Robbins 1981), and missing crepuscular species (rails, woodcock, owls, and goatsuckers). 5. Advantages of recording counts of individuals rather than checking only species presence at Miniroute stops are that: (1) relative abundance can be mapped rather than frequency only (a measure of frequency is already available in the number of blocks recording each species); (2) population change can be measured over a period of years when the next atlas is made; and (3) comparative abundance data are available for habitat correlations and other statistical applications (Luis et ale 1983). Disadvantages of recording counts are that: (1) many observers do not feel they can make accurate counts of individuals; and (2) a few species may be missed while observers are counting (an hypothesis that will be field-tested this summer). While counts of individuals may be more subject to observer differences than are frequency counts, both the numbers of birds and their frequencies are available when birds are counted. 6. Roadside counts produce slightly larger samples and more species than off-road counts. The main advantage of off-road coverage is to sample habitats that cannot be sampled from roadsides. 7. Miniroutes can be recommended to individual atlasers as an efficient means of detecting species and upgrading them from Possible to Probable, even when there is no statewide Miniroute program.

Transcriptome analysis of an apple (Malus × domestica) yellow fruit somatic mutation identifies a gene network module highly associated with anthocyanin and epigenetic regulation.

PubMed

El-Sharkawy, Islam; Liang, Dong; Xu, Kenong

2015-12-01

Using RNA-seq, this study analysed an apple (Malus×domestica) anthocyanin-deficient yellow-skin somatic mutant 'Blondee' (BLO) and its red-skin parent 'Kidd's D-8' (KID), the original name of 'Gala', to understand the molecular mechanisms underlying the mutation. A total of 3299 differentially expressed genes (DEGs) were identified between BLO and KID at four developmental stages and/or between two adjacent stages within BLO and/or KID. A weighted gene co-expression network analysis (WGCNA) of the DEGs uncovered a network module of 34 genes highly correlated (r=0.95, P=9.0×10(-13)) with anthocyanin contents. Although 12 of the 34 genes in the WGCNA module were characterized and known of roles in anthocyanin, the remainder 22 appear to be novel. Examining the expression of ten representative genes in the module in 14 diverse apples revealed that at least eight were significantly correlated with anthocyanin variation. MdMYB10 (MDP0000259614) and MdGST (MDP0000252292) were among the most suppressed module member genes in BLO despite being undistinguishable in their corresponding sequences between BLO and KID. Methylation assay of MdMYB10 and MdGST in fruit skin revealed that two regions (MR3 and MR7) in the MdMYB10 promoter exhibited remarkable differences between BLO and KID. In particular, methylation was high and progressively increased alongside fruit development in BLO while was correspondingly low and constant in KID. The methylation levels in both MR3 and MR7 were negatively correlated with anthocyanin content as well as the expression of MdMYB10 and MdGST. Clearly, the collective repression of the 34 genes explains the loss-of-colour in BLO while the methylation in MdMYB10 promoter is likely causal for the mutation. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Transcriptome analysis of an apple (Malus × domestica) yellow fruit somatic mutation identifies a gene network module highly associated with anthocyanin and epigenetic regulation

PubMed Central

El-Sharkawy, Islam; Liang, Dong; Xu, Kenong

2015-01-01

Using RNA-seq, this study analysed an apple (Malus×domestica) anthocyanin-deficient yellow-skin somatic mutant ‘Blondee’ (BLO) and its red-skin parent ‘Kidd’s D-8’ (KID), the original name of ‘Gala’, to understand the molecular mechanisms underlying the mutation. A total of 3299 differentially expressed genes (DEGs) were identified between BLO and KID at four developmental stages and/or between two adjacent stages within BLO and/or KID. A weighted gene co-expression network analysis (WGCNA) of the DEGs uncovered a network module of 34 genes highly correlated (r=0.95, P=9.0×10–13) with anthocyanin contents. Although 12 of the 34 genes in the WGCNA module were characterized and known of roles in anthocyanin, the remainder 22 appear to be novel. Examining the expression of ten representative genes in the module in 14 diverse apples revealed that at least eight were significantly correlated with anthocyanin variation. MdMYB10 (MDP0000259614) and MdGST (MDP0000252292) were among the most suppressed module member genes in BLO despite being undistinguishable in their corresponding sequences between BLO and KID. Methylation assay of MdMYB10 and MdGST in fruit skin revealed that two regions (MR3 and MR7) in the MdMYB10 promoter exhibited remarkable differences between BLO and KID. In particular, methylation was high and progressively increased alongside fruit development in BLO while was correspondingly low and constant in KID. The methylation levels in both MR3 and MR7 were negatively correlated with anthocyanin content as well as the expression of MdMYB10 and MdGST. Clearly, the collective repression of the 34 genes explains the loss-of-colour in BLO while the methylation in MdMYB10 promoter is likely causal for the mutation. PMID:26417021

Familial Alzheimer's disease mutations in presenilin 1 do not alter levels of the secreted amyloid-beta protein precursor generated by beta-secretase cleavage.

PubMed

Zhang, Can; Browne, Andrew; Kim, Doo Yeon; Tanzi, Rudolph E

2010-02-01

Alzheimer's disease (AD) is an insidious and progressive disease with a genetically complex and heterogenous etiology. More than 200 fully penetrant mutations in the amyloid beta-protein precursor (APP), presenilin 1 (or PSEN1), and presenilin 2 (PSEN2) have been linked to early-onset familial AD (FAD). 177 PSEN1 FAD mutations have been identified so far and account for more than approximately 80% of all FAD mutations. All PSEN1 FAD mutations can increase the Abeta42:Abeta40 ratio with seemingly different and incompletely understood mechanisms. A recent study has shown that the 286 amino acid N-terminal fragment of APP (N-APP), a proteolytic product of beta-secretase-derived secreted form of APP (sAPPbeta), could bind the death receptor, DR6, and lead to neurodegeneration. Here we asked whether PSEN1 FAD mutations lead to neurodegeneration by modulating sAPPbeta levels. All four different PSEN1 FAD mutations tested (in three mammalian cell lines) did not alter sAPPbeta levels. Therefore PS1 mutations do not appear to contribute to AD pathogenesis via altered production of sAPPbeta.

A novel class of Saccharomyces cerevisiae mutants specifically UV-sensitive to "petite" induction.

PubMed

Moustacchi, E; Perlman, P S; Mahler, H R

1976-11-17

A mutant of Saccharomyces cerevisiae has been isolated which, though exhibiting a normal response to nuclear genetic damage by ultraviolet light (UV), is more sensitive than its wild type specifically in the production of the cytoplasmic (rho-) mutation by this agent. Some of the features of this mutation which has been designated uvsrho 5 are: i) The mutation is recessive, it exhibits a Mendelian, and hence presumably nuclear, pattern of segregation, but manifests its effects specifically and pleiotropically on mitochondrial functions. ii) Mutant cells resemble their wild type parents in a) growth characteristics on glucose; b) in their UV induced dose response to lethality or nuclear mutation and c) the ability of their mitochondrial genome, upon mating with appropriate testers, of transmitting and recombining various markers, albeit with enhanced efficiency. Similarly, d) they are able to modulate the expression of mitochondrial mutagenesis by ethidium bromide. Thus their mitochondrial DNA appears genetically as competent as that of the wild type. iii) Mutant cells differ from their wild type parents in a) growth characteristics on glycerol; b) susceptibility to induction of the mitochondrial (rho-) mutation by various mutagens, in that the rate of spontaneous mutation is slightly and that by UV is significantly enhanced, whild that by ethidium bromide is greatly diminished. Conversely, c) modulating influences resulting in the repair of initial damage are diminished fro UV and stimulated in the case of Berenil. iv) The amount of mitochondrial DNA per cell appears elevated in the mutant, relative to wild type, and its rate of degradation subsequent to a mutagenic exposure to either UV or ethidium bromide is diminished. v) A self-consistent scheme to account for this and all other information so far available for the induction and modulation of the (rho-) mutation is presented. In a previous study it was shown that some nuclear mutants of Saccharomyces cerevisiae, more sensitive to lethal damage induced by ultraviolet light (rad) than their parent wild type (RAD), also exhibit a concomitant modification in sensitivity to both nuclear and cytoplasmic genetic damage (Moustacchi, 1971). However, another class of rad mutants respond to the induction of the cytoplasmic "petite" also designated as rho- (or rho-) mutation by UV in a manner indistinguishable from that of the RAD strain. One possible interpretation of this last observation is that some of the steps in the expression of the UV damage on mitochondrial (mt)DNA may be governed by other nuclear and cytoplasmic genetic determinants, the products of which may then act specifically on mitochondrial lesions. If this assumption is correct, it should be possible to find mutants with a normal response to nuclear damage but specifically UV-sensitive towards induction of (rho-)...

U.S. Fish and Wildlife Service breeding bird surveys: How can they be used in forest management?

Treesearch

William F. Laudenslayer

1988-01-01

Since 1965, the U.S. Fish and Wildlife and Canadian Wildlife Services have sponsored annual Brceding Bird Surveys (BBSs), which are done in the United States and Canada using standard procedures. Data resulting from individual surveys may have Cptential to answer certain management questions or serve to fill information gaps for relatively small geographic areas. A BBS...

Concept of Video Bookmark (Videomark) and Its Application to the Collaborative Indexing of Lecture Video in Video-Based Distance Education

ERIC Educational Resources Information Center

Haga, Hirohide

2004-01-01

This article describes the development of the video bookmark, hereinafter referred to as the videomark, and its application to the collaborative indexing of the lecture video in video-based distance education system. The combination of the videomark system with the bulletin board system (BBS), which is another network tool used for discussion, is…

Toward information management in corporations (7)

NASA Astrophysics Data System (ADS)

Yasuda, Naoyoshi

Personal computers and workstations have come into wide use. The high performance modems will be available at cheaper prices so that the bulletin-board system and electronic mail have been used by many people. This paper discusses the network system, and describes the electronic mail covering wider regions and BBS for research and development. It also describes how to handle document images by use of these measures.

A Safety Program that Integrated Behavior-Based Safety and Traditional Safety Methods and Its Effects on Injury Rates of Manufacturing Workers

ERIC Educational Resources Information Center

Hermann, Jaime A.; Ibarra, Guillermo V.; Hopkins, B. L.

2010-01-01

The present research examines the effects of a complex safety program that combined Behavior-Based Safety (BBS) and traditional safety methods. The study was conducted in an automobile parts plant in Mexico. Two sister plants served as comparison. Some of the components of the safety programs addressed behaviors of managers and included methods…

Mountain birdwatch: developing a coordinated monitoring program for high-elevation birds in the Atlantic northern forest

Treesearch

John D. Lloyd; Julie Hart; J. Dan Lambert

2010-01-01

Birds occupying high-elevation forests in the northeast are perceived to be at risk from a variety of external forces, most notably the potential loss and alteration of habitat associated with global climate change and the increased deployment of wind-energy facilities. However, the Breeding Bird Survey (BBS), a standardized national monitoring scheme widely used to...

Comparison of Ai Chi and Impairment-Based Aquatic Therapy for Older Adults With Balance Problems: A Clinical Study.

PubMed

Covill, Laura G; Utley, Cynthia; Hochstein, Cheryl

Older adults with balance deficits often fear falling and limit their mobility. Poor balance is multifactorial, influenced by medication interactions, musculoskeletal and sensory system changes, and poor neuromuscular response to changes in body positions. Aquatic physical therapy (APT) is an intervention used to improve balance and decrease falls. Ai Chi is a water-based exercise program. It incorporates slow movements of progressive difficulty utilizing the upper and lower extremities and trunk coordinated with deep breathing. It is used for relaxation, strengthening, and balance training. The purpose of this study was to determine whether Ai Chi provides better results than conventional impairment-based aquatic therapy (IBAT) for older adults with balance deficits. Thirty-two community-dwelling adults, 65 to 85 years old, were referred to 2 different community pools for APT. Fifteen participants received Ai Chi-based aquatic interventions and 17 participants received an IBAT program. Physical therapists trained in both programs completed interventions and determined discharge. Physical balance measures, which included the Berg Balance Scale (BBS) and Timed Up and Go (TUG), were collected pre- and posttherapy. Self-reported outcome measures, the Activities-Specific Balance Confidence Scale (ABC) and Numerical Pain Rating Scale (NPRS), were collected pre- and posttherapy and 3- and 6-month postdischarge. A 2-way (group by time) mixed-model analysis of covariance with initial outcome scores as a covariate revealed no difference between groups in any of the outcome measures (BBS, P = .53; TUG, P = .39; ABC, P = .63; NPRS, P = .27). Repeated-measures analysis and dependent t tests showed significant improvements in the BBS (P = .00) and TUG (P = .03) after APT. The ABC and NPRS did not improve significantly (ABC, P = .27; NPRS, P = .77). There were no significant differences found in balance measures, balance confidence, or pain levels for community-dwelling older adults between the Ai Chi and IBAT programs. Physical outcome measures improved with APT but patient-reported measures did not. Further study is indicated to determine the most effective treatment frequency and duration for this population.

Effects of Processing Conditions During Manufacture on Retronasal-Aroma Compounds from a Milk Coffee Drink.

PubMed

Ikeda, Michio; Akiyama, Masayuki; Hirano, Yuta; Miyazi, Kazuhiro; Kono, Masaya; Imayoshi, Yuriko; Iwabuchi, Hisakatsu; Onodera, Takeshi; Toko, Kiyoshi

2018-03-01

To develop a ready-to-drink (RTD) milk coffee retaining the original coffee flavor, the effects of processing conditions during manufacture on retronasal-arma (RA) compounds from the milk coffee were investigated by gas chromatography-mass spectrometry using an RA simulator (RAS). Thirteen of 46 detected compounds in the RAS effluent (RAS compounds) decreased significantly following pH adjustment of coffee (from pH 5.1 to 6.8) and 5 compounds increased. RAS compounds from coffee tended to decrease through the pH adjustment and subsequent sterilization. Significantly higher amounts of 13 RAS compounds were released from the milk coffee produced using a blending-after-sterilization (BAS) process without the pH adjustment than from that using a blending-before-sterilization (BBS) process with the pH adjustment. In BAS-processed milk coffee, significantly lower amounts of 8 high-volatility compounds and 1H-pyrrole were released from coffee containing infusion-sterilized (INF) milk than from coffee containing plate-sterilized (PLT) milk, whereas 3 low-volatility compounds were released significantly more from coffee using PLT milk. Principal component analysis revealed that the effect of the manufacturing process (BAS, BBS, or homemade (blending unsterilized coffee without pH adjustment with sterilized milk)) on milk coffee volatiles was larger than that of the sterilization method (INF or PLT) for milk, and that the sterilization method could result in different RAS volatile characteristics in BAS and homemade processes. In conclusion, a BAS process was found to be superior to a BBS process for the manufacture of an RTD milk coffee that retains volatile characteristics similar to that of a homemade milk coffee. Ready-to-drink (RTD) milk coffee manufactured using the conventional blending-before-sterilization process does not retain its original coffee flavor due to pH adjustment of the coffee during the process. The new blending-after-sterilization (BAS) process enabled the production of RTD milk coffee whose volatiles are closer to that of homemade milk coffee, as demonstrated by the results of RAS-GC-MS analysis. The BAS process has already been applied to the manufacture of RTD milk coffees in Japan. © 2018 Institute of Food Technologists®.

Validation of an ambulatory capacity measure in Parkinson disease: a construct derived from the Unified Parkinson's Disease Rating Scale.

PubMed

Parashos, Sotirios A; Elm, Jordan; Boyd, James T; Chou, Kelvin L; Dai, Lin; Mari, Zoltan; Morgan, John C; Sudarsky, Lewis; Wielinski, Catherine L

2015-01-01

A construct calculated as the sum of items 13-15, 29, 30 of the Unified Parkinson's Disease Rating Scale (UPDRS) has been used as an "Ambulatory Capacity Measure" (ACM) in Parkinson disease (PD). Its construct validity has never been examined. A similar construct, consisting of the mean value of the same UPDRS items has been used under the acronym PIGD as a measure of postural instability and gait disorder in PD. To examine the construct validity of the ACM and PIGD in PD. We analyzed data in an existing database of 340 PD patients, Hoehn and Yahr stages (HYS) 1-5 who participated in a study of falls. Number of falls (NOF) was recorded over 4 weeks, and UPDRS (mental, ADL, and motor subscales), HYS, Activities Based Confidence Scale (ABC), Freezing of Gait Questionnaire (FOG), Five Times Sit-to-Stand (FTSS), Timed Up-and Go (TUG), Gait Velocity (GV), and Berg Balance Scale (BBS) evaluations were performed. Internal consistency was assessed by Cronbach's alpha. Construct validity was assessed through correlations of the ACM and PIGD to these measures and to their summed-ranks. A coefficient of determination was calculated through linear regression. Mean age was 71.4, mean age at diagnosis 61.4 years; 46% were women; mean UPDRS subscale scores were: Mental 3.7; ADL 15.7; motor: 27.1; mean ACM was 6.51, and mean PIGD 1.30. Cronbach's alpha was 0.78 for both ACM and PIGD. Spearman correlation coefficients between the ACM/PIGD and ABC, FOG, TUG, GV and BBS were 0.69, 0.72, 0.67, 0.58, and 0.70 respectively. Correlation between the ACM/PIGD and summed-ranks of HYS, NOF, ABC, FOG, FTSS, TUG, GV and BBS was high (Spearman r = 0.823, p < 0.0001); 68% of the variability in the summed-ranks was explained by ACM/PIGD. The ACM and the PIGD are valid global measures and accurately reflect the combined effects of the various components of ambulatory capacity in PD patients with HY stages 1-4.

Ecosystem and human health impacts from increased corn production: vulnerability assessment of exposure to high nitrate concentrations in groundwater and blue baby syndrome

NASA Astrophysics Data System (ADS)

Garcia, V.; Cooter, E. J.

2013-12-01

The Renewable Fuel Standard (RFS) requires oil refiners to reach a target of 15 billion gallons of corn-based ethanol by 2022. However, there are concerns that the broad-scale use of corn as a source of ethanol may lead to unintended economic and environmental consequences. This study applies the geophysical relationships captured with linked meteorological, air quality and agriculture models to examine the impact of corn production before enactment of the RFS in 2002 and at the height of the RFS targets in 2022. In particular, we investigate the probability of high-levels of nitrate in groundwater resulting from increased corn production and then relate this vulnerability to the potential for infants to acquire Methemoglobinemia, or 'Blue Baby Syndrome'. Blue Baby Syndrome (BBS) is a potentially fatal condition that occurs when the hemoglobin (Fe2+) in an infant's red blood cells is oxidized to methemoglobin (Fe3+), preventing the uptake of oxygen from the baby's blood. Exposure to high levels of nitrate in groundwater occur near the intersection of areas where surface water can more readily leach into shallow aquifers, wells are the main source of drinking water, and high nitrogen inputs exist. We use a coupled meteorological, agricultural and air quality model to identify areas vulnerable to increased nitrate contamination and associated risk to acquiring BBS. We first verify the relationship between predictive variables (e.g., nitrogen deposition and fertilization rates, landcover, soils and aquifer type) and nitrate groundwater levels by applying a regression model to over 800 nitrate measurements taken from wells located throughout the US (Figure 1). We then apply the regression coefficients to the coupled model output to identify areas that are at an increased risk for high nitrate groundwater levels in 2022. Finally, we examine the potential change in risk for acquiring BBS resulting from increased corn production by applying an Oral Reference Dose (RfD) factor from the US EPA Integrated Risk Information System.

The Impact of Diabetic Neuropathy on Balance and on the Risk of Falls in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study.

PubMed

Timar, Bogdan; Timar, Romulus; Gaiță, Laura; Oancea, Cristian; Levai, Codrina; Lungeanu, Diana

2016-01-01

Diabetic neuropathy (DN) is a prevalent complication of Type 2 Diabetes Mellitus (T2DM) with a major impact on the health of the affected patient. We hypothesized that mediated by the dysfunctionalities associated with DN's three major components: sensitive (lack of motion associated sensory), motor (impairments in movement coordination) and autonomic (the presence of postural hypotension), the presence of DN may impair the balance in the affected patients. Our study's main aim is to evaluate the possible association between the presence and severity of DN and both the balance impairment and the risk of falls in patients with T2DM. In this cross-sectional study we enrolled, according to a consecutive-case population-based setting 198 patients with T2DM. The presence and severity of DN was evaluated using the Michigan Neuropathy Screening Instrument, a tool which allows both diagnosing and severity staging of DN. The balance impairment and the risk of falls were evaluated using four validated and standardized tools: Berg Balance Scale (BBS), Timed-up and Go test (TUG), Single Leg Stand test (SLS) and Fall Efficacy Scale (FES-I). The presence of DN was associated with significant decreases in the BBS score (40.5 vs. 43.7 points; p<0.001) and SLS time (9.3 vs. 10.3 seconds; p = 0.003) respectively increases in TUG time (8.9 vs. 7.6 seconds; p = 0.002) and FES-I score (38 vs. 33 points; p = 0.034). The MNSI score was reverse and significantly correlated with both BBS score (Spearman's r = -0.479; p<0.001) and SLS time (Spearman's r = -0.169; p = 0.017). In the multivariate regression model, we observed that patient's age, DN severity and depression's symptoms acted as independent, significant predictors for the risk of falls in patients with T2DM. The presence of DN in patients with DM is associated with impaired balance and with a consecutively increase in the risk of falls.

