Independent and additive effects of glutamic acid and methionine on yeast longevity.

PubMed

Wu, Ziyun; Song, Lixia; Liu, Shao Quan; Huang, Dejian

2013-01-01

It is established that glucose restriction extends yeast chronological and replicative lifespan, but little is known about the influence of amino acids on yeast lifespan, although some amino acids were reported to delay aging in rodents. Here we show that amino acid composition greatly alters yeast chronological lifespan. We found that non-essential amino acids (to yeast) methionine and glutamic acid had the most significant impact on yeast chronological lifespan extension, restriction of methionine and/or increase of glutamic acid led to longevity that was not the result of low acetic acid production and acidification in aging media. Remarkably, low methionine, high glutamic acid and glucose restriction additively and independently extended yeast lifespan, which could not be further extended by buffering the medium (pH 6.0). Our preliminary findings using yeasts with gene deletion demonstrate that glutamic acid addition, methionine and glucose restriction prompt yeast longevity through distinct mechanisms. This study may help to fill a gap in yeast model for the fast developing view that nutrient balance is a critical factor to extend lifespan.

Independent and Additive Effects of Glutamic Acid and Methionine on Yeast Longevity

PubMed Central

Wu, Ziyun; Song, Lixia; Liu, Shao Quan; Huang, Dejian

2013-01-01

It is established that glucose restriction extends yeast chronological and replicative lifespan, but little is known about the influence of amino acids on yeast lifespan, although some amino acids were reported to delay aging in rodents. Here we show that amino acid composition greatly alters yeast chronological lifespan. We found that non-essential amino acids (to yeast) methionine and glutamic acid had the most significant impact on yeast chronological lifespan extension, restriction of methionine and/or increase of glutamic acid led to longevity that was not the result of low acetic acid production and acidification in aging media. Remarkably, low methionine, high glutamic acid and glucose restriction additively and independently extended yeast lifespan, which could not be further extended by buffering the medium (pH 6.0). Our preliminary findings using yeasts with gene deletion demonstrate that glutamic acid addition, methionine and glucose restriction prompt yeast longevity through distinct mechanisms. This study may help to fill a gap in yeast model for the fast developing view that nutrient balance is a critical factor to extend lifespan. PMID:24244480

Cue-independent forgetting by intentional suppression - Evidence for inhibition as the mechanism of intentional forgetting.

PubMed

Wang, Yingying; Cao, Zhijun; Zhu, Zijian; Cai, Huaqian; Wu, Yanhong

2015-10-01

People are able to intentionally forget unwanted memories through voluntary suppression, as revealed by the Think/No-think (TNT) paradigm. However, the nature of intentional forgetting is controversial. Findings that forgetting is independent of retrieval cues suggest that inhibitory control underlies intentional forgetting, but this result is also in line with an interference account. To resolve this controversy, we have directly contrasted the cue-independent characteristic of suppression versus interference. A double-cue paradigm was used, in which two different cues were associated with the same target during initial memory formation. Only one cue-target association received further interference/suppression training. In the test phase, when both cues were used to retrieve the target, we found that interference caused memory impairment that was restricted to the trained cue-target association, while suppression induced forgetting that generalized to the independent cue-target association. Therefore, the effect of suppression differs from that of interference. The cue-independent forgetting by voluntary suppression indicates that the target memory itself is inhibited, providing evidence that the underlying mechanism of suppression-induced forgetting is inhibitory control. Copyright © 2015 Elsevier B.V. All rights reserved.

Gap junction- and hemichannel-independent actions of connexins.

PubMed

Jiang, Jean X; Gu, Sumin

2005-06-10

Connexins have been known to be the protein building blocks of gap junctions and mediate cell-cell communication. In contrast to the conventional dogma, recent evidence suggests that in addition to forming gap junction channels, connexins possess gap junction-independent functions. One important gap junction-independent function for connexins is to serve as the major functional component for hemichannels, the un-apposed halves of gap junctions. Hemichannels, as independent functional units, play roles that are different from that of gap junctions in the cell. The other functions of connexins appear to be gap junction- and hemichannel-independent. Published studies implicate the latter functions of connexins in cell growth, differentiation, tumorigenicity, injury, and apoptosis, although the mechanistic aspects of these actions remain largely unknown. In this review, gap junction- and hemichannel-independent functions of connexins are summarized, and the molecular mechanisms underlying these connexin functions are speculated and discussed.

Brief Report: An Independent Replication and Extension of Psychometric Evidence Supporting the Theory of Mind Inventory

ERIC Educational Resources Information Center

Greenslade, Kathryn J.; Coggins, Truman E.

2016-01-01

This study presents an independent replication and extension of psychometric evidence supporting the "Theory of Mind Inventory" ("ToMI"). Parents of 20 children with ASD (4; 1-6; 7 years; months) and 20 with typical development (3; 1-6; 5), rated their child's theory of mind abilities in everyday situations. Other parent report…

Evidence that Additions of Grignard Reagents to Aliphatic Aldehydes Do Not Involve Single-Electron-Transfer Processes.

PubMed

Otte, Douglas A L; Woerpel, K A

2015-08-07

Addition of allylmagnesium reagents to an aliphatic aldehyde bearing a radical clock gave only addition products and no evidence of ring-opened products that would suggest single-electron-transfer reactions. The analogous Barbier reaction also did not provide evidence for a single-electron-transfer mechanism in the addition step. Other Grignard reagents (methyl-, vinyl-, t-Bu-, and triphenylmethylmagnesium halides) also do not appear to add to an alkyl aldehyde by a single-electron-transfer mechanism.

Additional Interventions to Enhance the Effectiveness of Individual Placement and Support: A Rapid Evidence Assessment

PubMed Central

Boycott, Naomi; Schneider, Justine; McMurran, Mary

2012-01-01

Topic. Additional interventions used to enhance the effectiveness of individual placement and support (IPS). Aim. To establish whether additional interventions improve the vocational outcomes of IPS alone for people with severe mental illness. Method. A rapid evidence assessment of the literature was conducted for studies where behavioural or psychological interventions have been used to supplement standard IPS. Published and unpublished empirical studies of IPS with additional interventions were considered for inclusion. Conclusions. Six published studies were found which compared IPS alone to IPS plus a supplementary intervention. Of these, three used skills training and three used cognitive remediation. The contribution of each discrete intervention is difficult to establish. Some evidence suggests that work-related social skills and cognitive training are effective adjuncts, but this is an area where large RCTs are required to yield conclusive evidence. PMID:22685665

Ongoing Voluntary Settlement and Independent Agency: Evidence from China

PubMed Central

Feng, Jing; Ren, Xiaopeng; Ma, Xinran

2017-01-01

Voluntary frontier settlement leads to independent agency. Since this type of research has not yet been implemented in ongoing voluntary settlement frontiers, we conducted several cultural tasks to investigate Shenzhen, known as China’s ongoing “South Frontier,” which is composed mostly of people that have emigrated from other Chinese provinces within the past 30 years. We hypothesized that residents of Shenzhen are more independent than those in other regions of Mainland China. As predicted, residents of Shenzhen scored higher than China inland residents in self-reported independent beliefs and scored lower in nepotism. The results indicate that, even in a short-term ongoing frontier, voluntary settlement is associated with independent agency. PMID:28798712

On the status of cue independence as a criterion for memory inhibition: evidence against the covert blocking hypothesis.

PubMed

Weller, Peter D; Anderson, Michael C; Gómez-Ariza, Carlos J; Bajo, M Teresa

2013-07-01

Retrieving memories can impair recall of other related traces. Items affected by this retrieval-induced forgetting (RIF) are often less accessible when tested with independent probes, a characteristic known as cue independence. Cue independence has been interpreted as evidence for inhibitory mechanisms that suppress competing items during retrieval (M. C. Anderson & Spellman, 1995). Several authors, however, have proposed that apparent cue independence might instead reflect noninhibitory cue-dependent blocking mechanisms. In this view, when participants receive an independent probe test, they do not limit themselves to those probes but instead recall study cues covertly to aid performance. This strategy is thought to be self-defeating, because it reintroduces cues that instigate blocking, lending the appearance of generalized inhibition. M. C. Anderson (2003), in contrast, proposed that covert cuing masks cue-independent forgetting by providing a compound cuing advantage. Here, we replicated cue-independent RIF and documented how access to the original study cues influences this effect. In Experiments 1-2, we found that overtly providing category cues on independent probe tests never increased RIF. Indeed, when we provided categories selectively for items that should suffer the most blocking, a sizable reversal of RIF occurred, consistent with the masking hypothesis. Simply asking participants to covertly retrieve categories eliminated cue-independent RIF, contradicting predictions of the self-inflicted blocking account. Far from causing cue-independent forgetting, covert cuing masks it. These findings strongly support the inhibition account of RIF and, importantly, may explain why cue-independent forgetting is not always found. PsycINFO Database Record (c) 2013 APA, all rights reserved.

In vivo evidence that N-oleoylglycine acts independently of its conversion to oleamide.

PubMed

Chaturvedi, Shalini; Driscoll, William J; Elliot, Brenda M; Faraday, Martha M; Grunberg, Neil E; Mueller, Gregory P

2006-12-01

Oleamide (cis-9-octadecenamide) is a member of an emerging class of lipid-signaling molecules, the primary fatty acid amides. A growing body of evidence indicates that oleamide mediates fundamental neurochemical processes including sleep, thermoregulation, and nociception. Nevertheless, the mechanism for oleamide biosynthesis remains unknown. The leading hypothesis holds that oleamide is synthesized from oleoylglycine via the actions of the peptide amidating enzyme, peptidylglycine alpha-amidating monooxygenase (PAM). The present study investigated this hypothesis using pharmacologic treatments, physiologic assessments, and measurements of serum oleamide levels using a newly developed enzyme-linked immunosorbant assay (ELISA). Oleamide and oleoylglycine both induced profound hypothermia and decreased locomotion, over equivalent dose ranges and time courses, whereas, closely related compounds, stearamide and oleic acid, were essentially without effect. While the biologic actions of oleamide and oleoylglycine were equivalent, the two compounds differed dramatically with respect to their effects on serum levels of oleamide. Oleamide administration (80mg/kg) elevated blood-borne oleamide by eight-fold, whereas, the same dose of oleoylglycine had no effect on circulating oleamide levels. In addition, pretreatment with the established PAM inhibitor, disulfiram, produced modest reductions in the hypothermic responses to both oleoylglycine and oleamide, suggesting that the effects of disulfiram were not mediated through inhibition of PAM and a resulting decrease in the formation of oleamide from oleoylglycine. Collectively, these findings raise the possibilities that: (1) oleoylglycine possesses biologic activity that is independent of its conversion to oleamide and (2) the increased availability of oleoylglycine as a potential substrate does not drive the biosynthesis of oleamide.

In Vivo Evidence that N-Oleoylglycine Acts Independently of Its Conversion to Oleamide

PubMed Central

Chaturvedi, Shalini; Driscoll, William J.; Elliot, Brenda M.; Faraday, Martha M.; Grunberg, Neil E.; Mueller, Gregory P.

2006-01-01

Oleamide (cis-9-octadecenamide) is a member of an emerging class of lipid-signaling molecules, the primary fatty acid amides. A growing body of evidence indicates that oleamide mediates fundamental neurochemical processes including sleep, thermoregulation, and nociception. Nevertheless, the mechanism for oleamide biosynthesis remains unknown. The leading hypothesis holds that oleamide is synthesized from oleoylglycine via the actions of the peptide amidating enzyme, peptidylglycine alpha amidating monooxygenase (PAM). The present study investigated this hypothesis using pharmacologic treatments, physiologic assessments, and measurements of serum oleamide levels using a newly development enzyme-linked immunosorbant assay (ELISA). Oleamide and oleoylglycine both induced profound hypothermia and decreased locomotion, over equivalent dose ranges and time courses, whereas, closely related compounds, stearamide and oleic acid, were essentially without effect. While the biologic actions of oleamide and oleoylglycine were equivalent, the two compounds differed dramatically with respect to their effects on serum levels of oleamide. Oleamide administration (80 mg/kg) elevated blood-borne oleamide by eight-fold, whereas, the same dose of oleoylglycine had no effect on circulating oleamide levels. In addition, pretreatment with the established PAM inhibitor, disulfiram, produced modest reductions in the hypothermic responses to both oleoylglycine and oleamide, suggesting that the effects of disulfiram were not mediated through inhibition of PAM and a resulting decrease in the formation of oleamide from oleoylglycine. Collectively, these findings raise the possibilities that: (1) oleoylglycine possesses biologic activity that is independent of its conversion to oleamide, and (2) the increased availability of oleoylglycine as a potential substrate does not drive the biosynthesis of oleamide. PMID:17085322

Concentration Addition, Independent Action and Generalized Concentration Addition Models for Mixture Effect Prediction of Sex Hormone Synthesis In Vitro

PubMed Central

Hadrup, Niels; Taxvig, Camilla; Pedersen, Mikael; Nellemann, Christine; Hass, Ulla; Vinggaard, Anne Marie

2013-01-01

Humans are concomitantly exposed to numerous chemicals. An infinite number of combinations and doses thereof can be imagined. For toxicological risk assessment the mathematical prediction of mixture effects, using knowledge on single chemicals, is therefore desirable. We investigated pros and cons of the concentration addition (CA), independent action (IA) and generalized concentration addition (GCA) models. First we measured effects of single chemicals and mixtures thereof on steroid synthesis in H295R cells. Then single chemical data were applied to the models; predictions of mixture effects were calculated and compared to the experimental mixture data. Mixture 1 contained environmental chemicals adjusted in ratio according to human exposure levels. Mixture 2 was a potency adjusted mixture containing five pesticides. Prediction of testosterone effects coincided with the experimental Mixture 1 data. In contrast, antagonism was observed for effects of Mixture 2 on this hormone. The mixtures contained chemicals exerting only limited maximal effects. This hampered prediction by the CA and IA models, whereas the GCA model could be used to predict a full dose response curve. Regarding effects on progesterone and estradiol, some chemicals were having stimulatory effects whereas others had inhibitory effects. The three models were not applicable in this situation and no predictions could be performed. Finally, the expected contributions of single chemicals to the mixture effects were calculated. Prochloraz was the predominant but not sole driver of the mixtures, suggesting that one chemical alone was not responsible for the mixture effects. In conclusion, the GCA model seemed to be superior to the CA and IA models for the prediction of testosterone effects. A situation with chemicals exerting opposing effects, for which the models could not be applied, was identified. In addition, the data indicate that in non-potency adjusted mixtures the effects cannot always be

Independent effects of warming and nitrogen addition on plant phenology in the Inner Mongolian steppe

PubMed Central

Xia, Jianyang; Wan, Shiqiang

2013-01-01

Background and Aims Phenology is one of most sensitive traits of plants in response to regional climate warming. Better understanding of the interactive effects between warming and other environmental change factors, such as increasing atmosphere nitrogen (N) deposition, is critical for projection of future plant phenology. Methods A 4-year field experiment manipulating temperature and N has been conducted in a temperate steppe in northern China. Phenology, including flowering and fruiting date as well as reproductive duration, of eight plant species was monitored and calculated from 2006 to 2009. Key Results Across all the species and years, warming significantly advanced flowering and fruiting time by 0·64 and 0·72 d per season, respectively, which were mainly driven by the earliest species (Potentilla acaulis). Although N addition showed no impact on phenological times across the eight species, it significantly delayed flowering time of Heteropappus altaicus and fruiting time of Agropyron cristatum. The responses of flowering and fruiting times to warming or N addition are coupled, leading to no response of reproductive duration to warming or N addition for most species. Warming shortened reproductive duration of Potentilla bifurca but extended that of Allium bidentatum, whereas N addition shortened that of A. bidentatum. No interactive effect between warming and N addition was found on any phenological event. Such additive effects could be ascribed to the species-specific responses of plant phenology to warming and N addition. Conclusions The results suggest that the warming response of plant phenology is larger in earlier than later flowering species in temperate grassland systems. The effects of warming and N addition on plant phenology are independent of each other. These findings can help to better understand and predict the response of plant phenology to climate warming concurrent with other global change driving factors. PMID:23585496

Independent effects of warming and nitrogen addition on plant phenology in the Inner Mongolian steppe.

PubMed

Xia, Jianyang; Wan, Shiqiang

2013-06-01

Phenology is one of most sensitive traits of plants in response to regional climate warming. Better understanding of the interactive effects between warming and other environmental change factors, such as increasing atmosphere nitrogen (N) deposition, is critical for projection of future plant phenology. A 4-year field experiment manipulating temperature and N has been conducted in a temperate steppe in northern China. Phenology, including flowering and fruiting date as well as reproductive duration, of eight plant species was monitored and calculated from 2006 to 2009. Across all the species and years, warming significantly advanced flowering and fruiting time by 0·64 and 0·72 d per season, respectively, which were mainly driven by the earliest species (Potentilla acaulis). Although N addition showed no impact on phenological times across the eight species, it significantly delayed flowering time of Heteropappus altaicus and fruiting time of Agropyron cristatum. The responses of flowering and fruiting times to warming or N addition are coupled, leading to no response of reproductive duration to warming or N addition for most species. Warming shortened reproductive duration of Potentilla bifurca but extended that of Allium bidentatum, whereas N addition shortened that of A. bidentatum. No interactive effect between warming and N addition was found on any phenological event. Such additive effects could be ascribed to the species-specific responses of plant phenology to warming and N addition. The results suggest that the warming response of plant phenology is larger in earlier than later flowering species in temperate grassland systems. The effects of warming and N addition on plant phenology are independent of each other. These findings can help to better understand and predict the response of plant phenology to climate warming concurrent with other global change driving factors.

Additional Saturday rehabilitation improves functional independence and quality of life and reduces length of stay: a randomized controlled trial

PubMed Central

2013-01-01

Background Many inpatients receive little or no rehabilitation on weekends. Our aim was to determine what effect providing additional Saturday rehabilitation during inpatient rehabilitation had on functional independence, quality of life and length of stay compared to 5 days per week of rehabilitation. Methods This was a multicenter, single-blind (assessors) randomized controlled trial with concealed allocation and 12-month follow-up conducted in two publically funded metropolitan inpatient rehabilitation facilities in Melbourne, Australia. Patients were eligible if they were adults (aged ≥18 years) admitted for rehabilitation for any orthopedic, neurological or other disabling conditions excluding those admitted for slow stream rehabilitation/geriatric evaluation and management. Participants were randomly allocated to usual care Monday to Friday rehabilitation (control) or to Monday to Saturday rehabilitation (intervention). The additional Saturday rehabilitation comprised physiotherapy and occupational therapy. The primary outcomes were functional independence (functional independence measure (FIM); measured on an 18 to 126 point scale), health-related quality of life (EQ-5D utility index; measured on a 0 to 1 scale, and EQ-5D visual analog scale; measured on a 0 to 100 scale), and patient length of stay. Outcome measures were assessed on admission, discharge (primary endpoint), and at 6 and 12 months post discharge. Results We randomly assigned 996 adults (mean (SD) age 74 (13) years) to Monday to Saturday rehabilitation (n = 496) or usual care Monday to Friday rehabilitation (n = 500). Relative to admission scores, intervention group participants had higher functional independence (mean difference (MD) 2.3, 95% confidence interval (CI) 0.5 to 4.1, P = 0.01) and health-related quality of life (MD 0.04, 95% CI 0.01 to 0.07, P = 0.009) on discharge and may have had a shorter length of stay by 2 days (95% CI 0 to 4, P = 0.1) when compared to

Continuous track paths reveal additive evidence integration in multistep decision making.

PubMed

Buc Calderon, Cristian; Dewulf, Myrtille; Gevers, Wim; Verguts, Tom

2017-10-03

Multistep decision making pervades daily life, but its underlying mechanisms remain obscure. We distinguish four prominent models of multistep decision making, namely serial stage, hierarchical evidence integration, hierarchical leaky competing accumulation (HLCA), and probabilistic evidence integration (PEI). To empirically disentangle these models, we design a two-step reward-based decision paradigm and implement it in a reaching task experiment. In a first step, participants choose between two potential upcoming choices, each associated with two rewards. In a second step, participants choose between the two rewards selected in the first step. Strikingly, as predicted by the HLCA and PEI models, the first-step decision dynamics were initially biased toward the choice representing the highest sum/mean before being redirected toward the choice representing the maximal reward (i.e., initial dip). Only HLCA and PEI predicted this initial dip, suggesting that first-step decision dynamics depend on additive integration of competing second-step choices. Our data suggest that potential future outcomes are progressively unraveled during multistep decision making.

Male sexual orientation in independent samoa: evidence for fraternal birth order and maternal fecundity effects.

PubMed

VanderLaan, Doug P; Vasey, Paul L

2011-06-01

In Western cultures, male androphiles tend to have greater numbers of older brothers than male gynephiles (i.e., the fraternal birth order effect). In the non-Western nation of Independent Samoa, androphilic males (known locally as fa'afafine) have been shown to have greater numbers of older brothers, older sisters, and younger brothers (Vasey & VanderLaan, 2007). It is unclear, however, whether the observed older brother effect, in the context of the additional sibling category effects, represented a genuine fraternal birth order effect or was simply associated with elevated maternal fecundity. To differentiate between these two possibilities, this study employed a larger, independent replication sample of fa'afafine and gynephilic males from Independent Samoa. Fa'afafine had greater numbers of older brothers and sisters. The replication sample and the sample from Vasey and VanderLaan were then combined, facilitating a comparison that showed the older brother effect was significantly greater in magnitude than the older sister effect. These results suggest that fraternal birth order and maternal fecundity effects both exist in Samoa. The existence of these effects cross-culturally is discussed in the context of biological theories for the development of male androphilia.

Semantic Modelling of Digital Forensic Evidence

NASA Astrophysics Data System (ADS)

Kahvedžić, Damir; Kechadi, Tahar

The reporting of digital investigation results are traditionally carried out in prose and in a large investigation may require successive communication of findings between different parties. Popular forensic suites aid in the reporting process by storing provenance and positional data but do not automatically encode why the evidence is considered important. In this paper we introduce an evidence management methodology to encode the semantic information of evidence. A structured vocabulary of terms, ontology, is used to model the results in a logical and predefined manner. The descriptions are application independent and automatically organised. The encoded descriptions aim to help the investigation in the task of report writing and evidence communication and can be used in addition to existing evidence management techniques.

Germline mutations in candidate predisposition genes in individuals with cutaneous melanoma and at least two independent additional primary cancers.

PubMed

Pritchard, Antonia L; Johansson, Peter A; Nathan, Vaishnavi; Howlie, Madeleine; Symmons, Judith; Palmer, Jane M; Hayward, Nicholas K

2018-01-01

While a number of autosomal dominant and autosomal recessive cancer syndromes have an associated spectrum of cancers, the prevalence and variety of cancer predisposition mutations in patients with multiple primary cancers have not been extensively investigated. An understanding of the variants predisposing to more than one cancer type could improve patient care, including screening and genetic counselling, as well as advancing the understanding of tumour development. A cohort of 57 patients ascertained due to their cutaneous melanoma (CM) diagnosis and with a history of two or more additional non-cutaneous independent primary cancer types were recruited for this study. Patient blood samples were assessed by whole exome or whole genome sequencing. We focussed on variants in 525 pre-selected genes, including 65 autosomal dominant and 31 autosomal recessive cancer predisposition genes, 116 genes involved in the DNA repair pathway, and 313 commonly somatically mutated in cancer. The same genes were analysed in exome sequence data from 1358 control individuals collected as part of non-cancer studies (UK10K). The identified variants were classified for pathogenicity using online databases, literature and in silico prediction tools. No known pathogenic autosomal dominant or previously described compound heterozygous mutations in autosomal recessive genes were observed in the multiple cancer cohort. Variants typically found somatically in haematological malignancies (in JAK1, JAK2, SF3B1, SRSF2, TET2 and TYK2) were present in lymphocyte DNA of patients with multiple primary cancers, all of whom had a history of haematological malignancy and cutaneous melanoma, as well as colorectal cancer and/or prostate cancer. Other potentially pathogenic variants were discovered in BUB1B, POLE2, ROS1 and DNMT3A. Compared to controls, multiple cancer cases had significantly more likely damaging mutations (nonsense, frameshift ins/del) in tumour suppressor and tyrosine kinase genes and

20 CFR 10.116 - What additional evidence is needed in cases based on occupational disease?

Code of Federal Regulations, 2012 CFR

2012-04-01

... based on occupational disease? 10.116 Section 10.116 Employees' Benefits OFFICE OF WORKERS' COMPENSATION... of Proof § 10.116 What additional evidence is needed in cases based on occupational disease? (a) The... particular occupational diseases. The medical report should also include the information specified on the...

20 CFR 10.116 - What additional evidence is needed in cases based on occupational disease?

Code of Federal Regulations, 2013 CFR

2013-04-01

... based on occupational disease? 10.116 Section 10.116 Employees' Benefits OFFICE OF WORKERS' COMPENSATION... of Proof § 10.116 What additional evidence is needed in cases based on occupational disease? (a) The... particular occupational diseases. The medical report should also include the information specified on the...

20 CFR 10.116 - What additional evidence is needed in cases based on occupational disease?

Code of Federal Regulations, 2014 CFR

2014-04-01

... based on occupational disease? 10.116 Section 10.116 Employees' Benefits OFFICE OF WORKERS' COMPENSATION... of Proof § 10.116 What additional evidence is needed in cases based on occupational disease? (a) The... particular occupational diseases. The medical report should also include the information specified on the...

20 CFR 10.116 - What additional evidence is needed in cases based on occupational disease?

Code of Federal Regulations, 2011 CFR

2011-04-01

... based on occupational disease? 10.116 Section 10.116 Employees' Benefits OFFICE OF WORKERS' COMPENSATION... of Proof § 10.116 What additional evidence is needed in cases based on occupational disease? (a) The... occupational diseases. The medical report should also include the information specified on the checklist for...

20 CFR 10.116 - What additional evidence is needed in cases based on occupational disease?

Code of Federal Regulations, 2010 CFR

2010-04-01

... based on occupational disease? 10.116 Section 10.116 Employees' Benefits OFFICE OF WORKERS' COMPENSATION... of Proof § 10.116 What additional evidence is needed in cases based on occupational disease? (a) The... occupational diseases. The medical report should also include the information specified on the checklist for...

Mutations in RIT1 cause Noonan syndrome - additional functional evidence and expanding the clinical phenotype.

PubMed

Koenighofer, M; Hung, C Y; McCauley, J L; Dallman, J; Back, E J; Mihalek, I; Gripp, K W; Sol-Church, K; Rusconi, P; Zhang, Z; Shi, G-X; Andres, D A; Bodamer, O A

2016-03-01

RASopathies are a clinically heterogeneous group of conditions caused by mutations in 1 of 16 proteins in the RAS-mitogen activated protein kinase (RAS-MAPK) pathway. Recently, mutations in RIT1 were identified as a novel cause for Noonan syndrome. Here we provide additional functional evidence for a causal role of RIT1 mutations and expand the associated phenotypic spectrum. We identified two de novo missense variants p.Met90Ile and p.Ala57Gly. Both variants resulted in increased MEK-ERK signaling compared to wild-type, underscoring gain-of-function as the primary functional mechanism. Introduction of p.Met90Ile and p.Ala57Gly into zebrafish embryos reproduced not only aspects of the human phenotype but also revealed abnormalities of eye development, emphasizing the importance of RIT1 for spatial and temporal organization of the growing organism. In addition, we observed severe lymphedema of the lower extremity and genitalia in one patient. We provide additional evidence for a causal relationship between pathogenic mutations in RIT1, increased RAS-MAPK/MEK-ERK signaling and the clinical phenotype. The mutant RIT1 protein may possess reduced GTPase activity or a diminished ability to interact with cellular GTPase activating proteins; however the precise mechanism remains unknown. The phenotypic spectrum is likely to expand and includes lymphedema of the lower extremities in addition to nuchal hygroma. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Independent and additive repetition priming of motion direction and color in visual search.

PubMed

Kristjánsson, Arni

2009-03-01

Priming of visual search for Gabor patch stimuli, varying in color and local drift direction, was investigated. The task relevance of each feature varied between the different experimental conditions compared. When the target defining dimension was color, a large effect of color repetition was seen as well as a smaller effect of the repetition of motion direction. The opposite priming pattern was seen when motion direction defined the target--the effect of motion direction repetition was this time larger than for color repetition. Finally, when neither was task relevant, and the target defining dimension was the spatial frequency of the Gabor patch, priming was seen for repetition of both color and motion direction, but the effects were smaller than in the previous two conditions. These results show that features do not necessarily have to be task relevant for priming to occur. There is little interaction between priming following repetition of color and motion, these two features show independent and additive priming effects, most likely reflecting that the two features are processed at separate processing sites in the nervous system, consistent with previous findings from neuropsychology & neurophysiology. The implications of the findings for theoretical accounts of priming in visual search are discussed.

An ATM-independent S-phase checkpoint response involves CHK1 pathway

NASA Technical Reports Server (NTRS)

Zhou, Xiang-Yang; Wang, Xiang; Hu, Baocheng; Guan, Jun; Iliakis, George; Wang, Ya

2002-01-01

After exposure to genotoxic stress, proliferating cells actively slow down the DNA replication through a S-phase checkpoint to provide time for repair. We report that in addition to the ataxia-telangiectasia mutated (ATM)-dependent pathway that controls the fast response, there is an ATM-independent pathway that controls the slow response to regulate the S-phase checkpoint after ionizing radiation in mammalian cells. The slow response of S-phase checkpoint, which is resistant to wortmannin, sensitive to caffeine and UCN-01, and related to cyclin-dependent kinase phosphorylation, is much stronger in CHK1 overexpressed cells, and it could be abolished by Chk1 antisense oligonucleotides. These results provide evidence that the ATM-independent slow response of S-phase checkpoint involves CHK1 pathway.

Congruence of Additive and Non-Additive Effects on Gene Expression Estimated from Pedigree and SNP Data

PubMed Central

Powell, Joseph E.; Henders, Anjali K.; McRae, Allan F.; Kim, Jinhee; Hemani, Gibran; Martin, Nicholas G.; Dermitzakis, Emmanouil T.; Gibson, Greg

2013-01-01

There is increasing evidence that heritable variation in gene expression underlies genetic variation in susceptibility to disease. Therefore, a comprehensive understanding of the similarity between relatives for transcript variation is warranted—in particular, dissection of phenotypic variation into additive and non-additive genetic factors and shared environmental effects. We conducted a gene expression study in blood samples of 862 individuals from 312 nuclear families containing MZ or DZ twin pairs using both pedigree and genotype information. From a pedigree analysis we show that the vast majority of genetic variation across 17,994 probes is additive, although non-additive genetic variation is identified for 960 transcripts. For 180 of the 960 transcripts with non-additive genetic variation, we identify expression quantitative trait loci (eQTL) with dominance effects in a sample of 339 unrelated individuals and replicate 31% of these associations in an independent sample of 139 unrelated individuals. Over-dominance was detected and replicated for a trans association between rs12313805 and ETV6, located 4MB apart on chromosome 12. Surprisingly, only 17 probes exhibit significant levels of common environmental effects, suggesting that environmental and lifestyle factors common to a family do not affect expression variation for most transcripts, at least those measured in blood. Consistent with the genetic architecture of common diseases, gene expression is predominantly additive, but a minority of transcripts display non-additive effects. PMID:23696747

Congruence of additive and non-additive effects on gene expression estimated from pedigree and SNP data.