Whole-Organism Developmental Expression Profiling Identifies RAB-28 as a Novel Ciliary GTPase Associated with the BBSome and Intraflagellar Transport

PubMed Central

Sanders, Anna A. W. M.; Li, Chunmei; Kennedy, Julie; Cai, Jerry; Scheidel, Noemie; Kennedy, Breandán N.; Morin, Ryan D.; Leroux, Michel R.; Blacque, Oliver E.

2016-01-01

Primary cilia are specialised sensory and developmental signalling devices extending from the surface of most eukaryotic cells. Defects in these organelles cause inherited human disorders (ciliopathies) such as retinitis pigmentosa and Bardet-Biedl syndrome (BBS), frequently affecting many physiological and developmental processes across multiple organs. Cilium formation, maintenance and function depend on intracellular transport systems such as intraflagellar transport (IFT), which is driven by kinesin-2 and IFT-dynein motors and regulated by the Bardet-Biedl syndrome (BBS) cargo-adaptor protein complex, or BBSome. To identify new cilium-associated genes, we employed the nematode C. elegans, where ciliogenesis occurs within a short timespan during late embryogenesis when most sensory neurons differentiate. Using whole-organism RNA-Seq libraries, we discovered a signature expression profile highly enriched for transcripts of known ciliary proteins, including FAM-161 (FAM161A orthologue), CCDC-104 (CCDC104), and RPI-1 (RP1/RP1L1), which we confirm are cilium-localised in worms. From a list of 185 candidate ciliary genes, we uncover orthologues of human MAP9, YAP, CCDC149, and RAB28 as conserved cilium-associated components. Further analyses of C. elegans RAB-28, recently associated with autosomal-recessive cone-rod dystrophy, reveal that this small GTPase is exclusively expressed in ciliated neurons where it dynamically associates with IFT trains. Whereas inactive GDP-bound RAB-28 displays no IFT movement and diffuse localisation, GTP-bound (activated) RAB-28 concentrates at the periciliary membrane in a BBSome-dependent manner and undergoes bidirectional IFT. Functional analyses reveal that whilst cilium structure, sensory function and IFT are seemingly normal in a rab-28 null allele, overexpression of predicted GDP or GTP locked variants of RAB-28 perturbs cilium and sensory pore morphogenesis and function. Collectively, our findings present a new approach for identifying ciliary proteins, and unveil RAB28, a GTPase most closely related to the BBS protein RABL4/IFT27, as an IFT-associated cargo with BBSome-dependent cell autonomous and non-autonomous functions at the ciliary base. PMID:27930654

Whole-Organism Developmental Expression Profiling Identifies RAB-28 as a Novel Ciliary GTPase Associated with the BBSome and Intraflagellar Transport.

PubMed

Jensen, Victor L; Carter, Stephen; Sanders, Anna A W M; Li, Chunmei; Kennedy, Julie; Timbers, Tiffany A; Cai, Jerry; Scheidel, Noemie; Kennedy, Breandán N; Morin, Ryan D; Leroux, Michel R; Blacque, Oliver E

2016-12-01

Primary cilia are specialised sensory and developmental signalling devices extending from the surface of most eukaryotic cells. Defects in these organelles cause inherited human disorders (ciliopathies) such as retinitis pigmentosa and Bardet-Biedl syndrome (BBS), frequently affecting many physiological and developmental processes across multiple organs. Cilium formation, maintenance and function depend on intracellular transport systems such as intraflagellar transport (IFT), which is driven by kinesin-2 and IFT-dynein motors and regulated by the Bardet-Biedl syndrome (BBS) cargo-adaptor protein complex, or BBSome. To identify new cilium-associated genes, we employed the nematode C. elegans, where ciliogenesis occurs within a short timespan during late embryogenesis when most sensory neurons differentiate. Using whole-organism RNA-Seq libraries, we discovered a signature expression profile highly enriched for transcripts of known ciliary proteins, including FAM-161 (FAM161A orthologue), CCDC-104 (CCDC104), and RPI-1 (RP1/RP1L1), which we confirm are cilium-localised in worms. From a list of 185 candidate ciliary genes, we uncover orthologues of human MAP9, YAP, CCDC149, and RAB28 as conserved cilium-associated components. Further analyses of C. elegans RAB-28, recently associated with autosomal-recessive cone-rod dystrophy, reveal that this small GTPase is exclusively expressed in ciliated neurons where it dynamically associates with IFT trains. Whereas inactive GDP-bound RAB-28 displays no IFT movement and diffuse localisation, GTP-bound (activated) RAB-28 concentrates at the periciliary membrane in a BBSome-dependent manner and undergoes bidirectional IFT. Functional analyses reveal that whilst cilium structure, sensory function and IFT are seemingly normal in a rab-28 null allele, overexpression of predicted GDP or GTP locked variants of RAB-28 perturbs cilium and sensory pore morphogenesis and function. Collectively, our findings present a new approach for identifying ciliary proteins, and unveil RAB28, a GTPase most closely related to the BBS protein RABL4/IFT27, as an IFT-associated cargo with BBSome-dependent cell autonomous and non-autonomous functions at the ciliary base.

Wearable Sensor-Based Biofeedback Training for Balance and Gait in Parkinson Disease: A Pilot Randomized Controlled Trial.

PubMed

Carpinella, Ilaria; Cattaneo, Davide; Bonora, Gianluca; Bowman, Thomas; Martina, Laura; Montesano, Angelo; Ferrarin, Maurizio

2017-04-01

To analyze the feasibility and efficacy of a novel system (Gamepad [GAMing Experience in PArkinson's Disease]) for biofeedback rehabilitation of balance and gait in Parkinson disease (PD). Randomized controlled trial. Clinical rehabilitation gym. Subjects with PD (N=42) were randomized into experimental and physiotherapy without biofeedback groups. Both groups underwent 20 sessions of training for balance and gait. The experimental group performed tailored functional tasks using Gamepad. The system, based on wearable inertial sensors, provided users with real-time visual and acoustic feedback about their movement during the exercises. The physiotherapy group underwent individually structured physiotherapy without feedback. Assessments were performed by a blinded examiner preintervention, postintervention, and at 1-month follow-up. Primary outcomes were the Berg Balance Scale (BBS) and 10-m walk test (10MWT). Secondary outcomes included instrumental stabilometric indexes and the Tele-healthcare Satisfaction Questionnaire. Gamepad was well accepted by participants. Statistically significant between-group differences in BBS scores suggested better balance performances of the experimental group compared with the physiotherapy without biofeedback group both posttraining (experimental group-physiotherapy without biofeedback group: mean, 2.3±3.4 points; P=.047) and at follow-up (experimental group-physiotherapy without biofeedback group: mean, 2.7±3.3 points; P=.018). Posttraining stabilometric indexes showed that mediolateral body sway during upright stance was significantly reduced in the experimental group compared with the physiotherapy without biofeedback group (experimental group-physiotherapy without biofeedback group: -1.6±1.5mm; P=.003). No significant between-group differences were found in the other outcomes. Gamepad-based training was feasible and superior to physiotherapy without feedback in improving BBS performance and retaining it for 1 month. After training, 10MWT data were comparable between groups. Further development of the system is warranted to allow the autonomous use of Gamepad outside clinical settings, to enhance gait improvements, and to increase transfer of training effects to real-life contexts. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

AtNUDT7, a Negative Regulator of Basal Immunity in Arabidopsis, Modulates Two Distinct Defense Response Pathways and Is Involved in Maintaining Redox Homeostasis1[C][OA

PubMed Central

Ge, Xiaochun; Li, Guo-Jing; Wang, Sheng-Bing; Zhu, Huifen; Zhu, Tong; Wang, Xun; Xia, Yiji

2007-01-01

Plants have evolved complicated regulatory systems to control immune responses. Both positive and negative signaling pathways interplay to coordinate development of a resistance response with the appropriate amplitude and duration. AtNUDT7, a Nudix domain-containing protein in Arabidopsis (Arabidopsis thaliana) that hydrolyzes nucleotide derivatives, was found to be a negative regulator of the basal defense response, and its loss-of-function mutation results in enhanced resistance to infection by Pseudomonas syringae. The nudt7 mutation does not cause a strong constitutive disease resistance phenotype, but it leads to a heightened defense response, including accelerated activation of defense-related genes that can be triggered by pathogenic and nonpathogenic microorganisms. The nudt7 mutation enhances two distinct defense response pathways: one independent of and the other dependent on NPR1 and salicylic acid accumulation. In vitro enzymatic assays revealed that ADP-ribose and NADH are preferred substrates of NUDT7, and the hydrolysis activity of NUDT7 is essential for its biological function and is sensitive to inhibition by Ca2+. Further analyses indicate that ADP-ribose is not likely the physiological substrate of NUDT7. However, the nudt7 mutation leads to perturbation of cellular redox homeostasis and a higher level of NADH in pathogen-challenged leaves. The study suggests that the alteration in cellular antioxidant status caused by the nudt7 mutation primes the cells for the amplified defense response and NUDT7 functions to modulate the defense response to prevent excessive stimulation. PMID:17660350

Microenvironmental Regulation by Fibrillin-1

PubMed Central

Sengle, Gerhard; Tsutsui, Ko; Keene, Douglas R.; Tufa, Sara F.; Carlson, Eric J.; Charbonneau, Noe L.; Ono, Robert N.; Sasaki, Takako; Wirtz, Mary K.; Samples, John R.; Fessler, Liselotte I.; Fessler, John H.; Sekiguchi, Kiyotoshi; Hayflick, Susan J.; Sakai, Lynn Y.

2012-01-01

Fibrillin-1 is a ubiquitous extracellular matrix molecule that sequesters latent growth factor complexes. A role for fibrillin-1 in specifying tissue microenvironments has not been elucidated, even though the concept that fibrillin-1 provides extracellular control of growth factor signaling is currently appreciated. Mutations in FBN1 are mainly responsible for the Marfan syndrome (MFS), recognized by its pleiotropic clinical features including tall stature and arachnodactyly, aortic dilatation and dissection, and ectopia lentis. Each of the many different mutations in FBN1 known to cause MFS must lead to similar clinical features through common mechanisms, proceeding principally through the activation of TGFβ signaling. Here we show that a novel FBN1 mutation in a family with Weill-Marchesani syndrome (WMS) causes thick skin, short stature, and brachydactyly when replicated in mice. WMS mice confirm that this mutation does not cause MFS. The mutation deletes three domains in fibrillin-1, abolishing a binding site utilized by ADAMTSLIKE-2, -3, -6, and papilin. Our results place these ADAMTSLIKE proteins in a molecular pathway involving fibrillin-1 and ADAMTS-10. Investigations of microfibril ultrastructure in WMS humans and mice demonstrate that modulation of the fibrillin microfibril scaffold can influence local tissue microenvironments and link fibrillin-1 function to skin homeostasis and the regulation of dermal collagen production. Hence, pathogenetic mechanisms caused by dysregulated WMS microenvironments diverge from Marfan pathogenetic mechanisms, which lead to broad activation of TGFβ signaling in multiple tissues. We conclude that local tissue-specific microenvironments, affected in WMS, are maintained by a fibrillin-1 microfibril scaffold, modulated by ADAMTSLIKE proteins in concert with ADAMTS enzymes. PMID:22242013

The voltage-sensor quartet

PubMed Central

Bankston, J. R.; Kass, R. S.

2009-01-01

Decoding the workings of voltage-gated sodium channels is crucial because their mutation leads to severe disease and their activity is modulated by toxins and drugs. An innovative approach now allows such investigations. PMID:19005542

Neutropenia-associated ELANE mutations disrupting translation initiation produce novel neutrophil elastase isoforms

PubMed Central

Tidwell, Timothy; Wechsler, Jeremy; Nayak, Ramesh C.; Trump, Lisa; Salipante, Stephen J.; Cheng, Jerry C.; Donadieu, Jean; Glaubach, Taly; Corey, Seth J.; Grimes, H. Leighton; Lutzko, Carolyn; Cancelas, Jose A.

2014-01-01

Hereditary neutropenia is usually caused by heterozygous germline mutations in the ELANE gene encoding neutrophil elastase (NE). How mutations cause disease remains uncertain, but two hypotheses have been proposed. In one, ELANE mutations lead to mislocalization of NE. In the other, ELANE mutations disturb protein folding, inducing an unfolded protein response in the endoplasmic reticulum (ER). In this study, we describe new types of mutations that disrupt the translational start site. At first glance, they should block translation and are incompatible with either the mislocalization or misfolding hypotheses, which require mutant protein for pathogenicity. We find that start-site mutations, instead, force translation from downstream in-frame initiation codons, yielding amino-terminally truncated isoforms lacking ER-localizing (pre) and zymogen-maintaining (pro) sequences, yet retain essential catalytic residues. Patient-derived induced pluripotent stem cells recapitulate hematopoietic and molecular phenotypes. Expression of the amino-terminally deleted isoforms in vitro reduces myeloid cell clonogenic capacity. We define an internal ribosome entry site (IRES) within ELANE and demonstrate that adjacent mutations modulate IRES activity, independently of protein-coding sequence alterations. Some ELANE mutations, therefore, appear to cause neutropenia via the production of amino-terminally deleted NE isoforms rather than by altering the coding sequence of the full-length protein. PMID:24184683

ExScalibur: A High-Performance Cloud-Enabled Suite for Whole Exome Germline and Somatic Mutation Identification.

PubMed

Bao, Riyue; Hernandez, Kyle; Huang, Lei; Kang, Wenjun; Bartom, Elizabeth; Onel, Kenan; Volchenboum, Samuel; Andrade, Jorge

2015-01-01

Whole exome sequencing has facilitated the discovery of causal genetic variants associated with human diseases at deep coverage and low cost. In particular, the detection of somatic mutations from tumor/normal pairs has provided insights into the cancer genome. Although there is an abundance of publicly-available software for the detection of germline and somatic variants, concordance is generally limited among variant callers and alignment algorithms. Successful integration of variants detected by multiple methods requires in-depth knowledge of the software, access to high-performance computing resources, and advanced programming techniques. We present ExScalibur, a set of fully automated, highly scalable and modulated pipelines for whole exome data analysis. The suite integrates multiple alignment and variant calling algorithms for the accurate detection of germline and somatic mutations with close to 99% sensitivity and specificity. ExScalibur implements streamlined execution of analytical modules, real-time monitoring of pipeline progress, robust handling of errors and intuitive documentation that allows for increased reproducibility and sharing of results and workflows. It runs on local computers, high-performance computing clusters and cloud environments. In addition, we provide a data analysis report utility to facilitate visualization of the results that offers interactive exploration of quality control files, read alignment and variant calls, assisting downstream customization of potential disease-causing mutations. ExScalibur is open-source and is also available as a public image on Amazon cloud.

Modulation of HIV Protease Flexibility by the T80N Mutation

PubMed Central

Zhou, Hao; Li, Shangyang; Badger, John; Nalivaika, Ellen; Cai, Yufeng; Foulkes-Murzycki, Jennifer; Schiffer, Celia; Makowski, Lee

2015-01-01

The flexibility of HIV protease plays a critical role in enabling enzymatic activity and is required for substrate access to the active site. While the importance of flexibility in the flaps that cover the active site is well known, flexibility in other parts of the enzyme is also critical for function. One key region is a loop containing Thr 80 which forms the walls of the active site. Although not situated within the active site, amino acid Thr80 is absolutely conserved. The mutation T80N preserves the structure of the enzyme but catalytic activity is completely lost. To investigate the potential influence of the T80N mutation on HIVp flexibility, wide-angle scattering (WAXS) data was measured for a series of HIV protease variants. Starting with a calculated WAXS pattern from a rigid atomic model, the modulations in the intensity distribution caused by structural fluctuations in the protein were predicted by simple analytic methods and compared to the experimental data. An analysis of T80N WAXS data shows that this variant is significantly more rigid than the WT across all length scales. The effects of this single point mutation extend throughout the protein, so as to alter the mobility of amino acids in the enzymatic core. These results support the contentions that significant protein flexibility extends throughout HIV protease and is critical to catalytic function. PMID:25488402

Crystal Structure of a Fibroblast Growth Factor Homologous Factor (FHF) Defines a Conserved Surface on FHFs for Binding and Modulation of Voltage-gated Sodium Channels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goetz, R.; Dover, K; Laezza, F

2009-01-01

Voltage-gated sodium channels (Nav) produce sodium currents that underlie the initiation and propagation of action potentials in nerve and muscle cells. Fibroblast growth factor homologous factors (FHFs) bind to the intracellular C-terminal region of the Nav alpha subunit to modulate fast inactivation of the channel. In this study we solved the crystal structure of a 149-residue-long fragment of human FHF2A which unveils the structural features of the homology core domain of all 10 human FHF isoforms. Through analysis of crystal packing contacts and site-directed mutagenesis experiments we identified a conserved surface on the FHF core domain that mediates channel bindingmore » in vitro and in vivo. Mutations at this channel binding surface impaired the ability of FHFs to co-localize with Navs at the axon initial segment of hippocampal neurons. The mutations also disabled FHF modulation of voltage-dependent fast inactivation of sodium channels in neuronal cells. Based on our data, we propose that FHFs constitute auxiliary subunits for Navs.« less

Structure-function relations in the NTPase domain of the antiviral tRNA ribotoxin Escherichia coli PrrC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meineke, Birthe; Shuman, Stewart, E-mail: s-shuman@ski.mskcc.org

2012-06-05

Breakage of tRNA by Escherichia coli anticodon nuclease PrrC (EcoPrrC) underlies a host antiviral response to phage T4 infection. Expression of EcoPrrC is cytocidal in yeast, signifying that PrrC ribotoxicity crosses phylogenetic domain boundaries. EcoPrrC consists of an N-terminal NTPase module that resembles ABC transporters and a C-terminal nuclease module that is sui generis. PrrC homologs are prevalent in many other bacteria. Here we report that Haemophilus influenzae PrrC is toxic in E. coli and yeast. To illuminate structure-activity relations, we conducted a new round of mutational analysis of EcoPrrC guided by primary structure conservation among toxic PrrC homologs. Wemore » indentify 17 candidate active site residues in the NTPase module that are essential for toxicity in yeast when EcoPrrC is expressed at high gene dosage. Their functions could be educed by integrating mutational data with the atomic structure of the transition-state complex of a homologous ABC protein.« less

CEF1/CDC5 alleles modulate transitions between catalytic conformations of the spliceosome

PubMed Central

Query, Charles C.; Konarska, Maria M.

2012-01-01

Conformational change within the spliceosome is required between the first and second catalytic steps of pre-mRNA splicing. A prior genetic screen for suppressors of an intron mutant that stalls between the two steps yielded both prp8 and non-prp8 alleles that suppressed second-step splicing defects. We have now identified the strongest non-prp8 suppressors as alleles of the NTC (Prp19 complex) component, CEF1. These cef1 alleles generally suppress second-step defects caused by a variety of intron mutations, mutations in U6 snRNA, or deletion of the second-step protein factor Prp17, and they can activate alternative 3′ splice sites. Genetic and functional interactions between cef1 and prp8 alleles suggest that they modulate the same event(s) in the first-to-second-step transition, most likely by stabilization of the second-step spliceosome; in contrast, alleles of U6 snRNA that also alter this transition modulate a distinct event, most likely by stabilization of the first-step spliceosome. These results implicate a myb-like domain of Cef1/CDC5 in interactions that modulate conformational states of the spliceosome and suggest that alteration of these events affects splice site use, resulting in alternative splicing-like patterns in yeast. PMID:22408182

Mediator independently orchestrates multiple steps of preinitiation complex assembly in vivo

PubMed Central

Eyboulet, Fanny; Wydau-Dematteis, Sandra; Eychenne, Thomas; Alibert, Olivier; Neil, Helen; Boschiero, Claire; Nevers, Marie-Claire; Volland, Hervé; Cornu, David; Redeker, Virginie; Werner, Michel; Soutourina, Julie

2015-01-01

Mediator is a large multiprotein complex conserved in all eukaryotes, which has a crucial coregulator function in transcription by RNA polymerase II (Pol II). However, the molecular mechanisms of its action in vivo remain to be understood. Med17 is an essential and central component of the Mediator head module. In this work, we utilised our large collection of conditional temperature-sensitive med17 mutants to investigate Mediator's role in coordinating preinitiation complex (PIC) formation in vivo at the genome level after a transfer to a non-permissive temperature for 45 minutes. The effect of a yeast mutation proposed to be equivalent to the human Med17-L371P responsible for infantile cerebral atrophy was also analyzed. The ChIP-seq results demonstrate that med17 mutations differentially affected the global presence of several PIC components including Mediator, TBP, TFIIH modules and Pol II. Our data show that Mediator stabilizes TFIIK kinase and TFIIH core modules independently, suggesting that the recruitment or the stability of TFIIH modules is regulated independently on yeast genome. We demonstrate that Mediator selectively contributes to TBP recruitment or stabilization to chromatin. This study provides an extensive genome-wide view of Mediator's role in PIC formation, suggesting that Mediator coordinates multiple steps of a PIC assembly pathway. PMID:26240385

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tzeng, W.-P.; Frey, Teryl K.

The ratio of the subgenomic (SG) to genome RNA synthesized by rubella virus (RUB) replicons expressing the green fluorescent protein reporter gene (RUBrep/GFP) is substantially higher than the ratio of these species synthesized by RUB (4.3 for RUBrep/GFP vs. 1.3-1.4 for RUB). It was hypothesized that this modulation of the viral RNA synthesis was by one of the virus structural protein genes and it was found that introduction of the capsid (C) protein gene into the replicons as an in-frame fusion with GFP resulted in an increase of genomic RNA production (reducing the SG/genome RNA ratio), confirming the hypothesis andmore » showing that the C gene was the moiety responsible for the modulation effect. The N-terminal one-third of the C gene was required for the effect of be exhibited. A similar phenomenon was not observed with the replicons of Sindbis virus, a related Alphavirus. Interestingly, modulation was not observed when RUBrep/GFP was co-transfected with either other RUBrep or plasmid constructs expressing the C gene, demonstrating that modulation could occur only when the C gene was provided in cis. Mutations that prevented translation of the C protein failed to modulate RNA synthesis, indicating that the C protein was the moiety responsible for modulation; consistent with this conclusion, modulation of RNA synthesis was maintained when synonymous codon mutations were introduced at the 5' end of the C gene that changed the C gene sequence without altering the amino acid sequence of the C protein. These results indicate that C protein translated in proximity of viral replication complexes, possibly from newly synthesized SG RNA, participate in regulating the replication of viral RNA.« less

Nephrocalcinosis (Enamel Renal Syndrome) Caused by Autosomal Recessive FAM20A Mutations

PubMed Central

Jaureguiberry, Graciana; De la Dure-Molla, Muriel; Parry, David; Quentric, Mickael; Himmerkus, Nina; Koike, Toshiyasu; Poulter, James; Klootwijk, Enriko; Robinette, Steven L.; Howie, Alexander J.; Patel, Vaksha; Figueres, Marie-Lucile; Stanescu, Horia C.; Issler, Naomi; Nicholson, Jeremy K.; Bockenhauer, Detlef; Laing, Christopher; Walsh, Stephen B.; McCredie, David A.; Povey, Sue; Asselin, Audrey; Picard, Arnaud; Coulomb, Aurore; Medlar, Alan J.; Bailleul-Forestier, Isabelle; Verloes, Alain; Le Caignec, Cedric; Roussey, Gwenaelle; Guiol, Julien; Isidor, Bertrand; Logan, Clare; Shore, Roger; Johnson, Colin; Inglehearn, Christopher; Al-Bahlani, Suhaila; Schmittbuhl, Matthieu; Clauss, François; Huckert, Mathilde; Laugel, Virginie; Ginglinger, Emmanuelle; Pajarola, Sandra; Spartà, Giuseppina; Bartholdi, Deborah; Rauch, Anita; Addor, Marie-Claude; Yamaguti, Paulo M.; Safatle, Heloisa P.; Acevedo, Ana Carolina; Martelli-Júnior, Hercílio; dos Santos Netos, Pedro E.; Coletta, Ricardo D.; Gruessel, Sandra; Sandmann, Carolin; Ruehmann, Denise; Langman, Craig B.; Scheinman, Steven J.; Ozdemir-Ozenen, Didem; Hart, Thomas C.; Hart, P. Suzanne; Neugebauer, Ute; Schlatter, Eberhard; Houillier, Pascal; Gahl, William A.; Vikkula, Miikka; Bloch-Zupan, Agnès; Bleich, Markus; Kitagawa, Hiroshi; Unwin, Robert J.; Mighell, Alan; Berdal, Ariane; Kleta, Robert

2013-01-01

Background/Aims Calcium homeostasis requires regulated cellular and interstitial systems interacting to modulate the activity and movement of this ion. Disruption of these systems in the kidney results in nephrocalcinosis and nephrolithiasis, important medical problems whose pathogenesis is incompletely understood. Methods We investigated 25 patients from 16 families with unexplained nephrocalcinosis and characteristic dental defects (amelogenesis imperfecta, gingival hyperplasia, impaired tooth eruption). To identify the causative gene, we performed genome-wide linkage analysis, exome capture, next-generation sequencing, and Sanger sequencing. Results All patients had bi-allelic FAM20A mutations segregating with the disease; 20 different mutations were identified. Conclusions This au-tosomal recessive disorder, also known as enamel renal syndrome, of FAM20A causes nephrocalcinosis and amelogenesis imperfecta. We speculate that all individuals with biallelic FAM20A mutations will eventually show nephrocalcinosis. PMID:23434854

Novel hypomorphic mutation in IKBKG impairs NEMO-ubiquitylation causing ectodermal dysplasia, immunodeficiency, incontinentia pigmenti, and immune thrombocytopenic purpura.

PubMed

Ramírez-Alejo, Noé; Alcántara-Montiel, Julio C; Yamazaki-Nakashimada, Marco; Duran-McKinster, Carola; Valenzuela-León, Paola; Rivas-Larrauri, Francisco; Cedillo-Barrón, Leticia; Hernández-Rivas, Rosaura; Santos-Argumedo, Leopoldo

2015-10-01

NF-κB essential modulator (NEMO) is a component of the IKK complex, which participates in the activation of the NF-κB pathway. Hypomorphic mutations in the IKBKG gene result in different forms of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) in males without affecting carrier females. Here, we describe a hypomorphic and missense mutation, designated c.916G>A (p.D306N), which affects our patient, his mother, and his sister. This mutation did not affect NEMO expression; however, an immunoprecipitation assay revealed reduced ubiquitylation upon CD40-stimulation in the patient's cells. Functional studies have demonstrated reduced phosphorylation and degradation of IκBα, affecting NF-κB recruitment into the nucleus. The patient presented with clinical features of ectodermal dysplasia, immunodeficiency, and immune thrombocytopenic purpura, the latter of which has not been previously reported in a patient with NEMO deficiency. His mother and sister displayed incontinentia pigmenti indicating that, in addition to amorphic mutations, hypomorphic mutations in NEMO can affect females. Copyright © 2015 Elsevier Inc. All rights reserved.

Hotspot Mutations in KIT Receptor Differentially Modulate Its Allosterically Coupled Conformational Dynamics: Impact on Activation and Drug Sensitivity

PubMed Central

Chauvot de Beauchêne, Isaure; Allain, Ariane; Panel, Nicolas; Laine, Elodie; Trouvé, Alain; Dubreuil, Patrice; Tchertanov, Luba

2014-01-01

Receptor tyrosine kinase KIT controls many signal transduction pathways and represents a typical allosterically regulated protein. The mutation-induced deregulation of KIT activity impairs cellular physiological functions and causes serious human diseases. The impact of hotspots mutations (D816H/Y/N/V and V560G/D) localized in crucial regulatory segments, the juxtamembrane region (JMR) and the activation (A-) loop, on KIT internal dynamics was systematically studied by molecular dynamics simulations. The mutational outcomes predicted in silico were correlated with in vitro and in vivo activation rates and drug sensitivities of KIT mutants. The allosteric regulation of KIT in the native and mutated forms is described in terms of communication between the two remote segments, JMR and A-loop. A strong correlation between the communication profile and the structural and dynamical features of KIT in the native and mutated forms was established. Our results provide new insight on the determinants of receptor KIT constitutive activation by mutations and resistance of KIT mutants to inhibitors. Depiction of an intra-molecular component of the communication network constitutes a first step towards an integrated description of vast communication pathways established by KIT in physiopathological contexts. PMID:25079768

Estimation and enhancement of real-time software reliability through mutation analysis

NASA Technical Reports Server (NTRS)

Geist, Robert; Offutt, A. J.; Harris, Frederick C., Jr.

1992-01-01

A simulation-based technique for obtaining numerical estimates of the reliability of N-version, real-time software is presented. An extended stochastic Petri net is employed to represent the synchronization structure of N versions of the software, where dependencies among versions are modeled through correlated sampling of module execution times. Test results utilizing specifications for NASA's planetary lander control software indicate that mutation-based testing could hold greater potential for enhancing reliability than the desirable but perhaps unachievable goal of independence among N versions.

The effect of induced mutations on quantitative traits in Arabidopsis thaliana: Natural versus artificial conditions.

PubMed

Stearns, Frank W; Fenster, Charles B

2016-12-01

Mutations are the ultimate source of all genetic variations. New mutations are expected to affect quantitative traits differently depending on the extent to which traits contribute to fitness and the environment in which they are tested. The dogma is that the preponderance of mutations affecting fitness will be skewed toward deleterious while their effects on nonfitness traits will be bidirectionally distributed. There are mixed views on the role of stress in modulating these effects. We quantify mutation effects by inducing mutations in Arabidopsis thaliana (Columbia accession) using the chemical ethylmethane sulfonate. We measured the effects of new mutations relative to a premutation founder for fitness components under both natural (field) and artificial (growth room) conditions. Additionally, we measured three other quantitative traits, not expected to contribute directly to fitness, under artificial conditions. We found that induced mutations were equally as likely to increase as decrease a trait when that trait was not closely related to fitness (traits that were neither survivorship nor reproduction). We also found that new mutations were more likely to decrease fitness or fitness-related traits under more stressful field conditions than under relatively benign artificial conditions. In the benign condition, the effect of new mutations on fitness components was similar to traits not as closely related to fitness. These results highlight the importance of measuring the effects of new mutations on fitness and other traits under a range of conditions.

Assessment of Electronic Government Information Products

DTIC Science & Technology

1999-03-30

Center for Environmental Info. & Statistics CM Consumer Handbook for Reducing Solid Waste CM Envirofacts Warehouse CM EPA Online Library System (OLS) CP...Hazardous Waste Site Query (CERCLIS Data) CM Surf Your Watershed CM Test Methods for Evaluating Solid Waste : Physical/Chemical Methods (SW-846) CM...SGML because they consider it "intelligent data" that can automatically generate other formats (e.g., web, BBS, Fax on Demand) through templates and

A study on the effect of self bedside exercise program on resilience and activities of daily living for patients with hemiplegia

PubMed Central

Lee, Yang-Chool; Yi, Eun-Surk; Choi, Won-Ho; Lee, Byung-Mun; Cho, Sung-Bo; Kim, Ji-Youn

2015-01-01

The purpose of this study was to design a repeatable universal rehabilitation program in which patients with hemiplegia can participate voluntarily, complementing physical and occupational therapies to increase voluntary exercise practice rate. Also, this study attempted to identify the relationship between psychological resilience due to the implementation of self-bedside exercise and functional recovery of activity of daily living (ADL). 12 patients with hemiplegia voluntarily participated in 8 weeks of self-bedside exercise 5 times a day and more than 5 days a week. Their program implementation, resilience, activities of daily living (MBI), upper limb motor functions (MFT), and balance ability (BBS) were analyzed and compared before and after the program. Compared to before implementing the program, significant increases were found in resilience, MBI, BBS, and MFT in the affected side after the implementation, and the resilience scores showed statistically positive correlation in MBI and MFT. Also, the change in resilience before and after the program implementation showed a statistically positive correlation. Therefore, it can be concluded that the self-bedside exercise developed in this study had a positive effect on voluntary participation in exercise as well as resilience and ADL. However, many studies which complement the psychological aspects of hemiparetic patients with stroke are still needed. PMID:25830141

Covered self-expandable metal stents for benign biliary tract diseases.

PubMed

Baron, Todd H

2011-05-01

Benign biliary diseases are often managed endoscopically using plastic stents. Benign biliary strictures (BBS) respond to placement of multiple large-bore plastic stents, though requiring multiple procedures to place stents, and to exchange stents to prevent and/or treat stent occlusion. Bile leaks close using plastic stents, which divert bile away from the leak into the duodenum. Covered self-expandable metal stents (CSEMS), intended for palliation of malignant biliary obstruction, have been used to treat benign biliary diseases. Advantages include small predeployment and large postexpansion diameters. Lack of imbedding of the metal into the bile duct wall enables removability. For strictures, one CSEMS is inserted without need for dilation and remains in place for up to 6 months. Successful removal has been reported in all cases. Long-term stricture resolution is achieved in up to 92%. Adverse events include migration and new stricture formation. For treatment of complex bile leaks, the covering and large diameter allow successful closure in nearly all cases. Other uses of CSEMS include treatment of postsphincterotomy bleeding and closure of perforations. CSEMS show promise for treatment of BBS and complex biliary leaks. Successful resolution can be achieved in the majority of patients with the advantage of fewer procedures, which offsets their higher cost.

Ce3+/Yb3+/Er3+ triply doped bismuth borosilicate glass: a potential fiber material for broadband near-infrared fiber amplifiers

PubMed Central

Chu, Yushi; Ren, Jing; Zhang, Jianzhong; Peng, Gangding; Yang, Jun; Wang, Pengfei; Yuan, Libo

2016-01-01

Erbium doped bismuth borosilicate (BBS) glasses, possessing the broadest 1.55 μm near infrared (NIR) emission band among oxide glasses, stand out as excellent fiber material for optical fiber amplifiers. In this work, we demonstrate that both broadened and enhanced NIR emission of Er3+ can be obtained by sensibly combining the effects such as mixed glass former effect, phonon-assisted energy transfer (PAET) and de-excitation effect induced by codopant. Specially, by codoping CeO2 in a controlled manner, it leads to not only much improved optical quality of the glasses, enhanced NIR emission, but also significantly suppressed energy transfer up-conversion (ETU) luminescence which is detrimental to the NIR emission. Cerium incorporated in the glasses exists overwhelmingly as the trivalent oxidation state Ce3+ and its effects on the luminescence properties of Er3+ are discussed. Judd-Ofelt analysis is used to evaluate gain amplification of the glasses. The result indicates that Ce3+/Yb3+/Er3+ triply doped BBS glasses are promising candidate for erbium doped fiber amplifiers. The strategy described here can be readily extended to other rare-earth ions (REs) to improve the performance of REs doped fiber lasers and amplifiers. PMID:27646191

Nintendo Wii Fit for balance rehabilitation in patients with Parkinson's disease: A comparative study.

PubMed

Negrini, Stefano; Bissolotti, Luciano; Ferraris, Alessandro; Noro, Fulvia; Bishop, Mark D; Villafañe, Jorge Hugo

2017-01-01

Impaired postural stability places individuals with Parkinson's disease (PD) at an increased risk for falls. We evaluated the effectiveness of 10 vs. 15 sessions of Nintendo Wii Fit for balance recovery for outpatients PD. Twenty-seven patients, 48.1% female (66 ± 8 years), with PD. Patients with PD were consecutively assigned to one of two groups receiving either 10 or 15 sessions (low dose or high dose group, respectively) with Nintendo Wii Fit in recovering balancing ability. All outcome measures were collected at baseline, immediately following the intervention period, and 1-month following the end of the intervention. Falls risk test (FRT), Stability index (PST), Berg balance scale (BBS) and Tinetti scale. The patients undergoing the 10 sessions demonstrated significantly improvement on the balance performances (Tinetti balance and gait scales, BBS and BSF) (all, P < 0.05) as those undergoing 15 treatment with Nintendo Wii Fit, but no significant group effect or group-by-time interaction was detected for any of them, which suggests that both groups improved in the same way. The results suggest that functional improvement can be made in fewer visits during outpatient rehabilitation sessions with Nintendo Wii Fit improving the efficiency of intervention. Copyright © 2016 Elsevier Ltd. All rights reserved.

Using the North American Breeding Bird Survey as a tool for conservation: A critique of Bart et al. (2004)

USGS Publications Warehouse

Sauer, John R.; Link, William A.; Nichols, James D.; Royle, J. Andrew

2005-01-01

Bart et al. (2004) develop methods for predicting needed samples for estimation of long-term trends from Count survey data, and they apply these methods to the North American Breeding Bird Survey (BBS). They recommend adding approximately 40% more survey routes ill the BBS to allow for estimation of long-term (i.e., 20 year) trends for a collection of species. We critique several aspects of their analysis and suggest that their focus on long-term trends and expansion of the present survey design will provide limited benefits for conservation because it fails to either enhance the credibility of the survey or better tie the survey to regional management activities. A primary innovation claimed by Bart et al. (2004) is the incorporation of bias in estimation of study planning. We question the value of this approach, as it requires reliable estimates of range of future bias. We show that estimates of bias used by Bart et al. (2004) are speculative. Failure to obtain better estimates of this bias is likely to compromise the credibility of future analyses of the survey. We also note that the generic analysis of population trends that they provide is of questionable validity and is unlikely to be relevant for regions and species of management concern.

Analysis of EEG activity in response to binaural beats with different frequencies.

PubMed

Gao, Xiang; Cao, Hongbao; Ming, Dong; Qi, Hongzhi; Wang, Xuemin; Wang, Xiaolu; Chen, Runge; Zhou, Peng

2014-12-01

When two coherent sounds with nearly similar frequencies are presented to each ear respectively with stereo headphones, the brain integrates the two signals and produces a sensation of a third sound called binaural beat (BB). Although earlier studies showed that BB could influence behavior and cognition, common agreement on the mechanism of BB has not been reached yet. In this work, we employed Relative Power (RP), Phase Locking Value (PLV) and Cross-Mutual Information (CMI) to track EEG changes during BB stimulations. EEG signals were acquired from 13 healthy subjects. Five-minute BBs with four different frequencies were tested: delta band (1 Hz), theta band (5 Hz), alpha band (10 Hz) and beta band (20 Hz). We observed RP increase in theta and alpha bands and decrease in beta band during delta and alpha BB stimulations. RP decreased in beta band during theta BB, while RP decreased in theta band during beta BB. However, no clear brainwave entrainment effect was identified. Connectivity changes were detected following the variation of RP during BB stimulations. Our observation supports the hypothesis that BBs could affect functional brain connectivity, suggesting that the mechanism of BB-brain interaction is worth further study. Copyright © 2014. Published by Elsevier B.V.

Structure, molecular simulation, and release of aspirin from intercalated Zn-Al-layered double hydroxides.

PubMed

Meng, Zilin; Li, Xiaowei; Lv, Fengzhu; Zhang, Qian; Chu, Paul K; Zhang, Yihe

2015-11-01

Aspirin or acetylsalicylic acid (AA), a non-steroidal anti-inflammatory drug, is intercalated into Zn-Al-layered double hydroxides (ZnAl-LDHs) by co-precipitation and reconstruction methods. The composition, structure, and morphology of the intercalated products as well as their release behavior are determined experimentally and theoretically by Material Studio 5.5. Experimental results disclose the strong interaction between the LDHs sheets and AA in the intercalated ZnAl-LDHs produced by co-precipitation and slow release of AA from the intercalated ZnAl-LDHs in both phosphate buffered saline (PBS) and borate buffered saline (BBS) solutions. The percentage of AA released from the ZnAl-LDHs prepared by both methods in PBS (96.87% and 98.12%) are much more than those in BBS (68.59% and 81.22%) implying that both H4BO4(-) and H2PO4(-) can exchange with AA in the ZnAl-LDHs. After AA is released to PBS, ZnAl-LDHs break into small pieces. The experimental results are explained theoretically based on the calculation of the bonding energy between the anions and LDHs sheets as well as the AlO bond length change in the LDHs sheets. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparison of seven fall risk assessment tools in community-dwelling Korean older women.