PubMed

Powell, Joseph E; Henders, Anjali K; McRae, Allan F; Kim, Jinhee; Hemani, Gibran; Martin, Nicholas G; Dermitzakis, Emmanouil T; Gibson, Greg; Montgomery, Grant W; Visscher, Peter M

2013-05-01

There is increasing evidence that heritable variation in gene expression underlies genetic variation in susceptibility to disease. Therefore, a comprehensive understanding of the similarity between relatives for transcript variation is warranted--in particular, dissection of phenotypic variation into additive and non-additive genetic factors and shared environmental effects. We conducted a gene expression study in blood samples of 862 individuals from 312 nuclear families containing MZ or DZ twin pairs using both pedigree and genotype information. From a pedigree analysis we show that the vast majority of genetic variation across 17,994 probes is additive, although non-additive genetic variation is identified for 960 transcripts. For 180 of the 960 transcripts with non-additive genetic variation, we identify expression quantitative trait loci (eQTL) with dominance effects in a sample of 339 unrelated individuals and replicate 31% of these associations in an independent sample of 139 unrelated individuals. Over-dominance was detected and replicated for a trans association between rs12313805 and ETV6, located 4MB apart on chromosome 12. Surprisingly, only 17 probes exhibit significant levels of common environmental effects, suggesting that environmental and lifestyle factors common to a family do not affect expression variation for most transcripts, at least those measured in blood. Consistent with the genetic architecture of common diseases, gene expression is predominantly additive, but a minority of transcripts display non-additive effects.

Evidence for dose-additive effects of pyrethroids on motor activity in rats.

PubMed

Wolansky, Marcelo J; Gennings, Chris; DeVito, Michael J; Crofton, Kevin M

2009-10-01

Pyrethroids are neurotoxic insecticides used in a variety of indoor and outdoor applications. Previous research characterized the acute dose-effect functions for 11 pyrethroids administered orally in corn oil (1 mL/kg) based on assessment of motor activity. We used a mixture of these 11 pyrethroids and the same testing paradigm used in single-compound assays to test the hypothesis that cumulative neurotoxic effects of pyrethroid mixtures can be predicted using the default dose-addition theory. Mixing ratios of the 11 pyrethroids in the tested mixture were based on the ED30 (effective dose that produces a 30% decrease in response) of the individual chemical (i.e., the mixture comprised equipotent amounts of each pyrethroid). The highest concentration of each individual chemical in the mixture was less than the threshold for inducing behavioral effects. Adult male rats received acute oral exposure to corn oil (control) or dilutions of the stock mixture solution. The mixture of 11 pyrethroids was administered either simultaneously (2 hr before testing) or after a sequence based on times of peak effect for the individual chemicals (4, 2, and 1 hr before testing). A threshold additivity model was fit to the single-chemical data to predict the theoretical dose-effect relationship for the mixture under the assumption of dose additivity. When subthreshold doses of individual chemicals were combined in the mixtures, we found significant dose-related decreases in motor activity. Further, we found no departure from the predicted dose-additive curve regardless of the mixture dosing protocol used. In this article we present the first in vivo evidence on pyrethroid cumulative effects supporting the default assumption of dose addition.

ERP Evidence of Hemispheric Independence in Visual Word Recognition

ERIC Educational Resources Information Center

Nemrodov, Dan; Harpaz, Yuval; Javitt, Daniel C.; Lavidor, Michal

2011-01-01

This study examined the capability of the left hemisphere (LH) and the right hemisphere (RH) to perform a visual recognition task independently as formulated by the Direct Access Model (Fernandino, Iacoboni, & Zaidel, 2007). Healthy native Hebrew speakers were asked to categorize nouns and non-words (created from nouns by transposing two middle…

Origins of task-specific sensory-independent organization in the visual and auditory brain: neuroscience evidence, open questions and clinical implications.

PubMed

Heimler, Benedetta; Striem-Amit, Ella; Amedi, Amir

2015-12-01

Evidence of task-specific sensory-independent (TSSI) plasticity from blind and deaf populations has led to a better understanding of brain organization. However, the principles determining the origins of this plasticity remain unclear. We review recent data suggesting that a combination of the connectivity bias and sensitivity to task-distinctive features might account for TSSI plasticity in the sensory cortices as a whole, from the higher-order occipital/temporal cortices to the primary sensory cortices. We discuss current theories and evidence, open questions and related predictions. Finally, given the rapid progress in visual and auditory restoration techniques, we address the crucial need to develop effective rehabilitation approaches for sensory recovery. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Evidence for modality-independent order coding in working memory.

PubMed

Depoorter, Ann; Vandierendonck, André

2009-03-01

The aim of the present study was to investigate the representation of serial order in working memory, more specifically whether serial order is coded by means of a modality-dependent or a modality-independent order code. This was investigated by means of a series of four experiments based on a dual-task methodology in which one short-term memory task was embedded between the presentation and recall of another short-term memory task. Two aspects were varied in these memory tasks--namely, the modality of the stimulus materials (verbal or visuo-spatial) and the presence of an order component in the task (an order or an item memory task). The results of this study showed impaired primary-task recognition performance when both the primary and the embedded task included an order component, irrespective of the modality of the stimulus materials. If one or both of the tasks did not contain an order component, less interference was found. The results of this study support the existence of a modality-independent order code.

Sensitivity to food additives, vaso-active amines and salicylates: a review of the evidence.

PubMed

Skypala, Isabel J; Williams, M; Reeves, L; Meyer, R; Venter, C

2015-01-01

Although there is considerable literature pertaining to IgE and non IgE-mediated food allergy, there is a paucity of information on non-immune mediated reactions to foods, other than metabolic disorders such as lactose intolerance. Food additives and naturally occurring 'food chemicals' have long been reported as having the potential to provoke symptoms in those who are more sensitive to their effects. Diets low in 'food chemicals' gained prominence in the 1970s and 1980s, and their popularity remains, although the evidence of their efficacy is very limited. This review focuses on the available evidence for the role and likely adverse effects of both added and natural 'food chemicals' including benzoate, sulphite, monosodium glutamate, vaso-active or biogenic amines and salicylate. Studies assessing the efficacy of the restriction of these substances in the diet have mainly been undertaken in adults, but the paper will also touch on the use of such diets in children. The difficulty of reviewing the available evidence is that few of the studies have been controlled and, for many, considerable time has elapsed since their publication. Meanwhile dietary patterns and habits have changed hugely in the interim, so the conclusions may not be relevant for our current dietary norms. The conclusion of the review is that there may be some benefit in the removal of an additive or a group of foods high in natural food chemicals from the diet for a limited period for certain individuals, providing the diagnostic pathway is followed and the foods are reintroduced back into the diet to assess for the efficacy of removal. However diets involving the removal of multiple additives and food chemicals have the very great potential to lead to nutritional deficiency especially in the paediatric population. Any dietary intervention, whether for the purposes of diagnosis or management of food allergy or food intolerance, should be adapted to the individual's dietary habits and a suitably

Evidence for Dose-Additive Effects of Pyrethroids on Motor Activity in Rats

PubMed Central

Wolansky, Marcelo J.; Gennings, Chris; DeVito, Michael J.; Crofton, Kevin M.

2009-01-01

Background Pyrethroids are neurotoxic insecticides used in a variety of indoor and outdoor applications. Previous research characterized the acute dose–effect functions for 11 pyrethroids administered orally in corn oil (1 mL/kg) based on assessment of motor activity. Objectives We used a mixture of these 11 pyrethroids and the same testing paradigm used in single-compound assays to test the hypothesis that cumulative neurotoxic effects of pyrethroid mixtures can be predicted using the default dose–addition theory. Methods Mixing ratios of the 11 pyrethroids in the tested mixture were based on the ED30 (effective dose that produces a 30% decrease in response) of the individual chemical (i.e., the mixture comprised equipotent amounts of each pyrethroid). The highest concentration of each individual chemical in the mixture was less than the threshold for inducing behavioral effects. Adult male rats received acute oral exposure to corn oil (control) or dilutions of the stock mixture solution. The mixture of 11 pyrethroids was administered either simultaneously (2 hr before testing) or after a sequence based on times of peak effect for the individual chemicals (4, 2, and 1 hr before testing). A threshold additivity model was fit to the single-chemical data to predict the theoretical dose–effect relationship for the mixture under the assumption of dose additivity. Results When subthreshold doses of individual chemicals were combined in the mixtures, we found significant dose-related decreases in motor activity. Further, we found no departure from the predicted dose-additive curve regardless of the mixture dosing protocol used. Conclusion In this article we present the first in vivo evidence on pyrethroid cumulative effects supporting the default assumption of dose addition. PMID:20019907

Use of an evidence-based algorithm for patients with traumatic hemothorax reduces need for additional interventions.

PubMed

Dennis, Bradley M; Gondek, Stephen P; Guyer, Richard A; Hamblin, Susan E; Gunter, Oliver L; Guillamondegui, Oscar D

2017-04-01

Concerted management of the traumatic hemothorax is ill-defined. Surgical management of specific hemothoraces may be beneficial. A comprehensive strategy to delineate appropriate patients for additional procedures does not exist. We developed an evidence-based algorithm for hemothorax management. We hypothesize that the use of this algorithm will decrease additional interventions. A pre-/post-study was performed on all patients admitted to our trauma service with traumatic hemothorax from August 2010 to September 2013. An evidence-based management algorithm was initiated for the management of retained hemothoraces. Patients with length of stay (LOS) less than 24 hours or admitted during an implementation phase were excluded. Study data included age, Injury Severity Score, Abbreviated Injury Scale chest, mechanism of injury, ventilator days, intensive care unit (ICU) LOS, total hospital LOS, and interventions required. Our primary outcome was number of patients requiring more than 1 intervention. Secondary outcomes were empyema rate, number of patients requiring specific additional interventions, 28-day ventilator-free days, 28-day ICU-free days, hospital LOS, all-cause 6-month readmission rate. Standard statistical analysis was performed for all data. Six hundred forty-two patients (326 pre and 316 post) met the study criteria. There were no demographic differences in either group. The number of patients requiring more than 1 intervention was significantly reduced (49 pre vs. 28 post, p = 0.02). Number of patients requiring VATS decreased (27 pre vs. 10 post, p < 0.01). Number of catheters placed by interventional radiology increased (2 pre vs. 10 post, p = 0.02). Intrapleural thrombolytic use, open thoracotomy, empyema, and 6-month readmission rates were unchanged. The "post" group more ventilator-free days (median, 23.9 vs. 22.5, p = 0.04), but ICU and hospital LOS were unchanged. Using an evidence-based hemothorax algorithm reduced the number of patients

Promoting Independent Learning by Curriculum Design and Assessment

ERIC Educational Resources Information Center

Marshall, Gill

2007-01-01

Purpose: This paper evaluates whether the revalidated Magnetic Resonance Imaging (MRI) programme encourages independent learning by its curriculum design, delivery and assessment. Results: Evidence regarding the promotion of independent learning was gained from learners and external examiners. The scientific publications, presentations and posters…

Brief Report: An Independent Replication and Extension of Psychometric Evidence Supporting the Theory of Mind Inventory.

PubMed

Greenslade, Kathryn J; Coggins, Truman E

2016-08-01

This study presents an independent replication and extension of psychometric evidence supporting the Theory of Mind Inventory (ToMI). Parents of 20 children with ASD (4; 1-6; 7 years; months) and 20 with typical development (3; 1-6; 5), rated their child's theory of mind abilities in everyday situations. Other parent report and child behavioral assessments included the Social Responsiveness Scale-2, Vineland Adaptive Behavior Scales-2, Peabody Picture Vocabulary Test-4, and Clinical Evaluation of Language Fundamentals-Preschool, 2. Results revealed high internal consistency, expected developmental changes in children with typical development, expected group differences between children with and without ASD, and strong correlations with other measures of social and communication abilities. The ToMI demonstrates strong psychometrics, suggesting considerable utility in identifying theory of mind deficits in children with ASD.

Evidence for single metal two electron oxidative addition and reductive elimination at uranium.

PubMed

Gardner, Benedict M; Kefalidis, Christos E; Lu, Erli; Patel, Dipti; McInnes, Eric J L; Tuna, Floriana; Wooles, Ashley J; Maron, Laurent; Liddle, Stephen T

2017-12-01

Reversible single-metal two-electron oxidative addition and reductive elimination are common fundamental reactions for transition metals that underpin major catalytic transformations. However, these reactions have never been observed together in the f-block because these metals exhibit irreversible one- or multi-electron oxidation or reduction reactions. Here we report that azobenzene oxidises sterically and electronically unsaturated uranium(III) complexes to afford a uranium(V)-imido complex in a reaction that satisfies all criteria of a single-metal two-electron oxidative addition. Thermolysis of this complex promotes extrusion of azobenzene, where H-/D-isotopic labelling finds no isotopomer cross-over and the non-reactivity of a nitrene-trap suggests that nitrenes are not generated and thus a reductive elimination has occurred. Though not optimally balanced in this case, this work presents evidence that classical d-block redox chemistry can be performed reversibly by f-block metals, and that uranium can thus mimic elementary transition metal reactivity, which may lead to the discovery of new f-block catalysis.

Visuospatial Orientational Shifts: Evidence for Three Independent Mechanisms.

ERIC Educational Resources Information Center

Noonan, Michael; Axelrod, Seymour

While it is often assumed that a single mechanism underlies varied experimental evidences of selectivity, Berlyne (1969) suggested that attention-like selectivity may take place in a number of quite separate neural systems. This study examined the issue of visuospatial attention by investigating covert orientation or "looking out of the corner of…

Peptide-independent Recognition by Alloreactive Cytotoxic T Lymphocytes (CTL)

PubMed Central

Smith, Pamela A.; Brunmark, Anders; Jackson, Michael R.; Potter, Terry A.

1997-01-01

We have isolated several H-2Kb–alloreactive cytotoxic T cell clones and analyzed their reactivity for several forms of H-2Kb. These cytotoxic T lymphocytes (CTL) were elicited by priming with a skin graft followed by in vitro stimulation using stimulator cells that express an H-2Kb molecule unable to bind CD8. In contrast to most alloreactive T cells, these CTL were able to recognize H-2Kb on the surface of the antigen processing defective cell lines RMA-S and T2. Furthermore, this reactivity was not increased by the addition of an extract containing peptides from C57BL/6 (H-2b) spleen cells, nor was the reactivity decreased by treating the target cells with acid to remove peptides bound to MHC molecules. The CTL were also capable of recognizing targets expressing the mutant H-2Kbm8 molecule. These findings suggested that the clones recognized determinants on H-2Kb that were independent of peptide. Further evidence for this hypothesis was provided by experiments in which H-2Kb produced in Drosophila melanogaster cells and immobilized on the surface of a tissue culture plate was able to stimulate hybridomas derived from these alloreactive T cells. Precursor frequency analysis demonstrated that skin graft priming, whether with skin expressing the wild-type or the mutant H-2Kb molecule, is a strong stimulus to elicit peptide-independent CTL. Moreover, reconstitution experiments demonstrated that the peptide-independent CTL clones were capable of mediating rapid and complete rejection of H-2–incompatible skin grafts. These findings provide evidence that not all allorecognition is peptide dependent. PMID:9091576

Device-independent quantum key distribution

NASA Astrophysics Data System (ADS)

Hänggi, Esther

2010-12-01

In this thesis, we study two approaches to achieve device-independent quantum key distribution: in the first approach, the adversary can distribute any system to the honest parties that cannot be used to communicate between the three of them, i.e., it must be non-signalling. In the second approach, we limit the adversary to strategies which can be implemented using quantum physics. For both approaches, we show how device-independent quantum key distribution can be achieved when imposing an additional condition. In the non-signalling case this additional requirement is that communication is impossible between all pairwise subsystems of the honest parties, while, in the quantum case, we demand that measurements on different subsystems must commute. We give a generic security proof for device-independent quantum key distribution in these cases and apply it to an existing quantum key distribution protocol, thus proving its security even in this setting. We also show that, without any additional such restriction there always exists a successful joint attack by a non-signalling adversary.

High-Density SNP Screening of the Major Histocompatibility Complex in Systemic Lupus Erythematosus Demonstrates Strong Evidence for Independent Susceptibility Regions

PubMed Central

Barcellos, Lisa F.; May, Suzanne L.; Ramsay, Patricia P.; Quach, Hong L.; Lane, Julie A.; Nititham, Joanne; Noble, Janelle A.; Taylor, Kimberly E.; Quach, Diana L.; Chung, Sharon A.; Kelly, Jennifer A.; Moser, Kathy L.; Behrens, Timothy W.; Seldin, Michael F.; Thomson, Glenys; Harley, John B.; Gaffney, Patrick M.; Criswell, Lindsey A.

2009-01-01

A substantial genetic contribution to systemic lupus erythematosus (SLE) risk is conferred by major histocompatibility complex (MHC) gene(s) on chromosome 6p21. Previous studies in SLE have lacked statistical power and genetic resolution to fully define MHC influences. We characterized 1,610 Caucasian SLE cases and 1,470 parents for 1,974 MHC SNPs, the highly polymorphic HLA-DRB1 locus, and a panel of ancestry informative markers. Single-marker analyses revealed strong signals for SNPs within several MHC regions, as well as with HLA-DRB1 (global p = 9.99×10−16). The most strongly associated DRB1 alleles were: *0301 (odds ratio, OR = 2.21, p = 2.53×10−12), *1401 (OR = 0.50, p = 0.0002), and *1501 (OR = 1.39, p = 0.0032). The MHC region SNP demonstrating the strongest evidence of association with SLE was rs3117103, with OR = 2.44 and p = 2.80×10−13. Conditional haplotype and stepwise logistic regression analyses identified strong evidence for association between SLE and the extended class I, class I, class III, class II, and the extended class II MHC regions. Sequential removal of SLE–associated DRB1 haplotypes revealed independent effects due to variation within OR2H2 (extended class I, rs362521, p = 0.006), CREBL1 (class III, rs8283, p = 0.01), and DQB2 (class II, rs7769979, p = 0.003, and rs10947345, p = 0.0004). Further, conditional haplotype analyses demonstrated that variation within MICB (class I, rs3828903, p = 0.006) also contributes to SLE risk independent of HLA-DRB1*0301. Our results for the first time delineate with high resolution several MHC regions with independent contributions to SLE risk. We provide a list of candidate variants based on biologic and functional considerations that may be causally related to SLE risk and warrant further investigation. PMID:19851445

Model-Independent Evidence for J/ψp Contributions to Λ_{b}^{0}→J/ψpK^{-} Decays.

PubMed

Aaij, R; Abellán Beteta, C; 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; 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; Baker, S; 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; Betti, F; 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; Borgheresi, A; Borghi, S; Borisyak, M; Borsato, M; Boubdir, M; Bowcock, T J V; Bowen, E; Bozzi, C; Braun, S; Britsch, M; Britton, T; Brodzicka, J; 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; Chobanova, V; 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; 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; Dendek, A; Derkach, D; Deschamps, O; Dettori, F; Dey, B; Di Canto, A; Dijkstra, H; 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; Fazzini, D; 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; 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; 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; Gligorov, V V; Göbel, C; Golubkov, D; Golutvin, A; Gomes, A; Gotti, C; Grabalosa Gándara, M; Graciani Diaz, R; Granado Cardoso, L A; Graugés, E; Graverini, E; Graziani, G; Grecu, A; Griffith, P; Grillo, L; Grünberg, O; Gushchin, E; Guz, Yu; Gys, T; Hadavizadeh, T; Hadjivasiliou, C; Haefeli, G; Haen, C; Haines, S C; Hall, S; Hamilton, B; Han, X; Hansmann-Menzemer, S; Harnew, N; Harnew, S T; Harrison, J; He, J; Head, T; Heister, A; Hennessy, K; Henrard, P; Henry, L; Hernando Morata, J A; van Herwijnen, E; Heß, M; Hicheur, A; Hill, D; Hoballah, M; Hombach, C; Hongming, L; Hulsbergen, W; Humair, T; Hushchyn, M; Hussain, N; Hutchcroft, D; Idzik, M; Ilten, P; Jacobsson, R; Jaeger, A; Jalocha, J; Jans, E; Jawahery, A; John, M; Johnson, D; Jones, C R; Joram, C; Jost, B; Jurik, N; Kandybei, S; Kanso, W; Karacson, M; Karbach, T M; Karodia, S; Kecke, M; Kelsey, M; Kenyon, I R; Kenzie, M; Ketel, T; Khairullin, E; Khanji, B; Khurewathanakul, C; Kirn, T; Klaver, S; Klimaszewski, K; Kolpin, M; Komarov, I; Koopman, R F; Koppenburg, P; Kozeiha, M; Kravchuk, L; Kreplin, K; 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; Lambert, D; Lanfranchi, G; Langenbruch, C; Langhans, B; Latham, T; Lazzeroni, C; Le Gac, R; van Leerdam, J; Lees, J-P; Lefèvre, R; Leflat, A; Lefrançois, J; Lemaitre, F; Lemos Cid, E; Leroy, O; Lesiak, T; Leverington, B; Li, Y; Likhomanenko, T; Lindner, R; Linn, C; Lionetto, F; Liu, B; Liu, X; Loh, D; Longstaff, I; Lopes, J H; Lucchesi, D; Lucio Martinez, M; Luo, H; Lupato, A; Luppi, E; Lupton, O; Lusardi, N; Lusiani, A; Lyu, X; Machefert, F; Maciuc, F; Maev, O; Maguire, K; Malde, S; Malinin, A; Manca, G; Mancinelli, G; Manning, P; Mapelli, A; Maratas, J; Marchand, J F; Marconi, U; Marin Benito, C; 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; Maurin, B; Mazurov, A; McCann, M; McCarthy, J; McNab, A; McNulty, R; Meadows, B; Meier, F; Meissner, M; Melnychuk, D; Merk, M; Merli, A; Michielin, E; Milanes, D A; Minard, M-N; Mitzel, D S; Molina Rodriguez, J; Monroy, I A; Monteil, S; Morandin, M; Morawski, P; Mordà, A; Morello, M J; Moron, J; Morris, A B; Mountain, R; Muheim, F; Mulder, M M; Müller, D; Müller, J; Müller, K; Müller, V; Mussini, M; Muster, B; Naik, P; Nakada, T; Nandakumar, R; Nandi, A; Nasteva, I; Needham, M; Neri, N; Neubert, S; Neufeld, N; Neuner, M; Nguyen, A D; Nguyen-Mau, C; Niess, V; Nieswand, S; Niet, R; Nikitin, N; Nikodem, T; Novoselov, A; O'Hanlon, D P; Oblakowska-Mucha, A; Obraztsov, V; Ogilvy, S; Okhrimenko, O; Oldeman, R; Onderwater, C J G; Osorio Rodrigues, B; Otalora Goicochea, J M; Otto, A; Owen, P; Oyanguren, A; Palano, A; Palombo, F; Palutan, M; Panman, J; Papanestis, A; Pappagallo, M; Pappalardo, L L; Pappenheimer, C; Parker, W; Parkes, C; Passaleva, G; Patel, G D; Patel, M; Patrignani, C; Pearce, A; Pellegrino, A; Penso, G; Pepe Altarelli, M; Perazzini, S; Perret, P; Pescatore, L; Petridis, K; Petrolini, A; Petruzzo, M; Picatoste Olloqui, E; Pietrzyk, B; Pikies, M; Pinci, D; Pistone, A; Piucci, A; Playfer, S; Plo Casasus, M; Poikela, T; Polci, F; Poluektov, A; Polyakov, I; Polycarpo, E; Popov, A; Popov, D; Popovici, B; Potterat, C; Price, E; Price, J D; Prisciandaro, J; Pritchard, A; Prouve, C; Pugatch, V; Puig Navarro, A; Punzi, G; Qian, W; Quagliani, R; Rachwal, B; Rademacker, J H; Rama, M; Ramos Pernas, M; Rangel, M S; Raniuk, I; Raven, G; Redi, F; Reichert, S; Dos Reis, A 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; Romanovsky, V; Romero Vidal, A; Ronayne, J W; Rotondo, M; Ruf, T; Ruiz Valls, P; Saborido Silva, J J; Sagidova, N; Saitta, B; Salustino Guimaraes, V; 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; Schiller, M; Schindler, H; Schlupp, M; Schmelling, M; Schmelzer, T; Schmidt, B; Schneider, O; Schopper, A; 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; Shires, A; Siddi, B G; Silva Coutinho, R; Silva de Oliveira, L; Simi, G; Sirendi, M; Skidmore, N; Skwarnicki, T; Smith, E; Smith, I T; Smith, J; Smith, M; Snoek, H; Sokoloff, M D; Soler, F J P; Soomro, F; Souza, D; Souza De Paula, B; Spaan, B; Spradlin, P; Sridharan, S; Stagni, F; Stahl, M; Stahl, S; Stefkova, S; Steinkamp, O; Stenyakin, O; Stevenson, S; Stoica, S; Stone, S; Storaci, B; Stracka, S; Straticiuc, M; Straumann, U; Sun, L; Sutcliffe, W; Swientek, K; Swientek, S; Syropoulos, V; Szczekowski, M; Szumlak, T; T'Jampens, S; Tayduganov, A; Tekampe, T; Tellarini, G; Teubert, F; Thomas, C; Thomas, E; van Tilburg, J; Tisserand, V; Tobin, M; Tolk, S; Tomassetti, L; Tonelli, D; Topp-Joergensen, S; Tournefier, E; Tourneur, S; Trabelsi, K; Traill, M; Tran, M T; Tresch, M; Trisovic, A; Tsaregorodtsev, A; Tsopelas, P; Tuning, N; Ukleja, A; Ustyuzhanin, A; Uwer, U; Vacca, C; Vagnoni, V; Valat, S; Valenti, G; Vallier, A; Vazquez Gomez, R; Vazquez Regueiro, P; Vázquez Sierra, C; Vecchi, S; van Veghel, M; Velthuis, J J; Veltri, M; Veneziano, G; Vesterinen, M; Viaud, B; Vieira, D; Vieites Diaz, M; Vilasis-Cardona, X; Volkov, V; Vollhardt, A; Voong, D; Vorobyev, A; Vorobyev, V; Voß, C; de Vries, J A; Waldi, R; Wallace, C; Wallace, R; Walsh, J; Wang, J; Ward, D R; 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; Wishahi, J; Wislicki, W; Witek, M; Wormser, G; Wotton, S A; Wraight, K; Wright, S; Wyllie, K; Xie, Y; Xu, Z; Yang, Z; Yin, H; Yu, J; Yuan, X; Yushchenko, O; Zangoli, M; Zavertyaev, M; Zhang, L; Zhang, Y; Zhelezov, A; Zheng, Y; Zhokhov, A; Zhong, L; Zhukov, V; Zucchelli, S

2016-08-19

The data sample of Λ_{b}^{0}→J/ψpK^{-} decays acquired with the LHCb detector from 7 and 8 TeV pp collisions, corresponding to an integrated luminosity of 3  fb^{-1}, is inspected for the presence of J/ψp or J/ψK^{-} contributions with minimal assumptions about K^{-}p contributions. It is demonstrated at more than nine standard deviations that Λ_{b}^{0}→J/ψpK^{-} decays cannot be described with K^{-}p contributions alone, and that J/ψp contributions play a dominant role in this incompatibility. These model-independent results support the previously obtained model-dependent evidence for P_{c}^{+}→J/ψp charmonium-pentaquark states in the same data sample.

Language, gesture, and handedness: Evidence for independent lateralized networks.

PubMed

Häberling, Isabelle S; Corballis, Paul M; Corballis, Michael C

2016-09-01

Language, gesture, and handedness are in most people represented in the left cerebral hemisphere. To explore the relations among these attributes, we collected fMRI images in a large sample of left- and right-handers while they performed language tasks and watched action sequences. Regions of interest included the frontal and parietal areas previously identified as comprising an action-observation network, and the frontal and temporal areas comprising the primary areas for language production and comprehension. All of the language areas and most of the action-observation areas showed an overall left-hemispheric bias, despite the participation of equal numbers of left- and right-handers. A factor analysis of the laterality indices derived from the different areas during the tasks indicated three independent networks, one associated with language, one associated with handedness, and one representing action observation independent of handedness. Areas 44 and 45, which together make up Broca's area, were part of the language and action-observation networks, but were not included in the part of the action observation network that was related to handedness, which in turn was strongly linked to areas in the parietal lobe. These results suggest an evolutionary scenario in which the primate mirror neuron system (MNS) became increasingly lateralized, and later fissioned onto subsystems with one mediating language and the other mediating the execution and observation of manual actions. The second network is further subdivided into one dependent on hand preference and one that is not, providing new insight into the tripartite system of language, handedness, and praxis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Additivity pretraining and cue competition effects: developmental evidence for a reasoning-based account of causal learning.

PubMed

Simms, Victoria; McCormack, Teresa; Beckers, Tom

2012-04-01

The effect of additivity pretraining on blocking has been taken as evidence for a reasoning account of human and animal causal learning. If inferential reasoning underpins this effect, then developmental differences in the magnitude of this effect in children would be expected. Experiment 1 examined cue competition effects in children's (4- to 5-year-olds and 6- to 7-year-olds) causal learning using a new paradigm analogous to the food allergy task used in studies of human adult causal learning. Blocking was stronger in the older than the younger children, and additivity pretraining only affected blocking in the older group. Unovershadowing was not affected by age or by pretraining. In experiment 2, levels of blocking were found to be correlated with the ability to answer questions that required children to reason about additivity. Our results support an inferential reasoning explanation of cue competition effects. (c) 2012 APA, all rights reserved.

Major histocompatibility complex harbors widespread genotypic variability of non-additive risk of rheumatoid arthritis including epistasis.

PubMed

Wei, Wen-Hua; Bowes, John; Plant, Darren; Viatte, Sebastien; Yarwood, Annie; Massey, Jonathan; Worthington, Jane; Eyre, Stephen

2016-04-25

Genotypic variability based genome-wide association studies (vGWASs) can identify potentially interacting loci without prior knowledge of the interacting factors. We report a two-stage approach to make vGWAS applicable to diseases: firstly using a mixed model approach to partition dichotomous phenotypes into additive risk and non-additive environmental residuals on the liability scale and secondly using the Levene's (Brown-Forsythe) test to assess equality of the residual variances across genotype groups per marker. We found widespread significant (P < 2.5e-05) vGWAS signals within the major histocompatibility complex (MHC) across all three study cohorts of rheumatoid arthritis. We further identified 10 epistatic interactions between the vGWAS signals independent of the MHC additive effects, each with a weak effect but jointly explained 1.9% of phenotypic variance. PTPN22 was also identified in the discovery cohort but replicated in only one independent cohort. Combining the three cohorts boosted power of vGWAS and additionally identified TYK2 and ANKRD55. Both PTPN22 and TYK2 had evidence of interactions reported elsewhere. We conclude that vGWAS can help discover interacting loci for complex diseases but require large samples to find additional signals.

Independent walking as a major skill for the development of anticipatory postural control: evidence from adjustments to predictable perturbations.