PubMed

Kim, Taekyoung; Xiong, Shuping

2017-03-01

This study aimed to compare seven widely used fall risk assessment tools in terms of validity and practicality, and to provide a guideline for choosing appropriate fall risk assessment tools for elderly Koreans. Sixty community-dwelling Korean older women (30 fallers and 30 matched non-fallers) were evaluated. Performance measures of all tools were compared between the faller and non-faller groups through two sample t-tests. Receiver Operating Characteristic curves were generated with odds ratios for discriminant analysis. Results showed that four tools had significant discriminative power, and the shortened version of Falls Efficacy Scale (SFES) showed excellent discriminant validity, followed by Berg Balance Scale (BBS) with acceptable discriminant validity. The Mini Balance Evaluation System Test and Timed Up and Go, however, had limited discriminant validities. In terms of practicality, SFES was also excellent. These findings suggest that SFES is the most suitable tool for assessing the fall risks of community-dwelling Korean older women, followed by BBS. Practitioner Summary: There is no general guideline on which fall risk assessment tools are suitable for community-dwelling Korean older women. This study compared seven widely used assessment tools in terms of validity and practicality. Results suggested that the short Falls Efficacy Scale is the most suitable tool, followed by Berg Balance Scale.

Efficacy of virtual reality-based balance training versus the Biodex balance system training on the body balance of adults

PubMed Central

Ibrahim, Manal S.; Mattar, Ayman G.; Elhafez, Salam M.

2016-01-01

[Purpose] This study investigated efficacy of virtual reality (VR)-based balance training on enhancing balance and postural reactions of adults as a low-cost new modality compared to the established Biodex Balance System (BBS). [Subjects] Thirty normal adults of both genders were divided randomly into two equal-sized experimental groups of 15: BBS balance training and VR balance training. [Methods] The training programmes were conducted in 12 sessions, three 15-min sessions per week. The Nintendo® Wii Fit Plus (NWFP) and its balance board were used to train of the VR group. Each participant answered a questionnaire concerning usability, enjoyment, balance improvement, and fatigue at the end of the training programs. [Results] The study found a significant increase the measure of mean overall balance (OLB) in both groups. No significant difference was found between the groups, but a significant decrease in the mean balance-test time was found for both groups, with no significant difference between the two training methods. The VR programme was rated highly enjoyable by 81.8% of the group. [Conclusion] The Wii Fit Plus system with the balance board as a new VR balance-training technique, can be considered an effective and enjoyable tool for the training of adults’ body balance. PMID:26957722

Observation of B_{s}^{0}→D[over ¯]^{0}K_{S}^{0} and Evidence for B_{s}^{0}→D[over ¯]^{*}^{0}K_{S}^{0} Decays.

PubMed

Aaij, R; Abellán Beteta, C; Adeva, B; Adinolfi, M; Affolder, A; Ajaltouni, Z; Akar, S; Albrecht, J; Alessio, F; Alexander, M; Ali, S; Alkhazov, G; Alvarez Cartelle, P; Alves, A A; Amato, S; Amerio, S; Amhis, Y; An, L; Anderlini, L; Andreassi, G; Andreotti, M; Andrews, J E; Appleby, R B; Aquines Gutierrez, O; Archilli, F; d'Argent, P; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Baalouch, M; Bachmann, S; Back, J J; Badalov, A; Baesso, C; Baldini, W; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Batozskaya, V; Battista, V; Bay, A; Beaucourt, L; Beddow, J; Bedeschi, F; Bediaga, I; Bel, L J; Bellee, V; Belloli, N; Belyaev, I; Ben-Haim, E; Bencivenni, G; Benson, S; Benton, J; Berezhnoy, A; Bernet, R; Bertolin, A; Bettler, M-O; van Beuzekom, M; Bifani, S; Billoir, P; Bird, T; Birnkraut, A; Bizzeti, A; Blake, T; Blanc, F; Blouw, J; Blusk, S; Bocci, V; Bondar, A; Bondar, N; Bonivento, W; Borghi, S; Borisyak, M; Borsato, M; Bowcock, T J V; Bowen, E; Bozzi, C; Braun, S; Britsch, M; Britton, T; Brodzicka, J; Brook, N H; Buchanan, E; Burr, C; Bursche, A; Buytaert, J; Cadeddu, S; Calabrese, R; Calvi, M; Calvo Gomez, M; Campana, P; Campora Perez, D; Capriotti, L; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carniti, P; Carson, L; Carvalho Akiba, K; Casse, G; Cassina, L; Castillo Garcia, L; Cattaneo, M; Cauet, Ch; Cavallero, G; Cenci, R; Charles, M; Charpentier, Ph; Chatzikonstantinidis, G; Chefdeville, M; Chen, S; Cheung, S-F; Chiapolini, N; Chrzaszcz, M; Cid Vidal, X; Ciezarek, G; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Coco, V; Cogan, J; Cogneras, E; Cogoni, V; Cojocariu, L; Collazuol, G; Collins, P; Comerma-Montells, A; Contu, A; Cook, A; Coombes, M; Coquereau, S; Corti, G; Corvo, M; Couturier, B; Cowan, G A; Craik, D C; Crocombe, A; Cruz Torres, M; Cunliffe, S; Currie, R; D'Ambrosio, C; Dall'Occo, E; Dalseno, J; David, P N Y; Davis, A; De Aguiar Francisco, O; De Bruyn, K; De Capua, S; De Cian, M; De Miranda, J M; De Paula, L; De Simone, P; Dean, C-T; Decamp, D; Deckenhoff, M; Del Buono, L; Déléage, N; Demmer, M; Derkach, D; Deschamps, O; Dettori, F; Dey, B; Di Canto, A; Di Ruscio, F; Dijkstra, H; Donleavy, S; Dordei, F; Dorigo, M; Dosil Suárez, A; Dovbnya, A; Dreimanis, K; Dufour, L; Dujany, G; Dungs, K; Durante, P; Dzhelyadin, R; Dziurda, A; Dzyuba, A; Easo, S; Egede, U; Egorychev, V; Eidelman, S; Eisenhardt, S; Eitschberger, U; Ekelhof, R; Eklund, L; El Rifai, I; Elsasser, Ch; Ely, S; Esen, S; Evans, H M; Evans, T; Falabella, A; Färber, C; Farley, N; Farry, S; Fay, R; Ferguson, D; Fernandez Albor, V; Ferrari, F; Ferreira Rodrigues, F; Ferro-Luzzi, M; Filippov, S; Fiore, M; Fiorini, M; Firlej, M; Fitzpatrick, C; Fiutowski, T; Fleuret, F; Fohl, K; Fol, P; Fontana, M; Fontanelli, F; Forshaw, D C; Forty, R; Frank, M; Frei, C; Frosini, M; Fu, J; Furfaro, E; Gallas Torreira, A; Galli, D; Gallorini, S; Gambetta, S; Gandelman, M; Gandini, P; Gao, Y; García Pardiñas, J; Garra Tico, J; Garrido, L; Gascon, D; Gaspar, C; Gauld, R; Gavardi, L; Gazzoni, G; 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2016-04-22

The first observation of the B_{s}^{0}→D[over ¯]^{0}K_{S}^{0} decay mode and evidence for the B_{s}^{0}→D[over ¯]^{*0}K_{S}^{0} decay mode are reported. The data sample corresponds to an integrated luminosity of 3.0  fb^{-1} collected in pp collisions by LHCb at center-of-mass energies of 7 and 8 TeV. The branching fractions are measured to be B(B_{s}^{0}→D[over ¯]^{0}K[over ¯]^{0})=[4.3±0.5(stat)±0.3(syst)±0.3(frag)±0.6(norm)]×10^{-4},B(B_{s}^{0}→D[over ¯]^{*0}K[over ¯]^{0})=[2.8±1.0(stat)±0.3(syst)±0.2(frag)±0.4(norm)]×10^{-4},where the uncertainties are due to contributions coming from statistical precision, systematic effects, and the precision of two external inputs, the ratio f_{s}/f_{d} and the branching fraction of B^{0}→D[over ¯]^{0}K_{S}^{0}, which is used as a calibration channel.

Search for the lepton-flavour violating decays B ( s) 0 → e ± μ ∓

NASA Astrophysics Data System (ADS)

Aaij, R.; Adeva, B.; Adinolfi, M.; Ajaltouni, Z.; Akar, S.; Albrecht, J.; Alessio, F.; Alexander, M.; Alfonso Albero, A.; Ali, S.; Alkhazov, G.; Alvarez Cartelle, P.; Alves, A. A.; Amato, S.; Amerio, S.; Amhis, Y.; An, L.; Anderlini, L.; Andreassi, G.; Andreotti, M.; Andrews, J. E.; Appleby, R. B.; Archilli, F.; d'Argent, P.; Arnau Romeu, J.; Artamonov, A.; Artuso, M.; Aslanides, E.; Atzeni, M.; Auriemma, G.; Baalouch, M.; Babuschkin, I.; Bachmann, S.; Back, J. J.; Badalov, A.; Baesso, C.; Baker, S.; Balagura, V.; Baldini, W.; Baranov, A.; Barlow, R. J.; Barschel, C.; Barsuk, S.; Barter, W.; Baryshnikov, F.; Batozskaya, V.; Battista, V.; Bay, A.; Beaucourt, L.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Beiter, A.; Bel, L. 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M.; Massafferri, A.; Matev, R.; Mathad, A.; Mathe, Z.; Matteuzzi, C.; Mauri, A.; Maurice, E.; Maurin, B.; Mazurov, A.; McCann, M.; McNab, A.; McNulty, R.; Mead, J. V.; Meadows, B.; Meaux, C.; Meier, F.; Meinert, N.; Melnychuk, D.; Merk, M.; Merli, A.; Michielin, E.; Milanes, D. A.; Millard, E.; Minard, M.-N.; Minzoni, L.; Mitzel, D. S.; Mogini, A.; Molina Rodriguez, J.; Mombächer, T.; Monroy, I. A.; Monteil, S.; Morandin, M.; Morello, M. J.; Morgunova, O.; Moron, J.; Morris, A. B.; Mountain, R.; Muheim, F.; Mulder, M.; Müller, D.; Müller, J.; Müller, K.; Müller, V.; Naik, P.; Nakada, T.; Nandakumar, R.; Nandi, A.; Nasteva, I.; Needham, M.; Neri, N.; Neubert, S.; Neufeld, N.; Neuner, M.; Nguyen, T. D.; Nguyen-Mau, C.; Nieswand, S.; Niet, R.; Nikitin, N.; Nikodem, T.; Nogay, A.; O'Hanlon, D. P.; Oblakowska-Mucha, A.; Obraztsov, V.; Ogilvy, S.; Oldeman, R.; Onderwater, C. J. G.; Ossowska, A.; Otalora Goicochea, J. M.; Owen, P.; Oyanguren, A.; Pais, P. R.; Palano, A.; Palutan, M.; Papanestis, A.; Pappagallo, M.; Pappalardo, L. L.; Parker, W.; Parkes, C.; Passaleva, G.; Pastore, A.; Patel, M.; Patrignani, C.; Pearce, A.; Pellegrino, A.; Penso, G.; Pepe Altarelli, M.; Perazzini, S.; Perret, P.; Pescatore, L.; Petridis, K.; Petrolini, A.; Petrov, A.; Petruzzo, M.; Picatoste Olloqui, E.; Pietrzyk, B.; Pikies, M.; Pinci, D.; Pisani, F.; Pistone, A.; Piucci, A.; Placinta, V.; Playfer, S.; Plo Casasus, M.; Polci, F.; Poli Lener, M.; Poluektov, A.; Polyakov, I.; Polycarpo, E.; Pomery, G. J.; Ponce, S.; Popov, A.; Popov, D.; Poslavskii, S.; Potterat, C.; Price, E.; Prisciandaro, J.; Prouve, C.; Pugatch, V.; Puig Navarro, A.; Pullen, H.; Punzi, G.; Qian, W.; Quagliani, R.; Quintana, B.; Rachwal, B.; Rademacker, J. H.; Rama, M.; Ramos Pernas, M.; Rangel, M. S.; Raniuk, I.; Ratnikov, F.; Raven, G.; Ravonel Salzgeber, M.; Reboud, M.; Redi, F.; Reichert, S.; dos Reis, A. C.; Remon Alepuz, C.; Renaudin, V.; Ricciardi, S.; Richards, S.; Rihl, M.; Rinnert, K.; Rives Molina, V.; Robbe, P.; Robert, A.; Rodrigues, A. B.; Rodrigues, E.; Rodriguez Lopez, J. A.; Rogozhnikov, A.; Roiser, S.; Rollings, A.; Romanovskiy, V.; Romero Vidal, A.; Ronayne, J. W.; Rotondo, M.; Rudolph, M. S.; Ruf, T.; Ruiz Valls, P.; Ruiz Vidal, J.; Saborido Silva, J. J.; Sadykhov, E.; Sagidova, N.; Saitta, B.; Salustino Guimaraes, V.; Sanchez Mayordomo, C.; Sanmartin Sedes, B.; Santacesaria, R.; Santamarina Rios, C.; Santimaria, M.; Santovetti, E.; Sarpis, G.; Sarti, A.; Satriano, C.; Satta, A.; Saunders, D. M.; Savrina, D.; Schael, S.; Schellenberg, M.; Schiller, M.; Schindler, H.; Schmelling, M.; Schmelzer, T.; Schmidt, B.; Schneider, O.; Schopper, A.; Schreiner, H. F.; Schubiger, M.; Schune, M.-H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Semennikov, A.; Sepulveda, E. S.; Sergi, A.; Serra, N.; Serrano, J.; Sestini, L.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, V.; Siddi, B. G.; Silva Coutinho, R.; Silva de Oliveira, L.; Simi, G.; Simone, S.; Sirendi, M.; Skidmore, N.; Skwarnicki, T.; Smith, E.; Smith, I. T.; Smith, J.; Smith, M.; Soares Lavra, l.; Sokoloff, M. D.; Soler, F. J. P.; Souza De Paula, B.; Spaan, B.; Spradlin, P.; Sridharan, S.; Stagni, F.; Stahl, M.; Stahl, S.; Stefko, P.; Stefkova, S.; Steinkamp, O.; Stemmle, S.; Stenyakin, O.; Stepanova, M.; Stevens, H.; Stone, S.; Storaci, B.; Stracka, S.; Stramaglia, M. E.; Straticiuc, M.; Straumann, U.; Sun, J.; Sun, L.; Sutcliffe, W.; Swientek, K.; Syropoulos, V.; Szumlak, T.; Szymanski, M.; T'Jampens, S.; Tayduganov, A.; Tekampe, T.; Tellarini, G.; Teubert, F.; Thomas, E.; van Tilburg, J.; Tilley, M. J.; Tisserand, V.; Tobin, M.; Tolk, S.; Tomassetti, L.; Tonelli, D.; Toriello, F.; Tourinho Jadallah Aoude, R.; Tournefier, E.; Traill, M.; Tran, M. T.; Tresch, M.; Trisovic, A.; Tsaregorodtsev, A.; Tsopelas, P.; Tully, A.; Tuning, N.; Ukleja, A.; Usachov, A.; Ustyuzhanin, A.; Uwer, U.; Vacca, C.; Vagner, A.; Vagnoni, V.; Valassi, A.; Valat, S.; Valenti, G.; Vazquez Gomez, R.; Vazquez Regueiro, P.; Vecchi, S.; van Veghel, M.; Velthuis, J. J.; Veltri, M.; Veneziano, G.; Venkateswaran, A.; Verlage, T. A.; Vernet, M.; Vesterinen, M.; Viana Barbosa, J. V.; Viaud, B.; Vieira, D.; Vieites Diaz, M.; Viemann, H.; Vilasis-Cardona, X.; Vitti, M.; Volkov, V.; Vollhardt, A.; Voneki, B.; Vorobyev, A.; Vorobyev, V.; Voß, C.; de Vries, J. A.; Vázquez Sierra, C.; Waldi, R.; Wallace, C.; Wallace, R.; Walsh, J.; Wang, J.; Ward, D. R.; Wark, H. M.; Watson, N. K.; Websdale, D.; Weiden, A.; Weisser, C.; Whitehead, M.; Wicht, J.; Wilkinson, G.; Wilkinson, M.; Williams, M.; Williams, M. P.; Williams, M.; Williams, T.; Wilson, F. F.; Wimberley, J.; Winn, M.; Wishahi, J.; Wislicki, W.; Witek, M.; Wormser, G.; Wotton, S. A.; Wraight, K.; Wyllie, K.; Xie, Y.; Xu, M.; Xu, Z.; Yang, Z.; Yang, Z.; Yao, Y.; Yin, H.; Yu, J.; Yuan, X.; Yushchenko, O.; Zarebski, K. A.; Zavertyaev, M.; Zhang, L.; Zhang, Y.; Zhelezov, A.; Zheng, Y.; Zhu, X.; Zhukov, V.; Zonneveld, J. B.; Zucchelli, S.

2018-03-01

A search for the lepton-flavour violating decays B s 0 → e ± μ ∓ and B 0 → e ± μ ∓ is performed based on a sample of proton-proton collision data corresponding to an integrated luminosity of 3 fb-1, collected with the LHCb experiment at centre-of-mass energies of 7 and 8 TeV. The observed yields are consistent with the background-only hypothesis. Upper limits on the branching fraction of the B s 0 → e ± μ ∓ decays are evaluated both in the hypotheses of an amplitude completely dominated by the heavy eigenstate and by the light eigenstate. The results are @/@B({B}_s^0\\to {e}^{± }{μ}^{∓})<6.3(5.4)× 1{0}^{-9} and @/@B({B}_s^0\\to {e}^{± }{μ}^{∓})<7.2(6.0)× 1{0}^{-9} at 95% (90%) confidence level, respectively. The upper limit on the branching fraction of the B 0 → e ± μ ∓ decay is also evaluated, obtaining @/@B({B}^0\\to {e}^{± }{μ}^{∓})<1.3(1.0)× 1{0}^{-9} at 95% (90%) confidence level. These are the strongest limits on these decays to date. [Figure not available: see fulltext.

Reliability and validity of the Korean version of the community balance and mobility scale in patients with hemiplegia after stroke

PubMed Central

Lee, Kyoung-bo; Lee, Paul; Yoo, Sang-won; Kim, Young-dong

2016-01-01

[Purpose] The aim of this study was to translate and adapt the Community Balance and Mobility Scale (CB&M) into Korean (K-CB&M) and to verify the reliability and validity of scores obtained with Korean patients. [Subjects and Methods] A total of 16 subjects were recruited from St. Vincent’s Hospital in South Korea. At each testing session, subjects completed the K-CB&M, Berg balance scale (BBS), timed up and go test (TUG), and functional reaching test. All tests were administered by a physical therapist, and subjects completed the tests in an identical standardized order during all testing sessions. [Results] The inter- and intra-rater reliability coefficients were high for most subscores, while moderate inter-rater reliability was observed for the items “walking and looking” and “walk, look, and carry”, and moderate intra-rater reliability was observed for “forward to backward walking”. There was a positive correlation between the K-CB&M and BBS and a negative correlation between the K-CB&M and TUG in the convergent validity assessments. [Conclusion] The reliability and validity of the K-CB&M was high, suggesting that clinical practitioners treating Korean patients with hemiplegia can use this material for assessing static and dynamic balance. PMID:27630420

The OmpL porin does not modulate redox potential in the periplasmic space of Escherichia coli.

PubMed

Sardesai, Abhijit A; Genevaux, Pierre; Schwager, Françoise; Ang, Debbie; Georgopoulos, Costa

2003-04-01

The Escherichia coli DsbA protein is the major oxidative catalyst in the periplasm. Dartigalongue et al. (EMBO J., 19, 5980-5988, 2000) reported that null mutations in the ompL gene of E.coli fully suppress all phenotypes associated with dsbA mutants, i.e. sensitivity to the reducing agent dithiothreitol (DTT) and the antibiotic benzylpenicillin, lack of motility, reduced alkaline phosphatase activity and mucoidy. They showed that OmpL is a porin and hypothesized that ompL null mutations exert their suppressive effect by preventing efflux of a putative oxidizing-reducing compound into the medium. We have repeated these experiments using two different ompL null alleles in at least three different E.coli K-12 genetic backgrounds and have failed to reproduce any of the ompL suppressive effects noted above. Also, we show that, contrary to earlier results, ompL null mutations alone do not result in partial DTT sensitivity or partial motility, nor do they appreciably affect bacterial growth rates or block propagation of the male-specific bacteriophage M13. Thus, our findings clearly demonstrate that ompL plays no perceptible role in modulating redox potential in the periplasm of E.coli.

The melatonin-MT1 receptor axis modulates tumor growth in PTEN-mutated gliomas.

PubMed

Ma, Huihui; Wang, Zhen; Hu, Lei; Zhang, Shangrong; Zhao, Chenggang; Yang, Haoran; Wang, Hongzhi; Fang, Zhiyou; Wu, Lijun; Chen, Xueran

2018-02-19

More than 40% of glioma patients have tumors that harbor PTEN (phosphatase and tensin homologue deleted on chromosome ten) mutations; this disease is associated with poor therapeutic resistance and outcome. Such mutations are linked to increased cell survival and growth, decreased apoptosis, and drug resistance; thus, new therapeutic strategies focusing on inhibiting glioma tumorigenesis and progression are urgently needed. Melatonin, an indolamine produced and secreted predominantly by the pineal gland, mediates a variety of physiological functions and possesses antioxidant and antitumor properties. Here, we analyzed the relationship between PTEN and the inhibitory effect of melatonin in primary human glioma cells and cultured glioma cell lines. The results showed that melatonin can inhibit glioma cell growth both in culture and in vivo. This inhibition was associated with PTEN levels, which significantly correlated with the expression level of MT1 in patients. In fact, c-fos-mediated MT1 was shown to be a key modulator of the effect of melatonin on gliomas that harbor wild type PTEN. Taken together, these data suggest that melatonin-MT1 receptor complexes represent a potential target for the treatment of glioma. Copyright © 2018 Elsevier Inc. All rights reserved.

Phosphorylation of Mutationally Introduced Tyrosine in the Activation Loop of HER2 Confers Gain-of-Function Activity

PubMed Central

Hu, Zexi; Wan, Xiaobo; Hao, Rui; Zhang, Heng; Li, Li; Li, Lin; Xie, Qiang; Wang, Peng; Gao, Yibo; Chen, She; Wei, Min; Luan, Zhidong; Zhang, Aiqun; Huang, Niu; Chen, Liang

2015-01-01

Amplification, overexpression, and somatic mutation of the HER2 gene have been reported to play a critical role in tumorigenesis of various cancers. The HER2 H878Y mutation was recently reported in 11% of hepatocellular carcinoma (HCC) patients. However, its functional impact on the HER2 protein and its role in tumorigenesis has not been determined. Here, we show that HER2 H878Y is a gain-of-function mutation. Y878 represents a phosphorylation site, and phospho-Y878 interacts with R898 residue to stabilize the active conformation of HER2, thereby enhancing its kinase activity. H878Y mutant is transforming and the transformed cells are sensitive to HER2 kinase inhibitors. Thus, our study reveals the following novel mechanism underlying the tumorigenic function of the HER2 H878Y mutation: the introduction of a tyrosine residue into the kinase activation loop via mutagenesis modulates the conformation of the kinase, thereby enhancing its activity. PMID:25853726

Functional characterization of c-Mpl ectodomain mutations that underlie congenital amegakaryocytic thrombocytopenia.

PubMed

Varghese, Leila N; Zhang, Jian-Guo; Young, Samuel N; Willson, Tracy A; Alexander, Warren S; Nicola, Nicos A; Babon, Jeffrey J; Murphy, James M

2014-02-01

Activation of the cell surface receptor, c-Mpl, by the cytokine, thrombopoietin (TPO), underpins megakaryocyte and platelet production in mammals. In humans, mutations in c-Mpl have been identified as the molecular basis of Congenital Amegakaryocytic Thrombocytopenia (CAMT). Here, we show that CAMT-associated mutations in c-Mpl principally lead to defective receptor presentation on the cell surface. In contrast, one CAMT mutant c-Mpl, F104S, was expressed on the cell surface, but showed defective TPO binding and receptor activation. Using mutational analyses, we examined which residues adjacent to F104 within the membrane-distal cytokine receptor homology module (CRM) of c-Mpl comprise the TPO-binding epitope, revealing residues within the predicted Domain 1 E-F and A-B loops and Domain 2 F'-G' loop as key TPO-binding determinants. These studies underscore the importance of the c-Mpl membrane-distal CRM to TPO-binding and suggest that mutations within this CRM that perturb TPO binding could give rise to CAMT.

Inhibitory Ah Receptor-Androgen Receptor Crosstalk in Prostate Cancer

DTIC Science & Technology

2005-02-01

Balk,S.P. Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist. Cancer Res. 59:2511-2515, 1999. 5. Ris...expression, 24-hydroxylase activity, and inhibition of growth hydrocarbon receptor modulators ( SARMs ) for treatment of breast by lca,25-dihydroxyvitamin D3...Safe, A. McDougal, M.S. Gupta, K. Ramamoorthy, Selective Ah [20] D.M. Peehl, R.J. Skowronski, G.K. Leung, S.T. Wong, T.A. Stamey, receptor modulators

Endogenous estrogen status, but not genistein supplementation, modulates 7,12-dimethylbenz[a]anthracene-induced mutation in the liver cII gene of transgenic big blue rats.

PubMed

Chen, Tao; Hutts, Robert C; Mei, Nan; Liu, Xiaoli; Bishop, Michelle E; Shelton, Sharon; Manjanatha, Mugimane G; Aidoo, Anane

2005-06-01

A growing number of studies suggest that isoflavones found in soybeans have estrogenic activity and may safely alleviate the symptoms of menopause. One of these isoflavones, genistein, is commonly used by postmenopausal women as an alternative to hormone replacement therapy. Although sex hormones have been implicated as an important risk factor for the development of hepatocellular carcinoma, there are limited data on the potential effects of the estrogens, including phytoestrogens, on chemical mutagenesis in liver. Because of the association between mutation induction and the carcinogenesis process, we investigated whether endogenous estrogen and supplemental genistein affect 7,12-dimethylbenz[a]anthracene (DMBA)-induced mutagenesis in rat liver. Intact and ovariectomized female Big Blue rats were treated with 80 mg DMBA/kg body weight. Some of the rats also received a supplement of 1,000 ppm genistein. Sixteen weeks after the carcinogen treatment, the rats were sacrificed, their livers were removed, and mutant frequencies (MFs) and types of mutations were determined in the liver cII gene. DMBA significantly increased the MFs in liver for both the intact and ovariectomized rats. While there was no significant difference in MF between the ovariectomized and intact control animals, the mutation induction by DMBA in the ovariectomized groups was significantly higher than that in the intact groups. Dietary genistein did not alter these responses. Molecular analysis of the mutants showed that DMBA induced chemical-specific types of mutations in the liver cII gene. These results suggest that endogenous ovarian hormones have an inhibitory effect on liver mutagenesis by DMBA, whereas dietary genistein does not modulate spontaneous or DMBA-induced mutagenesis in either intact or ovariectomized rats.

Landscape of somatic mutations and clonal evolution in mantle cell lymphoma.

PubMed

Beà, Sílvia; Valdés-Mas, Rafael; Navarro, Alba; Salaverria, Itziar; Martín-Garcia, David; Jares, Pedro; Giné, Eva; Pinyol, Magda; Royo, Cristina; Nadeu, Ferran; Conde, Laura; Juan, Manel; Clot, Guillem; Vizán, Pedro; Di Croce, Luciano; Puente, Diana A; López-Guerra, Mónica; Moros, Alexandra; Roue, Gael; Aymerich, Marta; Villamor, Neus; Colomo, Lluís; Martínez, Antonio; Valera, Alexandra; Martín-Subero, José I; Amador, Virginia; Hernández, Luis; Rozman, Maria; Enjuanes, Anna; Forcada, Pilar; Muntañola, Ana; Hartmann, Elena M; Calasanz, María J; Rosenwald, Andreas; Ott, German; Hernández-Rivas, Jesús M; Klapper, Wolfram; Siebert, Reiner; Wiestner, Adrian; Wilson, Wyndham H; Colomer, Dolors; López-Guillermo, Armando; López-Otín, Carlos; Puente, Xose S; Campo, Elías

2013-11-05

Mantle cell lymphoma (MCL) is an aggressive tumor, but a subset of patients may follow an indolent clinical course. To understand the mechanisms underlying this biological heterogeneity, we performed whole-genome and/or whole-exome sequencing on 29 MCL cases and their respective matched normal DNA, as well as 6 MCL cell lines. Recurrently mutated genes were investigated by targeted sequencing in an independent cohort of 172 MCL patients. We identified 25 significantly mutated genes, including known drivers such as ataxia-telangectasia mutated (ATM), cyclin D1 (CCND1), and the tumor suppressor TP53; mutated genes encoding the anti-apoptotic protein BIRC3 and Toll-like receptor 2 (TLR2); and the chromatin modifiers WHSC1, MLL2, and MEF2B. We also found NOTCH2 mutations as an alternative phenomenon to NOTCH1 mutations in aggressive tumors with a dismal prognosis. Analysis of two simultaneous or subsequent MCL samples by whole-genome/whole-exome (n = 8) or targeted (n = 19) sequencing revealed subclonal heterogeneity at diagnosis in samples from different topographic sites and modulation of the initial mutational profile at the progression of the disease. Some mutations were predominantly clonal or subclonal, indicating an early or late event in tumor evolution, respectively. Our study identifies molecular mechanisms contributing to MCL pathogenesis and offers potential targets for therapeutic intervention.

IgV(H) and bcl6 somatic mutation analysis reveals the heterogeneity of cutaneous B-cell lymphoma, and indicates the presence of undisclosed local antigens.

PubMed

Franco, Renato; Camacho, Francisca I; Fernández-Vázquez, Amalia; Algara, Patrocinio; Rodríguez-Peralto, José L; De Rosa, Gaetano; Piris, Miguel A

2004-06-01

Our understanding of the ontology of B-cell lymphomas (BCL) has been improved by the study of mutational status of IgV(H) and bcl6 genes, but only a few cases of cutaneous BCL have been examined for this status. We analyzed IgV(H) and bcl6 somatic mutations in 10 cutaneous BCL, classified as follicular (three primary and one secondary), primary marginal zone (two cases), and diffuse large BCL (three primary and one secondary). We observed a lower rate (<2%) of IgV(H) mutation in all marginal zone lymphomas, and a preferential usage of V(H)2-70 (one primary follicular and two primary diffuse large BCL). Fewer than expected replacement mutations in framework regions (FR) were observed in three primary follicular lymphomas (FLs) and in all diffuse large BCL, indicating a negative antigen selection pressure. Ongoing mutations were observed in eight of 10 cases. Only two primary FLs and two diffuse large BCL showed bcl6 somatic mutation. These data support the heterogeneous nature of the different cutaneous BCL, and specifically the distinction between cutaneous follicular and marginal zone lymphomas. The biased usage of V(H)2-70, the low rate of replacement mutation in the FR, and the presence of ongoing mutation imply that local antigens could modulate the growth of primary cutaneous BCL.

Sarcomere protein gene mutations and inherited heart disease: a beta-cardiac myosin heavy chain mutation causing endocardial fibroelastosis and heart failure.

PubMed

Kamisago, Mitsuhiro; Schmitt, Joachim P; McNamara, Dennis; Seidman, Christine; Seidman, J G

2006-01-01

Inherited human cardiomyopathies often lead to heart failure. A common feature of these conditions is that affected individuals can express the disease causing mutations for many years without showing clinical signs of the disease. Previous studies have demonstrated that sarcomere protein gene mutations can cause either dilated cardiomyopathy or hypertrophic cardiomyopathy. Here we demonstrate that the Arg442His missense mutation in beta-cardiac myosin heavy chain (betaMHC) causes dilated cardiomyopathy, endocardial fibroelastosis and heart failure at a very early age. Using standard genetic engineering tools we and others have made murine models by introducing human disease causing mutations into mice. The central hypothesis of these studies has been that by identifying the pathophysiological pathways activated by these mutations we can define enzymatic activities that are modified during the disease process and which may be involved in pathways that involve more common forms of cardiac disease. Murine models bearing different mutant myosins are being used to address whether each disease causing mutant betaMHC activates the same or different cellular pathways. Dissecting the molecular pathways modulated by mutations in sarcomere protein genes as well as other genes has already demonstrated that there are multiple pathways leading to cardiac remodelling and heart failure. Defining the mechanisms by which mutations in the same genes activate different cellular pathways remains an important question.

Mutations in the LRRK2 Roc-COR tandem domain link Parkinson's disease to Wnt signalling pathways.

PubMed

Sancho, Rosa M; Law, Bernard M H; Harvey, Kirsten

2009-10-15

Mutations in PARK8, encoding LRRK2, are the most common known cause of Parkinson's disease. The LRRK2 Roc-COR tandem domain exhibits GTPase activity controlling LRRK2 kinase activity via an intramolecular process. We report the interaction of LRRK2 with the dishevelled family of phosphoproteins (DVL1-3), key regulators of Wnt (Wingless/Int) signalling pathways important for axon guidance, synapse formation and neuronal maintenance. Interestingly, DVLs can interact with and mediate the activation of small GTPases with structural similarity to the LRRK2 Roc domain. The LRRK2 Roc-COR domain and the DVL1 DEP domain were necessary and sufficient for LRRK2-DVL1 interaction. Co-expression of DVL1 increased LRRK2 steady-state protein levels, an effect that was dependent on the DEP domain. Strikingly, LRRK2-DVL1-3 interactions were disrupted by the familial PARK8 mutation Y1699C, whereas pathogenic mutations at residues R1441 and R1728 strengthened LRRK2-DVL1 interactions. Co-expression of DVL1 with LRRK2 in mammalian cells resulted in the redistribution of LRRK2 to typical cytoplasmic DVL1 aggregates in HEK293 and SH-SY5Y cells and co-localization in neurites and growth cones of differentiated dopaminergic SH-SY5Y cells. This is the first report of the modulation of a key LRRK2-accessory protein interaction by PARK8 Roc-COR domain mutations segregating with Parkinson's disease. Since the DVL1 DEP domain is known to be involved in the regulation of small GTPases, we propose that: (i) DVLs may influence LRRK2 GTPase activity, and (ii) Roc-COR domain mutations modulating LRRK2-DVL interactions indirectly influence kinase activity. Our findings also link LRRK2 to Wnt signalling pathways, suggesting novel pathogenic mechanisms and new targets for genetic analysis in Parkinson's disease.

Mutations in the LRRK2 Roc-COR tandem domain link Parkinson's disease to Wnt signalling pathways

PubMed Central

Sancho, Rosa M.; Law, Bernard M.H.; Harvey, Kirsten

2009-01-01

Mutations in PARK8, encoding LRRK2, are the most common known cause of Parkinson's disease. The LRRK2 Roc-COR tandem domain exhibits GTPase activity controlling LRRK2 kinase activity via an intramolecular process. We report the interaction of LRRK2 with the dishevelled family of phosphoproteins (DVL1-3), key regulators of Wnt (Wingless/Int) signalling pathways important for axon guidance, synapse formation and neuronal maintenance. Interestingly, DVLs can interact with and mediate the activation of small GTPases with structural similarity to the LRRK2 Roc domain. The LRRK2 Roc-COR domain and the DVL1 DEP domain were necessary and sufficient for LRRK2–DVL1 interaction. Co-expression of DVL1 increased LRRK2 steady-state protein levels, an effect that was dependent on the DEP domain. Strikingly, LRRK2–DVL1-3 interactions were disrupted by the familial PARK8 mutation Y1699C, whereas pathogenic mutations at residues R1441 and R1728 strengthened LRRK2–DVL1 interactions. Co-expression of DVL1 with LRRK2 in mammalian cells resulted in the redistribution of LRRK2 to typical cytoplasmic DVL1 aggregates in HEK293 and SH-SY5Y cells and co-localization in neurites and growth cones of differentiated dopaminergic SH-SY5Y cells. This is the first report of the modulation of a key LRRK2-accessory protein interaction by PARK8 Roc-COR domain mutations segregating with Parkinson's disease. Since the DVL1 DEP domain is known to be involved in the regulation of small GTPases, we propose that: (i) DVLs may influence LRRK2 GTPase activity, and (ii) Roc-COR domain mutations modulating LRRK2–DVL interactions indirectly influence kinase activity. Our findings also link LRRK2 to Wnt signalling pathways, suggesting novel pathogenic mechanisms and new targets for genetic analysis in Parkinson's disease. PMID:19625296

Group Balance Training Specifically Designed for Individuals With Alzheimer Disease: Impact on Berg Balance Scale, Timed Up and Go, Gait Speed, and Mini-Mental Status Examination.

PubMed

Ries, Julie D; Hutson, Janet; Maralit, Leslie A; Brown, Megan B

2015-01-01

Individuals with Alzheimer disease (IwAD) experience more frequent and more injurious falls than their cognitively intact peers. Evidence of balance and gait dysfunction is observed earlier in the course of Alzheimer disease (AD) than once believed. Balance training has been demonstrated to be effective in improving balance and decreasing falls in cognitively intact older adults but is not well studied in IwAD. This study was designed to analyze the effects of a group balance training program on balance and falls in IwAD. The program was developed specifically for IwAD, with explicit guidelines for communication/interaction and deliberate structure of training sessions catered to the motor learning needs of IwAD. This prospective, quasi-experimental, pretest-posttest design study describes the effects of a balance training program for a cohort of IwAD. Thirty IwAD were recruited from 3 adult day health centers; 22 completed at least 1 posttest session. Participants were tested with Berg Balance Scale (BBS), Timed Up and Go (TUG), Self-Selected Gait Speed (SSGS), Fast Gait Speed (FGS), and Mini-Mental Status Examination (MMSE) immediately before and after the 3-month intervention and again 3 months later. Group training was held at the adult day health centers for 45 minutes, twice per week. Sessions were characterized by massed, constant, and blocked practice of functional, relevant activities with considerable repetition. Ratio of participant to staff member never exceeded 3:1. Physical therapist staff members assured that participants were up on their feet the majority of each session and were individually challenged as much as possible. Repeated-measures analysis of variance (ANOVA) for BBS was significant (F = 15.04; df = 1.67/28.40; P = .000) with post hoc tests, revealing improvement between pretest and immediate posttest (P = .000) and decline in performance between immediate and 3-month posttest (P = .012). Repeated-measures ANOVA posttest for MMSE was significant (F = 5.12; df = 1.73/22.53; P = .018) with post hoc tests, showing no change in MMSE between pretest and immediate posttest but decline in MMSE when comparing immediate posttest with 3-month posttest (P = .038) and pretest with 3-month posttest (P = .019). Repeated-measures ANOVA for TUG, FGS, and SSGS were not significant. Immediate effects of the intervention as assessed by the a priori paired t tests (comparing pre- and immediate posttest data) revealed significant improvement in BBS (t = -7.010; df = 20; P = .000), TUG (t = 3.103; df = 20; P = .006), and FGS (t = -2.115; df = 19; P = .048), but not in SSGS (t = -1.456; df = 20; P = .161). The 3-month group balance training intervention designed specifically for IwAD was effective in improving balance and mobility, as evidenced by improved BBS and TUG performances. Cognition did not decline during the course of the intervention but did decline following the intervention, suggesting a possible protective effect. Given the promising findings, a larger-scale controlled study is warranted.

Effects of management practices on wetland birds: Yellow Rail

USGS Publications Warehouse

Goldade, Christopher M.; Dechant, Jill A.; Johnson, Douglas H.; Zimmerman, Amy L.; Jamison, Brent E.; Church, James O.; Euliss, Betty R.

2002-01-01

Information on the habitat requirements and effects of habitat management on wetland birds were summarized from information in more than 500 published and unpublished papers. A range map is provided to indicate the relative densities of the species in North America, based on Breeding Bird Survey (BBS) data. Although the BBS may not capture the presence of elusive waterbird species, the BBS is a standardized survey and the range maps, in many cases, represent the most consistent information available on species’ distributions. Although birds frequently are observed outside the breeding range indicated, the maps are intended to show areas where managers might concentrate their attention. It may be ineffectual to manage habitat at a site for a species that rarely occurs in an area. The species account begins with a brief capsule statement, which provides the fundamental components or keys to management for the species. A section on breeding range outlines the current breeding distribution of the species in North America, including areas that could not be mapped using BBS data. The suitable habitat section describes the breeding habitat and occasionally microhabitat characteristics of the species, especially those habitats that occur in the Great Plains. Details on habitat and microhabitat requirements often provide clues to how a species will respond to a particular management practice. A table near the end of the account complements the section on suitable habitat, and lists the specific habitat characteristics for the species by individual studies. The area requirements section provides details on territory and home range sizes, minimum area requirements, and the effects of patch size, edges, and other landscape and habitat features on abundance and productivity. It may be futile to manage a small block of suitable habitat for a species that has minimum area requirements that are larger than the area being managed. The section on brood parasitism summarizes information on intra- and interspecific parasitism, host responses to parasitism, and factors that influence parasitism, such as nest concealment and host density. The impact of management depends, in part, upon a species’ nesting phenology and biology. The section on breeding-season phenology and site fidelity includes details on spring arrival and fall departure for migratory populations in the Great Plains, peak breeding periods, the tendency to renest after nest failure or success, and the propensity to return to a previous breeding site. The duration and timing of breeding varies among regions and years. Species’ response to management summarizes the current knowledge and major findings in the literature on the effects of different management practices on the species. The section on management recommendations complements the previous section and summarizes recommendations for habitat management provided in the literature. The literature cited contains references to published and unpublished literature on the management effects and habitat requirements of the species. This section is not meant to be a complete bibliography; a searchable, annotated bibliography of published and unpublished papers dealing with habitat needs of wetland birds and their responses to habitat management is posted at the Web site mentioned below.