PubMed

Cignetti, Fabien; Zedka, Milan; Vaugoyeau, Marianne; Assaiante, Christine

2013-01-01

Although there is suggestive evidence that a link exists between independent walking and the ability to establish anticipatory strategy to stabilize posture, the extent to which this skill facilitates the development of anticipatory postural control remains largely unknown. Here, we examined the role of independent walking on the infants' ability to anticipate predictable external perturbations. Non-walking infants, walking infants and adults were sitting on a platform that produced continuous rotation in the frontal plane. Surface electromyography (EMG) of neck and lower back muscles and the positions of markers located on the platform, the upper body and the head were recorded. Results from cross-correlation analysis between rectified and filtered EMGs and platform movement indicated that although muscle activation already occurred before platform movement in non-walking infants, only walking infants demonstrated an adult-like ability for anticipation. Moreover, results from further cross-correlation analysis between segmental angular displacement and platform movement together with measures of balance control at the end-points of rotation of the platform evidenced two sorts of behaviour. The adults behaved as a non-rigid non-inverted pendulum, rather stabilizing head in space, while both the walking and non-walking infants followed the platform, behaving as a rigid inverted pendulum. These results suggest that the acquisition of independent walking plays a role in the development of anticipatory postural control, likely improving the internal model for the sensorimotor control of posture. However, despite such improvement, integrating the dynamics of an external object, here the platform, within the model to maintain balance still remains challenging in infants.

Independence screening for high dimensional nonlinear additive ODE models with applications to dynamic gene regulatory networks.

PubMed

Xue, Hongqi; Wu, Shuang; Wu, Yichao; Ramirez Idarraga, Juan C; Wu, Hulin

2018-05-02

Mechanism-driven low-dimensional ordinary differential equation (ODE) models are often used to model viral dynamics at cellular levels and epidemics of infectious diseases. However, low-dimensional mechanism-based ODE models are limited for modeling infectious diseases at molecular levels such as transcriptomic or proteomic levels, which is critical to understand pathogenesis of diseases. Although linear ODE models have been proposed for gene regulatory networks (GRNs), nonlinear regulations are common in GRNs. The reconstruction of large-scale nonlinear networks from time-course gene expression data remains an unresolved issue. Here, we use high-dimensional nonlinear additive ODEs to model GRNs and propose a 4-step procedure to efficiently perform variable selection for nonlinear ODEs. To tackle the challenge of high dimensionality, we couple the 2-stage smoothing-based estimation method for ODEs and a nonlinear independence screening method to perform variable selection for the nonlinear ODE models. We have shown that our method possesses the sure screening property and it can handle problems with non-polynomial dimensionality. Numerical performance of the proposed method is illustrated with simulated data and a real data example for identifying the dynamic GRN of Saccharomyces cerevisiae. Copyright © 2018 John Wiley & Sons, Ltd.

Economic incentives for financial and residential independence.

PubMed

Whittington, L A; Peters, H E

1996-02-01

In this paper we examine the impact of the resource of children and of their parents on the children's transition to residential and financial independence. Previous studies of this transition focused primarily on the impact of family structure and parent-child relationships on the decision to leave home, but much less in known about the role of economic factors in the transition to independence. Using data from the Panel Study of Income Dynamics (PSID) for the period 1968-1988, we estimate discrete-hazard models of the probability of achieving residential and financial independence. We find that the child's wage opportunities and the parents' income are important determinants of establishing independence. The effect of parental income changes with the child's age. We also find some evidence that federal tax policy influences the decision to become independent, although the magnitude of this effect is quite small.

Implicit attentional bias for facial emotion in dissociative seizures: Additional evidence.

PubMed

Pick, Susannah; Mellers, John D C; Goldstein, Laura H

2018-03-01

This study sought to extend knowledge about the previously reported preconscious attentional bias (AB) for facial emotion in patients with dissociative seizures (DS) by exploring whether the finding could be replicated, while controlling for concurrent anxiety, depression, and potentially relevant cognitive impairments. Patients diagnosed with DS (n=38) were compared with healthy controls (n=43) on a pictorial emotional Stroop test, in which backwardly masked emotional faces (angry, happy, neutral) were processed implicitly. The group with DS displayed a significantly greater AB to facial emotion relative to controls; however, the bias was not specific to negative or positive emotions. The group effect could not be explained by performance on standardized cognitive tests or self-reported depression/anxiety. The study provides additional evidence of a disproportionate and automatic allocation of attention to facial affect in patients with DS, including both positive and negative facial expressions. Such a tendency could act as a predisposing factor for developing DS initially, or may contribute to triggering individuals' seizures on an ongoing basis. Psychological interventions such as Cognitive Behavioral Therapy (CBT) or AB modification might be suitable approaches to target this bias in clinical practice. Copyright © 2018 Elsevier Inc. All rights reserved.

Compound risk judgment in tasks with both idiosyncratic and systematic risk: The "Robust Beauty" of additive probability integration.

PubMed

Sundh, Joakim; Juslin, Peter

2018-02-01

In this study, we explore how people integrate risks of assets in a simulated financial market into a judgment of the conjunctive risk that all assets decrease in value, both when assets are independent and when there is a systematic risk present affecting all assets. Simulations indicate that while mental calculation according to naïve application of probability theory is best when the assets are independent, additive or exemplar-based algorithms perform better when systematic risk is high. Considering that people tend to intuitively approach compound probability tasks using additive heuristics, we expected the participants to find it easiest to master tasks with high systematic risk - the most complex tasks from the standpoint of probability theory - while they should shift to probability theory or exemplar memory with independence between the assets. The results from 3 experiments confirm that participants shift between strategies depending on the task, starting off with the default of additive integration. In contrast to results in similar multiple cue judgment tasks, there is little evidence for use of exemplar memory. The additive heuristics also appear to be surprisingly context-sensitive, with limited generalization across formally very similar tasks. Copyright © 2017 Elsevier B.V. All rights reserved.

Evidence of repeated and independent saltational evolution in a peculiar genus of sphinx moths (Proserpinus: Sphingidae).

PubMed

Rubinoff, Daniel; Le Roux, Johannes J

2008-01-01

Saltational evolution in which a particular lineage undergoes relatively rapid, significant, and unparalleled change as compared with its closest relatives is rarely invoked as an alternative model to the dominant paradigm of gradualistic evolution. Identifying saltational events is an important first-step in assessing the importance of this discontinuous model in generating evolutionary novelty. We offer evidence for three independent instances of saltational evolution in a charismatic moth genus with only eight species. Maximum parsimony, maximum likelihood and Bayesian search criteria offered congruent, well supported phylogenies based on 1,965 base pairs of DNA sequence using the mitochondrial gene cytochrome oxidase subunit I, and the nuclear genes elongation factor-1 alpha and wingless. Using a comparative methods approach, we examined three taxa exhibiting novelty in the form of Batesian mimicry, host plant shift, and dramatic physiological differences in light of the phylogenetic data. All three traits appear to have evolved relatively rapidly and independently in three different species of Proserpinus. Each saltational species exhibits a markedly different and discrete example of discontinuous trait evolution while remaining canalized for other typical traits shared by the rest of the genus. All three saltational taxa show insignificantly different levels of overall genetic change as compared with their congeners, implying that their divergence is targeted to particular traits and not genome-wide. Such rapid evolution of novel traits in individual species suggests that the pace of evolution can be quick, dramatic, and isolated--even on the species level. These results may be applicable to other groups in which specific taxa have generated pronounced evolutionary novelty. Genetic mechanisms and methods for assessing such relatively rapid changes are postulated.

Cannabis Smoking and Diabetes Mellitus: Results from Meta-Analysis with Eight Independent Replication Samples

PubMed Central

Alshaarawy, Omayma; Anthony, James C.

2016-01-01

Background In preclinical animal studies, evidence links cannabis smoking (CS) with hyperphagia, obesity, and insulin resistance. Nonetheless, in humans, CS might protect against type 2 diabetes mellitus (DM). Here, we offer epidemiological estimates from eight independent replications from (1) the National Health and Nutrition Examination Surveys, and (2) the National Surveys on Drug Use and Health (2005-12). Methods For each national survey participant, computer-assisted self-interviews assess CS and physician-diagnosed DM; NHANES provides additional biomarker values and a composite DM diagnosis. Regression analyses produce estimates of CS-DM associations. Meta-analyses summarize the replication estimates. Results Recently active CS and DM are inversely associated. The meta-analytic summary odds ratio is 0.7 (95% CI = 0.6, 0.8). Conclusions Current evidence is too weak for causal inference, but there now is a more stable evidence base for new lines of clinical translational research on a possibly protective (or spurious) CS-DM association suggested in prior research. PMID:25978795

Evidence-Based Communication Practices for Children with Visual Impairments and Additional Disabilities: An Examination of Single-Subject Design Studies

ERIC Educational Resources Information Center

Parker, Amy T.; Grimmett, Eric S.; Summers, Sharon

2008-01-01

This review examines practices for building effective communication strategies for children with visual impairments, including those with additional disabilities, that have been tested by single-subject design methodology. The authors found 30 studies that met the search criteria and grouped intervention strategies to align any evidence of the…

Fitness and Adiposity Are Independently Associated with Cardiometabolic Risk in Youth

PubMed Central

Buchan, Duncan S.; Young, John D.; Boddy, Lynne M.; Malina, Robert M.; Baker, Julien S.

2013-01-01

Purpose. The purpose of the study was to examine the independent associations of adiposity and cardiorespiratory fitness with clustered cardiometabolic risk. Methods. A cross-sectional sample of 192 adolescents (118 boys), aged 14–16 years, was recruited from a South Lanarkshire school in the West of Scotland. Anthropometry and blood pressure were measured, and blood samples were taken. The 20 m multistage fitness test was the indicator of cardiorespiratory fitness (CRF). A clustered cardiometabolic risk score was constructed from HDL-C (inverted), LDL-C, HOMA, systolic blood pressure, and triglycerides. Interleukin-6, C-reactive protein, and adiponectin were also measured and examined relative to the clustered cardiometabolic risk score, CRF, and adiposity. Results. Although significant, partial correlations between BMI and waist circumference (WC) and both CRF and adiponectin were negative and weak to moderate, while correlations between the BMI and WC and CRP were positive but weak to moderate. Weak to moderate negative associations were also evident for adiponectin with CRP, IL-6, and clustered cardiometabolic risk. WC was positively associated while CRF was negatively associated with clustered cardiometabolic risk. With the additional adjustment for either WC or CRF, the independent associations with cardiometabolic risk persisted. Conclusion. WC and CRF are independently associated with clustered cardiometabolic risk in Scottish adolescents. PMID:23984329

Evidence of Repeated and Independent Saltational Evolution in a Peculiar Genus of Sphinx Moths (Proserpinus: Sphingidae)

PubMed Central

Rubinoff, Daniel; Le Roux, Johannes J.

2008-01-01

Background Saltational evolution in which a particular lineage undergoes relatively rapid, significant, and unparalleled change as compared with its closest relatives is rarely invoked as an alternative model to the dominant paradigm of gradualistic evolution. Identifying saltational events is an important first-step in assessing the importance of this discontinuous model in generating evolutionary novelty. We offer evidence for three independent instances of saltational evolution in a charismatic moth genus with only eight species. Methodology/Principal Findings Maximum parsimony, maximum likelihood and Bayesian search criteria offered congruent, well supported phylogenies based on 1,965 base pairs of DNA sequence using the mitochondrial gene cytochrome oxidase subunit I, and the nuclear genes elongation factor-1 alpha and wingless. Using a comparative methods approach, we examined three taxa exhibiting novelty in the form of Batesian mimicry, host plant shift, and dramatic physiological differences in light of the phylogenetic data. All three traits appear to have evolved relatively rapidly and independently in three different species of Proserpinus. Each saltational species exhibits a markedly different and discrete example of discontinuous trait evolution while remaining canalized for other typical traits shared by the rest of the genus. All three saltational taxa show insignificantly different levels of overall genetic change as compared with their congeners, implying that their divergence is targeted to particular traits and not genome-wide. Conclusions/Significance Such rapid evolution of novel traits in individual species suggests that the pace of evolution can be quick, dramatic, and isolated—even on the species level. These results may be applicable to other groups in which specific taxa have generated pronounced evolutionary novelty. Genetic mechanisms and methods for assessing such relatively rapid changes are postulated. PMID:19107205

Fetal Genotype and Maternal Glucose Have Independent and Additive Effects on Birth Weight.

PubMed

Hughes, Alice E; Nodzenski, Michael; Beaumont, Robin N; Talbot, Octavious; Shields, Beverley M; Scholtens, Denise M; Knight, Bridget A; Lowe, William L; Hattersley, Andrew T; Freathy, Rachel M

2018-05-01

Maternal glycemia is a key determinant of birth weight, but recent large-scale genome-wide association studies demonstrated an important contribution of fetal genetics. It is not known whether fetal genotype modifies the impact of maternal glycemia or whether it acts through insulin-mediated growth. We tested the effects of maternal fasting plasma glucose (FPG) and a fetal genetic score for birth weight on birth weight and fetal insulin in 2,051 European mother-child pairs from the Exeter Family Study of Childhood Health (EFSOCH) and the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. The fetal genetic score influenced birth weight independently of maternal FPG and impacted growth at all levels of maternal glycemia. For mothers with FPG in the top tertile, the frequency of large for gestational age (birth weight ≥90th centile) was 31.1% for offspring with the highest tertile genetic score and only 14.0% for those with the lowest tertile genetic score. Unlike maternal glucose, the fetal genetic score was not associated with cord insulin or C-peptide. Similar results were seen for HAPO participants of non-European ancestry ( n = 2,842 pairs). This work demonstrates that for any level of maternal FPG, fetal genetics has a major impact on fetal growth and acts predominantly through independent mechanisms. © 2018 by the American Diabetes Association.

The independent relationship between triglycerides and coronary heart disease.

PubMed

Morrison, Alan; Hokanson, John E

2009-01-01

The aim was to review epidemiologic studies to reassess whether serum levels of triglycerides should be considered independently of high-density lipoprotein-cholesterol (HDL-C) as a predictor of coronary heart disease (CHD). We systematically reviewed population-based cohort studies in which baseline serum levels of triglycerides and HDL-C were included as explanatory variables in multivariate analyses with the development of CHD (coronary events or coronary death) as dependent variable. A total of 32 unique reports describing 38 cohorts were included. The independent association between elevated triglycerides and risk of CHD was statistically significant in 16 of 30 populations without pre-existing CHD. Among populations with diabetes mellitus or pre-existing CHD, or the elderly, triglycerides were not significantly independently associated with CHD in any of 8 cohorts. Triglycerides and HDL-C were mutually exclusive predictors of coronary events in 12 of 20 analyses of patients without pre-existing CHD. Epidemiologic studies provide evidence of an association between triglycerides and the development of primary CHD independently of HDL-C. Evidence of an inverse relationship between triglycerides and HDL-C suggests that both should be considered in CHD risk estimation and as targets for intervention.

Evidence for actin cytoskeleton-dependent and -independent pathways for RelA/p65 nuclear translocation in endothelial cells.

PubMed

Fazal, Fabeha; Minhajuddin, Mohd; Bijli, Kaiser M; McGrath, James L; Rahman, Arshad

2007-02-09

Activation of the transcription factor NF-kappaB involves its release from the inhibitory protein IkappaBalpha in the cytoplasm and subsequently, its translocation to the nucleus. Whereas the events responsible for its release have been elucidated, mechanisms regulating the nuclear transport of NF-kappaB remain elusive. We now provide evidence for actin cytoskeleton-dependent and -independent mechanisms of RelA/p65 nuclear transport using the proinflammatory mediators, thrombin and tumor necrosis factor alpha, respectively. We demonstrate that thrombin alters the actin cytoskeleton in endothelial cells and interfering with these alterations, whether by stabilizing or destabilizing the actin filaments, prevents thrombin-induced NF-kappaB activation and consequently, expression of its target gene, ICAM-1. The blockade of NF-kappaB activation occurs downstream of IkappaBalpha degradation and is associated with impaired RelA/p65 nuclear translocation. Importantly, thrombin induces association of RelA/p65 with actin and this interaction is sensitive to stabilization/destabilization of the actin filaments. In parallel studies, stabilizing or destabilizing the actin filaments fails to inhibit RelA/p65 nuclear accumulation and ICAM-1 expression by tumor necrosis factor alpha, consistent with its inability to induce actin filament formation comparable with thrombin. Thus, these studies reveal the existence of actin cytoskeleton-dependent and -independent pathways that may be engaged in a stimulus-specific manner to facilitate RelA/p65 nuclear import and thereby ICAM-1 expression in endothelial cells.

Why Additional Presentations Help Identify a Stimulus

ERIC Educational Resources Information Center

Guest, Duncan; Kent, Christopher; Adelman, James S.

2010-01-01

Nosofsky (1983) reported that additional stimulus presentations within a trial increase discriminability in absolute identification, suggesting that each presentation creates an independent stimulus representation, but it remains unclear whether exposure duration or the formation of independent representations improves discrimination in such…

No retrieval-induced forgetting using item-specific independent cues: evidence against a general inhibitory account.

PubMed

Camp, Gino; Pecher, Diane; Schmidt, Henk G

2007-09-01

Retrieval practice with particular items from memory can impair the recall of related items on a later memory test. This retrieval-induced forgetting effect has been ascribed to inhibitory processes (M. C. Anderson & B. A. Spellman, 1995). A critical finding that distinguishes inhibitory from interference explanations is that forgetting is found with independent (or extralist) cues. In 4 experiments, the authors tested whether the forgetting effect is cue-independent. Forgetting was investigated for both studied and unstudied semantically related items. Retrieval-induced forgetting was not found using item-specific independent cues for either studied or unstudied items. However, forgetting was found for both item types when studied categories were used as cues. These results are not in line with a general inhibitory account, because this account predicts retrieval-induced forgetting with independent cues. Interference and context-specific inhibition are discussed as possible explanations for the data. 2007 APA

The Evidence Value Matrix for Diagnostic Imaging.

PubMed

Seidel, David; Frank, Richard A; Schmidt, Sebastian

2016-10-01

Evidence and value are independent factors that together affect the adoption of diagnostic imaging. For example, noncoverage decisions by reimbursement authorities can be justified by a lack of evidence and/or value. To create transparency and a common understanding among various stakeholders, we have proposed a two-dimensional matrix that allows classification of imaging devices into three distinct categories based on the available evidence and value: "question marks" (low value demonstrated in studies of any evidence level), "candidates" (high value demonstrated in retrospective case-control studies and smaller case series), and "stars" (high value demonstrated in large prospective cohort studies or, preferably, randomized controlled trials). We use several examples to illustrate the application of our matrix. A major benefit of the matrix includes the development of specific strategies for evidence and value generation. High-evidence/low-value studies are expensive and unlikely to convince decision makers, given the uncertainty of the impact on patient management and outcomes. Developing question marks into candidates first and then into stars will often be quicker and less expensive ("success sequence"). Only this more sophisticated and objective approach can justify the additional funding necessary to generate the evidence base to inform reimbursement by payers and adoption by providers. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Low testosterone and non-alcoholic fatty liver disease: Evidence for their independent association in men with chronic spinal cord injury.

PubMed

Barbonetti, Arcangelo; Caterina Vassallo, Maria Rosaria; Cotugno, Michele; Felzani, Giorgio; Francavilla, Sandro; Francavilla, Felice

2016-07-01

Non-alcoholic fatty liver disease (NAFLD) has been claimed as a liver phenotype of metabolic syndrome, which in turn is associated with male hypogonadism. We assessed whether an independent association between NAFLD and androgen deficiency could be revealed in men with chronic spinal cord injury (SCI), who exhibit a high prevalence of biochemical androgen deficiency and a combination of risk factors for metabolic syndrome. Fifty-five consecutive men with chronic SCI admitted to a rehabilitation program underwent clinical/biochemical evaluations and liver ultrasonography. NAFLD was diagnosed in 27 patients (49.1%). Men with NAFLD were older and exhibited significantly higher body mass index, Homeostatic model assessment of insulin resistance, triglycerides and gamma-glutamyl transpeptidase values, lower total and free testosterone levels and they were engaged in a significantly poorer weekly leisure time physical activity (LTPA). At the multiple logistic regression analysis, only total and free testosterone levels exhibited a significant independent association with NAFLD. The risk of having NAFLD increased indeed of 1% for each decrement of 1 ng/dL of total testosterone and of 3% for each decrement of 1 pg/mL of free testosterone, after adjustment for confounders. In men with total testosterone < 300 ng/dL (36.4%) the prevalence of NAFLD reached 85%: they had a risk of having NAFLD significantly higher (∼12-fold) than those with total testosterone ≥ 300 ng/dL, after adjustment for confounders. The evidence of an independent association between NAFLD and low testosterone is strongly reinforced by its demonstration in men with chronic SCI, in spite of the many confounders peculiar to this population.

Isogambogenic acid induces apoptosis-independent autophagic cell death in human non-small-cell lung carcinoma cells.

PubMed

Yang, Jianhong; Zhou, Yongzhao; Cheng, Xia; Fan, Yi; He, Shichao; Li, Shucai; Ye, Haoyu; Xie, Caifeng; Wu, Wenshuang; Li, Chunyan; Pei, Heying; Li, Luyuan; Wei, Zhe; Peng, Aihua; Wei, Yuquan; Li, Weimin; Chen, Lijuan

2015-01-09

To overcome drug resistance caused by apoptosis deficiency in patients with non-small cell lung carcinoma (NSCLC), there is a need to identify other means of triggering apoptosis-independent cancer cell death. We are the first to report that isogambogenic acid (iso-GNA) can induce apoptosis-independent autophagic cell death in human NSCLC cells. Several features of the iso-GNA-treated NSCLC cells indicated that iso-GNA induced autophagic cell death. First, there was no evidence of apoptosis or cleaved caspase 3 accumulation and activation. Second, iso-GNA treatment induced the formation of autophagic vacuoles, increased LC3 conversion, caused the appearance of autophagosomes and increased the expression of autophagy-related proteins. These findings provide evidence that iso-GNA induces autophagy in NSCLC cells. Third, iso-GNA-induced cell death was inhibited by autophagic inhibitors or by selective ablation of Atg7 and Beclin 1 genes. Furthermore, the mTOR inhibitor rapamycin increased iso-GNA-induced cell death by enhancing autophagy. Finally, a xenograft model provided additional evidence that iso-GNA exhibited anticancer effect through inducing autophagy-dependent cell death in NSCLC cells. Taken together, our results demonstrated that iso-GNA exhibited an anticancer effect by inducing autophagy-dependent cell death in NSCLC cells, which may be an effective chemotherapeutic agent that can be used against NSCLC in a clinical setting.

Isogambogenic acid induces apoptosis-independent autophagic cell death in human non-small-cell lung carcinoma cells

PubMed Central

Yang, Jianhong; Zhou, Yongzhao; Cheng, Xia; Fan, Yi; He, Shichao; Li, Shucai; Ye, Haoyu; Xie, Caifeng; Wu, Wenshuang; Li, Chunyan; Pei, Heying; Li, Luyuan; Wei, Zhe; Peng, Aihua; Wei, Yuquan; Li, Weimin; Chen, Lijuan

2015-01-01

To overcome drug resistance caused by apoptosis deficiency in patients with non-small cell lung carcinoma (NSCLC), there is a need to identify other means of triggering apoptosis-independent cancer cell death. We are the first to report that isogambogenic acid (iso-GNA) can induce apoptosis-independent autophagic cell death in human NSCLC cells. Several features of the iso-GNA-treated NSCLC cells indicated that iso-GNA induced autophagic cell death. First, there was no evidence of apoptosis or cleaved caspase 3 accumulation and activation. Second, iso-GNA treatment induced the formation of autophagic vacuoles, increased LC3 conversion, caused the appearance of autophagosomes and increased the expression of autophagy-related proteins. These findings provide evidence that iso-GNA induces autophagy in NSCLC cells. Third, iso-GNA-induced cell death was inhibited by autophagic inhibitors or by selective ablation of Atg7 and Beclin 1 genes. Furthermore, the mTOR inhibitor rapamycin increased iso-GNA-induced cell death by enhancing autophagy. Finally, a xenograft model provided additional evidence that iso-GNA exhibited anticancer effect through inducing autophagy-dependent cell death in NSCLC cells. Taken together, our results demonstrated that iso-GNA exhibited an anticancer effect by inducing autophagy-dependent cell death in NSCLC cells, which may be an effective chemotherapeutic agent that can be used against NSCLC in a clinical setting. PMID:25571970

Independent evaluation: insights from public accounting.

PubMed

Brown, Abigail B; Klerman, Jacob Alex

2012-06-01

Maintaining the independence of contract government program evaluation presents significant contracting challenges. The ideal outcome for an agency is often both the impression of an independent evaluation and a glowing report. In this, independent evaluation is like financial statement audits: firm management wants both a public accounting firm to attest to the fairness of its financial accounts and to be allowed to account for transactions as it sees fit. In both cases, the evaluation or audit is being conducted on behalf of outsiders--the public or shareholders--but is overseen by a party with significant interests at stake in the outcome-the agency being evaluated or executive management of the firm. We review the contracting strategies developed to maintain independence in auditing. We examine evidence on the effectiveness of professionalism, reputation, liability and owner oversight in constraining behavior in auditing. We then establish parallels with contracting for evaluations and apply these insights to changes that might maintain and improve evaluator independence. By analogy with the Sarbanes Oxley Act of 2002 reforms in auditing, we recommend exploring using a reformulated Technical Working Group to encourage more prompt release of more evaluation results and to help insulate evaluators from inappropriate pressure to change their results or analysis approach.

The independent relationship between triglycerides and coronary heart disease

PubMed Central

Morrison, Alan; Hokanson, John E

2009-01-01

Aims: The aim was to review epidemiologic studies to reassess whether serum levels of triglycerides should be considered independently of high-density lipoprotein-cholesterol (HDL-C) as a predictor of coronary heart disease (CHD). Methods and results: We systematically reviewed population-based cohort studies in which baseline serum levels of triglycerides and HDL-C were included as explanatory variables in multivariate analyses with the development of CHD (coronary events or coronary death) as dependent variable. A total of 32 unique reports describing 38 cohorts were included. The independent association between elevated triglycerides and risk of CHD was statistically significant in 16 of 30 populations without pre-existing CHD. Among populations with diabetes mellitus or pre-existing CHD, or the elderly, triglycerides were not significantly independently associated with CHD in any of 8 cohorts. Triglycerides and HDL-C were mutually exclusive predictors of coronary events in 12 of 20 analyses of patients without pre-existing CHD. Conclusions: Epidemiologic studies provide evidence of an association between triglycerides and the development of primary CHD independently of HDL-C. Evidence of an inverse relationship between triglycerides and HDL-C suggests that both should be considered in CHD risk estimation and as targets for intervention. PMID:19436658

Additive effects of word frequency and stimulus quality: the influence of trial history and data transformations.

PubMed

Balota, David A; Aschenbrenner, Andrew J; Yap, Melvin J

2013-09-01

A counterintuitive and theoretically important pattern of results in the visual word recognition literature is that both word frequency and stimulus quality produce large but additive effects in lexical decision performance. The additive nature of these effects has recently been called into question by Masson and Kliegl (in press), who used linear mixed effects modeling to provide evidence that the additive effects were actually being driven by previous trial history. Because Masson and Kliegl also included semantic priming as a factor in their study and recent evidence has shown that semantic priming can moderate the additivity of word frequency and stimulus quality (Scaltritti, Balota, & Peressotti, 2012), we reanalyzed data from 3 published studies to determine if previous trial history moderated the additive pattern when semantic priming was not also manipulated. The results indicated that previous trial history did not influence the joint influence of word frequency and stimulus quality. More important, and independent of Masson and Kliegl's conclusions, we also show how a common transformation used in linear mixed effects analyses to normalize the residuals can systematically alter the way in which two variables combine to influence performance. Specifically, using transformed, rather than raw reaction times, consistently produces more underadditive patterns. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Independent and additive interaction between polymorphisms of tumor necrosis factor α-308 and lymphotoxin α+252 on risk of hepatocellular carcinoma related to hepatitis B.

PubMed

Tsai, Jung-Fa; Chen, Shinn-Chern; Lin, Zu-Yau; Dai, Chia-Yen; Huang, Jee-Fu; Yu, Min-Lung; Chuang, Wan-Long

2017-09-01

This case-control study was aimed to assess the effect of genetic variants of tumor necrosis factor (TNF) α-308 and lymphotoxin (LT) α+252 on development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Their gene-gene interaction was also investigated. We enrolled 200 pairs of age- and sex-matched patients with cirrhotic HBV-HCC and unrelated patients with HBV-cirrhosis alone. Polymorphisms of TNFα-308 and LTα+252 were genotyped. Synergy index was used to calculate interaction between the variant genotypes. The results indicated that the frequency distribution of the variant genotypes (TNFα-308 G/A and LTα+252 G/G) in patients with HCC were significantly higher than those in patients with cirrhosis alone. Multivariate analysis indicated that TNFα-308 G/A (odds ratio [OR], 2.34) and LTα+252 G/G (OR, 2.04) were independent risk factors for HCC. By the clinical characteristics of study population, multivariate analysis demonstrated that independent factors associated with harboring the variant genotypes included cirrhosis with Child-Pugh C (OR = 6.47 in cases and OR = 11.56 in controls) and thrombocytopenia (OR = 8.86 in cases and OR = 7.74 in controls). Calculation of synergy index (SI) indicated that there are additive interaction between TNFα-308 G/A and LTα+252 G/G on risk of HCC (SI = 1.29). There are independent and additive interactions between TNFα-308 G/A and LTα+252 G/G on risk for HBV-HCC. They correlated with advanced hepatic fibrosis and severe liver damage, which might contribute to a higher risk for HCC. Copyright © 2017 Kaohsiung Medical University. Published by Elsevier Taiwan. All rights reserved.

A conservative method of testing whether combination analgesics produce additive or synergistic effects using evidence from acute pain and migraine.

PubMed

Moore, R A; Derry, C J; Derry, S; Straube, S; McQuay, H J

2012-04-01

Fixed-dose combination analgesics are used widely, and available both on prescription and over-the-counter. Combination drugs should provide more analgesia than with any single drug in the combination, but there is no evidence in humans about whether oral combinations have just additive effects, or are synergistic or even subadditive. We suggest that the measured result for the combination would be the summation of the absolute benefit increase (effect of active drug minus effect of placebo) of each component of a combination if effects were (merely) additive, and greater than the sum of the absolute benefits if they were synergistic. We tested measured effects of combination analgesics against the sum of the absolute benefits in acute pain and migraine using meta-analysis where individual components and combinations were tested against placebo in the same trials, and verified the result with meta-analyses where individual components and combinations were tested against placebo in different trials. Results showed that expected numbers needed to treat (NNT) for additive effects were generally within the 95% confidence interval of measured NNTs. This was true for combinations of paracetamol plus ibuprofen and paracetamol plus opioids in acute pain, and naproxen plus sumatriptan in migraine, but not where efficacy was very low or very high, nor combinations of paracetamol plus dextropropoxyphene. There was no evidence of synergy, defined as supra-additive effects. © 2011 European Federation of International Association for the Study of Pain Chapters.

The Independent Associations of Physical Activity and Sleep with Cognitive Function in Older Adults.