Effects of management practices on wetland birds: Virginia rail

USGS Publications Warehouse

Zimmerman, Amy L.; Dechant, Jill A.; Jamison, Brent E.; Johnson, Douglas H.; Goldade, Christopher M.; Church, James O.; Euliss, Betty R.

2002-01-01

Information on the habitat requirements and effects of habitat management on wetland birds were summarized from information in more than 500 published and unpublished papers. A range map is provided to indicate the relative densities of the species in North America, based on Breeding Bird Survey (BBS) data. Although the BBS may not capture the presence of elusive waterbird species, the BBS is a standardized survey and the range maps, in many cases, represent the most consistent information available on species’ distributions. Although birds frequently are observed outside the breeding range indicated, the maps are intended to show areas where managers might concentrate their attention. It may be ineffectual to manage habitat at a site for a species that rarely occurs in an area. The species account begins with a brief capsule statement, which provides the fundamental components or keys to management for the species. A section on breeding range outlines the current breeding distribution of the species in North America, including areas that could not be mapped using BBS data. The suitable habitat section describes the breeding habitat and occasionally microhabitat characteristics of the species, especially those habitats that occur in the Great Plains. Details on habitat and microhabitat requirements often provide clues to how a species will respond to a particular management practice. A table near the end of the account complements the section on suitable habitat, and lists the specific habitat characteristics for the species by individual studies. The area requirements section provides details on territory and home range sizes, minimum area requirements, and the effects of patch size, edges, and other landscape and habitat features on abundance and productivity. It may be futile to manage a small block of suitable habitat for a species that has minimum area requirements that are larger than the area being managed. The section on brood parasitism summarizes information on intra- and interspecific parasitism, host responses to parasitism, and factors that influence parasitism, such as nest concealment and host density. The impact of management depends, in part, upon a species’ nesting phenology and biology. The section on breeding-season phenology and site fidelity includes details on spring arrival and fall departure for migratory populations in the Great Plains, peak breeding periods, the tendency to renest after nest failure or success, and the propensity to return to a previous breeding site. The duration and timing of breeding varies among regions and years. Species’ response to management summarizes the current knowledge and major findings in the literature on the effects of different management practices on the species. The section on management recommendations complements the previous section and summarizes recommendations for habitat management provided in the literature. The literature cited contains references to published and unpublished literature on the management effects and habitat requirements of the species. This section is not meant to be a complete bibliography; a searchable, annotated bibliography of published and unpublished papers dealing with habitat needs of wetland birds and their responses to habitat management is posted at the Web site mentioned below.

Effects of management practices on wetland birds: Black tern

USGS Publications Warehouse

Zimmerman, Amy L.; Dechant, Jill A.; Johnson, Douglas A.; Goldade, Christopher M.; Jamison, Brent E.; Euliss, Betty R.

2002-01-01

Information on the habitat requirements and effects of habitat management on wetland birds were summarized from information in more than 500 published and unpublished papers. A range map is provided to indicate the relative densities of the species in North America, based on Breeding Bird Survey (BBS) data. Although the BBS may not capture the presence of elusive waterbird species, the BBS is a standardized survey and the range maps, in many cases, represent the most consistent information available on species’ distributions. Although birds frequently are observed outside the breeding range indicated, the maps are intended to show areas where managers might concentrate their attention. It may be ineffectual to manage habitat at a site for a species that rarely occurs in an area. The species account begins with a brief capsule statement, which provides the fundamental components or keys to management for the species. A section on breeding range outlines the current breeding distribution of the species in North America, including areas that could not be mapped using BBS data. The suitable habitat section describes the breeding habitat and occasionally microhabitat characteristics of the species, especially those habitats that occur in the Great Plains. Details on habitat and microhabitat requirements often provide clues to how a species will respond to a particular management practice. A table near the end of the account complements the section on suitable habitat, and lists the specific habitat characteristics for the species by individual studies. The area requirements section provides details on territory and home range sizes, minimum area requirements, and the effects of patch size, edges, and other landscape and habitat features on abundance and productivity. It may be futile to manage a small block of suitable habitat for a species that has minimum area requirements that are larger than the area being managed. The section on brood parasitism summarizes information on intra- and interspecific parasitism, host responses to parasitism, and factors that influence parasitism, such as nest concealment and host density. The impact of management depends, in part, upon a species’ nesting phenology and biology. The section on breeding-season phenology and site fidelity includes details on spring arrival and fall departure for migratory populations in the Great Plains, peak breeding periods, the tendency to renest after nest failure or success, and the propensity to return to a previous breeding site. The duration and timing of breeding varies among regions and years. Species’ response to management summarizes the current knowledge and major findings in the literature on the effects of different management practices on the species. The section on management recommendations complements the previous section and summarizes recommendations for habitat management provided in the literature. The literature cited contains references to published and unpublished literature on the management effects and habitat requirements of the species. This section is not meant to be a complete bibliography; a searchable, annotated bibliography of published and unpublished papers dealing with habitat needs of grassland birds and their responses to habitat management is posted at the Web site mentioned below.

Effects of management practices on wetland birds: American Avocet

USGS Publications Warehouse

Dechant, Jill A.; Zimmerman, Amy L.; Johnson, Douglas H.; Goldade, Christopher M.; Jamison, Brent E.; Euliss, Betty R.

2002-01-01

Information on the habitat requirements and effects of habitat management on wetland birds were summarized from information in more than 500 published and unpublished papers. A range map is provided to indicate the relative densities of the species in North America, based on Breeding Bird Survey (BBS) data. Although the BBS may not capture the presence of elusive waterbird species, the BBS is a standardized survey and the range maps, in many cases, represent the most consistent information available on species’ distributions. Although birds frequently are observed outside the breeding range indicated, the maps are intended to show areas where managers might concentrate their attention. It may be ineffectual to manage habitat at a site for a species that rarely occurs in an area. The species account begins with a brief capsule statement, which provides the fundamental components or keys to management for the species. A section on breeding range outlines the current breeding distribution of the species in North America, including areas that could not be mapped using BBS data. The suitable habitat section describes the breeding habitat and occasionally microhabitat characteristics of the species, especially those habitats that occur in the Great Plains. Details on habitat and microhabitat requirements often provide clues to how a species will respond to a particular management practice. A table near the end of the account complements the section on suitable habitat, and lists the specific habitat characteristics for the species by individual studies. The area requirements section provides details on territory and home range sizes, minimum area requirements, and the effects of patch size, edges, and other landscape and habitat features on abundance and productivity. It may be futile to manage a small block of suitable habitat for a species that has minimum area requirements that are larger than the area being managed. The section on brood parasitism summarizes information on intra- and interspecific parasitism, host responses to parasitism, and factors that influence parasitism, such as nest concealment and host density. The impact of management depends, in part, upon a species’ nesting phenology and biology. The section on breeding-season phenology and site fidelity includes details on spring arrival and fall departure for migratory populations in the Great Plains, peak breeding periods, the tendency to renest after nest failure or success, and the propensity to return to a previous breeding site. The duration and timing of breeding varies among regions and years. Species’ response to management summarizes the current knowledge and major findings in the literature on the effects of different management practices on the species. The section on management recommendations complements the previous section and summarizes recommendations for habitat management provided in the literature. The literature cited contains references to published and unpublished literature on the management effects and habitat requirements of the species. This section is not meant to be a complete bibliography; a searchable, annotated bibliography of published and unpublished papers dealing with habitat needs of wetland birds and their responses to habitat management is posted at the Web site mentioned below.

Present-day stress state in the Outokumpu deep drill hole, Finland

NASA Astrophysics Data System (ADS)

Pierdominici, Simona; Ask, Maria; Kukkonen, Ilmo; Kueck, Jochem

2017-04-01

This study aims to investigate the present-day stress field in the Outokumpu area, eastern Finland, using interpretation of borehole failure on acoustic image logs in a 2516 m deep hole. Two main objectives of this study are: i. to constrain the orientation of maximum horizontal stress by mapping the occurrence of stress-induced deformation features using two sets of borehole televiewer data, which were collected in 2006 and 2011; and ii. to investigate whether any time dependent deformation of the borehole wall has occurred (creep). The Outokumpu deep hole was drilled during 2004-2005 to study deep structures and seismic reflectors within the Outokumpu formation and conducted within the International Continental Scientific Drilling Program (ICDP). The hole was continuously core-drilled into Paleoproterozoic formation of metasediments, ophiolite-derived altered ultrabasic rocks and pegmatitic granite. In 2006 and 2011 two downhole logging campaigns were performed by the Operational Support Group of ICDP to acquire a set of geophysical data. Here we focus on a specific downhole logging measurement, the acoustic borehole televiewer (BHTV), to determine the present-day stress field in the Outokumpu area. We constrain the orientation and magnitude of in situ stress tensor based on borehole wall failures detected along a 2516 m deep hole. Horizontal stress orientation was determined by interpreting borehole breakouts (BBs) and drilling-induced tensile fractures (DIFs) from BHTV logs. BBs are stress-induced enlargements of the borehole cross section and occur in two opposite zones at angles around the borehole where the wellbore stress concentration (hoop stress) exceeds the value required to cause compressive failure of intact rock. DIFs are caused by tensile failure of the borehole wall and form at two opposite spots on the borehole where the stress concentration is lower than the tensile strength of the rock. This occurs at angles 90° apart from the center of the breakout zone. Acoustic imaging logs provide a high-resolution oriented picture of the borehole wall that allows for the direct observation of BBs, which appear as two almost vertical swaths on the borehole image separated by 180°. BBs show poor sonic reflectivity and long travel times due to the many small brittle fractures and the resulting spalling. DIFs appear as two narrow stripes of low reflectivity separated by 180° and typically sub-parallel or slightly inclined to the borehole axis. The analysis of these images shows a distinct compressive failure area consistent with major geological and tectonic lineaments of the area. Deviations from this trend reflect local structural perturbations. Additionally, the 2006 and 2011 dataset are used to compare the changes of breakout geometry and to quantify the growth of the breakouts in this time span from differences in width, length and depth to estimate the magnitude of the horizontal stress tensors. Our study contributes to understand the structure of the shallow crust in the Outokumpu area by defining the current stress field. Furthermore, a detailed understanding of the regional stress field is a fundamental contribution in several research areas such as exploration and exploitation of underground resources, and geothermal reservoir studies.

ExScalibur: A High-Performance Cloud-Enabled Suite for Whole Exome Germline and Somatic Mutation Identification

PubMed Central

Huang, Lei; Kang, Wenjun; Bartom, Elizabeth; Onel, Kenan; Volchenboum, Samuel; Andrade, Jorge

2015-01-01

Whole exome sequencing has facilitated the discovery of causal genetic variants associated with human diseases at deep coverage and low cost. In particular, the detection of somatic mutations from tumor/normal pairs has provided insights into the cancer genome. Although there is an abundance of publicly-available software for the detection of germline and somatic variants, concordance is generally limited among variant callers and alignment algorithms. Successful integration of variants detected by multiple methods requires in-depth knowledge of the software, access to high-performance computing resources, and advanced programming techniques. We present ExScalibur, a set of fully automated, highly scalable and modulated pipelines for whole exome data analysis. The suite integrates multiple alignment and variant calling algorithms for the accurate detection of germline and somatic mutations with close to 99% sensitivity and specificity. ExScalibur implements streamlined execution of analytical modules, real-time monitoring of pipeline progress, robust handling of errors and intuitive documentation that allows for increased reproducibility and sharing of results and workflows. It runs on local computers, high-performance computing clusters and cloud environments. In addition, we provide a data analysis report utility to facilitate visualization of the results that offers interactive exploration of quality control files, read alignment and variant calls, assisting downstream customization of potential disease-causing mutations. ExScalibur is open-source and is also available as a public image on Amazon cloud. PMID:26271043

Mutation of SIMPLE in Charcot–Marie–Tooth 1C alters production of exosomes

PubMed Central

Zhu, Hong; Guariglia, Sara; Yu, Raymond Y. L.; Li, Wenjing; Brancho, Deborah; Peinado, Hector; Lyden, David; Salzer, James; Bennett, Craig; Chow, Chi-Wing

2013-01-01

Charcot–Marie–Tooth (CMT) disease is an inherited neurological disorder. Mutations in the small integral membrane protein of the lysosome/late endosome (SIMPLE) account for the rare autosomal-dominant demyelination in CMT1C patients. Understanding the molecular basis of CMT1C pathogenesis is impeded, in part, by perplexity about the role of SIMPLE, which is expressed in multiple cell types. Here we show that SIMPLE resides within the intraluminal vesicles of multivesicular bodies (MVBs) and inside exosomes, which are nanovesicles secreted extracellularly. Targeting of SIMPLE to exosomes is modulated by positive and negative regulatory motifs. We also find that expression of SIMPLE increases the number of exosomes and secretion of exosome proteins. We engineer a point mutation on the SIMPLE allele and generate a physiological mouse model that expresses CMT1C-mutated SIMPLE at the endogenous level. We find that CMT1C mouse primary embryonic fibroblasts show decreased number of exosomes and reduced secretion of exosome proteins, in part due to improper formation of MVBs. CMT1C patient B cells and CMT1C mouse primary Schwann cells show similar defects. Together the data indicate that SIMPLE regulates the production of exosomes by modulating the formation of MVBs. Dysregulated endosomal trafficking and changes in the landscape of exosome-mediated intercellular communications may place an overwhelming burden on the nervous system and account for CMT1C molecular pathogenesis. PMID:23576546

Mutations causing syndromic autism define an axis of synaptic pathophysiology.

PubMed

Auerbach, Benjamin D; Osterweil, Emily K; Bear, Mark F

2011-11-23

Tuberous sclerosis complex and fragile X syndrome are genetic diseases characterized by intellectual disability and autism. Because both syndromes are caused by mutations in genes that regulate protein synthesis in neurons, it has been hypothesized that excessive protein synthesis is one core pathophysiological mechanism of intellectual disability and autism. Using electrophysiological and biochemical assays of neuronal protein synthesis in the hippocampus of Tsc2(+/-) and Fmr1(-/y) mice, here we show that synaptic dysfunction caused by these mutations actually falls at opposite ends of a physiological spectrum. Synaptic, biochemical and cognitive defects in these mutants are corrected by treatments that modulate metabotropic glutamate receptor 5 in opposite directions, and deficits in the mutants disappear when the mice are bred to carry both mutations. Thus, normal synaptic plasticity and cognition occur within an optimal range of metabotropic glutamate-receptor-mediated protein synthesis, and deviations in either direction can lead to shared behavioural impairments.

Targeted sequencing identifies associations between IL7R-JAK mutations and epigenetic modulators in T-cell acute lymphoblastic leukemia

PubMed Central

Vicente, Carmen; Schwab, Claire; Broux, Michaël; Geerdens, Ellen; Degryse, Sandrine; Demeyer, Sofie; Lahortiga, Idoya; Elliott, Alannah; Chilton, Lucy; La Starza, Roberta; Mecucci, Cristina; Vandenberghe, Peter; Goulden, Nicholas; Vora, Ajay; Moorman, Anthony V.; Soulier, Jean; Harrison, Christine J.; Clappier, Emmanuelle; Cools, Jan

2015-01-01

T-cell acute lymphoblastic leukemia is caused by the accumulation of multiple oncogenic lesions, including chromosomal rearrangements and mutations. To determine the frequency and co-occurrence of mutations in T-cell acute lymphoblastic leukemia, we performed targeted re-sequencing of 115 genes across 155 diagnostic samples (44 adult and 111 childhood cases). NOTCH1 and CDKN2A/B were mutated/deleted in more than half of the cases, while an additional 37 genes were mutated/deleted in 4% to 20% of cases. We found that IL7R-JAK pathway genes were mutated in 27.7% of cases, with JAK3 mutations being the most frequent event in this group. Copy number variations were also detected, including deletions of CREBBP or CTCF and duplication of MYB. FLT3 mutations were rare, but a novel extracellular mutation in FLT3 was detected and confirmed to be transforming. Furthermore, we identified complex patterns of pairwise associations, including a significant association between mutations in IL7R-JAK genes and epigenetic regulators (WT1, PRC2, PHF6). Our analyses showed that IL7R-JAK genetic lesions did not confer adverse prognosis in T-cell acute lymphoblastic leukemia cases enrolled in the UK ALL2003 trial. Overall, these results identify interconnections between the T-cell acute lymphoblastic leukemia genome and disease biology, and suggest a potential clinical application for JAK inhibitors in a significant proportion of patients with T-cell acute lymphoblastic leukemia. PMID:26206799

Clinical and mutational spectrum in Korean patients with Rubinstein-Taybi syndrome: the spectrum of brain MRI abnormalities.

PubMed

Lee, Jin Sook; Byun, Christine K; Kim, Hunmin; Lim, Byung Chan; Hwang, Hee; Choi, Ji Eun; Hwang, Yong Seung; Seong, Moon-Woo; Park, Sung Sup; Kim, Ki Joong; Chae, Jong-Hee

2015-04-01

Rubinstein-Taybi syndrome (RSTS) is one of the neurodevelopmental disorders caused by mutations of epigenetic genes. The CREBBP gene is the most common causative gene, encoding the CREB-binding protein with histone acetyltransferase (HAT) activity, an epigenetic modulator. To date, there have been few reports on the structural abnormalities of the brain in RSTS patients. In addition, there are no reports on the analysis of CREBBP mutations in Korean RSTS patients. We performed mutational analyses on 16 unrelated patients with RSTS, with diagnosis based on the typical clinical features. Their medical records and brain MRI images were reviewed retrospectively. Ten of 16 patients (62.5%) had mutations in the CREBBP gene. The mutations included five frameshift mutations (31.2%), two nonsense mutations (12.5%), and three multiexon deletions (18.8%). There were no remarkable significant differences in the clinical features between those with and without a CREBBP mutation, although brain MRI abnormalities were more frequently observed in those with a CREBBP mutation. Seven of 10 patients in whom brain imaging was performed had structural abnormalities, including Chiari malformation type 1, thinning of the corpus callosum, and delayed myelination. There were no differences in delayed development or cognitive impairment between those with and without abnormal brain images, while epilepsy was involved in two patients who had abnormalities on brain MRI images. We investigated the spectrum of CREBBP mutations in Korean patients with RSTS for the first time. Eight novel mutations extended the genetic spectrum of CREBBP mutations in RSTS patients. This is also the first study showing the prevalence and spectrum of abnormalities on brain MRI in RSTS patients. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Hcfc1b, a zebrafish ortholog of HCFC1, regulates craniofacial development by modulating mmachc expression.

PubMed

Quintana, Anita M; Geiger, Elizabeth A; Achilly, Nate; Rosenblatt, David S; Maclean, Kenneth N; Stabler, Sally P; Artinger, Kristin B; Appel, Bruce; Shaikh, Tamim H

2014-12-01

Mutations in HCFC1 (MIM300019), have been recently associated with cblX (MIM309541), an X-linked, recessive disorder characterized by multiple congenital anomalies including craniofacial abnormalities. HCFC1 is a transcriptional co-regulator that modulates the expression of numerous downstream target genes including MMACHC, but it is not clear how these HCFC1 targets play a role in the clinical manifestations of cblX. To begin to elucidate the mechanism by which HCFC1 modulates disease phenotypes, we have carried out loss of function analyses in the developing zebrafish. Of the two HCFC1 orthologs in zebrafish, hcfc1a and hcfc1b, the loss of hcfc1b specifically results in defects in craniofacial development. Subsequent analysis revealed that hcfc1b regulates cranial neural crest cell differentiation and proliferation within the posterior pharyngeal arches. Further, the hcfc1b-mediated craniofacial abnormalities were rescued by expression of human MMACHC, a downstream target of HCFC1 that is aberrantly expressed in cblX. Furthermore, we tested distinct human HCFC1 mutations for their role in craniofacial development and demonstrated variable effects on MMACHC expression in humans and craniofacial development in zebrafish. Notably, several individuals with mutations in either HCFC1 or MMACHC have been reported to have mild to moderate facial dysmorphia. Thus, our data demonstrates that HCFC1 plays a role in craniofacial development, which is in part mediated through the regulation of MMACHC expression. Copyright © 2014 Elsevier Inc. All rights reserved.

CFTR Modulators for the Treatment of Cystic Fibrosis.

PubMed

Pettit, Rebecca S; Fellner, Chris

2014-07-01

Defects in a single gene lead to the defective proteins that cause cystic fibrosis, making the disease an ideal candidate for mutation-targeted therapy. Although ivacaftor is currently the only FDA-approved CFTR modifier, others are in development.

[Genetic hypophosphatemia: recent advances in physiopathogenic concept].

PubMed

Beraud, G; Perimenis, P; Velayoudom, Fr-L; Wemeau, J-L; Vantyghem, M-Chr

2005-04-01

Renal proximal tubular reabsorption of phosphate and intestinal absorption both regulate phosphate homeostasis. Brush-border membrane Npt2a cotransporter is the key element in proximal tubular P (i) reabsorption. Inactivating mutations of Npt2a cause bone demineralisation and urolithiasis. An excess of a phosphaturic factor, called "Phosphatonin", could modulate phosphate reabsorption by inhibition on Npt2a. Inactivating mutation of PHEX, an endopeptidase-membrane coding gene, is responsible for X-linked Hypophosphatemia (XLH), because of an impaired degradation of phosphatonine by PHEX product. Autosomic Dominant Hypophosphatemic Rickets (ADHR) is explained by a mutation preventing FGF23 (one of the best identified phosphatonines) from cleavage. According recent data, FGF23, MEPE (Matrix Extracellular Phosphoglycoprotein) et FRP4 (frizzled related protein-4) are 3 putative "phosphatonines".

MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone

PubMed Central

Li, Chunmei; Kennedy, Julie; Garcia-Gonzalo, Francesc R.; Romani, Marta; De Mori, Roberta; Bruel, Ange-Line; Gaillard, Dominique; Doray, Bérénice; Lopez, Estelle; Rivière, Jean-Baptiste; Faivre, Laurence; Thauvin-Robinet, Christel; Reiter, Jeremy F.; Blacque, Oliver E.; Valente, Enza Maria; Leroux, Michel R.

2016-01-01

Cilia have a unique diffusion barrier (“gate”) within their proximal region, termed transition zone (TZ), that compartmentalises signalling proteins within the organelle. The TZ is known to harbour two functional modules/complexes (Meckel syndrome [MKS] and Nephronophthisis [NPHP]) defined by genetic interaction, interdependent protein localisation (hierarchy), and proteomic studies. However, the composition and molecular organisation of these modules and their links to human ciliary disease are not completely understood. Here, we reveal Caenorhabditis elegans CEP-290 (mammalian Cep290/Mks4/Nphp6 orthologue) as a central assembly factor that is specific for established MKS module components and depends on the coiled coil region of MKS-5 (Rpgrip1L/Rpgrip1) for TZ localisation. Consistent with a critical role in ciliary gate function, CEP-290 prevents inappropriate entry of membrane-associated proteins into cilia and keeps ARL-13 (Arl13b) from leaking out of cilia via the TZ. We identify a novel MKS module component, TMEM-218 (Tmem218), that requires CEP-290 and other MKS module components for TZ localisation and functions together with the NPHP module to facilitate ciliogenesis. We show that TZ localisation of TMEM-138 (Tmem138) and CDKL-1 (Cdkl1/Cdkl2/Cdkl3/Cdlk4 related), not previously linked to a specific TZ module, similarly depends on CEP-290; surprisingly, neither TMEM-138 or CDKL-1 exhibit interdependent localisation or genetic interactions with core MKS or NPHP module components, suggesting they are part of a distinct, CEP-290-associated module. Lastly, we show that families presenting with Oral-Facial-Digital syndrome type 6 (OFD6) have likely pathogenic mutations in CEP-290-dependent TZ proteins, namely Tmem17, Tmem138, and Tmem231. Notably, patient fibroblasts harbouring mutated Tmem17, a protein not yet ciliopathy-associated, display ciliogenesis defects. Together, our findings expand the repertoire of MKS module-associated proteins—including the previously uncharacterised mammalian Tmem80—and suggest an MKS-5 and CEP-290-dependent assembly pathway for building a functional TZ. PMID:26982032

Molecular mechanics and dynamics characterization of an in silico mutated protein: a stand-alone lab module or support activity for in vivo and in vitro analyses of targeted proteins.

PubMed

Chiang, Harry; Robinson, Lucy C; Brame, Cynthia J; Messina, Troy C

2013-01-01

Over the past 20 years, the biological sciences have increasingly incorporated chemistry, physics, computer science, and mathematics to aid in the development and use of mathematical models. Such combined approaches have been used to address problems from protein structure-function relationships to the workings of complex biological systems. Computer simulations of molecular events can now be accomplished quickly and with standard computer technology. Also, simulation software is freely available for most computing platforms, and online support for the novice user is ample. We have therefore created a molecular dynamics laboratory module to enhance undergraduate student understanding of molecular events underlying organismal phenotype. This module builds on a previously described project in which students use site-directed mutagenesis to investigate functions of conserved sequence features in members of a eukaryotic protein kinase family. In this report, we detail the laboratory activities of a MD module that provide a complement to phenotypic outcomes by providing a hypothesis-driven and quantifiable measure of predicted structural changes caused by targeted mutations. We also present examples of analyses students may perform. These laboratory activities can be integrated with genetics or biochemistry experiments as described, but could also be used independently in any course that would benefit from a quantitative approach to protein structure-function relationships. Copyright © 2013 Wiley Periodicals, Inc.

Mediator independently orchestrates multiple steps of preinitiation complex assembly in vivo.

PubMed

Eyboulet, Fanny; Wydau-Dematteis, Sandra; Eychenne, Thomas; Alibert, Olivier; Neil, Helen; Boschiero, Claire; Nevers, Marie-Claire; Volland, Hervé; Cornu, David; Redeker, Virginie; Werner, Michel; Soutourina, Julie

2015-10-30

Mediator is a large multiprotein complex conserved in all eukaryotes, which has a crucial coregulator function in transcription by RNA polymerase II (Pol II). However, the molecular mechanisms of its action in vivo remain to be understood. Med17 is an essential and central component of the Mediator head module. In this work, we utilised our large collection of conditional temperature-sensitive med17 mutants to investigate Mediator's role in coordinating preinitiation complex (PIC) formation in vivo at the genome level after a transfer to a non-permissive temperature for 45 minutes. The effect of a yeast mutation proposed to be equivalent to the human Med17-L371P responsible for infantile cerebral atrophy was also analyzed. The ChIP-seq results demonstrate that med17 mutations differentially affected the global presence of several PIC components including Mediator, TBP, TFIIH modules and Pol II. Our data show that Mediator stabilizes TFIIK kinase and TFIIH core modules independently, suggesting that the recruitment or the stability of TFIIH modules is regulated independently on yeast genome. We demonstrate that Mediator selectively contributes to TBP recruitment or stabilization to chromatin. This study provides an extensive genome-wide view of Mediator's role in PIC formation, suggesting that Mediator coordinates multiple steps of a PIC assembly pathway. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Naturally Occurring Deletion Mutants of the Pig-Specific, Intestinal Crypt Epithelial Cell Protein CLCA4b without Apparent Phenotype

PubMed Central

Plog, Stephanie; Klymiuk, Nikolai; Binder, Stefanie; Van Hook, Matthew J.; Thoreson, Wallace B.; Gruber, Achim D.; Mundhenk, Lars

2015-01-01

The human CLCA4 (chloride channel regulator, calcium-activated) modulates the intestinal phenotype of cystic fibrosis (CF) patients via an as yet unknown pathway. With the generation of new porcine CF models, species-specific differences between human modifiers of CF and their porcine orthologs are considered critical for the translation of experimental data. Specifically, the porcine ortholog to the human CF modulator gene CLCA4 has recently been shown to be duplicated into two separate genes, CLCA4a and CLCA4b. Here, we characterize the duplication product, CLCA4b, in terms of its genomic structure, tissue and cellular expression patterns as well as its in vitro electrophysiological properties. The CLCA4b gene is a pig-specific duplication product of the CLCA4 ancestor and its protein is exclusively expressed in small and large intestinal crypt epithelial cells, a niche specifically occupied by no other porcine CLCA family member. Surprisingly, a unique deleterious mutation of the CLCA4b gene is spread among modern and ancient breeds in the pig population, but this mutation did not result in an apparent phenotype in homozygously affected animals. Electrophysiologically, neither the products of the wild type nor of the mutated CLCA4b genes were able to evoke a calcium-activated anion conductance, a consensus feature of other CLCA proteins. The apparently pig-specific duplication of the CLCA4 gene with unique expression of the CLCA4b protein variant in intestinal crypt epithelial cells where the porcine CFTR is also present raises the question of whether it may modulate the porcine CF phenotype. Moreover, the naturally occurring null variant of CLCA4b will be valuable for the understanding of CLCA protein function and their relevance in modulating the CF phenotype. PMID:26474299

Identifying module biomarkers from gastric cancer by differential correlation network

PubMed Central

Liu, Xiaoping; Chang, Xiao

2016-01-01

Gastric cancer (stomach cancer) is a severe disease caused by dysregulation of many functionally correlated genes or pathways instead of the mutation of individual genes. Systematic identification of gastric cancer biomarkers can provide insights into the mechanisms underlying this deadly disease and help in the development of new drugs. In this paper, we present a novel network-based approach to predict module biomarkers of gastric cancer that can effectively distinguish the disease from normal samples. Specifically, by assuming that gastric cancer has mainly resulted from dysfunction of biomolecular networks rather than individual genes in an organism, the genes in the module biomarkers are potentially related to gastric cancer. Finally, we identified a module biomarker with 27 genes, and by comparing the module biomarker with known gastric cancer biomarkers, we found that our module biomarker exhibited a greater ability to diagnose the samples with gastric cancer. PMID:27703371

Efficient exon skipping of SGCG mutations mediated by phosphorodiamidate morpholino oligomers.

PubMed

Wyatt, Eugene J; Demonbreun, Alexis R; Kim, Ellis Y; Puckelwartz, Megan J; Vo, Andy H; Dellefave-Castillo, Lisa M; Gao, Quan Q; Vainzof, Mariz; Pavanello, Rita C M; Zatz, Mayana; McNally, Elizabeth M

2018-05-03

Exon skipping uses chemically modified antisense oligonucleotides to modulate RNA splicing. Therapeutically, exon skipping can bypass mutations and restore reading frame disruption by generating internally truncated, functional proteins to rescue the loss of native gene expression. Limb-girdle muscular dystrophy type 2C is caused by autosomal recessive mutations in the SGCG gene, which encodes the dystrophin-associated protein γ-sarcoglycan. The most common SGCG mutations disrupt the transcript reading frame abrogating γ-sarcoglycan protein expression. In order to treat most SGCG gene mutations, it is necessary to skip 4 exons in order to restore the SGCG transcript reading frame, creating an internally truncated protein referred to as Mini-Gamma. Using direct reprogramming of human cells with MyoD, myogenic cells were tested with 2 antisense oligonucleotide chemistries, 2'-O-methyl phosphorothioate oligonucleotides and vivo-phosphorodiamidate morpholino oligomers, to induce exon skipping. Treatment with vivo-phosphorodiamidate morpholino oligomers demonstrated efficient skipping of the targeted exons and corrected the mutant reading frame, resulting in the expression of a functional Mini-Gamma protein. Antisense-induced exon skipping of SGCG occurred in normal cells and those with multiple distinct SGCG mutations, including the most common 521ΔT mutation. These findings demonstrate a multiexon-skipping strategy applicable to the majority of limb-girdle muscular dystrophy 2C patients.

A Novel NHERF1 Mutation in Human Breast Cancer and Effects on Malignant Progression.

PubMed

Yang, Xiaomei; Du, Guifang; Yu, Zhen; Si, Yang; Martin, Tracey A; He, Junqi; Cheng, Shan; Jiang, Wen G

2017-01-01

Na + /H + exchanger regulatory factor 1 (NHERF1) has been reported to interact with post-synaptic density protein/Drosophila disc large tumour suppressor/zonula occludens 1 protein (PDZ) binding proteins by its two PDZ domains. These associations have effects on cellular signal transductions. NHERF1 has also been indicated as a cancer-related gene in several solid tumour types. We identified a novel mutation (A190D), of the PDZ2 domain of NHERF1 in breast cancer tissues. NHERF1 A190D mutation abolished NHERF1 modulation of proliferation and migration. In this study, we found that NHERF1 A190D mutation increased nuclear localisation of the protein compared to wild-type NHERF1. It has been reported that YES-associated protein (YAP) interacts with NHERF1. Here we found that NHERF1 A190D mutation increased the binding affinity between NHERF1 and YAP, which inhibited the phosphorylation of YAP. These data suggest that wild-type NHERF1 acts as a tumour suppressor, while NHERF1 A190D mutation abolishes the tumour-suppressive effect in cancer cells, due to A190D mutation-mediated nuclear NHERF1 translocation and induction of YAP phosphorylation. Copyright© 2017 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

A novel mutation of laminin β2 (LAMB2) in two siblings with renal failure.

PubMed

Falix, Farah A; Bennebroek, Carlien A M; van der Zwaag, Bert; Lapid-Gortzak, Ruth; Florquin, Sandrine; Oosterveld, Michiel J S

2017-04-01

This report describes a novel mutation of LAMB2, the gene associated with Pierson syndrome (microcoria-congenital nephrosis syndrome), in two female siblings. The c.970T>C p.(Cys324Arg) mutation in the LAMB2 gene affects one of the eight highly conserved cysteine residues within the first EGF-like module of the laminin β2 protein. These residues form disulfide bonds in order to achieve a correct 3D structure of the protein. The reported phenotype is considered a relatively mild variant of Pierson syndrome and is associated with later-onset (18 months) therapy-resistant nephrotic syndrome leading to renal failure, and ocular abnormalities consisting of high myopia, microcoria, diverse retinal abnormalities, hence a low level of visual acuity. Importantly, the reported LAMB2 mutation was associated with normal neurological development in both siblings. this report presents the variability of the renal, ocular and neurological phenotypes associated with LAMB2 mutations and underscores the importance of ophthalmologic examination in all children with unexplained renal insufficiency or nephrotic syndrome. What is known • LAMB2 mutations are associated with Pierson syndrome • Pierson syndrome is associated with congenital nephrotic syndrome, microcoria and neurological deficits What is new • A novel mutation in the LAMB2 gene in two female siblings • Genotype and clinical phenotype description of a novel LAMB2 mutation.

Mechanistic study on the nuclear modifier gene MSS1 mutation suppressing neomycin sensitivity of the mitochondrial 15S rRNA C1477G mutation in Saccharomyces cerevisiae.

PubMed

Zhou, Qiyin; Wang, Wei; He, Xiangyu; Zhu, Xiaoyu; Shen, Yaoyao; Yu, Zhe; Wang, Xuexiang; Qi, Xuchen; Zhang, Xuan; Fan, Mingjie; Dai, Yu; Yang, Shuxu; Yan, Qingfeng

2014-01-01

The phenotypic manifestation of mitochondrial DNA (mtDNA) mutations can be modulated by nuclear genes and environmental factors. However, neither the interaction among these factors nor their underlying mechanisms are well understood. The yeast Saccharomyces cerevisiae mtDNA 15S rRNA C1477G mutation (PR) corresponds to the human 12S rRNA A1555G mutation. Here we report that a nuclear modifier gene mss1 mutation suppresses the neomycin-sensitivity phenotype of a yeast C1477G mutant in fermentable YPD medium. Functional assays show that the mitochondrial function of the yeast C1477G mutant was impaired severely in YPD medium with neomycin. Moreover, the mss1 mutation led to a significant increase in the steady-state level of HAP5 (heme activated protein), which greatly up-regulated the expression of glycolytic transcription factors RAP1, GCR1, and GCR2 and thus stimulated glycolysis. Furthermore, the high expression of the key glycolytic enzyme genes HXK2, PFK1 and PYK1 indicated that enhanced glycolysis not only compensated for the ATP reduction from oxidative phosphorylation (OXPHOS) in mitochondria, but also ensured the growth of the mss1(PR) mutant in YPD medium with neomycin. This study advances our understanding of the phenotypic manifestation of mtDNA mutations.

Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids.

PubMed

Matano, Mami; Date, Shoichi; Shimokawa, Mariko; Takano, Ai; Fujii, Masayuki; Ohta, Yuki; Watanabe, Toshiaki; Kanai, Takanori; Sato, Toshiro

2015-03-01

Human colorectal tumors bear recurrent mutations in genes encoding proteins operative in the WNT, MAPK, TGF-β, TP53 and PI3K pathways. Although these pathways influence intestinal stem cell niche signaling, the extent to which mutations in these pathways contribute to human colorectal carcinogenesis remains unclear. Here we use the CRISPR-Cas9 genome-editing system to introduce multiple such mutations into organoids derived from normal human intestinal epithelium. By modulating the culture conditions to mimic that of the intestinal niche, we selected isogenic organoids harboring mutations in the tumor suppressor genes APC, SMAD4 and TP53, and in the oncogenes KRAS and/or PIK3CA. Organoids engineered to express all five mutations grew independently of niche factors in vitro, and they formed tumors after implantation under the kidney subcapsule in mice. Although they formed micrometastases containing dormant tumor-initiating cells after injection into the spleen of mice, they failed to colonize in the liver. In contrast, engineered organoids derived from chromosome-instable human adenomas formed macrometastatic colonies. These results suggest that 'driver' pathway mutations enable stem cell maintenance in the hostile tumor microenvironment, but that additional molecular lesions are required for invasive behavior.

Mutated-leptin gene transfer induces increases in body weight by electroporation and hydrodynamics-based gene delivery in mice.

PubMed

Xiang, Lan; Murai, Atsushi; Muramatsu, Tatsuo

2005-12-01

To investigate whether in vivo gene transfer causes leptin-antagonistic effects on food intake, animal body weight and fat tissue weight, the R128Q mutated-leptin gene, an R to Q substitution at position 128 of mouse leptin, was transferred into mouse liver and leg muscle by electroporation and hydrodynamics-based gene delivery. Mutated-leptin gene transfer by electroporation caused significant increases in body weight at 5 days and after (5.4% increase relative to control; p<0.05). Hydrodynamics-based gene delivery of the mutated-leptin gene also caused an increase in body weight (3.0% increase relative to control; p<0.05). Mutated-leptin gene transfer by electroporation significantly increased the tissue weight of epididymal white fat and neuropeptide Y mRNA expression in the hypothalamus compared with those of the control group 3 weeks after gene transfer (p<0.05). These results suggest that mutated-leptin gene transfer successfully produced leptin-antagonistic effects by modulating the central regulator of energy homeostasis. Also, the extent of leptin-antagonistic effects by electroporation was much higher than hydrodynamics-based gene delivery, with at least single gene transfer.

Expressivity of hearing loss in cases with Usher syndrome type IIA.

PubMed

Sadeghi, André M; Cohn, Edward S; Kimberling, William J; Halvarsson, Glenn; Möller, Claes

2013-12-01

The purpose of this study was to compare the genotype/phenotype relationship between siblings with identical USH2A pathologic mutations and the consequent audiologic phenotypes, in particular degree of hearing loss (HL). Decade audiograms were also compared among two groups of affected subjects with different mutations of USH2A. DNA samples from patients with Usher syndrome type II were analysed. The audiological features of patients and affected siblings with USH2A mutations were also examined to identify genotype-phenotype correlations. Genetic and audiometric examinations were performed in 18 subjects from nine families with Usher syndrome type IIA. Three different USH2A mutations were identified in the affected subjects. Both similarities and differences of the auditory phenotype were seen in families with several affected siblings. A variable degree of hearing loss, ranging from mild to profound, was observed among affected subjects. No significant differences in hearing thresholds were found the group of affected subjects with different pathological mutations. Our results indicate that mutations in the USH2A gene and the resulting phenotype are probably modulated by other variables, such as modifying genes, epigenetics or environmental factors which may be of importance for better understanding the etiology of Usher syndrome.

Favorable outcome of patients with acute myeloid leukemia harboring a low-allelic burden FLT3-ITD mutation and concomitant NPM1 mutation: relevance to post-remission therapy.