PubMed

Falck, Ryan S; Best, John R; Davis, Jennifer C; Liu-Ambrose, Teresa

2018-01-01

Current evidence suggests physical activity (PA) and sleep are important for cognitive health; however, few studies examining the role of PA and sleep for cognitive health have measured these behaviors objectively. We cross-sectionally examined whether 1) higher PA is associated with better cognitive performance independently of sleep quality; 2) higher sleep quality is associated with better cognitive performance independently of PA; and 3) whether higher PA is associated with better sleep quality. We measured PA, subjective sleep quality using the Pittsburgh Sleep Quality Index (PSQI), and objective sleep quality (i.e., fragmentation, efficiency, duration, and latency) using the MotionWatch8© in community-dwelling adults (N = 137; aged 55+). Cognitive function was indexed using the Alzheimer's Disease Assessment Scale-Plus. Correlation analyses were performed to determine relationships between PA, sleep quality, and cognitive function. We then used latent variable modelling to examine the relationships of PA with cognitive function independently of sleep quality, sleep quality with cognitive function independently of PA, and PA with sleep quality. We found greater PA was associated with better cognitive performance independently of 1) PSQI (β= -0.03; p < 0.01); 2) sleep fragmentation (β= -0.02; p < 0.01); 3) sleep duration (β= -0.02; p < 0.01); and 4) sleep latency (β= -0.02; p < 0.01). In addition, better sleep efficiency was associated with better cognitive performance independently of PA (β= -0.01; p = 0.04). We did not find any associations between PA and sleep quality. PA is associated with better cognitive performance independently of sleep quality, and sleep efficiency is associated with better cognitive performance independently of PA. However, PA is not associated with sleep quality and thus PA and sleep quality may be related to cognitive performance through independent mechanisms.

Are Independent Probes Truly Independent?

ERIC Educational Resources Information Center

Camp, Gino; Pecher, Diane; Schmidt, Henk G.; Zeelenberg, Rene

2009-01-01

The independent cue technique has been developed to test traditional interference theories against inhibition theories of forgetting. In the present study, the authors tested the critical criterion for the independence of independent cues: Studied cues not presented during test (and unrelated to test cues) should not contribute to the retrieval…

Independent Axes of Genetic Variation and Parallel Evolutionary Divergence Of Opercle Bone Shape in Threespine Stickleback

PubMed Central

Kimmel, Charles B.; Cresko, William A.; Phillips, Patrick C.; Ullmann, Bonnie; Currey, Mark; von Hippel, Frank; Kristjánsson, Bjarni K.; Gelmond, Ofer; McGuigan, Katrina

2014-01-01

Evolution of similar phenotypes in independent populations is often taken as evidence of adaptation to the same fitness optimum. However, the genetic architecture of traits might cause evolution to proceed more often toward particular phenotypes, and less often toward others, independently of the adaptive value of the traits. Freshwater populations of Alaskan threespine stickleback have repeatedly evolved the same distinctive opercle shape after divergence from an oceanic ancestor. Here we demonstrate that this pattern of parallel evolution is widespread, distinguishing oceanic and freshwater populations across the Pacific Coast of North America and Iceland. We test whether this parallel evolution reflects genetic bias by estimating the additive genetic variance– covariance matrix (G) of opercle shape in an Alaskan oceanic (putative ancestral) population. We find significant additive genetic variance for opercle shape and that G has the potential to be biasing, because of the existence of regions of phenotypic space with low additive genetic variation. However, evolution did not occur along major eigenvectors of G, rather it occurred repeatedly in the same directions of high evolvability. We conclude that the parallel opercle evolution is most likely due to selection during adaptation to freshwater habitats, rather than due to biasing effects of opercle genetic architecture. PMID:22276538

Developing Independent Listening Skills for English as an Additional Language Students

ERIC Educational Resources Information Center

Picard, Michelle; Velautham, Lalitha

2016-01-01

This paper describes an action research project to develop online, self-access listening resources mirroring the authentic academic contexts experienced by graduate university students. Current listening materials for English as an Additional Language (EAL) students mainly use Standard American English or Standard British pronunciation, and far…

Changes in Faculty Composition at Independent Colleges

ERIC Educational Resources Information Center

Morphew, Christopher; Ward, Kelly; Wolf-Wendel, Lisa

2016-01-01

This report provides empirical evidence about specific trends in faculty staffing, roles, and responsibilities at smaller private liberal arts institutions in the United States, with a focus on the more than 600 four-year colleges and universities that are members of the Council of Independent Colleges. It also addresses how the changing…

Independent effects of colour on object identification and memory.

PubMed

Lloyd-Jones, Toby J; Nakabayashi, Kazuyo

2009-02-01

We examined the effects of colour on object identification and memory using a study-test priming procedure with a coloured-object decision task at test (i.e., deciding whether an object is correctly coloured). Objects were selected to have a single associated colour and were either correctly or incorrectly coloured. In addition, object shape and colour were either spatially integrated (i.e., colour fell on the object surface) or spatially separated (i.e., colour formed the background to the object). Transforming the colour of an object from study to test (e.g., from a yellow banana to a purple banana) reduced priming of response times, as compared to when the object was untransformed. This utilization of colour information in object memory was not contingent upon colour falling on the object surface or whether the resulting configuration was of a correctly or incorrectly coloured object. In addition, we observed independent effects of colour on response times, whereby coloured-object decisions were more efficient for correctly than for incorrectly coloured objects but only when colour fell on the object surface. These findings provide evidence for two distinct mechanisms of shape-colour binding in object processing.

The evidence for clinically significant bias in plasma glucose between liquid and lyophilized citrate buffer additive.

PubMed

Juricic, Gordana; Saracevic, Andrea; Kopcinovic, Lara Milevoj; Bakliza, Ana; Simundic, Ana-Maria

2016-12-01

Citrate buffer additive has been suggested to be of supreme performance in inhibiting glycolysis. However, there is little evidence in the literature regarding the comparability of glucose concentrations in liquid and lyophilized citrate buffer containing tubes. The aim of this study was to compare glucose concentrations in tubes containing liquid (Glucomedics) and lyophilized citrate buffer (Terumo VENOSAFE™ Glycemia) additive, measured immediately after centrifugation. Blood was collected from forty volunteers into both Glucomedics and Venosafe Glycemia tubes. Blood was centrifuged within 15min from venipuncture and glucose concentration was measured immediately after centrifugation, on the Abbott Architect analyzer. Differences between glucose concentrations in Glucomedics and Terumo tubes were tested using the paired t-test. Mean bias was calculated and compared to recommended quality specification for glucose (i.e. 2.2%). Glucose concentration in Terumo tubes was 3.4% lower than in Glucomedics tubes (P<0.001). The mean bias was clinically significant. There is a clinically significant difference between glucose concentrations in liquid and lyophilized citrate buffer additive tubes (Glucomedics vs. Terumo tubes) measured immediately after centrifugation. This difference may affect the patient outcome due to the misclassification of diabetes. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Making Mavericks: Preparing Musicians for Independent Artistic Culture

ERIC Educational Resources Information Center

Canham, Nicole L.

2016-01-01

This essay explores the role that maverick qualities--"independent or unorthodox behaviour" ("The Oxford Dictionary," 2015)--play in developing and sustaining musician employability. Whilst career education for musicians often highlights new career models (Bridgstock, 2005), there is limited evidence of how these concepts work…

Modes of independence while informal caregiving.

PubMed

Tellioğlu, Hilda; Hensely-Schinkinger, Susanne; Pinatti De Carvalho, Aparecido Fabiano

2015-01-01

This paper is about understanding and conceptualizing the notion of independence in the context of caregiving. Based on the current studies and on our ethnographic and design research in an AAL project (TOPIC) we introduce a model of independence consisting of four dimensions: action, finance, decision, and emotion. These interrelated dimensions are described and discussed in the setting of informal caregiving. Some additional examples are shown to illustrate how to reduce the dependence of informal caregivers before concluding the paper.

Concentration addition and independent action model: Which is better in predicting the toxicity for metal mixtures on zebrafish larvae.

PubMed

Gao, Yongfei; Feng, Jianfeng; Kang, Lili; Xu, Xin; Zhu, Lin

2018-01-01

The joint toxicity of chemical mixtures has emerged as a popular topic, particularly on the additive and potential synergistic actions of environmental mixtures. We investigated the 24h toxicity of Cu-Zn, Cu-Cd, and Cu-Pb and 96h toxicity of Cd-Pb binary mixtures on the survival of zebrafish larvae. Joint toxicity was predicted and compared using the concentration addition (CA) and independent action (IA) models with different assumptions in the toxic action mode in toxicodynamic processes through single and binary metal mixture tests. Results showed that the CA and IA models presented varying predictive abilities for different metal combinations. For the Cu-Cd and Cd-Pb mixtures, the CA model simulated the observed survival rates better than the IA model. By contrast, the IA model simulated the observed survival rates better than the CA model for the Cu-Zn and Cu-Pb mixtures. These findings revealed that the toxic action mode may depend on the combinations and concentrations of tested metal mixtures. Statistical analysis of the antagonistic or synergistic interactions indicated that synergistic interactions were observed for the Cu-Cd and Cu-Pb mixtures, non-interactions were observed for the Cd-Pb mixtures, and slight antagonistic interactions for the Cu-Zn mixtures. These results illustrated that the CA and IA models are consistent in specifying the interaction patterns of binary metal mixtures. Copyright © 2017 Elsevier B.V. All rights reserved.

Model-independent Evidence for Dark Energy Evolution from Baryon Acoustic Oscillations

NASA Astrophysics Data System (ADS)

Sahni, V.; Shafieloo, A.; Starobinsky, A. A.

2014-10-01

Baryon acoustic oscillations (BAOs) allow us to determine the expansion history of the universe, thereby shedding light on the nature of dark energy. Recent observations of BAOs in the Sloan Digital Sky Survey (SDSS) DR9 and DR11 have provided us with statistically independent measurements of H(z) at redshifts of 0.57 and 2.34, respectively. We show that these measurements can be used to test the cosmological constant hypothesis in a model-independent manner by means of an improved version of the Om diagnostic. Our results indicate that the SDSS DR11 measurement of H(z) = 222 ± 7 km s-1 Mpc-1 at z = 2.34, when taken in tandem with measurements of H(z) at lower redshifts, imply considerable tension with the standard ΛCDM model. Our estimation of the new diagnostic Omh 2 from SDSS DR9 and DR11 data, namely, Omh 2 ≈ 0.122 ± 0.01, which is equivalent to Ω0m h 2 for the spatially flat ΛCDM model, is in tension with the value Ω0m h 2 = 0.1426 ± 0.0025 determined for ΛCDM from Planck+WP. This tension is alleviated in models in which the cosmological constant was dynamically screened (compensated) in the past. Such evolving dark energy models display a pole in the effective equation of state of dark energy at high redshifts, which emerges as a smoking gun test for these theories.

Apology in the criminal justice setting: evidence for including apology as an additional component in the legal system.

PubMed

Petrucci, Carrie J

2002-01-01

The criminal justice system has reached unprecedented scope in the United States, with over 6.4 million people under some type of supervision. Remedies that have the potential to reduce this number are continually being sought. This article analyzes an innovative strategy currently being reconsidered in criminal justice: the apology. Despite a legal system that only sporadically acknowledges it, evidence for the use of apology is supported by social science research, current criminal justice theories, case law, and empirical studies. Social psychological, sociological and socio-legal studies pinpoint the elements and function of apology, what makes apologies effective, and concerns about apology if it were implemented in the criminal justice system. Theoretical evidence is examined (including restorative justice, therapeutic jurisprudence, crime, shame, and reintegration) to explore the process of apology in the criminal justice context. Attribution theory and social conduct theory are used to explain the apology process specifically for victims and offenders. A brief examination of case law reveals that though apology has no formal place in criminal law, it has surfaced recently under the federal sentencing guidelines. Finally, empirical evidence in criminal justice settings reveals that offenders want to apologize and victims desire an apology. Moreover, by directly addressing the harmful act, apology may be the link to reduced recidivism for offenders, as well as empowerment for victims. This evidence combined suggests that apology is worthy of further study as a potentially valuable addition to the criminal justice process. Copyright 2002 John Wiley & Sons, Ltd.

An Additional Baurusuchid from the Cretaceous of Brazil with Evidence of Interspecific Predation among Crocodyliformes

PubMed Central

Godoy, Pedro L.; Montefeltro, Felipe C.; Norell, Mark A.; Langer, Max C.

2014-01-01

A new Baurusuchidae (Crocodyliformes, Mesoeucrocodylia), Aplestosuchus sordidus, is described based on a nearly complete skeleton collected in deposits of the Adamantina Formation (Bauru Group, Late Cretaceous) of Brazil. The nesting of the new taxon within Baurusuchidae can be ensured based on several exclusive skull features of this clade, such as the quadrate depression, medial approximation of the prefrontals, rostral extension of palatines (not reaching the level of the rostral margin of suborbital fenestrae), cylindrical dorsal portion of palatine bar, ridge on the ectopterygoid-jugal articulation, and supraoccipital with restricted thin transversal exposure in the caudalmost part of the skull roof. A newly proposed phylogeny of Baurusuchidae encompasses A. sordidus and recently described forms, suggesting its sixter-taxon relationship to Baurusuchus albertoi, within Baurusuchinae. Additionally, the remains of a sphagesaurid crocodyliform were preserved in the abdominal cavity of the new baurusuchid. Direct fossil evidence of behavioral interaction among fossil crocodyliforms is rare and mostly restricted to bite marks resulting from predation, as well as possible conspecific male-to-male aggression. This is the first time that a direct and unmistaken evidence of predation between different taxa of this group is recorded as fossils. This discovery confirms that baurusuchids were top predators of their time, with sphagesaurids occupying a lower trophic position, possibly with a more generalist diet. PMID:24809508

Voluntary settlement and the spirit of independence: evidence from Japan's "Northern frontier".

PubMed

Kitayama, Shinobu; Ishii, Keiko; Imada, Toshie; Takemura, Kosuke; Ramaswamy, Jenny

2006-09-01

The authors hypothesized that economically motivated voluntary settlement in the frontier fosters independent agency. While illuminating the historical origin of American individualism, this hypothesis can be most powerfully tested in a region that is embedded in a broader culture of interdependence and yet has undergone a recent history of such settlement. The authors therefore examined residents of Japan's northern island (Hokkaido). Hokkaido was extensively settled by ethnic Japanese beginning in the 1870s and for several decades thereafter. Many of the current residents of Hokkaido are the descendents of the original settlers from this period. As predicted, Japanese socialized and/or immersed in Hokkaido were nearly as likely as European Americans in North America to associate happiness with personal achievement (Study 1), to show a personal dissonance effect wherein self-justification is motivated by a threat to personal self-images (Study 2), and to commit a dispositional bias in causal attribution (Study 3). In contrast, these marker effects of independent agency were largely absent for non-Hokkaido residents in Japan. Implications for theories of cultural change and persistence are discussed. ((c) 2006 APA, all rights reserved).

Independent School Leadership: Heads, Boards, and Strategic Thinking

ERIC Educational Resources Information Center

Baker, Troy; Campbell, Stephen; Ostroff, David

2016-01-01

This study seeks to identify and assess factors that contribute to effective independent school governance at the board of trustees level. A review of extant literature reveals two major challenges: (a) definitions and standards of board effectiveness are inconsistent, and (b) there is very little empirical evidence to support existing definitions…

Impaired hippocampus-dependent and -independent learning in IL-6 deficient mice.

PubMed

Baier, Paul Christian; May, Ulrike; Scheller, Jürgen; Rose-John, Stefan; Schiffelholz, Thomas

2009-06-08

Interleukin-6 (IL-6) is a cytokine that, in addition to its essential role in the function of the immune system, is present in the central nervous system (CNS). In particular, pathologically increased CNS IL-6 has been linked to impairments in memory performance. Thus, the aim of our present study was to investigate hippocampus-dependent and -independent memory, in combination with exploratory and anxiety related behaviour in IL-6 knock-out (IL-6KO) mice. The experiments were performed with 9 male IL-6KO and 9 age matched male wild-type (CTRL) mice. Hippocampus-dependent learning was assessed with the Morris water maze (MWM), hippocampus-independent learning with the novel object recognition memory test (NORM). The test-battery for additional behavioural assessments included open field (OF), elevated plus maze (EPM) and forced swim test (FST). IL-6KO mice showed impaired memory processes in the NORM as well in the MWM test. This could not be explained by reduced general activity or increased baseline anxiety. But, there was evidence for a higher susceptibility for stress and reduced exploratory behaviour in IL-6KO mice. In conclusion, absent CNS IL-6 does not lead to an improvement in memory function, but instead to an impairment. As "too little and too much spoils everything", our findings do not contradict the hypothesis of an involvement of IL-6 in memory processes. However, it remains unclear if impairments of memory are a specific result of disturbed IL-6 signalling, or rather an epiphenomenon associated with reduced exploratory behaviour and stress resistance.

Hydrogenase-independent uptake and metabolism of electrons by the archaeon Methanococcus maripaludis

PubMed Central

Lohner, Svenja T; Deutzmann, Jörg S; Logan, Bruce E; Leigh, John; Spormann, Alfred M

2014-01-01

Direct, shuttle-free uptake of extracellular, cathode-derived electrons has been postulated as a novel mechanism of electron metabolism in some prokaryotes that may also be involved in syntrophic electron transport between two microorganisms. Experimental proof for direct uptake of cathodic electrons has been mostly indirect and has been based on the absence of detectable concentrations of molecular hydrogen. However, hydrogen can be formed as a transient intermediate abiotically at low cathodic potentials (<−414 mV) under conditions of electromethanogenesis. Here we provide genetic evidence for hydrogen-independent uptake of extracellular electrons. Methane formation from cathodic electrons was observed in a wild-type strain of the methanogenic archaeon Methanococcus maripaludis as well as in a hydrogenase-deletion mutant lacking all catabolic hydrogenases, indicating the presence of a hydrogenase-independent mechanism of electron catabolism. In addition, we discovered a new route for hydrogen or formate production from cathodic electrons: Upon chemical inhibition of methanogenesis with 2-bromo-ethane sulfonate, hydrogen or formate accumulated in the bioelectrochemical cells instead of methane. These results have implications for our understanding on the diversity of microbial electron uptake and metabolism. PMID:24844759

Hydrogenase-independent uptake and metabolism of electrons by the archaeon Methanococcus maripaludis.

PubMed

Lohner, Svenja T; Deutzmann, Jörg S; Logan, Bruce E; Leigh, John; Spormann, Alfred M

2014-08-01

Direct, shuttle-free uptake of extracellular, cathode-derived electrons has been postulated as a novel mechanism of electron metabolism in some prokaryotes that may also be involved in syntrophic electron transport between two microorganisms. Experimental proof for direct uptake of cathodic electrons has been mostly indirect and has been based on the absence of detectable concentrations of molecular hydrogen. However, hydrogen can be formed as a transient intermediate abiotically at low cathodic potentials (<-414 mV) under conditions of electromethanogenesis. Here we provide genetic evidence for hydrogen-independent uptake of extracellular electrons. Methane formation from cathodic electrons was observed in a wild-type strain of the methanogenic archaeon Methanococcus maripaludis as well as in a hydrogenase-deletion mutant lacking all catabolic hydrogenases, indicating the presence of a hydrogenase-independent mechanism of electron catabolism. In addition, we discovered a new route for hydrogen or formate production from cathodic electrons: Upon chemical inhibition of methanogenesis with 2-bromo-ethane sulfonate, hydrogen or formate accumulated in the bioelectrochemical cells instead of methane. These results have implications for our understanding on the diversity of microbial electron uptake and metabolism.

Cultural variation in implicit independence: An extension of Kitayama et al. ().

PubMed

Park, Jiyoung; Uchida, Yukiko; Kitayama, Shinobu

2016-08-01

Previous research shows that European Americans are consistently more independent (or less interdependent) than Japanese when implicit indices are used to assess independence (vs. interdependence). The present work extended this evidence by including a novel implicit association test (IAT), as an index of implicit attitude towards independence and interdependence. Consistent with the previous findings, as compared to Japanese, Americans were significantly higher in multiple indices of implicit independence (vs. interdependence) including personal (vs. social) self-definition, experience of disengaging (vs. engaging) emotions and personal (vs. social) form of happiness. Furthermore, as compared to Japanese, Americans had a significantly more positive implicit attitude towards independence assessed with the IAT. As also observed in the previous research, explicit measures showed inconsistent cross-cultural patterns. Lastly, we observed little statistical within-culture coherence among the implicit measures of independence (vs. interdependence), consistent with a view that the implicit indices capture alternative ways for individuals to achieve the cultural mandate of independence or interdependence. © 2015 International Union of Psychological Science.

Independent Representation of Parts and the Relations between Them: Evidence from Integrative Agnosia

ERIC Educational Resources Information Center

Behrmann, Marlene; Peterson, Mary A.; Moscovitch, Morris; Suzuki, Satoru

2006-01-01

Whether objects are represented as a collection of parts whose relations are coded independently remains a topic of ongoing discussion among theorists in the domain of shape perception. S. M., an individual with integrative agnosia, and neurologically intact ("normal") individuals learned initially to identify 4 target objects constructed of 2…

Smoking as a Crucial Independent Determinant of Stroke

PubMed Central

Paul, Seana L; Thrift, Amanda G; Donnan, Geoffrey A

2004-01-01

Background Although smoking is known to be powerful risk factor for other vascular diseases, such as cardiac and peripheral vascular disease, only relatively recently has evidence for the role of smoking in the development of stroke been established. The reasons for this advance lie in the acknowledgement that stroke is a heterogeneous disease, in which its subtypes are associated with different risk factors. Furthermore, improvements in the stringency of epidemiological studies and the greater use of CT scanning have enabled the role of smoking in the development of stroke to be elucidated. Summary of review This is a qualitative examination of high quality epidemiological studies in which the role of smoking and passive smoking, as a risk factor for cerebral infarction, intracerebral haemorrhage and subarachnoid haemorrhage, is examined. In addition, the pathological mechanisms by which smoking or passive smoking may contribute to the development of stroke are reviewed. Conclusion Smoking is a crucial independent determinant of cerebral infarction and subarachnoid haemorrhage, however its role in intracerebral haemorrhage is unclear. Although studies are limited, there is evidence that exposure to passive smoking may also increase the risk of stroke. Smoking appears to be involved in the pathogenesis of stroke via direct injury to the vasculature and also by altering haemodynamic factors within the circulation. Importantly, smoking is modifiable risk factor for stroke. Therefore, the encouragement of smoking cessation may result in a substantial reduction in the incidence of this devastating disease.

Smoking as a Crucial Independent Determinant of Stroke

PubMed Central

Paul, Seana L; Thrift, Amanda G; Donnan, Geoffrey A

2004-01-01

Background Although smoking is known to be powerful risk factor for other vascular diseases, such as cardiac and peripheral vascular disease, only relatively recently has evidence for the role of smoking in the development of stroke been established. The reasons for this advance lie in the acknowledgement that stroke is a heterogeneous disease, in which its subtypes are associated with different risk factors. Furthermore, improvements in the stringency of epidemiological studies and the greater use of CT scanning have enabled the role of smoking in the development of stroke to be elucidated. Summary of review This is a qualitative examination of high quality epidemiological studies in which the role of smoking and passive smoking, as a risk factor for cerebral infarction, intracerebral haemorrhage and subarachnoid haemorrhage, is examined. In addition, the pathological mechanisms by which smoking or passive smoking may contribute to the development of stroke are reviewed. Conclusion Smoking is a crucial independent determinant of cerebral infarction and subarachnoid haemorrhage, however its role in intracerebral haemorrhage is unclear. Although studies are limited, there is evidence that exposure to passive smoking may also increase the risk of stroke. Smoking appears to be involved in the pathogenesis of stroke via direct injury to the vasculature and also by altering haemodynamic factors within the circulation. Importantly, smoking is modifiable risk factor for stroke. Therefore, the encouragement of smoking cessation may result in a substantial reduction in the incidence of this devastating disease. PMID:19570273

Consumer perspectives on nurse practitioners and independent practice.

PubMed

Brown, Deonne J

2007-10-01

The purposes of this study were to report the results of a survey for determining the feasibility and sustainability of independently managed nurse practitioner (NP) practices, to identify the characteristics of consumers who would likely choose an independent NP practice, to assess consumer needs, and to define a target market for competitively positioning NPs. An anonymous electronic survey of 1000 employees (response rate = 21%) at a large nonprofit organization in King County, Washington. This organization employs persons in a wide range of socioeconomic and vocational situations. Descriptive statistics and chi-square analyses were applied to determine associations between demographic characteristics and having used an NP or having the intent to use an independent NP practice. Most respondents knew about NPs, and the majority had seen an NP for their care. Most were satisfied or very satisfied with NP care. A much larger percentage (90%) than previous studies knew about NPs; 58% had seen an NP for their care, making NPs the most used practitioner alternative to physicians. Evidence suggests that NP users are more likely to be female and younger. Eighty-two percent of NP users were satisfied or very satisfied with the care they had received compared to a 70% satisfaction rate for current providers. Women, relatively younger respondents, those who had seen a physician assistant or NP, and those who considered NPs to provide quality and more personalized care were significantly more likely to indicate that they would choose an independent NP practice in their community. Based on a standard marketing formula, 30% of the sample in this study would be expected to change their health care to such a practice. This is the first descriptive study to suggest widespread acceptance of NPs as independent practitioners. Compared to a 1985 study of Seattle residents, consumers are far more likely to know about NPs. Consumer studies such as this one identify the characteristics

Are independent probes truly independent?

PubMed

Camp, Gino; Pecher, Diane; Schmidt, Henk G; Zeelenberg, René

2009-07-01

The independent cue technique has been developed to test traditional interference theories against inhibition theories of forgetting. In the present study, the authors tested the critical criterion for the independence of independent cues: Studied cues not presented during test (and unrelated to test cues) should not contribute to the retrieval process. Participants first studied a subset of cues (e.g., rope) that were subsequently studied together with a target in a 2nd study phase (e.g., rope-sailing, sunflower-yellow). In the test phase, an extralist category cue (e.g., sports, color) was presented, and participants were instructed to recall an item from the study list that was a member of the category (e.g., sailing, yellow). The experiments showed that previous study of the paired-associate word (e.g., rope) enhanced category cued recall even though this word was not presented at test. This experimental demonstration of covert cuing has important implications for the effectiveness of the independent cue technique.

On an Additive Semigraphoid Model for Statistical Networks With Application to Pathway Analysis.

PubMed

Li, Bing; Chun, Hyonho; Zhao, Hongyu

2014-09-01

We introduce a nonparametric method for estimating non-gaussian graphical models based on a new statistical relation called additive conditional independence, which is a three-way relation among random vectors that resembles the logical structure of conditional independence. Additive conditional independence allows us to use one-dimensional kernel regardless of the dimension of the graph, which not only avoids the curse of dimensionality but also simplifies computation. It also gives rise to a parallel structure to the gaussian graphical model that replaces the precision matrix by an additive precision operator. The estimators derived from additive conditional independence cover the recently introduced nonparanormal graphical model as a special case, but outperform it when the gaussian copula assumption is violated. We compare the new method with existing ones by simulations and in genetic pathway analysis.

Reconciling catch differences from multiple fishery independent gill net surveys

USGS Publications Warehouse

Kraus, Richard T.; Vandergoot, Christopher; Kocovsky, Patrick M.; Rogers, Mark W.; Cook, H. Andrew; Brenden, Travis O.

2017-01-01

Fishery independent gill net surveys provide valuable demographic information for population assessment and resource management, but relative to net construction, the effects of ancillary species, and environmental variables on focal species catch rates are poorly understood. In response, we conducted comparative deployments with three unique, inter-agency, survey gill nets used to assess walleye Sander vitreus in Lake Erie. We used an information-theoretic approach with Akaike’s second-order information criterion (AICc) to evaluate linear mixed models of walleye catch as a function of net type (multifilament and two types of monofilament netting), mesh size (categorical), Secchi depth, temperature, water depth, catch of ancillary species, and interactions among selected variables. The model with the greatest weight of evidence showed that walleye catches were positively associated with potential prey and intra-guild predators and negatively associated with water depth and temperature. In addition, the multifilament net had higher average walleye catches than either of the two monofilament nets. Results from this study both help inform decisions about proposed gear changes to stock assessment surveys in Lake Erie, and advance our understanding of how multispecies associations explain variation in gill net catches. Of broader interest to fishery-independent gill net studies, effects of abiotic variables and ancillary species on focal specie’s catch rates were small in comparison with net characteristics of mesh size or twine type.

Negative Regulation of Autophagy by Sulfide Is Independent of Reactive Oxygen Species.

PubMed

Laureano-Marín, Ana M; Moreno, Inmaculada; Romero, Luis C; Gotor, Cecilia

2016-06-01

Accumulating experimental evidence in mammalian, and recently plant, systems has led to a change in our understanding of the role played by hydrogen sulfide in life processes. In plants, hydrogen sulfide mitigates stress and regulates important plant processes such as photosynthesis, stomatal movement, and autophagy, although the underlying mechanism is not well known. In this study, we provide new experimental evidence that, together with our previous findings, demonstrates the role of hydrogen sulfide in regulating autophagy. We used green fluorescent protein fluorescence associated with autophagic bodies and immunoblot analysis of the ATG8 protein to show that sulfide (and no other molecules such as sulfur-containing molecules or ammonium) was able to inhibit the autophagy induced in Arabidopsis (Arabidopsis thaliana) roots under nitrogen deprivation. Our results showed that sulfide was unable to scavenge reactive oxygen species generated by nitrogen limitation, in contrast to well-established reducers. In addition, reducers were unable to inhibit the accumulation of autophagic bodies and ATG8 protein forms to the same extent as sulfide. Therefore, we conclude that sulfide represses autophagy via a mechanism that is independent of redox conditions. © 2016 American Society of Plant Biologists. All Rights Reserved.

Expanded HTA, Legitimacy and Independence

PubMed Central

Syrett, Keith

2016-01-01

This brief commentary seeks to develop the analysis of Daniels, Porteny and Urrutia of the implications of expansion of the scope of health technology assessment (HTA) beyond issues of safety, efficacy, and cost-effectiveness. Drawing in particular on experience in the United Kingdom, it suggests that such expansion can be understood not only as a response to the problem of insufficiency of evidence, but also to that of legitimacy. However, as expansion of HTA also renders it more visibly political in character, it is plausible that its legitimacy may be undermined, rather than enhanced by, independence from the policy process. PMID:27694685

46 CFR 355.5 - Additional material.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 8 2011-10-01 2011-10-01 false Additional material. 355.5 Section 355.5 Shipping... STATES CITIZENSHIP § 355.5 Additional material. If additional material is determined to be essential to clarify or support the evidence of U.S. citizenship, such material shall be furnished by the...

46 CFR 355.5 - Additional material.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 8 2014-10-01 2014-10-01 false Additional material. 355.5 Section 355.5 Shipping... STATES CITIZENSHIP § 355.5 Additional material. If additional material is determined to be essential to clarify or support the evidence of U.S. citizenship, such material shall be furnished by the...

46 CFR 355.5 - Additional material.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 8 2013-10-01 2013-10-01 false Additional material. 355.5 Section 355.5 Shipping... STATES CITIZENSHIP § 355.5 Additional material. If additional material is determined to be essential to clarify or support the evidence of U.S. citizenship, such material shall be furnished by the...

Clinical validity of new genetic biomarkers of irinotecan neutropenia: an independent replication study.

PubMed

Crona, D J; Ramirez, J; Qiao, W; de Graan, A-J; Ratain, M J; van Schaik, R H N; Mathijssen, R H J; Rosner, G L; Innocenti, F

2016-02-01

The overall goal of this study was to provide evidence for the clinical validity of nine genetic variants in five genes previously associated with irinotecan neutropenia and pharmacokinetics. Variants associated with absolute neutrophil count (ANC) nadir and/or irinotecan pharmacokinetics in a discovery cohort of cancer patients were genotyped in an independent replication cohort of 108 cancer patients. Patients received single-agent irinotecan every 3 weeks. For ANC nadir, we replicated UGT1A1*28, UGT1A1*93 and SLCO1B1*1b in univariate analyses. For irinotecan area under the concentration-time curve (AUC0-24), we replicated ABCC2 -24C>T; however, ABCC2 -24C>T only predicted a small fraction of the variance. For SN-38 AUC0-24 and the glucuronidation ratio, we replicated UGT1A1*28 and UGT1A1*93. In addition to UGT1A1*28, this study independently validated UGT1A1*93 and SLCO1B1*1b as new predictors of irinotecan neutropenia. Further demonstration of their clinical utility will optimize irinotecan therapy in cancer patients.

Additional weekend therapy may reduce length of rehabilitation stay after stroke: a meta-analysis of individual patient data.

PubMed

English, Coralie; Shields, Nora; Brusco, Natasha K; Taylor, Nicholas F; Watts, Jennifer J; Peiris, Casey; Bernhardt, Julie; Crotty, Maria; Esterman, Adrian; Segal, Leonie; Hillier, Susan

2016-07-01

Among people receiving inpatient rehabilitation after stroke, does additional weekend physiotherapy and/or occupational therapy reduce the length of rehabilitation hospital stay compared to those who receive a weekday-only service, and does this change after controlling for individual factors? Does additional weekend therapy improve the ability to walk and perform activities of daily living, measured at discharge? Does additional weekend therapy improve health-related quality of life, measured 6 months after discharge from rehabilitation? Which individual, clinical and hospital characteristics are associated with shorter length of rehabilitation hospital stay? This study pooled individual data from two randomised, controlled trials (n=350) using an individual patient data meta-analysis and multivariate regression. People with stroke admitted to inpatient rehabilitation facilities. Additional weekend therapy (physiotherapy and/or occupational therapy) compared to usual care (5 days/week therapy). Length of rehabilitation hospital stay, independence in activities of daily living measured with the Functional Independence Measure, walking speed and health-related quality of life. Participants who received weekend therapy had a shorter length of rehabilitation hospital stay. In the un-adjusted analysis, this was not statistically significant (MD -5.7 days, 95% CI -13.0 to 1.5). Controlling for hospital site, age, walking speed and Functional Independence Measure score on admission, receiving weekend therapy was significantly associated with a shorter length of rehabilitation hospital stay (β=7.5, 95% CI 1.7 to 13.4, p=0.001). There were no significant between-group differences in Functional Independence Measure scores (MD 1.9 points, 95% CI -2.8 to 6.6), walking speed (MD 0.06 m/second, 95% CI -0.15 to 0.04) or health-related quality of life (SMD -0.04, 95% CI -0.26 to 0.19) at discharge. Modest evidence indicates that additional weekend therapy might reduce

Inhibitory effects of thought substitution in the think/no-think task: evidence from independent cues.

PubMed

del Prete, Francesco; Hanczakowski, Maciej; Bajo, Maria Teresa; Mazzoni, Giuliana

2015-01-01

When people try not to think about a certain item, they can accomplish this goal by using a thought substitution strategy and think about something else. Research conducted with the think/no-think (TNT) paradigm indicates that such strategy leads subsequently to forgetting the information participants tried not to think about. The present study pursued two goals. First, it investigated the mechanism of forgetting due to thought substitution, contrasting the hypothesis by which forgetting is due to blocking caused by substitutes with the hypothesis that forgetting is due to inhibition (using an independent cue methodology). Second, a boundary condition for forgetting due to thought substitution was examined by creating conditions under which the generation of appropriate substitutes would be impaired. In two experiments, participants completed a TNT task under thought substitution instructions in which either words or pseudo-words were used as original cues and memory was assessed with original and independent cues. The results revealed forgetting in both original and independent cue tests, supporting the inhibitory account of thought substitution, but only when cues were words, and not when they were non-words, pointing to the ineffectiveness of a thought substitution strategy when original cues lack semantic content.

A comparison of the weights-of-evidence method and probabilistic neural networks

USGS Publications Warehouse

Singer, Donald A.; Kouda, Ryoichi

1999-01-01

The need to integrate large quantities of digital geoscience information to classify locations as mineral deposits or nondeposits has been met by the weights-of-evidence method in many situations. Widespread selection of this method may be more the result of its ease of use and interpretation rather than comparisons with alternative methods. A comparison of the weights-of-evidence method to probabilistic neural networks is performed here with data from Chisel Lake-Andeson Lake, Manitoba, Canada. Each method is designed to estimate the probability of belonging to learned classes where the estimated probabilities are used to classify the unknowns. Using these data, significantly lower classification error rates were observed for the neural network, not only when test and training data were the same (0.02 versus 23%), but also when validation data, not used in any training, were used to test the efficiency of classification (0.7 versus 17%). Despite these data containing too few deposits, these tests of this set of data demonstrate the neural network's ability at making unbiased probability estimates and lower error rates when measured by number of polygons or by the area of land misclassified. For both methods, independent validation tests are required to ensure that estimates are representative of real-world results. Results from the weights-of-evidence method demonstrate a strong bias where most errors are barren areas misclassified as deposits. The weights-of-evidence method is based on Bayes rule, which requires independent variables in order to make unbiased estimates. The chi-square test for independence indicates no significant correlations among the variables in the Chisel Lake–Andeson Lake data. However, the expected number of deposits test clearly demonstrates that these data violate the independence assumption. Other, independent simulations with three variables show that using variables with correlations of 1.0 can double the expected number of deposits

Cognitive Abilities Independent of IQ Correlate with Regional Brain Structure

ERIC Educational Resources Information Center

Johnson, Wendy; Jung, Rex E.; Colom, Roberto; Haier, Richard J.

2008-01-01

There is increasing evidence relating psychometric measures of general intelligence and reasoning to regional brain structure and function assessed with a variety of neuroimaging techniques. Cognitive dimensions independent of general intelligence can also be identified psychometrically and studied for any neuroanatomical correlates. Here we…

Capital Investment by Independent and System-Affiliated Hospitals

PubMed Central

Carroll, Nathan W.; Smith, Dean G.; Wheeler, John R. C.

2015-01-01

Capital expenditures are a critical part of hospitals’ efforts to maintain quality of patient care and financial stability. Over the past 20 years, finding capital to fund these expenditures has become increasingly challenging for hospitals, particularly independent hospitals. Independent hospitals struggling to find ways to fund necessary capital investment are often advised that their best strategy is to join a multi-hospital system. There is scant empirical evidence to support the idea that system membership improves independent hospitals’ ability to make capital expenditures. Using data from the American Hospital Association and Medicare Cost Reports, we use difference-in-difference methods to examine changes in capital expenditures for independent hospitals that joined multi-hospital systems between 1997 and 2008. We find that in the first 5 years after acquisition, capital expenditures increase by an average of almost $16 000 per bed annually, as compared with non-acquired hospitals. In later years, the difference in capital expenditure is smaller and not statistically significant. Our results do not suggest that increases in capital expenditures vary by asset age or the size of the acquiring system. PMID:26105571

Capital Investment by Independent and System-Affiliated Hospitals.

PubMed

Carroll, Nathan W; Smith, Dean G; Wheeler, John R C

2015-01-01

Capital expenditures are a critical part of hospitals' efforts to maintain quality of patient care and financial stability. Over the past 20 years, finding capital to fund these expenditures has become increasingly challenging for hospitals, particularly independent hospitals. Independent hospitals struggling to find ways to fund necessary capital investment are often advised that their best strategy is to join a multi-hospital system. There is scant empirical evidence to support the idea that system membership improves independent hospitals' ability to make capital expenditures. Using data from the American Hospital Association and Medicare Cost Reports, we use difference-in-difference methods to examine changes in capital expenditures for independent hospitals that joined multi-hospital systems between 1997 and 2008. We find that in the first 5 years after acquisition, capital expenditures increase by an average of almost $16,000 per bed annually, as compared with non-acquired hospitals. In later years, the difference in capital expenditure is smaller and not statistically significant. Our results do not suggest that increases in capital expenditures vary by asset age or the size of the acquiring system. © The Author(s) 2015.

Tic20 forms a channel independent of Tic110 in chloroplasts

PubMed Central

2011-01-01

Background The Tic complex (Translocon at the inner envelope membrane of chloroplasts) mediates the translocation of nuclear encoded chloroplast proteins across the inner envelope membrane. Tic110 forms one prominent protein translocation channel. Additionally, Tic20, another subunit of the complex, was proposed to form a protein import channel - either together with or independent of Tic110. However, no experimental evidence for Tic20 channel activity has been provided so far. Results We performed a comprehensive biochemical and electrophysiological study to characterize Tic20 in more detail and to gain a deeper insight into its potential role in protein import into chloroplasts. Firstly, we compared transcript and protein levels of Tic20 and Tic110 in both Pisum sativum and Arabidopsis thaliana. We found the Tic20 protein to be generally less abundant, which was particularly pronounced in Arabidopsis. Secondly, we demonstrated that Tic20 forms a complex larger than 700 kilodalton in the inner envelope membrane, which is clearly separate from Tic110, migrating as a dimer at about 250 kilodalton. Thirdly, we defined the topology of Tic20 in the inner envelope, and found its N- and C-termini to be oriented towards the stromal side. Finally, we successfully reconstituted overexpressed and purified full-length Tic20 into liposomes. Using these Tic20-proteoliposomes, we could demonstrate for the first time that Tic20 can independently form a cation selective channel in vitro. Conclusions The presented data provide first biochemical evidence to the notion that Tic20 can act as a channel protein within the chloroplast import translocon complex. However, the very low abundance of Tic20 in the inner envelope membranes indicates that it cannot form a major protein translocation channel. Furthermore, the independent complex formation of Tic20 and Tic110 argues against a joint channel formation. Thus, based on the observed channel activity of Tic20 in proteoliposomes, we

On an additive partial correlation operator and nonparametric estimation of graphical models.

PubMed

Lee, Kuang-Yao; Li, Bing; Zhao, Hongyu

2016-09-01

We introduce an additive partial correlation operator as an extension of partial correlation to the nonlinear setting, and use it to develop a new estimator for nonparametric graphical models. Our graphical models are based on additive conditional independence, a statistical relation that captures the spirit of conditional independence without having to resort to high-dimensional kernels for its estimation. The additive partial correlation operator completely characterizes additive conditional independence, and has the additional advantage of putting marginal variation on appropriate scales when evaluating interdependence, which leads to more accurate statistical inference. We establish the consistency of the proposed estimator. Through simulation experiments and analysis of the DREAM4 Challenge dataset, we demonstrate that our method performs better than existing methods in cases where the Gaussian or copula Gaussian assumption does not hold, and that a more appropriate scaling for our method further enhances its performance.

On an additive partial correlation operator and nonparametric estimation of graphical models

PubMed Central

Li, Bing; Zhao, Hongyu

2016-01-01

Abstract We introduce an additive partial correlation operator as an extension of partial correlation to the nonlinear setting, and use it to develop a new estimator for nonparametric graphical models. Our graphical models are based on additive conditional independence, a statistical relation that captures the spirit of conditional independence without having to resort to high-dimensional kernels for its estimation. The additive partial correlation operator completely characterizes additive conditional independence, and has the additional advantage of putting marginal variation on appropriate scales when evaluating interdependence, which leads to more accurate statistical inference. We establish the consistency of the proposed estimator. Through simulation experiments and analysis of the DREAM4 Challenge dataset, we demonstrate that our method performs better than existing methods in cases where the Gaussian or copula Gaussian assumption does not hold, and that a more appropriate scaling for our method further enhances its performance. PMID:29422689

Intermanual transfer effects in sequential tactuomotor learning: evidence for effector independent coding.

PubMed

van Mier, Hanneke I; Petersen, Steven E

2006-01-01

Results from our earlier brain imaging studies regarding motor learning have shown different areas activated during naive and practiced performance. When right handed participants moved a pen either with the dominant or non-dominant hand continuously through a cut-out maze as quickly and accurately as possible, practice resulted in decreased brain activity in right premotor and parietal areas as well as left cerebellum, while increased activity was found in the supplementary motor area (SMA). These lateralized practiced-related changes in brain activation suggest effector-independent abstract coding of information. To test this hypothesis more extensively, intermanual transfer of learning was examined in 24 male and female participants (12 right- and 12 left-handed) using the same maze-learning task. It was hypothesized that if an abstract representation of the movement is learned and stored, intermanual transfer effects should be more pronounced when participants transferred to a same maze as opposed to a mirror image of the maze. Errors and velocity were measured during the following conditions: initial naive performance (Naive); after practice on the maze (Prac); during intermanual transfer to the same maze (Transfer Identical); and to the mirror maze (Transfer Mirror). Transfer direction was tested from the dominant to non-dominant hand and vice versa. No significant differences were found between right- and left-handed participants, males and females, and transfer directions. However, intermanual transfer of learning was significantly greater to the identical maze as opposed to the mirror maze. These results showed that learning was indeed taking place at an abstract effector independent level.

Using quantum principles to develop independent continuing nursing education programs.

PubMed

Zurlinden, Jeffrey; Pepsnik, Dawn

2013-01-01

Innovations in health care call for fresh approaches to continuing nursing education that support lateral relationships, teamwork, and collaboration. To foster this transformation, we devised the following education principles: Everyone teaches, everyone learns; embrace probability; information is dynamic; and trust professionals to practice professionally. These principles guided the development of seven independent, practice-specific, evidence-based continuing nursing education programs totaling 21.5 contact hours for casual-status nurses who practiced as childbirth educators. The programs were popular, promoted teamwork, and increased communication about evidence-based practice.

Bicarbonate-dependent and -independent intracellular pH regulatory mechanisms in rat hepatocytes. Evidence for Na+-HCO3- cotransport.

PubMed Central

Gleeson, D; Smith, N D; Boyer, J L

1989-01-01

Using the pH-sensitive dye 2,7-bis(carboxyethyl)-5(6)-carboxy-fluorescein and a continuously perfused subconfluent hepatocyte monolayer cell culture system, we studied rat hepatocyte intracellular pH (pHi) regulation in the presence (+HCO3-) and absence (-HCO3-) of bicarbonate. Baseline pHi was higher (7.28 +/- 09) in +HCO3- than in -HCO3- (7.16 +/- 0.14). Blocking Na+/H+ exchange with amiloride had no effect on pHi in +HCO3- but caused reversible 0.1-0.2-U acidification in -HCO3- or in +HCO3- after preincubation in the anion transport inhibitor 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS). Acute Na+ replacement in +HCO3- alos caused acidification which was amiloride independent but DIDS inhibitible. The recovery of pHi from an intracellular acid load (maximum H+ efflux rate) was 50% higher in +HCO3- than in -HCO3-. Amiloride inhibited H+ effluxmax by 75% in -HCO3- but by only 27% in +HCO3-. The amiloride-independent pHi recovery in +HCO3- was inhibited 50-63% by DIDS and 79% by Na+ replacement but was unaffected by depletion of intracellular Cl-, suggesting that Cl-/HCO3- exchange is not involved. Depolarization of hepatocytes (raising external K+ from 5 to 25 mM) caused reversible 0.05-0.1-U alkalinization, which, however, was neither Na+ nor HCO3- dependent, nor DIDS inhibitible, findings consistent with electroneutral HCO3- transport. We conclude that Na+-HCO3- cotransport, in addition to Na+/H+ exchange, is an important regulator of pHi in rat hepatocytes. PMID:2544626

Abdominal obesity, an independent cardiovascular risk factor in Indian subcontinent: A clinico epidemiological evidence summary.

PubMed

Prasad, D S; Kabir, Zubair; Dash, A K; Das, B C

2011-10-01

Evidence is emerging that obesity-associated cardiovascular disorders (CVD) show variations across regions and ethnicities. However, it is unclear if there are distinctive patterns of abdominal obesity contributing to an increased CVD risk in South Asians. Also, potential underlying mechanistic pathways of such unique patterns are not comprehensively reported in South Asians. This review sets out to examine both. A comprehensive database search strategy was undertaken, namely, PubMed, Embase and Cochrane Library, applying specific search terms for potentially relevant published literature in English language. Grey literature, including scientific meeting abstracts, expert consultations, text books and government/non-government publications were also retrieved. South Asians have 3-5% higher body fat than whites, at any given body mass index. Additional distinctive features, such as South Asian phenotype, low adipokine production, lower lean body mass, ethno-specific socio-cultural and economic factors, were considered as potential contributors to an early age-onset of obesity-linked CVD risk in South Asians. Proven cost-effective anti-obesity strategies, including the development of ethno-specific clinical risk assessment tools, should be adopted early in the life-course to prevent premature CVD deaths and morbidity in South Asians.

Calibrating EASY-Care independence scale to improve accuracy

PubMed Central

Jotheeswaran, A. T.; Dias, Amit; Philp, Ian; Patel, Vikram; Prince, Martin

2016-01-01

Background there is currently limited support for the reliability and validity of the EASY-Care independence scale, with little work carried out in low- or middle-income countries. Therefore, we assessed the internal construct validity and hierarchical and classical scaling properties among frail dependent older people in the community. Objective we assessed the internal construct validity and hierarchical and classical scaling properties among frail dependent older people in the community. Methods three primary care physicians administered EASY-Care comprehensive geriatric assessment for 150 frail and/or dependent older people in the primary care setting. A Mokken model was applied to investigate hierarchical scaling properties of EASY-Care independence scale, and internal consistency (Cronbach's alpha) of the scale was also examined. Results we found that EASY-Care independence scale is highly internally consistent and is a strong hierarchical scale, hence providing strong evidence for unidimensionality. However, two items in the scale (unable to use telephone and manage finances) had much lower item Loevinger H coefficients than others. Exclusion of these two items improved the overall internal consistency of the scale. Conclusions the strong performance of the EASY-Care independence scale among community-dwelling frail older people is encouraging. This study confirms that EASY-Care independence scale is highly internally consistent and a strong hierarchical scale. PMID:27496925

Early additional food and fluids for healthy breastfed full-term infants.

PubMed

Smith, Hazel A; Becker, Genevieve E

2016-08-30

Health organisations recommend exclusive breastfeeding for six months. However, the addition of other fluids or foods before six months is common in many countries. Recently, research has suggested that introducing solid food at around four months of age while the baby continues to breastfeed is more protective against developing food allergies compared to exclusive breastfeeding for six months. Other studies have shown that the risks associated with non-exclusive breastfeeding are dependent on the type of additional food or fluid given. Given this background we felt it was important to update the previous version of this review to incorporate the latest findings from studies examining exclusive compared to non-exclusive breastfeeding. To assess the benefits and harms of additional food or fluid for full-term healthy breastfeeding infants and to examine the timing and type of additional food or fluid. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 March 2016) and reference lists of all relevant retrieved papers. Randomised or quasi-randomised controlled trials in infants under six months of age comparing exclusive breastfeeding versus breastfeeding with any additional food or fluids. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Two review authors assessed the quality of the evidence using the GRADE approach. We included 11 trials (2542 randomised infants/mothers). Nine trials (2226 analysed) provided data on outcomes of interest to this review. The variation in outcome measures and time points made it difficult to pool results from trials. Data could only be combined in a meta-analysis for one primary (breastfeeding duration) and one secondary (weight change) outcome. None of the trials reported on physiological jaundice. Infant mortality was only reported in one trial.For the majority of older trials, the description of study methods was inadequate to

When Does Frequency-Independent Selection Maintain Genetic Variation?

PubMed

Novak, Sebastian; Barton, Nicholas H

2017-10-01

Frequency-independent selection is generally considered as a force that acts to reduce the genetic variation in evolving populations, yet rigorous arguments for this idea are scarce. When selection fluctuates in time, it is unclear whether frequency-independent selection may maintain genetic polymorphism without invoking additional mechanisms. We show that constant frequency-independent selection with arbitrary epistasis on a well-mixed haploid population eliminates genetic variation if we assume linkage equilibrium between alleles. To this end, we introduce the notion of frequency-independent selection at the level of alleles, which is sufficient to prove our claim and contains the notion of frequency-independent selection on haploids. When selection and recombination are weak but of the same order, there may be strong linkage disequilibrium; numerical calculations show that stable equilibria are highly unlikely. Using the example of a diallelic two-locus model, we then demonstrate that frequency-independent selection that fluctuates in time can maintain stable polymorphism if linkage disequilibrium changes its sign periodically. We put our findings in the context of results from the existing literature and point out those scenarios in which the possible role of frequency-independent selection in maintaining genetic variation remains unclear. Copyright © 2017 by the Genetics Society of America.

Negative Regulation of Autophagy by Sulfide Is Independent of Reactive Oxygen Species1

PubMed Central

Laureano-Marín, Ana M.; Moreno, Inmaculada

2016-01-01

Accumulating experimental evidence in mammalian, and recently plant, systems has led to a change in our understanding of the role played by hydrogen sulfide in life processes. In plants, hydrogen sulfide mitigates stress and regulates important plant processes such as photosynthesis, stomatal movement, and autophagy, although the underlying mechanism is not well known. In this study, we provide new experimental evidence that, together with our previous findings, demonstrates the role of hydrogen sulfide in regulating autophagy. We used green fluorescent protein fluorescence associated with autophagic bodies and immunoblot analysis of the ATG8 protein to show that sulfide (and no other molecules such as sulfur-containing molecules or ammonium) was able to inhibit the autophagy induced in Arabidopsis (Arabidopsis thaliana) roots under nitrogen deprivation. Our results showed that sulfide was unable to scavenge reactive oxygen species generated by nitrogen limitation, in contrast to well-established reducers. In addition, reducers were unable to inhibit the accumulation of autophagic bodies and ATG8 protein forms to the same extent as sulfide. Therefore, we conclude that sulfide represses autophagy via a mechanism that is independent of redox conditions. PMID:27208225

New insights on stromules: stroma filled tubules extended by independent plastids.

PubMed

Schattat, Martin H; Klösgen, Ralf Bernd; Mathur, Jaideep

2012-09-01

The recognition of stromules as sporadically extended stroma filled tubules from all kinds of plastids constitutes one of the major insights that resulted from the direct application of green fluorescent protein aided imaging of living plant cells. Observations of dynamic green fluorescent stromules strongly suggested that plastids frequently interact with each other while photo-bleaching of interconnected plastids indicated that proteins can move within the stroma filled tubules. These observations readily fit into the prevailing concept of the endosymbiogenic origins of plastids and provided stromules the status of conduits for inter-plastid communication and macromolecule transfer. However, experimental evidence obtained recently through the use of photoconvertible protein labeled stromules strongly supports plastid independence rather than their interconnectivity. Additional information on stress conditions inducing stromules and observations on their alignment with other organelles suggests that the major role of stromules is to increase the interactive surface of a plastid with the rest of the cytoplasm.

Additional specimen of Microraptor provides unique evidence of dinosaurs preying on birds

PubMed Central

O'Connor, Jingmai; Zhou, Zhonghe; Xu, Xing

2011-01-01

Preserved indicators of diet are extremely rare in the fossil record; even more so is unequivocal direct evidence for predator–prey relationships. Here, we report on a unique specimen of the small nonavian theropod Microraptor gui from the Early Cretaceous Jehol biota, China, which has the remains of an adult enantiornithine bird preserved in its abdomen, most likely not scavenged, but captured and consumed by the dinosaur. We provide direct evidence for the dietary preferences of Microraptor and a nonavian dinosaur feeding on a bird. Further, because Jehol enantiornithines were distinctly arboreal, in contrast to their cursorial ornithurine counterparts, this fossil suggests that Microraptor hunted in trees thereby supporting inferences that this taxon was also an arborealist, and provides further support for the arboreality of basal dromaeosaurids. PMID:22106278

10 CFR 431.174 - Additional requirements applicable to Voluntary Independent Certification Program participants.

Code of Federal Regulations, 2011 CFR

2011-01-01

... CONSERVATION ENERGY EFFICIENCY PROGRAM FOR CERTAIN COMMERCIAL AND INDUSTRIAL EQUIPMENT Provisions for Commercial Heating, Ventilating, Air-Conditioning and Water Heating Products § 431.174 Additional... commercial HVAC and WH product, as described in § 431.176, and that complies with all requirements imposed by...

What Influences Parents' Fear about Children's Independent Mobility? Evidence from a State-Wide Survey of Australian Parents.

PubMed

Bennetts, Shannon K; Cooklin, Amanda R; Crawford, Sharinne; D'Esposito, Fabrizio; Hackworth, Naomi J; Green, Julie; Matthews, Jan; Strazdins, Lyndall; Zubrick, Stephen R; Nicholson, Jan M

2018-03-01

To identify factors associated with generalized and stranger-specific parental fear (PF) about children's independent mobility (CIM), a critical aspect of physical activity. Cross-sectional survey; random sampling frame, minimum quotas of fathers, rural residents. State of Victoria, Australia. Parents of children aged 9 to 15 years (n = 1779), 71% response rate. Validated measures of PF and fear of strangers (FoS); parent, child, social, and environmental factors. Unadjusted and adjusted linear regression stratified by child age (9-10; 11-13; 14-15). Adjusted models explained a substantial proportion of variance across all age groups (PF: 33.6%-36.7%; FoS: 39.1%-44.0%). Perceived disapproval from others was consistently associated with both outcomes (PF: β =.11 to 23, p ≤ .05; FoS: β =.17-.21, p ≤ .001) as was parents' perception of children's competence to travel safely (PF: β = -.24 to -.11, p ≤ .05; FoS: β = -.16 to -.13, p ≤ .01). Factors associated with FoS included having a female child (β = -.21 to -.13, p ≤ .001), language other than English (β = .09 to.11, p ≤ .01), and low levels of parent education (β = -.14 to -08, p ≤ .05). The current study suggests that social norms, child competence, and perceptions about the benefits of CIM underpin PF. This evidence informs the development of interventions to reduce PF and promote CIM and children's physical activity.

Self-efficacy is independently associated with brain volume in older women.

PubMed

Davis, Jennifer C; Nagamatsu, Lindsay S; Hsu, Chun Liang; Beattie, B Lynn; Liu-Ambrose, Teresa

2012-07-01

ageing is highly associated with neurodegeneration and atrophy of the brain. Evidence suggests that personality variables are risk factors for reduced brain volume. We examine whether falls-related self-efficacy is independently associated with brain volume. a cross-sectional analysis of whether falls-related self-efficacy is independently associated with brain volumes (total, grey and white matter). Three multivariate regression models were constructed. Covariates included in the models were age, global cognition, systolic blood pressure, functional comorbidity index and current physical activity level. MRI scans were acquired from 79 community-dwelling senior women aged 65-75 years old. Falls-related self-efficacy was assessed by the activities-specific balance confidence (ABC) scale. after accounting for covariates, falls-related self-efficacy was independently associated with both total brain volume and total grey matter volume. The final model for total brain volume accounted for 17% of the variance, with the ABC score accounting for 8%. For total grey matter volume, the final model accounted for 24% of the variance, with the ABC score accounting for 10%. we provide novel evidence that falls-related self-efficacy, a modifiable risk factor for healthy ageing, is positively associated with total brain volume and total grey matter volume. ClinicalTrials.gov Identifier: NCT00426881.

Independence.

ERIC Educational Resources Information Center

Stephenson, Margaret E.

2000-01-01

Discusses the four planes of development and the periods of creation and crystallization within each plane. Identifies the type of independence that should be achieved by the end of the first two planes of development. Maintains that it is through individual work on the environment that one achieves independence. (KB)

A common genetic variant in FOXP2 is associated with language-based learning (dis)abilities: Evidence from two Italian independent samples.

PubMed

Mozzi, Alessandra; Riva, Valentina; Forni, Diego; Sironi, Manuela; Marino, Cecilia; Molteni, Massimo; Riva, Stefania; Guerini, Franca R; Clerici, Mario; Cagliani, Rachele; Mascheretti, Sara

2017-04-24

Language-based Learning Disabilities (LLDs) encompass a group of complex, comorbid, and developmentally associated deficits in communication. Language impairment and developmental dyslexia (DD) represent the most recognized forms of LLDs. Substantial genetic correlations exist between language and reading (dis)abilities. Common variants in the FOXP2 gene were consistently associated with language- and reading-related neuropsychological and neuroanatomical phenotypes. We tested the effect of a FOXP2 common variant, that is, rs6980093 (A/G), on quantitative measures of language and reading in two independent Italian samples: a population-based cohort of 699 subjects (3-11 years old) and a sample of 572 children with DD (6-18 years old). rs6980093 modulates expressive language in the general population sample, with an effect on fluency scores. In the DD sample, the variant showed an association with the accuracy in the single word reading task. rs6980093 shows distinct genetic models of association in the two cohorts, with a dominant effect of the G allele in the general population sample and heterozygote advantage in the DD cohort. We provide preliminary evidence that rs6980093 associates with language and reading (dis)abilities in two independent Italian cohorts. rs6980093 is an intronic SNP, suggesting that it (or a linked variant) modulates phenotypic association via regulation of FOXP2 expression. Because FOXP2 brain expression is finely regulated, both temporally and spatially, it is possible that the two alleles at rs6980093 differentially modulate expression levels in a developmental stage- or brain area-specific manner. This might help explaining the heterozygote advantage effect and the different genetic models in the two cohorts. © 2017 Wiley Periodicals, Inc.

Signal sequence-independent targeting of MID2 mRNA to the endoplasmic reticulum by the yeast RNA-binding protein Khd1p.

PubMed

Syed, Muhammad Ibrahim; Moorthy, Balaji T; Jenner, Andreas; Fetka, Ingrid; Jansen, Ralf-Peter

2018-05-17

Localization of mRNAs depends on specific RNA-binding proteins (RBPs) and critically contributes not only to cell polarization but also to basal cell function. The yeast RBP Khd1p binds to several hundred mRNAs, the majority of which encodes secreted or membrane proteins. We demonstrate that a subfraction of Khd1p associates with artificial liposomes and endoplasmic reticulum (ER), and that Khd1p endomembrane association is partially dependent on its binding to RNA. ER targeting of at least two mRNAs, MID2 and SLG1/WSC1, requires KHD1 but is independent of their translation. Together, our results suggest interdependence of Khd1p and mRNA for their targeting to the ER and presents additional evidence for signal sequence-independent, RBP-mediated mRNA targeting. © 2018 Federation of European Biochemical Societies.

Review of NASA's Evidence Reports on Human Health Risks. 2015 Letter Report

NASA Technical Reports Server (NTRS)

Scott-Conner, Carol E. H.; Masys, Daniel R.; Liverman, Catharyn T.