PubMed

Pratcorona, Marta; Brunet, Salut; Nomdedéu, Josep; Ribera, Josep Maria; Tormo, Mar; Duarte, Rafael; Escoda, Lourdes; Guàrdia, Ramon; Queipo de Llano, M Paz; Salamero, Olga; Bargay, Joan; Pedro, Carmen; Martí, Josep Maria; Torrebadell, Montserrat; Díaz-Beyá, Marina; Camós, Mireia; Colomer, Dolors; Hoyos, Montserrat; Sierra, Jorge; Esteve, Jordi

2013-04-04

Risk associated to FLT3 internal tandem duplication (FLT3-ITD) in patients with acute myeloid leukemia (AML) may depend on mutational burden and its interaction with other mutations. We analyzed the effect of FLT3-ITD/FLT3 wild-type (FLT3wt) ratio depending on NPM1 mutation (NPM1mut) in 303 patients with intermediate-risk cytogenetics AML treated with intensive chemotherapy. Among NPM1mut patients, FLT3wt and low ratio (<0.5) subgroups showed similar overall survival, relapse risk, and leukemia-free survival, whereas high ratio (≥0.5) patients had a worse outcome. In NPM1wt AML, FLT3-ITD subgroups showed a comparable outcome, with higher risk of relapse and shortened overall survival than FLT3wt patients. Allogeneic stem cell transplantation in CR1 was associated with a reduced relapse risk in all molecular subgroups with the exception of NPM1mut AML with absent or low ratio FLT3-ITD. In conclusion, effect of FLT3 burden is modulated by NPM1 mutation, especially in patients with a low ratio.

Mutation detection in the human HSP70B′ gene by denaturing high-performance liquid chromatography

PubMed Central

Hecker, Karl H.; Asea, Alexzander; Kobayashi, Kaoru; Green, Stacy; Tang, Dan; Calderwood, Stuart K.

2000-01-01

Variances, particularly single nucleotide polymorphisms (SNP), in the genomic sequence of individuals are the primary key to understanding gene function as it relates to differences in the susceptibility to disease, environmental influences, and therapy. In this report, the HSP70B′ gene is the target sequence for mutation detection in biopsy samples from human prostate cancer patients undergoing combined hyperthermia and radiation therapy at the Dana-Farber Cancer Institute, using temperature-modulated heteroduplex analysis (TMHA). The underlying principles of TMHA for mutation detection using DHPLC technology are discussed. The procedures involved in amplicon design for mutation analysis by DHPLC are detailed. The melting behavior of the complete coding sequence of the target gene is characterized using WAVEMAKERTM software. Four overlapping amplicons, which span the complete coding region of the HSP70B′ gene, amenable to mutation detection by DHPLC were identified based on the software-predicted melting profile of the target sequence. TMHA was performed on PCR products of individual amplicons of the HSP70B′ gene on the WAVE® Nucleic Acid Fragment Analysis System. The criteria for mutation calling by comparing wild-type and mutant chromatographic patterns are discussed. PMID:11189446

Mutation detection in the human HSP7OB' gene by denaturing high-performance liquid chromatography.

PubMed

Hecker, K H; Asea, A; Kobayashi, K; Green, S; Tang, D; Calderwood, S K

2000-11-01

Variances, particularly single nucleotide polymorphisms (SNP), in the genomic sequence of individuals are the primary key to understanding gene function as it relates to differences in the susceptibility to disease, environmental influences, and therapy. In this report, the HSP70B' gene is the target sequence for mutation detection in biopsy samples from human prostate cancer patients undergoing combined hyperthermia and radiation therapy at the Dana-Farber Cancer Institute, using temperature-modulated heteroduplex analysis (TMHA). The underlying principles of TMHA for mutation detection using DHPLC technology are discussed. The procedures involved in amplicon design for mutation analysis by DHPLC are detailed. The melting behavior of the complete coding sequence of the target gene is characterized using WAVEMAKER software. Four overlapping amplicons, which span the complete coding region of the HSP70B' gene, amenable to mutation detection by DHPLC were identified based on the software-predicted melting profile of the target sequence. TMHA was performed on PCR products of individual amplicons of the HSP70B' gene on the WAVE Nucleic Acid Fragment Analysis System. The criteria for mutation calling by comparing wild-type and mutant chromatographic patterns are discussed.

Exploring environmental causes of altered ras effects: fragmentation plus integration?

PubMed

Porta, Miquel; Ayude, Daniel; Alguacil, Juan; Jariod, Manuel

2003-02-01

Mutations in ras genes are the most common abnormality of oncogenes in human cancer and a major example of activation by point mutation. Experimental and epidemiological studies support the notion that Ki-ras activation and expression may be chemically related. We discuss the potential role of several environmental compounds in the induction or promotion of ras mutations in humans, with a focus on exocrine pancreatic cancer, the human tumor with the highest prevalence at diagnosis of Ki-ras mutations. Organochlorine compounds, organic solvents, and coffee compounds may play an indirect role in causing Ki-ras mutations, rather than as direct inducers of the mutations. Although for some organochlorine compounds the induction of point mutations in ras oncogenes cannot be excluded, it seems more likely that the effects of these compounds are mediated through nongenomic or indirectly genotoxic mechanisms of action. Organic solvents also may act via enzymatic induction of ras mutagens or by providing a proliferation advantage to ras-mutated cell clones. In exocrine pancreatic cancer, caffeine, other coffee compounds, or other factors with which coffee drinking is associated could modulate Ki-ras activation by interfering with DNA repair, cell-cycle checkpoints, and apoptosis. Asbestos, cigarette smoking, and some dietary factors also may be involved in the initiation or the promotion of Ki-ras mutations in lung and colon cancers. Further development of the mechanistic scenarios proposed here could contribute to a meaningful integration of biological, clinical, and environmental knowledge on the causes of altered ras effects. Copyright 2003 Wiley-Liss, Inc.

Circulating progranulin as a biomarker for neurodegenerative diseases.

PubMed

Ghidoni, Roberta; Paterlini, Anna; Benussi, Luisa

2012-01-01

Progranulin is a growth factor involved in the regulation of multiple processes including tumorigenesis, wound repair, development, and inflammation. The recent discovery that mutations in the gene encoding for progranulin (GRN) cause frontotemporal lobar degeneration (FTLD), and other neurodegenerative diseases leading to dementia, has brought renewed interest in progranulin and its functions in the central nervous system. GRN null mutations cause protein haploinsufficiency, leading to a significant decrease in progranulin levels that can be detected in plasma, serum and cerebrospinal fluid (CSF) of mutation carriers. The dosage of circulating progranulin sped up the identification of GRN mutations thus favoring genotype-phenotype correlation studies. Researchers demonstrated that, in GRN null mutation carriers, the shortage of progranulin invariably precedes clinical symptoms and thus mutation carriers are "captured" regardless of their disease status. GRN is a particularly appealing gene for drug targeting, in the way that boosting its expression may be beneficial for mutation carriers, preventing or delaying the onset of GRN-related neurodegenerative diseases. Physiological regulation of progranulin expression level is only partially known. Progranulin expression reflects mutation status and, intriguingly, its levels can be modulated by some additional factor (i.e. genetic background; drugs). Thus, factors increasing the production and secretion of progranulin from the normal gene are promising potential therapeutic avenues. In conclusion, peripheral progranulin is a nonintrusive highly accurate biomarker for early identification of mutation carriers and for monitoring future treatments that might boost the level of this protein.

Circulating progranulin as a biomarker for neurodegenerative diseases

PubMed Central

Ghidoni, Roberta; Paterlini, Anna; Benussi, Luisa

2012-01-01

Progranulin is a growth factor involved in the regulation of multiple processes including tumorigenesis, wound repair, development, and inflammation. The recent discovery that mutations in the gene encoding for progranulin (GRN) cause frontotemporal lobar degeneration (FTLD), and other neurodegenerative diseases leading to dementia, has brought renewed interest in progranulin and its functions in the central nervous system. GRN null mutations cause protein haploinsufficiency, leading to a significant decrease in progranulin levels that can be detected in plasma, serum and cerebrospinal fluid (CSF) of mutation carriers. The dosage of circulating progranulin sped up the identification of GRN mutations thus favoring genotype-phenotype correlation studies. Researchers demonstrated that, in GRN null mutation carriers, the shortage of progranulin invariably precedes clinical symptoms and thus mutation carriers are “captured” regardless of their disease status. GRN is a particularly appealing gene for drug targeting, in the way that boosting its expression may be beneficial for mutation carriers, preventing or delaying the onset of GRN-related neurodegenerative diseases. Physiological regulation of progranulin expression level is only partially known. Progranulin expression reflects mutation status and, intriguingly, its levels can be modulated by some additional factor (i.e. genetic background; drugs). Thus, factors increasing the production and secretion of progranulin from the normal gene are promising potential therapeutic avenues. In conclusion, peripheral progranulin is a nonintrusive highly accurate biomarker for early identification of mutation carriers and for monitoring future treatments that might boost the level of this protein. PMID:23383391

The effect of single-task and dual-task balance exercise programs on balance performance in adults with osteoporosis: a randomized controlled preliminary trial.

PubMed

Konak, H E; Kibar, S; Ergin, E S

2016-11-01

Osteoporosis is a serious disease characterized by muscle weakness in the lower extremities, shortened length of trunk, and increased dorsal kyphosis leading to poor balance performance. Although balance impairment increases in adults with osteoporosis, falls and fall-related injuries have been shown to occur mainly during the dual-task performance. Several studies have shown that dual-task performance was improved with specific repetitive dual-task exercises. The aims of this study were to compare the effect of single- and dual-task balance exercise programs on static balance, dynamic balance, and activity-specific balance confidence in adults with osteoporosis and to assess the effectiveness of dual-task balance training on gait speed under dual-task conditions. Older adults (N = 42) (age range, 45-88 years) with osteoporosis were randomly assigned into two groups. Single-task balance training group was given single-task balance exercises for 4 weeks, whereas dual-task balance training group received dual-task balance exercises. Participants received 45-min individualized training session, three times a week. Static balance was evaluated by one-leg stance (OLS) and a kinesthetic ability trainer (KAT) device. Dynamic balance was measured by the Berg Balance Scale (BBS), Time Up and Go (TUG) test, and gait speed. Self-confidence was assessed with the Activities-specific Balance Confidence (ABC-6) scale. Assessments were performed at baseline and after the 4-week program. At the end of the treatment periods, KAT score, BBS score, time in OLS and TUG, gait speeds under single- and dual-task conditions, and ABC-6 scale scores improved significantly in all patients (p < 0.05). However, BBS and gait speeds under single- and dual-task conditions showed significantly greater improvement in the dual-task balance training group than in the single-task balance training group (p < 0.05). ABC-6 scale scores improved more in the single-task balance training group than in the dual-task balance training group (p < 0.05). A 4-week single- and dual-task balance exercise programs are effective in improving static balance, dynamic balance, and balance confidence during daily activities in older adults with osteoporosis. However, single- and dual-task gait speeds showed greater improvement following the application of a specific type of dual-task exercise programs. 24102014-2.

Opportunities for exercise during pullet rearing, Part II: Long-term effects on bone characteristics of adult laying hens at the end-of-lay.

PubMed

Casey-Trott, T M; Korver, D R; Guerin, M T; Sandilands, V; Torrey, S; Widowski, T M

2017-08-01

Osteoporosis in laying hens has been a production and welfare concern for several decades. The objective of this study was to determine whether differing opportunities for exercise during pullet rearing influences long-term bone quality characteristics in end-of-lay hens. A secondary objective was to assess whether differing opportunities for exercise in adult housing systems alters bone quality characteristics in end-of-lay hens. Four flock replicates of 588 Lohmann Selected Leghorn-Lite pullets were reared in either conventional cages (Conv) or an aviary rearing system (Avi) and placed into conventional cages (CC), 30-bird furnished cages (FC-S), or 60-bird furnished cages (FC-L) for adult housing. Wing and leg bones were collected at the end-of-lay to quantify bone composition and strength using quantitative computed tomography and bone breaking strength (BBS). At the end-of-lay, Avi hens had greater total and cortical cross-sectional area (P < 0.05) for the radius and tibia, greater total bone mineral content of the radius (P < 0.001), and greater tibial cortical bone mineral content (P = 0.029) than the Conv hens; however, total bone mineral density of the radius (P < 0.001) and cortical bone mineral density of the radius and tibia (P < 0.001) were greater in the Conv hens. Hens in the FC-L had greater total bone mineral density for the radius and tibia (P < 0.05) and greater trabecular bone mineral density for the radius (P = 0.027), compared to hens in the FC-S and CC. Total bone mineral content of the tibia (P = 0.030) and cortical bone mineral content of the radius (P = 0.030) and tibia (P = 0.013) were greater in the FC-L compared to the CC. The humerus of Conv hens had greater BBS than the Avi hens (P < 0.001), and the tibiae of FC-L and FC-S hens had greater BBS than CC hens (P = 0.006). Increased opportunities for exercise offered by the aviary rearing system provided improved bone quality characteristics lasting through to the end-of-lay. © The Author 2017. Published by Oxford University Press on behalf of Poultry Science Association.

The anticonvulsant stiripentol acts directly on the GABAA receptor as a positive allosteric modulator

PubMed Central

Fisher, Janet L.

2009-01-01

SUMMARY Stiripentol(STP) has been used as co-therapy for treatment of epilepsy for many years. Its mechanism of action has long been considered to be indirect, as it inhibits the enzymes responsible for metabolism of other anticonvulsant agents. However, a recent report suggested that STP might also act at the neuronal level, increasing inhibitory GABAergic neurotransmission. We examined the effect of STP on the functional properties of recombinant GABAA receptors (GABARs) and found that it was a positive allosteric modulator of these ion channels. Its activity showed some dependence on subunit composition, with greater potentiation of α3-containing receptors and reduced potentiation when the β1 or ε subunits were present. STP caused a leftward shift in the GABA concentration-response relationship, but did not increase the peak response of the receptors to a maximal GABA concentration. Although STP shares some functional characteristics with the neurosteroids, its activity was not inhibited by a neurosteroid site antagonist and was unaffected by a mutation in the α3 subunit that reduced positive modulation by neurosteroids. The differential effect of STP on β1- and β2/β3-containing receptors was not altered by mutations within the second transmembrane domain that affect modulation by loreclezole. These findings suggest that STP acts as a direct allosteric modulator of the GABAR at a site distinct from many commonly used anti-convulsant, sedative and anxiolytic drugs. Its higher activity at α3-containing receptors as well as its activity at δ-containing receptors may provide a unique opportunity to target selected populations of GABARs. PMID:18585399

Roles of conserved arginines in ATP-binding domains of AAA+ chaperone ClpB from Thermus thermophilus.

PubMed

Yamasaki, Takashi; Nakazaki, Yosuke; Yoshida, Masasuke; Watanabe, Yo-hei

2011-07-01

ClpB, a member of the expanded superfamily of ATPases associated with diverse cellular activities (AAA+), forms a ring-shaped hexamer and cooperates with the DnaK chaperone system to reactivate aggregated proteins in an ATP-dependent manner. The ClpB protomer consists of an N-terminal domain, an AAA+ module (AAA-1), a middle domain, and a second AAA+ module (AAA-2). Each AAA+ module contains highly conserved WalkerA and WalkerB motifs, and two arginines (AAA-1) or one arginine (AAA-2). Here, we investigated the roles of these arginines (Arg322, Arg323, and Arg747) of ClpB from Thermus thermophilus in the ATPase cycle and chaperone function by alanine substitution. These mutations did not affect nucleotide binding, but did inhibit the hydrolysis of the bound ATP and slow the threading of the denatured protein through the central pore of the T. thermophilus ClpB ring, which severely impaired the chaperone functions. Previously, it was demonstrated that ATP binding to the AAA-1 module induced motion of the middle domain and stabilized the ClpB hexamer. However, the arginine mutations of the AAA-1 module destabilized the ClpB hexamer, even though ATP-induced motion of the middle domain was not affected. These results indicated that the three arginines are crucial for ATP hydrolysis and chaperone activity, but not for ATP binding. In addition, the two arginines in AAA-1 and the ATP-induced motion of the middle domain independently contribute to the stabilization of the hexamer. © 2011 The Authors Journal compilation © 2011 FEBS.

The N-terminal strand modulates immunoglobulin light chain fibrillogenesis.

PubMed

del Pozo-Yauner, Luis; Wall, Jonathan S; González Andrade, Martín; Sánchez-López, Rosana; Rodríguez-Ambriz, Sandra L; Pérez Carreón, Julio I; Ochoa-Leyva, Adrián; Fernández-Velasco, D Alejandro

2014-01-10

It has been suggested that the N-terminal strand of the light chain variable domain (V(L)) protects the molecule from aggregation by hindering spurious intermolecular contacts. We evaluated the impact of mutations in the N-terminal strand on the thermodynamic stability and kinetic of fibrillogenesis of the V(L) protein 6aJL2. Mutations in this strand destabilized the protein in a position-dependent manner, accelerating the fibrillogenesis by shortening the lag time; an effect that correlated with the extent of destabilization. In contrast, the effect on the kinetics of fibril elongation, as assessed in seeding experiments was of different nature, as it was not directly dependant on the degree of destabilization. This finding suggests different factors drive the nucleation-dependent and elongation phases of light chain fibrillogenesis. Finally, taking advantage of the dependence of the Trp fluorescence upon environment, four single Trp substitutions were made in the N-terminal strand, and changes in solvent exposure during aggregation were evaluated by acrylamide-quenching. The results suggest that the N-terminal strand is buried in the fibrillar state of 6aJL2 protein. This finding suggest a possible explanation for the modulating effect exerted by the mutations in this strand on the aggregation behavior of 6aJL2 protein. Copyright © 2013 Elsevier Inc. All rights reserved.

Conserved residues in Lassa fever virus Z protein modulate viral infectivity at the level of the ribonucleoprotein.

PubMed

Capul, Althea A; de la Torre, Juan Carlos; Buchmeier, Michael J

2011-04-01

Arenaviruses are negative-strand RNA viruses that cause human diseases such as lymphocytic choriomeningitis, Bolivian hemorrhagic fever, and Lassa hemorrhagic fever. No licensed vaccines exist, and current treatment is limited to ribavirin. The prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV), is a model for dissecting virus-host interactions in persistent and acute disease. The RING finger protein Z has been identified as the driving force of arenaviral budding and acts as the viral matrix protein. While residues in Z required for viral budding have been described, residues that govern the Z matrix function(s) have yet to be fully elucidated. Because this matrix function is integral to viral assembly, we reasoned that this would be reflected in sequence conservation. Using sequence alignment, we identified several conserved residues in Z outside the RING and late domains. Nine residues were each mutated to alanine in Lassa fever virus Z. All of the mutations affected the expression of an LCMV minigenome and the infectivity of virus-like particles, but to greatly varying degrees. Interestingly, no mutations appeared to affect Z-mediated budding or association with viral GP. Our findings provide direct experimental evidence supporting a role for Z in the modulation of the activity of the viral ribonucleoprotein (RNP) complex and its packaging into mature infectious viral particles.

NFκB is a central regulator of protein quality control in response to protein aggregation stresses via autophagy modulation

PubMed Central

Nivon, Mathieu; Fort, Loïc; Muller, Pascale; Richet, Emma; Simon, Stéphanie; Guey, Baptiste; Fournier, Maëlenn; Arrigo, André-Patrick; Hetz, Claudio; Atkin, Julie D.; Kretz-Remy, Carole

2016-01-01

During cell life, proteins often misfold, depending on particular mutations or environmental changes, which may lead to protein aggregates that are toxic for the cell. Such protein aggregates are the root cause of numerous diseases called “protein conformational diseases,” such as myofibrillar myopathy and familial amyotrophic lateral sclerosis. To fight against aggregates, cells are equipped with protein quality control mechanisms. Here we report that NFκB transcription factor is activated by misincorporation of amino acid analogues into proteins, inhibition of proteasomal activity, expression of the R120G mutated form of HspB5 (associated with myofibrillar myopathy), or expression of the G985R and G93A mutated forms of superoxide dismutase 1 (linked to familial amyotrophic lateral sclerosis). This noncanonical stimulation of NFκB triggers the up-regulation of BAG3 and HspB8 expression, two activators of selective autophagy, which relocalize to protein aggregates. Then NFκB-dependent autophagy allows the clearance of protein aggregates. Thus NFκB appears as a central and major regulator of protein aggregate clearance by modulating autophagic activity. In this context, the pharmacological stimulation of this quality control pathway might represent a valuable strategy for therapies against protein conformational diseases. PMID:27075172