2016-01-01

NASA has requested a study from the Institute of Medicine (IOM) to provide an independent review of more than 30 evidence reports on human health risks for long duration and exploration spaceflight. The evidence reports, which are publicly available, are categorized into five broad categories: (1) behavioral health and performance; (2) human health countermeasures (with a focus on bone metabolism and orthopedics, nutrition, immunology, and cardiac and pulmonary physiology); (3) radiation; (4) human factors issues; and (5) exploration medical capabilities. The reports are revised on an ongoing basis to incorporate new scientific information. In conducting this study, an IOM ad hoc committee will build on the 2008 IOM report Review of NASA's Human Research Program Evidence Books. That report provided an assessment of the process used for developing the evidence reports and provided an initial review of the evidence reports that had been completed at that time. Each year, NASA staff will identify a set of evidence reports for committee review. Over the course of the study all evidence reports will be reviewed. The committee will hold an annual scientific workshop to receive input on the evidence reports it is reviewing that year and an update on the recent literature. The committee will issue an annual letter report that addresses the following questions relevant to each evidence report: 1. Does the evidence report provide sufficient evidence, as well as sufficient risk context, that the risk is of concern for long-term space missions? 2. Does the evidence report make the case for the research gaps presented? 3. Are there any additional gaps in knowledge or areas of fundamental research that should be considered to enhance the basic understanding of this specific risk? 4. Does the evidence report address relevant interactions among risks? 5. Is input from additional disciplines needed? 6. Is the breadth of the cited literature sufficient? 7. What is the overall

Independently Controlled Wing Stroke Patterns in the Fruit Fly Drosophila melanogaster

PubMed Central

Chakraborty, Soma; Bartussek, Jan; Fry, Steven N.; Zapotocky, Martin

2015-01-01

Flies achieve supreme flight maneuverability through a small set of miniscule steering muscles attached to the wing base. The fast flight maneuvers arise from precisely timed activation of the steering muscles and the resulting subtle modulation of the wing stroke. In addition, slower modulation of wing kinematics arises from changes in the activity of indirect flight muscles in the thorax. We investigated if these modulations can be described as a superposition of a limited number of elementary deformations of the wing stroke that are under independent physiological control. Using a high-speed computer vision system, we recorded the wing motion of tethered flying fruit flies for up to 12 000 consecutive wing strokes at a sampling rate of 6250 Hz. We then decomposed the joint motion pattern of both wings into components that had the minimal mutual information (a measure of statistical dependence). In 100 flight segments measured from 10 individual flies, we identified 7 distinct types of frequently occurring least-dependent components, each defining a kinematic pattern (a specific deformation of the wing stroke and the sequence of its activation from cycle to cycle). Two of these stroke deformations can be associated with the control of yaw torque and total flight force, respectively. A third deformation involves a change in the downstroke-to-upstroke duration ratio, which is expected to alter the pitch torque. A fourth kinematic pattern consists in the alteration of stroke amplitude with a period of 2 wingbeat cycles, extending for dozens of cycles. Our analysis indicates that these four elementary kinematic patterns can be activated mutually independently, and occur both in isolation and in linear superposition. The results strengthen the available evidence for independent control of yaw torque, pitch torque, and total flight force. Our computational method facilitates systematic identification of novel patterns in large kinematic datasets. PMID:25710715

Independently controlled wing stroke patterns in the fruit fly Drosophila melanogaster.

PubMed

Chakraborty, Soma; Bartussek, Jan; Fry, Steven N; Zapotocky, Martin

2015-01-01

Flies achieve supreme flight maneuverability through a small set of miniscule steering muscles attached to the wing base. The fast flight maneuvers arise from precisely timed activation of the steering muscles and the resulting subtle modulation of the wing stroke. In addition, slower modulation of wing kinematics arises from changes in the activity of indirect flight muscles in the thorax. We investigated if these modulations can be described as a superposition of a limited number of elementary deformations of the wing stroke that are under independent physiological control. Using a high-speed computer vision system, we recorded the wing motion of tethered flying fruit flies for up to 12,000 consecutive wing strokes at a sampling rate of 6250 Hz. We then decomposed the joint motion pattern of both wings into components that had the minimal mutual information (a measure of statistical dependence). In 100 flight segments measured from 10 individual flies, we identified 7 distinct types of frequently occurring least-dependent components, each defining a kinematic pattern (a specific deformation of the wing stroke and the sequence of its activation from cycle to cycle). Two of these stroke deformations can be associated with the control of yaw torque and total flight force, respectively. A third deformation involves a change in the downstroke-to-upstroke duration ratio, which is expected to alter the pitch torque. A fourth kinematic pattern consists in the alteration of stroke amplitude with a period of 2 wingbeat cycles, extending for dozens of cycles. Our analysis indicates that these four elementary kinematic patterns can be activated mutually independently, and occur both in isolation and in linear superposition. The results strengthen the available evidence for independent control of yaw torque, pitch torque, and total flight force. Our computational method facilitates systematic identification of novel patterns in large kinematic datasets.

Iterative Strain-Gage Balance Calibration Data Analysis for Extended Independent Variable Sets

NASA Technical Reports Server (NTRS)

Ulbrich, Norbert Manfred

2011-01-01

A new method was developed that makes it possible to use an extended set of independent calibration variables for an iterative analysis of wind tunnel strain gage balance calibration data. The new method permits the application of the iterative analysis method whenever the total number of balance loads and other independent calibration variables is greater than the total number of measured strain gage outputs. Iteration equations used by the iterative analysis method have the limitation that the number of independent and dependent variables must match. The new method circumvents this limitation. It simply adds a missing dependent variable to the original data set by using an additional independent variable also as an additional dependent variable. Then, the desired solution of the regression analysis problem can be obtained that fits each gage output as a function of both the original and additional independent calibration variables. The final regression coefficients can be converted to data reduction matrix coefficients because the missing dependent variables were added to the data set without changing the regression analysis result for each gage output. Therefore, the new method still supports the application of the two load iteration equation choices that the iterative method traditionally uses for the prediction of balance loads during a wind tunnel test. An example is discussed in the paper that illustrates the application of the new method to a realistic simulation of temperature dependent calibration data set of a six component balance.

Independent Evaluation of Middle School-Based Drug Prevention Curricula: A Systematic Review.

PubMed

Flynn, Anna B; Falco, Mathea; Hocini, Sophia

2015-11-01

Lack of robust program evaluation has hindered the effectiveness of school-based drug abuse prevention curricula overall. Independently evaluated randomized controlled trials (RCTs) of universal, middle school-based drug abuse prevention curricula are the most useful indicators of whether such programs are effective or ineffective. To conduct a systematic review identifying independently evaluated RCTs of universal, middle school-based drug abuse prevention curricula; extract data on study quality and substance use outcomes; and assess evidence of program effectiveness. PsycInfo, Educational Resources Information Center, Science Citation Index, Social Science Citation Index, Cumulative Index to Nursing and Allied Health Literature, MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched between January 1, 1984, and March 15, 2015. Search terms included variations of drug, alcohol, tobacco, and marijuana use, as well as school, prevention, and effectiveness. Studies included in the review were RCTs carried out by independent evaluators of universal school-based drug prevention curricula available for dissemination in the United States that reported alcohol, tobacco, marijuana, or other drug use outcomes. Two researchers extracted data on study quality and outcomes independently using a data extraction form and met to resolve disagreements. A total of 5071 publications were reviewed, with 13 articles meeting final inclusion criteria. Of the 13 articles, 6 RCTs of 4 distinct school-based curricula were identified for inclusion. Outcomes were reported for 42 single-drug measures in the independent RCTs, with just 3 presenting statistically significant (P < .05) differences between the intervention group and the control group. One program revealed statistically significant positive effects at final follow-up (Lions-Quest Skills for Adolescence). The results of our review demonstrate the dearth of independent research that appropriately

Independent Research (IR) and Independent Exploratory Development (IED)

DTIC Science & Technology

1994-08-01

in the Workplace . Independent research/independent exploratory development, IR/IED...Exclusion Rate differences Over a Cut Score Domain, An Examination of Cognitive and Motivational Effects of Employee Interventions, and Cultural Diversity

QSAR prediction of additive and non-additive mixture toxicities of antibiotics and pesticide.

PubMed

Qin, Li-Tang; Chen, Yu-Han; Zhang, Xin; Mo, Ling-Yun; Zeng, Hong-Hu; Liang, Yan-Peng

2018-05-01

Antibiotics and pesticides may exist as a mixture in real environment. The combined effect of mixture can either be additive or non-additive (synergism and antagonism). However, no effective predictive approach exists on predicting the synergistic and antagonistic toxicities of mixtures. In this study, we developed a quantitative structure-activity relationship (QSAR) model for the toxicities (half effect concentration, EC 50 ) of 45 binary and multi-component mixtures composed of two antibiotics and four pesticides. The acute toxicities of single compound and mixtures toward Aliivibrio fischeri were tested. A genetic algorithm was used to obtain the optimized model with three theoretical descriptors. Various internal and external validation techniques indicated that the coefficient of determination of 0.9366 and root mean square error of 0.1345 for the QSAR model predicted that 45 mixture toxicities presented additive, synergistic, and antagonistic effects. Compared with the traditional concentration additive and independent action models, the QSAR model exhibited an advantage in predicting mixture toxicity. Thus, the presented approach may be able to fill the gaps in predicting non-additive toxicities of binary and multi-component mixtures. Copyright © 2018 Elsevier Ltd. All rights reserved.

Can an Online Tool Support Contemporary Independent Music Teaching and Learning?

ERIC Educational Resources Information Center

Brook, Julia; Upitis, Rena

2015-01-01

The body of research examining deliberate practice and self-regulation in musical instruction has grown extensively over the past several decades, while at the same time many practices in the independent music studio remain unchanged and/or under-researched. Compelling evidence indicates that students with high levels of self-regulation experience…

Headteacher Career Paths in UK Independent Secondary Coeducational Schools: Gender Issues

ERIC Educational Resources Information Center

McLay, Margaret

2008-01-01

This article presents evidence of the similarities and differences in the career paths of men and women who have achieved headships in UK independent coeducational schools. The research comprised a pilot study of interviews with nine female headteachers and a questionnaire sent to male and female heads of coeducational secondary schools. It…

Self-efficacy is independently associated with brain volume in older women

PubMed Central

Davis, Jennifer C.; Nagamatsu, Lindsay S.; Hsu, Chun Liang; Beattie, B. Lynn; Liu-Ambrose, Teresa

2015-01-01

Background Aging is highly associated with neurodegeneration and atrophy of the brain. Evidence suggests that personality variables are risk factors for reduced brain volume. We examine whether falls-related self-efficacy is independently associated with brain volume. Method A cross-sectional analysis of whether falls-related self-efficacy is independently associated with brain volumes (total, grey, and white matter). Three multivariate regression models were constructed. Covariates included in the models were age, global cognition, systolic blood pressure, functional comorbidity index, and current physical activity level. MRI scans were acquired from 79 community-dwelling senior women aged 65 to 75 years old. Falls-related self-efficacy was assessed by the Activities Specific Balance Confidence (ABC) Scale. Results After accounting for covariates, falls-related self-efficacy was independently associated with both total brain volume and total grey matter volume. The final model for total brain volume accounted for 17% of the variance, with the ABC score accounting for 8%. For total grey matter volume, the final model accounted for 24% of the variance, with the ABC score accounting for 10%. Conclusion We provide novel evidence that falls-related self-efficacy, a modifiable risk factor for healthy aging, is positively associated with total brain volume and total grey matter volume. Trial Registration ClinicalTrials.gov Identifier: NCT00426881. PMID:22436405

Evidence for an independent third Usutu virus introduction into Germany.

PubMed

Ziegler, Ute; Fast, Christine; Eiden, Martin; Bock, Sabine; Schulze, Christoph; Hoeper, Dirk; Ochs, Andreas; Schlieben, Patricia; Keller, Markus; Zielke, Dorothee E; Luehken, Renke; Cadar, Daniel; Walther, Doreen; Schmidt-Chanasit, Jonas; Groschup, Martin H

2016-08-30

Usutu virus (USUV) is an arbovirus within the genus flavivirus, which was first introduced to Southern Europe approximately twenty years ago causing epizootics among wild and captive birds. In Germany USUV was initially discovered in wild birds, mainly Common blackbirds (Turdus merula), in the Upper Rhine valley in southwest of the country in 2011 and has not spread much northwards since. Phylogenetic analyses revealed that the still ongoing USUV epidemic is caused by two different USUV strains, USUV-Germany belonging to the USUV Europe 3 lineage and USUV-Bonn belonging to the USUV Africa 3 lineage. The two strains were introduced independently. In August 2015 a new USUV strain, named USUV-Berlin, was isolated in Vero cells from two carcasses of juvenile Great grey owls (Strix nebulosa) kept in the Zoological Garden Berlin, which had suffered from a hyperacute fatal systemic infection. Both owls carried high USUV genome loads. Full-length USUV genomes sequences were determined and phylogenetic analysis demonstrated a close relationship with a Spanish mosquito-derived sequence from 2006. Immunohistochemical antigen detection in organ samples of the owls showed the typical USUV infection patterns. According to the phylogenetic analysis, USUV-Berlin belongs to the Africa 2 lineage, and can thus be distinguished from the other strains circulating in Germany. Repeated findings of different USUV strains suggest more frequent introductions into Central Europe and a higher mobility of this virus than assumed to date. Copyright © 2016 Elsevier B.V. All rights reserved.

Evidence for conjugated linoleic acid-induced embryonic mortality that is independent of egg storage conditions and changes in egg relative fatty acids.

PubMed

Leone, V A; Stransky, D L; Aydin, R; Cook, M E

2009-09-01

Three experiments were performed to determine the effect of conjugated linoleic acid (CLA) on embryonic development in the absence of vitelline membrane disruption. In experiment 1, when eggs from control and CLA (0.5%)-fed hens were stored at 21 or 15 degrees C for 48 h, mineral movement between the yolk and albumen was not observed (with the exception of Mg and Na). Also, it was found that CLA-induced changes in yolk fatty acid content (e.g., increased saturated fatty acids and CLA) had begun to change after 5 d of feeding hens CLA, and no differences were detected in fatty acid composition after 14 d. In experiment 2, the hatchability of eggs incubated directly after oviposition or stored 24 h at 21 or 15 degrees C was determined from hens fed control or 0.5% CLA diets. Regardless of storage conditions, CLA reduced hatchability. These data showed that CLA elicits negative effects on hatchability independent of vitelline membrane disruption or egg storage condition. In experiment 3, eggs were collected from hens fed 0 or 1% CLA daily for 3 wk, stored at 21 degrees C for 24 h, and incubated. Not only did CLA decrease hatchability, the data showed as the days of CLA feeding increased, the days of survival during incubation decreased. Average days of embryonic survival during incubation for the CLA group diminished to 18.0, 13.4, and 6.3 d for wk 1, 2, and 3 of CLA feeding, respectively, and control remained at 20.6, 20.8, and 19.8 for the 3 wk. These studies suggested that without the disruption of the vitelline membrane, hatchability and embryonic days of survival were significantly reduced by maternal CLA feeding in comparison to control-fed hens. Evidence that embryos die earlier the longer the hens are fed CLA, even though no additional changes in the fatty acid content of eggs were found, suggested that factors other than storage and egg yolk fatty acid composition played a role in CLA-induced embryonic mortality.

Mechanical dyssynchrony is additive to ECG criteria and independently associated with reverse remodelling and clinical response to cardiac resynchronisation therapy in patients with advanced heart failure

PubMed Central

Bank, Alan J; Gage, Ryan M; Marek, Josef J; Onishi, Toshinari; Burns, Kevin V; Schwartzman, David; Saba, Samir; Gorcsan, John

2015-01-01

Background QRS duration and morphology are known established predictors of cardiac resynchronisation therapy (CRT) response, whereas mechanical dyssynchrony is not. Our aim was to determine if mechanical dyssynchrony provides independent prognostic information on CRT response. Methods We studied 369 consecutive patients with heart failure (HF) with low ejection fraction (EF) and widened QRS receiving CRT. Radial dyssynchrony (septal-posterior radial peak strain delay ≥130 ms by speckle tracking) assessment was possible in 318 patients (86%). Associations with left ventricular end-systolic volume (LVESV) changes were examined using linear regression, and clinical outcomes analysed using Cox regression adjusted for multiple established outcome correlates. Results Patients with radial dyssynchrony before CRT (64%) had greater improvements in EF (8.8±9.4 vs 6.1±9.7 units, p=0.04) and LVESV (−30±41 vs −10±30 mL, p<0.01). Radial dyssynchrony was independently associated with reduction in LVESV (regression coefficient −10.5 mL, 95% CI −20.5 to −0.5, p=0.040) as was left bundle-branch block (−17.7 mL, −27.6 to −7.7, p=0.001). Patients with radial dyssynchrony had a 46% lower incidence of death, transplant or implantation of a left ventricular assist device (adjusted HR 0.54, 95% CI 0.31 to 0.92, p=0.02) and a 39% lower incidence of death or HF hospitalisation (0.61, 0.40 to 0.93, p=0.02) over 2 years. Conclusions Radial dyssynchrony was associated with significant improvements in LVESV and clinical outcomes following CRT and is independent of QRS duration or morphology, and additive to current ECG selection criteria to predict response to CRT. PMID:25973213

Effectiveness of additional supervised exercises compared with conventional treatment alone in patients with acute lateral ankle sprains: systematic review

PubMed Central

van Ochten, John; Luijsterburg, Pim A J; van Middelkoop, Marienke; Koes, Bart W; Bierma-Zeinstra, Sita M A

2010-01-01

Objective To summarise the effectiveness of adding supervised exercises to conventional treatment compared with conventional treatment alone in patients with acute lateral ankle sprains. Design Systematic review. Data sources Medline, Embase, Cochrane Central Register of Controlled Trials, Cinahl, and reference screening. Study selection Included studies were randomised controlled trials, quasi-randomised controlled trials, or clinical trials. Patients were adolescents or adults with an acute lateral ankle sprain. The treatment options were conventional treatment alone or conventional treatment combined with supervised exercises. Two reviewers independently assessed the risk of bias, and one reviewer extracted data. Because of clinical heterogeneity we analysed the data using a best evidence synthesis. Follow-up was classified as short term (up to two weeks), intermediate (two weeks to three months), and long term (more than three months). Results 11 studies were included. There was limited to moderate evidence to suggest that the addition of supervised exercises to conventional treatment leads to faster and better recovery and a faster return to sport at short term follow-up than conventional treatment alone. In specific populations (athletes, soldiers, and patients with severe injuries) this evidence was restricted to a faster return to work and sport only. There was no strong evidence of effectiveness for any of the outcome measures. Most of the included studies had a high risk of bias, with few having adequate statistical power to detect clinically relevant differences. Conclusion Additional supervised exercises compared with conventional treatment alone have some benefit for recovery and return to sport in patients with ankle sprain, though the evidence is limited or moderate and many studies are subject to bias. PMID:20978065

The Giardia cell cycle progresses independently of the anaphase-promoting complex

PubMed Central

Gourguechon, Stéphane; Holt, Liam J.; Cande, W. Zacheus

2013-01-01

Summary Most cell cycle regulation research has been conducted in model organisms representing a very small part of the eukaryotic domain. The highly divergent human pathogen Giardia intestinalis is ideal for studying the conservation of eukaryotic pathways. Although Giardia has many cell cycle regulatory components, its genome lacks all anaphase-promoting complex (APC) components. In the present study, we show that a single mitotic cyclin in Giardia is essential for progression into mitosis. Strikingly, Giardia cyclin B lacks the conserved N-terminal motif required for timely degradation mediated by the APC and ubiquitin conjugation. Expression of Giardia cyclin B in fission yeast is toxic, leading to a prophase arrest, and this toxicity is suppressed by the addition of a fission yeast degradation motif. Cyclin B is degraded during mitosis in Giardia cells, but this degradation appears to be independent of the ubiquitination pathway. Other putative APC substrates, aurora and polo-like kinases, also show no evidence of ubiquitination. This is the first example of mitosis not regulated by the APC and might reflect an evolutionary ancient form of cell cycle regulation. PMID:23525017

Pupillary responses reveal infants' discrimination of facial emotions independent of conscious perception.

PubMed

Jessen, Sarah; Altvater-Mackensen, Nicole; Grossmann, Tobias

2016-05-01

Sensitive responding to others' emotions is essential during social interactions among humans. There is evidence for the existence of subcortically mediated emotion discrimination processes that occur independent of conscious perception in adults. However, only recently work has begun to examine the development of automatic emotion processing systems during infancy. In particular, it is unclear whether emotional expressions impact infants' autonomic nervous system regardless of conscious perception. We examined this question by measuring pupillary responses while subliminally and supraliminally presenting 7-month-old infants with happy and fearful faces. Our results show greater pupil dilation, indexing enhanced autonomic arousal, in response to happy compared to fearful faces regardless of conscious perception. Our findings suggest that, early in ontogeny, emotion discrimination occurs independent of conscious perception and is associated with differential autonomic responses. This provides evidence for the view that automatic emotion processing systems are an early-developing building block of human social functioning. Copyright © 2016 Elsevier B.V. All rights reserved.

Septic tank additive impacts on microbial populations.

PubMed

Pradhan, S; Hoover, M T; Clark, G H; Gumpertz, M; Wollum, A G; Cobb, C; Strock, J

2008-01-01

Environmental health specialists, other onsite wastewater professionals, scientists, and homeowners have questioned the effectiveness of septic tank additives. This paper describes an independent, third-party, field scale, research study of the effects of three liquid bacterial septic tank additives and a control (no additive) on septic tank microbial populations. Microbial populations were measured quarterly in a field study for 12 months in 48 full-size, functioning septic tanks. Bacterial populations in the 48 septic tanks were statistically analyzed with a mixed linear model. Additive effects were assessed for three septic tank maintenance levels (low, intermediate, and high). Dunnett's t-test for tank bacteria (alpha = .05) indicated that none of the treatments were significantly different, overall, from the control at the statistical level tested. In addition, the additives had no significant effects on septic tank bacterial populations at any of the septic tank maintenance levels. Additional controlled, field-based research iswarranted, however, to address additional additives and experimental conditions.

The Value of Collaborative Research before Independent Research in Undergraduate Music Education

ERIC Educational Resources Information Center

Harney, Kristin

2017-01-01

Increasing evidence points to the importance of undergraduate research in teacher education programs. Before undertaking independent research, it is essential that music education students gain exposure to a range of research skills and develop basic research competencies. In this study, I explored the influence of a semester-long collaborative…

On the presumption of evidentiary independence: can confessions corrupt eyewitness identifications?

PubMed

Hasel, Lisa E; Kassin, Saul M

2009-01-01

A confession is potent evidence, persuasive to judges and juries. Is it possible that a confession can also affect other evidence? The present study tested the hypothesis that a confession will alter eyewitnesses' identification decisions. Two days after witnessing a staged theft and making an identification decision from a lineup that did not include the thief, participants were told that certain lineup members had confessed or denied guilt during a subsequent interrogation. Among those participants who had made a selection but were told that another lineup member confessed, 61% changed their identifications. Among those participants who had not made an identification, 50% went on to select the confessor when his identity was known. These findings challenge the presumption in law that different forms of evidence are independent and suggest an important overlooked mechanism by which innocent confessors are wrongfully convicted: Potentially exculpatory evidence is corrupted by a confession itself.

Clonazepam responsive opsoclonus myoclonus syndrome: additional evidence in favour of fastigial nucleus disinhibition hypothesis?

PubMed

Paliwal, Vimal Kumar; Chandra, Satish; Verma, Ritu; Kalita, Jayantee; Misra, Usha K

2010-05-01

Opsoclonus myoclonus syndrome is a rare paraneoplastic syndrome seen in 50% of children with neuroblastoma. Neural generator of opsoclonus and myoclonus is not known but evidences suggest the role of fastigial nucleus disinhibition from the loss of function of inhibitory (GABAergic) Purkinje cells in the cerebellum. We present a child with paraneoplastic opsoclonus myoclonus syndrome who responded well to clonazepam. Response to clonazepam is an evidence for the involvement of GABAergic neural circuits in the genesis of opsoclonus myoclonus syndrome and is in agreement with fastigial nucleus disinhibition hypothesis.

Quantitative orientation-independent differential interference contrast (DIC) microscopy

NASA Astrophysics Data System (ADS)

Shribak, Michael; LaFountain, James; Biggs, David; Inoué, Shinya

2007-02-01

We describe a new DIC technique, which records phase gradients within microscopic specimens independently of their orientation. The proposed system allows the generation of images representing the distribution of dry mass (optical path difference) in the specimen. Unlike in other forms of interference microscopes, this approach does not require a narrow illuminating cone. The orientation-independent differential interference contrast (OI-DIC) system can also be combined with orientation-independent polarization (OI-Pol) measurements to yield two complementary images: one showing dry mass distribution (which is proportional to refractive index) and the other showing distribution of birefringence (due to structural or internal anisotropy). With a model specimen used for this work -- living spermatocytes from the crane fly, Nephrotoma suturalis --- the OI-DIC image clearly reveals the detailed shape of the chromosomes while the polarization image quantitatively depicts the distribution of the birefringent microtubules in the spindle, both without any need for staining or other modifications of the cell. We present examples of a pseudo-color combined image incorporating both orientation-independent DIC and polarization images of a spermatocyte at diakinesis and metaphase of meiosis I. Those images provide clear evidence that the proposed technique can reveal fine architecture and molecular organization in live cells without perturbation associated with staining or fluorescent labeling. The phase image was obtained using optics having a numerical aperture 1.4, thus achieving a level of resolution never before achieved with any interference microscope.

Evidence-Based Toxicology.

PubMed

Hoffmann, Sebastian; Hartung, Thomas; Stephens, Martin

Evidence-based toxicology (EBT) was introduced independently by two groups in 2005, in the context of toxicological risk assessment and causation as well as based on parallels between the evaluation of test methods in toxicology and evidence-based assessment of diagnostics tests in medicine. The role model of evidence-based medicine (EBM) motivated both proposals and guided the evolution of EBT, whereas especially systematic reviews and evidence quality assessment attract considerable attention in toxicology.Regarding test assessment, in the search of solutions for various problems related to validation, such as the imperfectness of the reference standard or the challenge to comprehensively evaluate tests, the field of Diagnostic Test Assessment (DTA) was identified as a potential resource. DTA being an EBM discipline, test method assessment/validation therefore became one of the main drivers spurring the development of EBT.In the context of pathway-based toxicology, EBT approaches, given their objectivity, transparency and consistency, have been proposed to be used for carrying out a (retrospective) mechanistic validation.In summary, implementation of more evidence-based approaches may provide the tools necessary to adapt the assessment/validation of toxicological test methods and testing strategies to face the challenges of toxicology in the twenty first century.

10 CFR 431.175 - Additional requirements applicable to non-Voluntary Independent Certification Program participants.

Code of Federal Regulations, 2011 CFR

2011-01-01

... CONSERVATION ENERGY EFFICIENCY PROGRAM FOR CERTAIN COMMERCIAL AND INDUSTRIAL EQUIPMENT Provisions for Commercial Heating, Ventilating, Air-Conditioning and Water Heating Products § 431.175 Additional... manufacturer that is not a VICP participant with respect to a particular type of commercial HVAC and WH product...

GlycA and hsCRP are independent and additive predictors of future cardiovascular events among patients undergoing angiography: The intermountain heart collaborative study.

PubMed

Muhlestein, Joseph B; May, Heidi T; Galenko, Oxana; Knowlton, Kirk U; Otvos, James D; Connelly, Margery A; Lappe, Donald L; Anderson, Jeffrey L

2018-04-06

GlycA is an inflammatory marker that is raised in patients with cardiometabolic diseases and associated with cardiovascular (CV) events. We sought to determine if GlycA adds independent value to hsCRP for CV risk prediction. Patients in the Intermountain Heart Collaborative Study who underwent coronary angiography and had plasma GlycA and hsCRP levels were studied (n = 2996). Patients were followed for 7.0 ± 2.8 years. GlycA and hsCRP were moderately correlated (r = 0.46, P < .0001). GlycA and hsCRP concentrations were stratified into high and low categories by their median values. Multivariable cox hazard regression was utilized to determine the associations of GlycA quartiles, as well as high and low categories of GlycA and hsCRP, with major adverse cardiovascular events (MACE) defined as the composite of death, myocardial infarction (MI), heart failure (HF) hospitalization, and stroke. The highest GlycA quartile was associated with future MACE [HR: 1.43; 95% CI: 1.22-1.69; P < .0001]. Patients with high GlycA and high hsCRP had more diabetes, hyperlipidemia, hypertension, HF, renal failure and MI, but not coronary artery disease. High GlycA and hsCRP (H/H) versus low GlycA and hsCRP (L/L) was associated with MACE, death and HF hospitalization, but not MI or stroke. Combined MACE rates were 33.5%, 41.3%, 35.7% and 49.1% for L/L, L/H, H/L and H/H categories of GlycA/hsCRP, respectively (P-trend < .0001). The interaction between GlycA and hsCRP was significant for the outcome of death (P = .03). In this study, levels of GlycA and hsCRP were independent and additive markers of risk for MACE, death and HF hospitalization. Copyright © 2018. Published by Elsevier Inc.

Consequences of non-random species loss for decomposition dynamics: Experimental evidence for additive and non-additive effects

Treesearch

Becky A. Ball; Mark D. Hunter; John S. Kominoski; Christopher M. Swan; Mark A. Bradford

2008-01-01

Although litter decomposition is a fundamental ecological process, most of our understanding comes from studies of single-species decay. Recently, litter-mixing studies have tested whether monoculture data can be applied to mixed-litter systems. These studies have mainly attempted to detect non-additive effects of litter mixing, which address potential consequences of...

Development and implementation of a nurse-led walk-in centre: evidence lost in translation?

PubMed

Desborough, Jane; Parker, Rhian; Forrest, Laura

2013-07-01

The design of the first Australian public nurse-led primary care walk-in centre was modelled on those established in the English National Health Service (NHS). An independent evaluation of the first 12 months of operation of the Australian Capital Territory (ACT) Health walk-in centre, in 2011, analysed the translation of evidence from the national evaluation of the NHS walk-in centres to the policy development and implementation of the ACT walk-in centre. Whilst in a number of ways the evidence was used well, our interest for this paper was to examine three areas identified as problematic and to identify the points at which the evidence was lost or diluted. In addition to data obtained through nurse and key stakeholder interviews for the evaluation, an analysis was undertaken of documents on the planning and establishment of the ACT walk-in centre, either provided to the evaluation team or made publicly available. Three areas were identified as problematic in the way that evidence from the NHS evaluation was translated: the use of clinical decision support software (CDSS); the marketing of the walk-in centre; and its location. Our examination indicates that despite seeking evidence to inform the development of the ACT walk-in centre, the evidence was not fully used and some clear lessons ignored, resulting in much of the evidence being lost in translation.

Additives to local anesthetics for peripheral nerve blocks: Evidence, limitations, and recommendations.

PubMed

Bailard, Neil S; Ortiz, Jaime; Flores, Roland A

2014-03-01

The therapeutic rationale, clinical effectiveness, and potential adverse effects of medications used in combination with local anesthetics for peripheral nerve block therapy are reviewed. A wide range of agents have been tested as adjuncts to peripheral nerve blocks, which are commonly performed for regional anesthesia during or after hand or arm surgery, neck or spine surgery, and other procedures. Studies to determine the comparative merits of nerve block adjuncts are complicated by the wide variety of coadministered local anesthetics and sites of administration and by the heterogeneity of primary endpoints. Sodium bicarbonate has been shown to speed the onset of mepivacaine nerve blocks but delay the onset of others. Epinephrine has been shown to prolong sensory nerve blockade and delay systemic uptake of local anesthetics, thus reducing the risk of anesthetic toxicity. Tramadol, buprenorphine, dexamethasone, and clonidine appear to be effective additives in some situations. Midazolam, magnesium, dexmedetomidine, and ketamine cannot be routinely recommended as nerve block additives due to a dearth of supportive data, modest efficacy, and (in the case of ketamine) significant adverse effects. Recent studies suggest that administering additives intravenously or intramuscularly can provide many of the benefits of perineural administration while reducing the potential for neurotoxicity, contamination, and other hazards. Some additives to local anesthetics can hasten the onset of nerve block, prolong block duration, or reduce toxicity. On the other hand, poorly selected or unnecessary additives may not have the desired effect and may even expose patients to unnecessary risks.

Membrane-association of mRNA decapping factors is independent of stress in budding yeast

PubMed Central

Huch, Susanne; Gommlich, Jessie; Muppavarapu, Mridula; Beckham, Carla; Nissan, Tracy

2016-01-01

Recent evidence has suggested that the degradation of mRNA occurs on translating ribosomes or alternatively within RNA granules called P bodies, which are aggregates whose core constituents are mRNA decay proteins and RNA. In this study, we examined the mRNA decapping proteins, Dcp1, Dcp2, and Dhh1, using subcellular fractionation. We found that decapping factors co-sediment in the polysome fraction of a sucrose gradient and do not alter their behaviour with stress, inhibition of translation or inhibition of the P body formation. Importantly, their localisation to the polysome fraction is independent of the RNA, suggesting that these factors may be constitutively localised to the polysome. Conversely, polysomal and post-polysomal sedimentation of the decapping proteins was abolished with the addition of a detergent, which shifts the factors to the non-translating RNP fraction and is consistent with membrane association. Using a membrane flotation assay, we observed the mRNA decapping factors in the lower density fractions at the buoyant density of membrane-associated proteins. These observations provide further evidence that mRNA decapping factors interact with subcellular membranes, and we suggest a model in which the mRNA decapping factors interact with membranes to facilitate regulation of mRNA degradation. PMID:27146487

Membrane-association of mRNA decapping factors is independent of stress in budding yeast.

PubMed

Huch, Susanne; Gommlich, Jessie; Muppavarapu, Mridula; Beckham, Carla; Nissan, Tracy

2016-05-05

Recent evidence has suggested that the degradation of mRNA occurs on translating ribosomes or alternatively within RNA granules called P bodies, which are aggregates whose core constituents are mRNA decay proteins and RNA. In this study, we examined the mRNA decapping proteins, Dcp1, Dcp2, and Dhh1, using subcellular fractionation. We found that decapping factors co-sediment in the polysome fraction of a sucrose gradient and do not alter their behaviour with stress, inhibition of translation or inhibition of the P body formation. Importantly, their localisation to the polysome fraction is independent of the RNA, suggesting that these factors may be constitutively localised to the polysome. Conversely, polysomal and post-polysomal sedimentation of the decapping proteins was abolished with the addition of a detergent, which shifts the factors to the non-translating RNP fraction and is consistent with membrane association. Using a membrane flotation assay, we observed the mRNA decapping factors in the lower density fractions at the buoyant density of membrane-associated proteins. These observations provide further evidence that mRNA decapping factors interact with subcellular membranes, and we suggest a model in which the mRNA decapping factors interact with membranes to facilitate regulation of mRNA degradation.

Pressure independence of granular flow through an aperture.

PubMed

Aguirre, M A; Grande, J G; Calvo, A; Pugnaloni, L A; Géminard, J-C

2010-06-11

We experimentally demonstrate that the flow rate of granular material through an aperture is controlled by the exit velocity imposed on the particles and not by the pressure at the base, contrary to what is often assumed in previous work. This result is achieved by studying the discharge process of a dense packing of monosized disks through an orifice. The flow is driven by a conveyor belt. This two-dimensional horizontal setup allows us to independently control the velocity at which the disks escape the horizontal silo and the pressure in the vicinity of the aperture. The flow rate is found to be proportional to the belt velocity, independent of the amount of disks in the container and, thus, independent of the pressure in the outlet region. In addition, this specific configuration makes it possible to get information on the system dynamics from a single image of the disks that rest on the conveyor belt after the discharge.

Genome-wide association analysis reveals putative Alzheimer's disease susceptibility loci in addition to APOE.

PubMed

Bertram, Lars; Lange, Christoph; Mullin, Kristina; Parkinson, Michele; Hsiao, Monica; Hogan, Meghan F; Schjeide, Brit M M; Hooli, Basavaraj; Divito, Jason; Ionita, Iuliana; Jiang, Hongyu; Laird, Nan; Moscarillo, Thomas; Ohlsen, Kari L; Elliott, Kathryn; Wang, Xin; Hu-Lince, Diane; Ryder, Marie; Murphy, Amy; Wagner, Steven L; Blacker, Deborah; Becker, K David; Tanzi, Rudolph E

2008-11-01

Alzheimer's disease (AD) is a genetically complex and heterogeneous disorder. To date four genes have been established to either cause early-onset autosomal-dominant AD (APP, PSEN1, and PSEN2(1-4)) or to increase susceptibility for late-onset AD (APOE5). However, the heritability of late-onset AD is as high as 80%, (6) and much of the phenotypic variance remains unexplained to date. We performed a genome-wide association (GWA) analysis using 484,522 single-nucleotide polymorphisms (SNPs) on a large (1,376 samples from 410 families) sample of AD families of self-reported European descent. We identified five SNPs showing either significant or marginally significant genome-wide association with a multivariate phenotype combining affection status and onset age. One of these signals (p = 5.7 x 10(-14)) was elicited by SNP rs4420638 and probably reflects APOE-epsilon4, which maps 11 kb proximal (r2 = 0.78). The other four signals were tested in three additional independent AD family samples composed of nearly 2700 individuals from almost 900 families. Two of these SNPs showed significant association in the replication samples (combined p values 0.007 and 0.00002). The SNP (rs11159647, on chromosome 14q31) with the strongest association signal also showed evidence of association with the same allele in GWA data generated in an independent sample of approximately 1,400 AD cases and controls (p = 0.04). Although the precise identity of the underlying locus(i) remains elusive, our study provides compelling evidence for the existence of at least one previously undescribed AD gene that, like APOE-epsilon4, primarily acts as a modifier of onset age.

Replacing and Additive Horizontal Gene Transfer in Streptococcus

PubMed Central

Choi, Sang Chul; Rasmussen, Matthew D.; Hubisz, Melissa J.; Gronau, Ilan; Stanhope, Michael J.; Siepel, Adam

2012-01-01

The prominent role of Horizontal Gene Transfer (HGT) in the evolution of bacteria is now well documented, but few studies have differentiated between evolutionary events that predominantly cause genes in one lineage to be replaced by homologs from another lineage (“replacing HGT”) and events that result in the addition of substantial new genomic material (“additive HGT”). Here in, we make use of the distinct phylogenetic signatures of replacing and additive HGTs in a genome-wide study of the important human pathogen Streptococcus pyogenes (SPY) and its close relatives S. dysgalactiae subspecies equisimilis (SDE) and S. dysgalactiae subspecies dysgalactiae (SDD). Using recently developed statistical models and computational methods, we find evidence for abundant gene flow of both kinds within each of the SPY and SDE clades and of reduced levels of exchange between SPY and SDD. In addition, our analysis strongly supports a pronounced asymmetry in SPY–SDE gene flow, favoring the SPY-to-SDE direction. This finding is of particular interest in light of the recent increase in virulence of pathogenic SDE. We find much stronger evidence for SPY–SDE gene flow among replacing than among additive transfers, suggesting a primary influence from homologous recombination between co-occurring SPY and SDE cells in human hosts. Putative virulence genes are correlated with transfer events, but this correlation is found to be driven by additive, not replacing, HGTs. The genes affected by additive HGTs are enriched for functions having to do with transposition, recombination, and DNA integration, consistent with previous findings, whereas replacing HGTs seen to influence a more diverse set of genes. Additive transfers are also found to be associated with evidence of positive selection. These findings shed new light on the manner in which HGT has shaped pathogenic bacterial genomes. PMID:22617954

GJ 581 update: Additional evidence for a Super-Earth in the habitable zone

NASA Astrophysics Data System (ADS)

Vogt, S. S.; Butler, R. P.; Haghighipour, N.

2012-08-01

We present an analysis of the significantly expanded HARPS 2011 radial velocity data set for GJ 581 that was presented by Forveille et al. (2011). Our analysis reaches substantially different conclusions regarding the evidence for a Super-Earth-mass planet in the star's Habitable Zone. We were able to reproduce their reported χν2 and RMS values only after removing some outliers from their models and refitting the trimmed down RV set. A suite of 4000 N-body simulations of their Keplerian model all resulted in unstable systems and revealed that their reported 3.6σ detection of e=0.32 for the eccentricity of GJ 581e is manifestly incompatible with the system's dynamical stability. Furthermore, their Keplerian model, when integrated only over the time baseline of the observations, significantly increases the χν2 and demonstrates the need for including non-Keplerian orbital precession when modeling this system. We find that a four-planet model with all of the planets on circular or nearly circular orbits provides both an excellent self-consistent fit to their RV data and also results in a very stable configuration. The periodogram of the residuals to a 4-planet all-circular-orbit model reveals significant peaks that suggest one or more additional planets in this system. We conclude that the present 240-point HARPS data set, when analyzed in its entirety, and modeled with fully self-consistent stable orbits, by and of itself does offer significant support for a fifth signal in the data with a period near 32 days. This signal has a false alarm probability of <4 % and is consistent with a planet of minimum mass 2.2 M_⊙, orbiting squarely in the star's habitable zone at 0.13 AU, where liquid water on planetary surfaces is a distinct possibility.

Evidence for curricular and instructional design approaches in undergraduate medical education: An umbrella review.

PubMed

Onyura, Betty; Baker, Lindsay; Cameron, Blair; Friesen, Farah; Leslie, Karen

2016-01-01

An umbrella review compiles evidence from multiple reviews into a single accessible document. This umbrella review synthesizes evidence from systematic reviews on curricular and instructional design approaches in undergraduate medical education, focusing on learning outcomes. We conducted bibliographic database searches in Medline, EMBASE and ERIC from database inception to May 2013 inclusive, and digital keyword searches of leading medical education journals. We identified 18,470 abstracts; 467 underwent duplicate full-text scrutiny. Thirty-six articles met all eligibility criteria. Articles were abstracted independently by three authors, using a modified Kirkpatrick model for evaluating learning outcomes. Evidence for the effectiveness of diverse educational approaches is reported. This review maps out empirical knowledge on the efficacy of a broad range of educational approaches in medical education. Critical knowledge gaps, and lapses in methodological rigour, are discussed, providing valuable insight for future research. The findings call attention to the need for adopting evaluative strategies that explore how contextual variabilities and individual (teacher/learner) differences influence efficacy of educational interventions. Additionally, the results underscore that extant empirical evidence does not always provide unequivocal answers about what approaches are most effective. Educators should incorporate best available empirical knowledge with experiential and contextual knowledge.

Electrophysiological evidence for phenomenal consciousness.

PubMed

Revonsuo, Antti; Koivisto, Mika

2010-09-01

Abstract Recent evidence from event-related brain potentials (ERPs) lends support to two central theses in Lamme's theory. The earliest ERP correlate of visual consciousness appears over posterior visual cortex around 100-200 ms after stimulus onset. Its scalp topography and time window are consistent with recurrent processing in the visual cortex. This electrophysiological correlate of visual consciousness is mostly independent of later ERPs reflecting selective attention and working memory functions. Overall, the ERP evidence supports the view that phenomenal consciousness of a visual stimulus emerges earlier than access consciousness, and that attention and awareness are served by distinct neural processes.

pH-independent immediate release polymethacrylate formulations--an observational study.

PubMed

Claeys, Bart; Vandeputte, Reinout; De Geest, Bruno G; Remon, Jean Paul; Vervaet, Chris

2016-01-01

Using Eudragit® E PO (EudrE) as a polymethacrylate carrier, the aim of the study was to develop a pH-independent dosage form containing ibuprofen (IBP) as an active compound via chemical modification of the polymer (i.e. quaternization of amine function) or via the addition of dicarboxylic acids (succinic, glutaric and adipic acid) to create a pH micro-environment during dissolution. Biconvex tablets (diameter: 10 mm; height: 5 mm) were produced via hot melt extrusion and injection molding. In vitro dissolution experiments revealed that a minimum of 25% of quaternization was sufficient to partially (up to pH 5) eliminate the pH-dependent effect of the EudrE/IBP formulation. The addition of dicarboxylic acids did not alter IBP release in a pH 1 and 3 medium as the dimethyl amino groups of EudrE are already fully protonated, while in a pH 5 solvent IBP release was significantly improved (cf. from 0% to 92% release after 1 h dissolution experiments upon the addition of 20 wt.% succinic acid). Hence, both approaches resulted in a pH-independent (up to pH 5) immediate release formulation. However, the presence of a positively charged polymer induced stability issues (recrystallization of API) and the formulations containing dicarboxylic acids were classified as mechanically unstable. Hence, further research is needed to obtain a pH-independent immediate release formulation while using EudrE as a polmethacrylate carrier.

Animate and Inanimate Objects in Human Visual Cortex: Evidence for Task-Independent Category Effects

ERIC Educational Resources Information Center

Wiggett, Alison J.; Pritchard, Iwan C.; Downing, Paul E.

2009-01-01

Evidence from neuropsychology suggests that the distinction between animate and inanimate kinds is fundamental to human cognition. Previous neuroimaging studies have reported that viewing animate objects activates ventrolateral visual brain regions, whereas inanimate objects activate ventromedial regions. However, these studies have typically…

Observational evidence and strength of evidence domains: case examples

PubMed Central

2014-01-01

Background Systematic reviews of healthcare interventions most often focus on randomized controlled trials (RCTs). However, certain circumstances warrant consideration of observational evidence, and such studies are increasingly being included as evidence in systematic reviews. Methods To illustrate the use of observational evidence, we present case examples of systematic reviews in which observational evidence was considered as well as case examples of individual observational studies, and how they demonstrate various strength of evidence domains in accordance with current Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Center (EPC) methods guidance. Results In the presented examples, observational evidence is used when RCTs are infeasible or raise ethical concerns, lack generalizability, or provide insufficient data. Individual study case examples highlight how observational evidence may fulfill required strength of evidence domains, such as study limitations (reduced risk of selection, detection, performance, and attrition); directness; consistency; precision; and reporting bias (publication, selective outcome reporting, and selective analysis reporting), as well as additional domains of dose-response association, plausible confounding that would decrease the observed effect, and strength of association (magnitude of effect). Conclusions The cases highlighted in this paper demonstrate how observational studies may provide moderate to (rarely) high strength evidence in systematic reviews. PMID:24758494

Interpretation and use of evidence in state policymaking: a qualitative analysis

PubMed Central

Apollonio, Dorie E; Bero, Lisa A

2017-01-01

Introduction Researchers advocating for evidence-informed policy have attempted to encourage policymakers to develop a greater understanding of research and researchers to develop a better understanding of the policymaking process. Our aim was to apply findings drawn from studies of the policymaking process, specifically the theory of policy windows, to identify strategies used to integrate evidence into policymaking and points in the policymaking process where evidence was more or less relevant. Methods Our observational study relied on interviews conducted with 24 policymakers from the USA who had been trained to interpret scientific research in multiple iterations of an evidence-based workshop. Participants were asked to describe cases where they had been involved in making health policy and to provide examples in which research was used, either successfully or unsuccessfully. Interviews were transcribed, independently coded by multiple members of the study team and analysed for content using key words, concepts identified by participants and concepts arising from review of the texts. Results Our results suggest that policymakers who focused on health issues used multiple strategies to encourage evidence-informed policymaking. The respondents used a strict definition of what constituted evidence, and relied on their experience with research to discourage the use of less rigorous research. Their experience suggested that evidence was less useful in identifying problems, encouraging political action or ensuring feasibility and more useful in developing policy alternatives. Conclusions Past research has suggested multiple strategies to increase the use of evidence in policymaking, including the development of rapid-response research and policy-oriented summaries of data. Our findings suggest that these strategies may be most relevant to the policymaking stream, which develops policy alternatives. In addition, we identify several strategies that policymakers and

[Evidence and Evidence Gaps - an Introduction].

PubMed

Dreier, G; Löhler, J

2016-04-01

Treating patients requires the inclusion of existing evidence in any health care decision, to be able to choose the best diagnosis or treatment measure or to make valid prognosis statements for a particular patient in consideration of the physician's own expertise.The basis are clinical trials, the results of which are ideally gathered in systematic reviews, rated, summarized and published. In addition to the GCP (Good Clinical Practice)-compliant planning, conducting and analysis of clinical studies it is essential, that all study results are made publicly available, in order to avoid publication bias. This includes the public registration of planned and discontinued trials. In the last 25 years, the evidence-based medicine (EbM) has increasingly found its way into clinical practice and research. Here EbM is closely associated with the names Archibald Cochrane and David Sackett. In Germany, both the German Cochrane Centre (DCZ) and the network of evidence-based medicine (DNEbM) were established approximately 15 years ago. In the international Cochrane Collaboration clinicians and other scientists like statisticians interdisciplinary work side by side to develop the methods of evidence-based medicine and to address the topics of evidence generation and processing as well as the transfer of knowledge. Challenge: Existing evidence primarily serves doctors to support their decision-making, but is also the basis for providing scientific proof for a health care intervention's benefit to patients and ultimately payers/health insurances. The closure of existing evidence gaps requires substantial human and financial resources, a complex organizational structure and can only succeed with the involvement of clinical and methodological expertise and specific knowledge in the field of clinical research. In addition, the knowledge must be transferred into practice, using journals, guidelines, conferences, databases, information portals with processed evidence and not least the

Genetic evidence that two independent S-loci control RNase-based self-incompatibility in diploid strawberry

PubMed Central

Bošković, Radovan I.; Sargent, Daniel J.; Tobutt, Kenneth R.

2010-01-01

The self-incompatibility mechanism that reduces inbreeding in many plants of the Rosaceae is attributed to a multi-allelic S locus which, in the Prunoideae and Maloideae subfamilies, comprises two complementary genes, a stylar-expressed S-RNase and a pollen-expressed SFB. To elucidate incompatibility in the subfamily Rosoideae, stylar-specific RNases and self-(in)compatibility status were analysed in various diploid strawberries, especially Fragaria nubicola and F. viridis, both self-incompatible, and F. vesca, self-compatible, and in various progenies derived from them. Unexpectedly, two unlinked RNase loci, S and T, were found, encoding peptides distinct from Prunoideae and Maloideae S-RNases; the presence of a single active allele at either is sufficient to confer self-incompatibility. By contrast, in diploid Maloideae and Prunoideae a single locus encodes S-RNases that share several conserved regions and two active alleles are required for self-incompatibility. Our evidence implicates the S locus in unilateral inter-specific incompatibility and shows that S and T RNases can, remarkably, confer not only allele-specific rejection of cognate pollen but also unspecific rejection of Sn Tn pollen, where n indicates a null allele, consistent with the the presence of the pollen component, SFB, activating the cognitive function of these RNases. Comparison of relevant linkage groups between Fragaria and Prunus suggests that Prunus S-RNases, unique in having two introns, may have resulted from gene conversion in an ancestor of Prunus. In addition, it is shown that there is a non-S locus that is essential for self-incompatibility in diploid Fragaria. PMID:20008462

Genetic evidence that two independent S-loci control RNase-based self-incompatibility in diploid strawberry.

PubMed

Bosković, Radovan I; Sargent, Daniel J; Tobutt, Kenneth R

2010-03-01

The self-incompatibility mechanism that reduces inbreeding in many plants of the Rosaceae is attributed to a multi-allelic S locus which, in the Prunoideae and Maloideae subfamilies, comprises two complementary genes, a stylar-expressed S-RNase and a pollen-expressed SFB. To elucidate incompatibility in the subfamily Rosoideae, stylar-specific RNases and self-(in)compatibility status were analysed in various diploid strawberries, especially Fragaria nubicola and F. viridis, both self-incompatible, and F. vesca, self-compatible, and in various progenies derived from them. Unexpectedly, two unlinked RNase loci, S and T, were found, encoding peptides distinct from Prunoideae and Maloideae S-RNases; the presence of a single active allele at either is sufficient to confer self-incompatibility. By contrast, in diploid Maloideae and Prunoideae a single locus encodes S-RNases that share several conserved regions and two active alleles are required for self-incompatibility. Our evidence implicates the S locus in unilateral inter-specific incompatibility and shows that S and T RNases can, remarkably, confer not only allele-specific rejection of cognate pollen but also unspecific rejection of Sn Tn pollen, where n indicates a null allele, consistent with the the presence of the pollen component, SFB, activating the cognitive function of these RNases. Comparison of relevant linkage groups between Fragaria and Prunus suggests that Prunus S-RNases, unique in having two introns, may have resulted from gene conversion in an ancestor of Prunus. In addition, it is shown that there is a non-S locus that is essential for self-incompatibility in diploid Fragaria.

Bariatric surgery insurance requirements independently predict surgery dropout.

PubMed

Love, Kaitlin M; Mehaffey, J Hunter; Safavian, Dana; Schirmer, Bruce; Malin, Steven K; Hallowell, Peter T; Kirby, Jennifer L

2017-05-01

Many insurance companies have considerable prebariatric surgery requirements despite a lack of evidence for improved clinical outcomes. The hypothesis of this study is that insurance-specific requirements will be associated with a decreased progression to surgery and increased delay in time to surgery. Retrospective data collection was performed for patients undergoing bariatric surgery evaluation from 2010-2015. Patients who underwent surgery (SGY; n = 827; mean body mass index [BMI] 49.1) were compared with those who did not (no-SGY; n = 648; mean BMI: 49.4). Univariate and multivariate analysis were performed to identify specific co-morbidity and insurance specific predictors of surgical dropout and time to surgery. A total of 1475 patients using 12 major insurance payors were included. Univariate analysis found insurance requirements associated with surgical drop out included longer median diet duration (no-SGY = 6 mo; SGY = 3 mo; P<.001); primary care physician letter of necessity (P<.0001); laboratory testing (P = .019); and evaluation by cardiology (P<.001), pulmonology (P<.0001), or psychiatry (P = .0003). Using logistic regression to control for co-morbidities, longer diet requirement (odds ratio [OR] .88, P<.0001), primary care physician letter (OR .33, P<.0001), cardiology evaluation (OR .22, P = .038), and advanced laboratory testing (OR 5.75, P = .019) independently predicted surgery dropout. Additionally, surgical patients had an average interval between initial visit and surgery of 5.8±4.6 months with significant weight gain (2.1 kg, P<.0001). Many prebariatric surgery insurance requirements were associated with lack of patient progression to surgery in this study. In addition, delays in surgery were associated with preoperative weight gain. Although prospective and multicenter studies are needed, these findings have major policy implications suggesting insurance requirements may need to be reconsidered to improve medical care. Copyright © 2017

Public Reception of Climate Science: Coherence, Reliability, and Independence.

PubMed

Hahn, Ulrike; Harris, Adam J L; Corner, Adam

2016-01-01

Possible measures to mitigate climate change require global collective actions whose impacts will be felt by many, if not all. Implementing such actions requires successful communication of the reasons for them, and hence the underlying climate science, to a degree that far exceeds typical scientific issues which do not require large-scale societal response. Empirical studies have identified factors, such as the perceived level of consensus in scientific opinion and the perceived reliability of scientists, that can limit people's trust in science communicators and their subsequent acceptance of climate change claims. Little consideration has been given, however, to recent formal results within philosophy concerning the relationship between truth, the reliability of evidence sources, the coherence of multiple pieces of evidence/testimonies, and the impact of (non-)independence between sources of evidence. This study draws on these results to evaluate exactly what has (and, more important, has not yet) been established in the empirical literature about the factors that bias the public's reception of scientific communications about climate change. Copyright © 2015 Cognitive Science Society, Inc.

The evidence for Shiatsu: a systematic review of Shiatsu and acupressure

PubMed Central

2011-01-01

Background Shiatsu, similar to acupressure, uses finger pressure, manipulations and stretches, along Traditional Chinese Medicine meridians. Shiatsu is popular in Europe, but lacks reviews on its evidence-base. Methods Acupressure and Shiatsu clinical trials were identified using the MeSH term 'acupressure' in: EBM reviews; AMED; BNI; CINAHL; EMBASE; MEDLINE; PsycARTICLES; Science Direct; Blackwell Synergy; Ingenta Select; Wiley Interscience; Index to Theses and ZETOC. References of articles were checked. Inclusion criteria were Shiatsu or acupressure administered manually/bodily, published after January 1990. Two reviewers performed independent study selection and evaluation of study design and reporting, using standardised checklists (CONSORT, TREND, CASP and STRICTA). Results Searches identified 1714 publications. Final inclusions were 9 Shiatsu and 71 acupressure studies. A quarter were graded A (highest quality). Shiatsu studies comprised 1 RCT, three controlled non-randomised, one within-subjects, one observational and 3 uncontrolled studies investigating mental and physical health issues. Evidence was of insufficient quantity and quality. Acupressure studies included 2 meta-analyses, 6 systematic reviews and 39 RCTs. Strongest evidence was for pain (particularly dysmenorrhoea, lower back and labour), post-operative nausea and vomiting. Additionally quality evidence found improvements in sleep in institutionalised elderly. Variable/poor quality evidence existed for renal disease symptoms, dementia, stress, anxiety and respiratory conditions. Appraisal tools may be inappropriate for some study designs. Potential biases included focus on UK/USA databases, limited grey literature, and exclusion of qualitative and pre-1989 studies. Conclusions Evidence is improving in quantity, quality and reporting, but more research is needed, particularly for Shiatsu, where evidence is poor. Acupressure may be beneficial for pain, nausea and vomiting and sleep. PMID:21982157

Independent effects of motivation and spatial attention in the human visual cortex.

PubMed

Bayer, Mareike; Rossi, Valentina; Vanlessen, Naomi; Grass, Annika; Schacht, Annekathrin; Pourtois, Gilles

2017-01-01

Motivation and attention constitute major determinants of human perception and action. Nonetheless, it remains a matter of debate whether motivation effects on the visual cortex depend on the spatial attention system, or rely on independent pathways. This study investigated the impact of motivation and spatial attention on the activity of the human primary and extrastriate visual cortex by employing a factorial manipulation of the two factors in a cued pattern discrimination task. During stimulus presentation, we recorded event-related potentials and pupillary responses. Motivational relevance increased the amplitudes of the C1 component at ∼70 ms after stimulus onset. This modulation occurred independently of spatial attention effects, which were evident at the P1 level. Furthermore, motivation and spatial attention had independent effects on preparatory activation as measured by the contingent negative variation; and pupil data showed increased activation in response to incentive targets. Taken together, these findings suggest independent pathways for the influence of motivation and spatial attention on the activity of the human visual cortex. © The Author (2016). Published by Oxford University Press.

PCAF interacts with tax and stimulates tax transactivation in a histone acetyltransferase-independent manner.

PubMed

Jiang, H; Lu, H; Schiltz, R L; Pise-Masison, C A; Ogryzko, V V; Nakatani, Y; Brady, J N

1999-12-01

Recent studies have shown that the p300/CREB binding protein (CBP)-associated factor (PCAF) is involved in transcriptional activation. PCAF activity has been shown strongly associated with histone acetyltransferase (HAT) activity. In this report, we present evidence for a HAT-independent transcription function that is activated in the presence of the human T-cell leukemia virus type 1 (HTLV-1) Tax protein. In vitro and in vivo GST-Tax pull-down and coimmunoprecipitation experiments demonstrate that there is a direct interaction between Tax and PCAF, independent of p300/CBP. PCAF can be recruited to the HTLV-1 Tax responsive element in the presence of Tax, and PCAF cooperates with Tax in vivo to activate transcription from the HTLV-1 LTR over 10-fold. Point mutations at Tax amino acid 318 (TaxS318A) or 319 to 320 (Tax M47), which have decreased or no activity on the HTLV-1 promoter, are defective for PCAF binding. Strikingly, the ability of PCAF to stimulate Tax transactivation is not solely dependent on the PCAF HAT domain. Two independent PCAF HAT mutants, which knock out acetyltransferase enzyme activity, activate Tax transactivation to approximately the same level as wild-type PCAF. In contrast, p300 stimulation of Tax transactivation is HAT dependent. These studies provide experimental evidence that PCAF contains a coactivator transcription function independent of the HAT activity on the viral long terminal repeat.

PCAF Interacts with Tax and Stimulates Tax Transactivation in a Histone Acetyltransferase-Independent Manner

PubMed Central

Jiang, Hua; Lu, Hanxin; Schiltz, R. Louis; Pise-Masison, Cynthia A.; Ogryzko, Vasily V.; Nakatani, Yoshihiro; Brady, John N.

1999-01-01

Recent studies have shown that the p300/CREB binding protein (CBP)-associated factor (PCAF) is involved in transcriptional activation. PCAF activity has been shown strongly associated with histone acetyltransferase (HAT) activity. In this report, we present evidence for a HAT-independent transcription function that is activated in the presence of the human T-cell leukemia virus type 1 (HTLV-1) Tax protein. In vitro and in vivo GST-Tax pull-down and coimmunoprecipitation experiments demonstrate that there is a direct interaction between Tax and PCAF, independent of p300/CBP. PCAF can be recruited to the HTLV-1 Tax responsive element in the presence of Tax, and PCAF cooperates with Tax in vivo to activate transcription from the HTLV-1 LTR over 10-fold. Point mutations at Tax amino acid 318 (TaxS318A) or 319 to 320 (Tax M47), which have decreased or no activity on the HTLV-1 promoter, are defective for PCAF binding. Strikingly, the ability of PCAF to stimulate Tax transactivation is not solely dependent on the PCAF HAT domain. Two independent PCAF HAT mutants, which knock out acetyltransferase enzyme activity, activate Tax transactivation to approximately the same level as wild-type PCAF. In contrast, p300 stimulation of Tax transactivation is HAT dependent. These studies provide experimental evidence that PCAF contains a coactivator transcription function independent of the HAT activity on the viral long terminal repeat. PMID:10567539

Evidence-based surgery: barriers, solutions, and the role of evidence synthesis.

PubMed

Garas, George; Ibrahim, Amel; Ashrafian, Hutan; Ahmed, Kamran; Patel, Vanash; Okabayashi, Koji; Skapinakis, Petros; Darzi, Ara; Athanasiou, Thanos

2012-08-01

Surgery is a rapidly evolving field, making the rigorous testing of emerging innovations vital. However, most surgical research fails to employ randomized controlled trials (RCTs) and has particularly been based on low-quality study designs. Subsequently, the analysis of data through meta-analysis and evidence synthesis is particularly difficult. Through a systematic review of the literature, this article explores the barriers to achieving a strong evidence base in surgery and offers potential solutions to overcome the barriers. Many barriers exist to evidence-based surgical research. They include enabling factors, such as funding, time, infrastructure, patient preference, ethical issues, and additionally barriers associated with specific attributes related to researchers, methodologies, or interventions. Novel evidence synthesis techniques in surgery are discussed, including graphics synthesis, treatment networks, and network meta-analyses that help overcome many of the limitations associated with existing techniques. They offer the opportunity to assess gaps and quantitatively present inconsistencies within the existing evidence of RCTs. Poorly or inadequately performed RCTs and meta-analyses can give rise to incorrect results and thus fail to inform clinical practice or revise policy. The above barriers can be overcome by providing academic leadership and good organizational support to ensure that adequate personnel, resources, and funding are allocated to the researcher. Training in research methodology and data interpretation can ensure that trials are conducted correctly and evidence is adequately synthesized and disseminated. The ultimate goal of overcoming the barriers to evidence-based surgery includes the improved quality of patient care in addition to enhanced patient outcomes.

Endothelial atypical cannabinoid receptor: do we have enough evidence?

PubMed Central

Bondarenko, Alexander I

2014-01-01

Cannabinoids and their synthetic analogues affect a broad range of physiological functions, including cardiovascular variables. Although direct evidence is still missing, the relaxation of a vast range of vascular beds induced by cannabinoids is believed to involve a still unidentified non-CB1, non-CB2 Gi/o protein-coupled receptor located on endothelial cells, the so called endothelial cannabinoid receptor (eCB receptor). Evidence for the presence of an eCB receptor comes mainly from vascular relaxation studies, which commonly employ pertussis toxin as an indicator for GPCR-mediated signalling. In addition, a pharmacological approach is widely used to attribute the relaxation to eCB receptors. Recent findings have indicated a number of GPCR-independent targets for both agonists and antagonists of the presumed eCB receptor, warranting further investigations and cautious interpretation of the vascular relaxation studies. This review will provide a brief historical overview on the proposed novel eCB receptor, drawing attention to the discrepancies between the studies on the pharmacological profile of the eCB receptor and highlighting the Gi/o protein-independent actions of the eCB receptor inhibitors widely used as selective compounds. As the eCB receptor represents an attractive pharmacological target for a number of cardiovascular abnormalities, defining its molecular identity and the extent of its regulation of vascular function will have important implications for drug discovery. This review highlights the need to re-evaluate this subject in a thoughtful and rigorous fashion. More studies are needed to differentiate Gi/o protein-dependent endothelial cannabinoid signalling from that involving the classical CB1 and CB2 receptors as well as its relevance for pathophysiological conditions. PMID:25073723

Model-independent confirmation of the Z ( 4430 ) - state

DOE PAGES

Aaij, R.; Adeva, B.; Adinolfi, M.; ...

2015-12-29

Here, the decay B 0→ψ(2S)K +π - is analyzed using 3 fb -1 of pp collision data collected with the LHCb detector. A model-independent description of the ψ(2S)π mass spectrum is obtained, using as input the Kπ mass spectrum and angular distribution derived directly from data, without requiring a theoretical description of resonance shapes or their interference. The hypothesis that the ψ(2S)π mass spectrum can be described in terms of Kπ reflections alone is rejected with more than 8σ significance. This provides confirmation, in a model-independent way, of the need for an additional resonant component in the mass region ofmore » the Z(4430) - exotic state.« less

Modulation of Additive and Interactive Effects in Lexical Decision by Trial History

ERIC Educational Resources Information Center

Masson, Michael E. J.; Kliegl, Reinhold

2013-01-01

Additive and interactive effects of word frequency, stimulus quality, and semantic priming have been used to test theoretical claims about the cognitive architecture of word-reading processes. Additive effects among these factors have been taken as evidence for discrete-stage models of word reading. We present evidence from linear mixed-model…

Identifying reliable independent components via split-half comparisons

PubMed Central

Groppe, David M.; Makeig, Scott; Kutas, Marta

2011-01-01

Independent component analysis (ICA) is a family of unsupervised learning algorithms that have proven useful for the analysis of the electroencephalogram (EEG) and magnetoencephalogram (MEG). ICA decomposes an EEG/MEG data set into a basis of maximally temporally independent components (ICs) that are learned from the data. As with any statistic, a concern with using ICA is the degree to which the estimated ICs are reliable. An IC may not be reliable if ICA was trained on insufficient data, if ICA training was stopped prematurely or at a local minimum (for some algorithms), or if multiple global minima were present. Consequently, evidence of ICA reliability is critical for the credibility of ICA results. In this paper, we present a new algorithm for assessing the reliability of ICs based on applying ICA separately to split-halves of a data set. This algorithm improves upon existing methods in that it considers both IC scalp topographies and activations, uses a probabilistically interpretable threshold for accepting ICs as reliable, and requires applying ICA only three times per data set. As evidence of the method’s validity, we show that the method can perform comparably to more time intensive bootstrap resampling and depends in a reasonable manner on the amount of training data. Finally, using the method we illustrate the importance of checking the reliability of ICs by demonstrating that IC reliability is dramatically increased by removing the mean EEG at each channel for each epoch of data rather than the mean EEG in a prestimulus baseline. PMID:19162199

Associations of children's independent mobility and active travel with physical activity, sedentary behaviour and weight status: a systematic review.

PubMed

Schoeppe, Stephanie; Duncan, Mitch J; Badland, Hannah; Oliver, Melody; Curtis, Carey

2013-07-01

Health benefits from children's independent mobility and active travel beyond school travel are largely unexplored. This review synthesized the evidence for associations of independent mobility and active travel to various destinations with physical activity, sedentary behaviour and weight status. Systematic review. A systematic search in six databases (PubMed, Scopus, CINAHL, SportDiscus, PsychInfo, TRIS) for papers published between January 1990 and March 2012 was undertaken, focussing on children aged 3-18 years. Study inclusion and methodological quality were independently assessed by two reviewers. 52 studies were included. Most studies focussed solely on active travel to and/or from school, and showed significant positive associations with physical activity. The same relationship was detected for active travel to leisure-related places and independent mobility with physical activity. An inverse relationship between active travel to school and weight status was evident but findings were inconsistent. Few studies examined correlations between active travel to school and self-reported screen-time or objectively measured sedentary behaviour, and findings were unclear. Studies on independent mobility suggested that children who have the freedom to play outdoors and travel actively without adult supervision accumulate more physical activity than those who do not. Further investigation of children's active travel to leisure-related destinations, measurement of diverse sedentary behaviour beyond simply screen-based activities, and consistent thresholds for objectively measured sedentary behaviour in children will clarify the inconsistent evidence base on associations of active travel with sedentary behaviour and weight status. Copyright © 2012 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

PRN 96-1: Tolerance Enforcement Methods - Independent Laboratory Validation by Petitioner

EPA Pesticide Factsheets

This notice is intended to clarify the requirements for submission of an Independent Laboratory Validation to accompany new pesticide analytical methods and does not contain additional data requirements.This notice supersedes PR Notice 88-5.

Clinical utilization and cost outcomes from an integrative medicine independent physician association: an additional 3-year update.

PubMed

Sarnat, Richard L; Winterstein, James; Cambron, Jerrilyn A

2007-05-01

Our initial report analyzed clinical and cost utilization data from the years 1999 to 2002 for an integrative medicine independent physician association (IPA) whose primary care physicians (PCPs) were exclusively doctors of chiropractic. This report updates the subsequent utilization data from the IPA for the years 2003 to 2005 and includes first-time comparisons in data points among PCPs of different licensures who were oriented toward complementary and alternative medicine (CAM). Independent physician association-incurred claims and stratified random patient surveys were descriptively analyzed for clinical utilization, cost offsets, and member satisfaction compared with conventional medical IPA normative values. Comparisons to our original publication's comparative blinded data, using nonrandom matched comparison groups, were descriptively analyzed for differences in age/sex demographics and disease profiles to examine sample bias. Clinical and cost utilization based on 70,274 member-months over a 7-year period demonstrated decreases of 60.2% in-hospital admissions, 59.0% hospital days, 62.0% outpatient surgeries and procedures, and 85% pharmaceutical costs when compared with conventional medicine IPA performance for the same health maintenance organization product in the same geography and time frame. During the past 7 years, and with a larger population than originally reported, the CAM-oriented PCPs using a nonsurgical/nonpharmaceutical approach demonstrated reductions in both clinical and cost utilization when compared with PCPs using conventional medicine alone. Decreased utilization was uniformly achieved by all CAM-oriented PCPs, regardless of their licensure. The validity and generalizability of this observation are guarded given the lack of randomization, lack of statistical analysis possible, and potentially biased data in this population.

Unliganded fibroblast growth factor receptor 1 forms density-independent dimers.

PubMed

Comps-Agrar, Laëtitia; Dunshee, Diana Ronai; Eaton, Dan L; Sonoda, Junichiro

2015-10-02

Fibroblast growth factors receptors (FGFRs) are thought to initiate intracellular signaling cascades upon ligand-induced dimerization of the extracellular domain. Although the existence of unliganded FGFR1 dimers on the surface of living cells has been proposed, this notion remains rather controversial. Here, we employed time-resolved Förster resonance energy transfer combined with SNAP- and ACP-tag labeling in COS7 cells to monitor dimerization of full-length FGFR1 at the cell-surface with or without the coreceptor βKlotho. Using this approach we observed homodimerization of unliganded FGFR1 that is independent of its surface density. The homo-interaction signal observed for FGFR1 was indeed as robust as that obtained for epidermal growth factor receptor (EGFR) and was further increased by the addition of activating ligands or pathogenic mutations. Mutational analysis indicated that the kinase and the transmembrane domains, rather than the extracellular domain, mediate the ligand-independent FGFR1 dimerization. In addition, we observed a formation of a higher order ligand-independent complex by the c-spliced isoform of FGFR1 and βKlotho. Collectively, our approach provides novel insights into the assembly and dynamics of the full-length FGFRs on the cell surface. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Model-Independent Bounds on Kinetic Mixing

DOE PAGES

Hook, Anson; Izaguirre, Eder; Wacker, Jay G.

2011-01-01

New Abelimore » an vector bosons can kinetically mix with the hypercharge gauge boson of the Standard Model. This letter computes the model-independent limits on vector bosons with masses from 1 GeV to 1 TeV. The limits arise from the numerous e + e − experiments that have been performed in this energy range and bound the kinetic mixing by ϵ ≲ 0.03 for most of the mass range studied, regardless of any additional interactions that the new vector boson may have.« less

No Generalization of Practice for Nonzero Simple Addition

ERIC Educational Resources Information Center

Campbell, Jamie I. D.; Beech, Leah C.

2014-01-01

Several types of converging evidence have suggested recently that skilled adults solve very simple addition problems (e.g., 2 + 1, 4 + 2) using a fast, unconscious counting algorithm. These results stand in opposition to the long-held assumption in the cognitive arithmetic literature that such simple addition problems normally are solved by fact…

Intellectual developmental disorders in Mexico: a call for programmes promoting independence and inclusion.

PubMed

Katz, Gregorio; Corona, Edgar; Lazcano-Ponce, Eduardo

2016-08-01

This paper describes an innovative institution, Capacitación y Desarrollo Integral AC (CADI - Comprehensive Training and Development), created in Mexico to develop evidence-based interventions grounded in the principles of inclusion, independence, social and health equity that promote the well-being of persons with intellectual developmental disorder older than 14 years.

Genome-wide Association Analysis Reveals Putative Alzheimer's Disease Susceptibility Loci in Addition to APOE

PubMed Central

Bertram, Lars; Lange, Christoph; Mullin, Kristina; Parkinson, Michele; Hsiao, Monica; Hogan, Meghan F.; Schjeide, Brit M.M.; Hooli, Basavaraj; DiVito, Jason; Ionita, Iuliana; Jiang, Hongyu; Laird, Nan; Moscarillo, Thomas; Ohlsen, Kari L.; Elliott, Kathryn; Wang, Xin; Hu-Lince, Diane; Ryder, Marie; Murphy, Amy; Wagner, Steven L.; Blacker, Deborah; Becker, K. David; Tanzi, Rudolph E.

2008-01-01

Alzheimer's disease (AD) is a genetically complex and heterogeneous disorder. To date four genes have been established to either cause early-onset autosomal-dominant AD (APP, PSEN1, and PSEN21–4) or to increase susceptibility for late-onset AD (APOE5). However, the heritability of late-onset AD is as high as 80%,6 and much of the phenotypic variance remains unexplained to date. We performed a genome-wide association (GWA) analysis using 484,522 single-nucleotide polymorphisms (SNPs) on a large (1,376 samples from 410 families) sample of AD families of self-reported European descent. We identified five SNPs showing either significant or marginally significant genome-wide association with a multivariate phenotype combining affection status and onset age. One of these signals (p = 5.7 × 10−14) was elicited by SNP rs4420638 and probably reflects APOE-ɛ4, which maps 11 kb proximal (r2 = 0.78). The other four signals were tested in three additional independent AD family samples composed of nearly 2700 individuals from almost 900 families. Two of these SNPs showed significant association in the replication samples (combined p values 0.007 and 0.00002). The SNP (rs11159647, on chromosome 14q31) with the strongest association signal also showed evidence of association with the same allele in GWA data generated in an independent sample of ∼1,400 AD cases and controls (p = 0.04). Although the precise identity of the underlying locus(i) remains elusive, our study provides compelling evidence for the existence of at least one previously undescribed AD gene that, like APOE-ɛ4, primarily acts as a modifier of onset age. PMID:18976728

Additional evidence on the use of personal ornaments in the Middle Paleolithic of North Africa

PubMed Central

d'Errico, Francesco; Vanhaeren, Marian; Barton, Nick; Bouzouggar, Abdeljalil; Mienis, Henk; Richter, Daniel; Hublin, Jean-Jacques; McPherron, Shannon P.; Lozouet, Pierre

2009-01-01

Recent investigations into the origins of symbolism indicate that personal ornaments in the form of perforated marine shell beads were used in the Near East, North Africa, and SubSaharan Africa at least 35 ka earlier than any personal ornaments in Europe. Together with instances of pigment use, engravings, and formal bone tools, personal ornaments are used to support an early emergence of behavioral modernity in Africa, associated with the origin of our species and significantly predating the timing for its dispersal out of Africa. Criticisms have been leveled at the low numbers of recovered shells, the lack of secure dating evidence, and the fact that documented examples were not deliberately shaped. In this paper, we report on 25 additional shell beads from four Moroccan Middle Paleolithic sites. We review their stratigraphic and chronological contexts and address the issue of these shells having been deliberately modified and used. We detail the results of comparative analyses of modern, fossil, and archaeological assemblages and microscopic examinations of the Moroccan material. We conclude that Nassarius shells were consistently used for personal ornamentation in this region at the end of the last interglacial. Absence of ornaments at Middle Paleolithic sites postdating Marine Isotope Stage 5 raises the question of the possible role of climatic changes in the disappearance of this hallmark of symbolic behavior before its reinvention 40 ka ago. Our results suggest that further inquiry is necessary into the mechanisms of cultural transmission within early Homo sapiens populations. PMID:19717433

The dependency paradox in close relationships: accepting dependence promotes independence.

PubMed

Feeney, Brooke C

2007-02-01

Using multiple methods, this investigation tested the hypothesis that a close relationship partner's acceptance of dependence when needed (e.g., sensitive responsiveness to distress cues) is associated with less dependence, more autonomous functioning, and more self-sufficiency (as opposed to more dependence) on the part of the supported individual. In two studies, measures of acceptance of dependency needs and independent functioning were obtained through couple member reports, by observing couple members' behaviors during laboratory interactions, by observing responses to experimentally manipulated partner assistance provided during an individual laboratory task, and by following couples over a period of 6 months to examine independent goal striving as a function of prior assessments of dependency acceptance. Results provided converging evidence in support of the proposed hypothesis. Implications of the importance of close relationships for optimal individual functioning are discussed. ((c) 2007 APA, all rights reserved).

Stimulus information contaminates summation tests of independent neural representations of features

NASA Technical Reports Server (NTRS)

Shimozaki, Steven S.; Eckstein, Miguel P.; Abbey, Craig K.

2002-01-01

Many models of visual processing assume that visual information is analyzed into separable and independent neural codes, or features. A common psychophysical test of independent features is known as a summation study, which measures performance in a detection, discrimination, or visual search task as the number of proposed features increases. Improvement in human performance with increasing number of available features is typically attributed to the summation, or combination, of information across independent neural coding of the features. In many instances, however, increasing the number of available features also increases the stimulus information in the task, as assessed by an optimal observer that does not include the independent neural codes. In a visual search task with spatial frequency and orientation as the component features, a particular set of stimuli were chosen so that all searches had equivalent stimulus information, regardless of the number of features. In this case, human performance did not improve with increasing number of features, implying that the improvement observed with additional features may be due to stimulus information and not the combination across independent features.

Pharmacological and Chemical Effects of Cigarette Additives

PubMed Central

Rabinoff, Michael; Caskey, Nicholas; Rissling, Anthony; Park, Candice

2007-01-01

We investigated tobacco industry documents and other sources for evidence of possible pharmacological and chemical effects of tobacco additives. Our findings indicated that more than 100 of 599 documented cigarette additives have pharmacological actions that camouflage the odor of environmental tobacco smoke emitted from cigarettes, enhance or maintain nicotine delivery, could increase the addictiveness of cigarettes, and mask symptoms and illnesses associated with smoking behaviors. Whether such uses were specifically intended for these agents is unknown. Our results provide a clear rationale for regulatory control of tobacco additives. PMID:17666709

Intellectual developmental disorders in Mexico: a call for programmes promoting independence and inclusion

PubMed Central

Katz, Gregorio; Corona, Edgar

2016-01-01

This paper describes an innovative institution, Capacitación y Desarrollo Integral AC (CADI – Comprehensive Training and Development), created in Mexico to develop evidence-based interventions grounded in the principles of inclusion, independence, social and health equity that promote the well-being of persons with intellectual developmental disorder older than 14 years. PMID:29093910

Exploring the relation between positive emotions and the functional status of older adults living independently: a systematic review.

PubMed

Cabrita, Miriam; Lamers, Sanne M A; Trompetter, Hester R; Tabak, Monique; Vollenbroek-Hutten, Miriam M R

2017-11-01

Literature suggests that positive emotions positively influence physiological parameters but their relation to functioning in the daily life of older adults living independently remains unclear. The present work aims to investigate the relation between positive emotions and functional status in daily life of older people living independently. A systematic literature review was conducted using the PubMed, PsycINFO and Scopus electronic databases. Included works were peer-reviewed empirical studies that analysed the relation between positive emotions and ability to perform activities of daily living with older adults living independently. After removal of duplicates, 10 out of 963 papers met the inclusion criteria. Cross-sectional studies (n = 6) provided limited evidence about a relation between positive emotions and functioning in daily life. However, longitudinal studies (n = 4) provide significant evidence for an interaction between the two factors, suggesting that time influences this interaction. The variety on the design and samples of the studies included in this review does not allow a cohesive conclusion of the results. Nevertheless, limited evidence suggests that higher frequency in the experience of positive emotions might be associated with lower functional limitations. The issue of causality in emotions-functioning remains unclear from the review. Further observational studies are highly recommended, supported by innovative technologies.

Smed-Evi/Wntless is required for beta-catenin-dependent and -independent processes during planarian regeneration.

PubMed

Adell, Teresa; Salò, Emili; Boutros, Michael; Bartscherer, Kerstin

2009-03-01

Planarians can regenerate a whole animal from only a small piece of their body, and have become an important model for stem cell biology. To identify regenerative processes dependent on Wnt growth factors in the planarian Schmidtea mediterranea (Smed), we analyzed RNAi phenotypes of Evi, a transmembrane protein specifically required for the secretion of Wnt ligands. We show that, during regeneration, Smed-evi loss-of-function prevents posterior identity, leading to two-headed planarians that resemble Smed-beta-catenin1 RNAi animals. In addition, we observe regeneration defects of the nervous system that are not found after Smed-beta-catenin1 RNAi. By systematic knockdown of all putative Smed Wnts in regenerating planarians, we identify Smed-WntP-1 and Smed-Wnt11-2 as the putative posterior organizers, and demonstrate that Smed-Wnt5 is a regulator of neuronal organization and growth. Thus, our study provides evidence that planarian Wnts are major regulators of regeneration, and that they signal through beta-catenin-dependent and -independent pathways.

Aging society and gerontechnology: a solution for an independent living?

PubMed

Piau, A; Campo, E; Rumeau, P; Vellas, B; Nourhashémi, F

2014-01-01

Recent studies report that the majority of older adults wish to live in their own homes, for as long as possible. This creates a growing interest in technologies to enable older people to remain living independently at home. The purpose of this article is to provide a narrative review of current technology appropriate for older adults' home use. The key research questions were as follow: 1- What is the evidence demonstrating that gerontechnologies are effective in enabling independent living? 2- What are devices designed specifically for frail elderly persons ? Several publications were identified about devices targeting social isolation (videophonic communication, affective orthotic devices or companion-type robots, personal emergency response systems [security]), autonomy loss (technologies for maintenance of autonomy in the activities of daily living) and cognitive disorders (cognitive orthotics, wandering management systems, telemonitoring). Very few articles dealt specifically with the frail older person. In particular, there was extremely limited evidence on use and efficacy of these devices within this population. There is a need to obtain a consensus on definition of the technologies, and also to revisit work strategies and develop innovative business models. To meet this goal, we need to create a network of technological companies, aging services organizations, end-users, academics, and government representatives to explore the real needs of the frail older population and to develop and validate new devices promoting aging at home.

The Lifestyle Interventions and Independence for Elders Study: design and methods.

PubMed

Fielding, Roger A; Rejeski, W Jack; Blair, Steven; Church, Tim; Espeland, Mark A; Gill, Thomas M; Guralnik, Jack M; Hsu, Fang-Chi; Katula, Jeffrey; King, Abby C; Kritchevsky, Stephen B; McDermott, Mary M; Miller, Michael E; Nayfield, Susan; Newman, Anne B; Williamson, Jeff D; Bonds, Denise; Romashkan, Sergei; Hadley, Evan; Pahor, Marco

2011-11-01

As the number of older adults in the United States rises, maintaining functional independence among older Americans has emerged as a major clinical and public health priority. Older people who lose mobility are less likely to remain in the community; demonstrate higher rates of morbidity, mortality, and hospitalizations; and experience a poorer quality of life. Several studies have shown that regular physical activity improves functional limitations and intermediate functional outcomes, but definitive evidence showing that major mobility disability can be prevented is lacking. A Phase 3 randomized controlled trial is needed to fill this evidence gap. The Lifestyle Interventions and Independence for Elders (LIFE) Study is a Phase 3 multicenter randomized controlled trial designed to compare a supervised moderate-intensity physical activity program with a successful aging health education program in 1,600 sedentary older persons followed for an average of 2.7 years. LIFE's primary outcome is major mobility disability, defined as the inability to walk 400 m. Secondary outcomes include cognitive function, serious fall injuries, persistent mobility disability, the combined outcome of major mobility disability or death, disability in activities of daily living, and cost-effectiveness. Results of this study are expected to have important public health implications for the large and growing population of older sedentary men and women.

Chemesthesis and taste: evidence of independent processing of sensation intensity.

PubMed

Green, Barry G; Alvarez-Reeves, Marty; George, Pravin; Akirav, Carol

2005-11-15

The ability to perceive taste from temperature alone ("thermal taste") was recently shown to predict higher perceptual responsiveness to gustatory and olfactory stimuli. This relationship was hypothesized to be due in part to individual differences in CNS processes involved in flavor perception. Here we report three experiments that tested whether subjects who differ in responsiveness to thermal taste and/or chemical taste also differ in responsiveness to oral chemesthesis. In experiment 1, subjects identified as 'thermal tasters' (TTs) or 'thermal non-tasters' (TnTs) used the general Labeled Magnitude Scale to rate the intensity of sensations produced on the tongue tip by capsaicin, menthol, sucrose, NaCl, citric acid, and QSO4. TTs rated all four taste stimuli higher than did TnTs, whereas sensations of burning/stinging/pricking and temperature from capsaicin and menthol did not differ significantly between groups. In experiment 2, testing with capsaicin on both the front and back of the tongue confirmed there was no difference in ratings of burning/stinging/pricking when subjects were grouped according to the ability to perceive thermal taste. In experiment 3, subjects were classified as high- or low-tasters according to their ratings of sucrose sweetness rather than thermal taste. No group difference was found for perception of capsaicin even when presented in mixture with sucrose or NaCl. The results are discussed in the context of previous evidence of an association between chemesthesis and sensitivity to the bitter tastant PROP, and in terms of the various peripheral and central neural processes that may underlie intensity perception in taste and chemesthesis.

The virtues of evidence.

PubMed

Zarkovich, Erica; Upshur, R E G

2002-01-01

Evidence-based medicine has been defined as the conscientious and judicious use of current best evidence in making clinical decisions. This paper will attempt to explicate the terms "conscientious" and "judicious" within the evidence-based medicine definition. It will be argued that "conscientious" and "judicious" represent virtue terms derived from virtue ethics and virtue epistemology. The identification of explicit virtue components in the definition and therefore conception of evidence-based medicine presents an important starting point in the connection between virtue theories and medicine itself. In addition, a unification of virtue theories and evidence-based medicine will illustrate the need for future research in order to combine the fields of virtue-based approaches and clinical practice.

Spatial Variance in Resting fMRI Networks of Schizophrenia Patients: An Independent Vector Analysis

PubMed Central

Gopal, Shruti; Miller, Robyn L.; Michael, Andrew; Adali, Tulay; Cetin, Mustafa; Rachakonda, Srinivas; Bustillo, Juan R.; Cahill, Nathan; Baum, Stefi A.; Calhoun, Vince D.

2016-01-01

Spatial variability in resting functional MRI (fMRI) brain networks has not been well studied in schizophrenia, a disease known for both neurodevelopmental and widespread anatomic changes. Motivated by abundant evidence of neuroanatomical variability from previous studies of schizophrenia, we draw upon a relatively new approach called independent vector analysis (IVA) to assess this variability in resting fMRI networks. IVA is a blind-source separation algorithm, which segregates fMRI data into temporally coherent but spatially independent networks and has been shown to be especially good at capturing spatial variability among subjects in the extracted networks. We introduce several new ways to quantify differences in variability of IVA-derived networks between schizophrenia patients (SZs = 82) and healthy controls (HCs = 89). Voxelwise amplitude analyses showed significant group differences in the spatial maps of auditory cortex, the basal ganglia, the sensorimotor network, and visual cortex. Tests for differences (HC-SZ) in the spatial variability maps suggest, that at rest, SZs exhibit more activity within externally focused sensory and integrative network and less activity in the default mode network thought to be related to internal reflection. Additionally, tests for difference of variance between groups further emphasize that SZs exhibit greater network variability. These results, consistent with our prediction of increased spatial variability within SZs, enhance our understanding of the disease and suggest that it is not just the amplitude of connectivity that is different in schizophrenia, but also the consistency in spatial connectivity patterns across subjects. PMID:26106217

Transcranial Direct Current Stimulation Does Not Influence the Speed-Accuracy Tradeoff in Perceptual Decision-making: Evidence from Three Independent Studies.

PubMed

de Hollander, Gilles; Labruna, Ludovica; Sellaro, Roberta; Trutti, Anne; Colzato, Lorenza S; Ratcliff, Roger; Ivry, Richard B; Forstmann, Birte U

2016-09-01

In perceptual decision-making tasks, people balance the speed and accuracy with which they make their decisions by modulating a response threshold. Neuroimaging studies suggest that this speed-accuracy tradeoff is implemented in a corticobasal ganglia network that includes an important contribution from the pre-SMA. To test this hypothesis, we used anodal transcranial direct current stimulation (tDCS) to modulate neural activity in pre-SMA while participants performed a simple perceptual decision-making task. Participants viewed a pattern of moving dots and judged the direction of the global motion. In separate trials, they were cued to either respond quickly or accurately. We used the diffusion decision model to estimate the response threshold parameter, comparing conditions in which participants received sham or anodal tDCS. In three independent experiments, we failed to observe an influence of tDCS on the response threshold. Additional, exploratory analyses showed no influence of tDCS on the duration of nondecision processes or on the efficiency of information processing. Taken together, these findings provide a cautionary note, either concerning the causal role of pre-SMA in decision-making or on the utility of tDCS for modifying response caution in decision-making tasks.

Combinations of Adefovir with Nucleoside Analogs Produce Additive Antiviral Effects against Hepatitis B Virus In Vitro

PubMed Central

Delaney, William E.; Yang, Huiling; Miller, Michael D.; Gibbs, Craig S.; Xiong, Shelly

2004-01-01

Combination therapies may be required for long-term management of some patients chronically infected with hepatitis B virus (HBV). Adefovir is a nucleotide analog that has similar activity against wild-type and lamivudine-resistant HBV. In contrast to lamivudine, clinical resistance to the prodrug adefovir dipivoxil emerges infrequently. Based on its clinical efficacy and low frequency of resistance, adefovir dipivoxil may form an important component of combination regimens. We therefore investigated the in vitro antiviral efficacy of combinations of adefovir with other nucleoside analogs (lamivudine, entecavir, emtricitabine [FTC],and telbivudine [L-dT]) and the nucleotide analog tenofovir. Using a novel stable cell line that expresses high levels of wild-type HBV, we assayed the antiviral activity of each drug alone and in combination with adefovir. All two-drug combinations resulted in greater antiviral effects than treatments with single agents and could be characterized as additive by the Bliss independence model. Analysis using the Loewe additivity model indicated that adefovir exerted additive antiviral effects when combined with lamivudine, FTC, or L-dT and moderately synergistic effects when combined with entecavir or tenofovir. There was no evidence of cytotoxicity with any of the drugs when used alone or in combination at the tested doses. PMID:15388423

Toward More Evidence-Based Practice

PubMed Central

Hotelling, Barbara A.

2005-01-01

Childbirth educators are responsible for providing expectant parents with evidence-based information. In this column, the author suggests resources where educators can find evidence-based research for best practices. Additionally, the author describes techniques for childbirth educators to use in presenting research-based information in their classes. A sample of Web sites and books that offer evidence-based resources for expectant parents is provided. PMID:17273422

Contextual Effect of Wealth on Independence: An Examination through Regional Differences in China.

PubMed

Takemura, Kosuke; Hamamura, Takeshi; Guan, Yanjun; Suzuki, Satoko

2016-01-01

The current study disentangled two different effects of wealth on psychological tendency toward independence: one is an effect exerted at the individual level (i.e., being rich) and the other one is a contextual effect (i.e., being surrounded by rich individuals). Past research has found a stronger tendency toward independence among people in economically developed societies. This association has often been explained as a result of a greater amount of choices, and thus more opportunities to express individuality that wealth affords individuals. In addition to this individual-level process, theories in cultural psychology imply that the wealth-independence link also reflects social processes-living in a rich society, regardless of one's own wealth, promotes independence (contextual effect of wealth on independence). Through a large-scale survey in China, using multilevel analyses, we found that wealth had both the individual-level effect and contextual effect on independence as well as related psychological tendencies (influence orientation and generalized trust), suggesting that individuals are more likely to be independent with greater personal wealth and when surrounded by wealthy others. Possible processes through which independence is promoted by liing in a wealthy area are discussed.

Contextual Effect of Wealth on Independence: An Examination through Regional Differences in China

PubMed Central

Takemura, Kosuke; Hamamura, Takeshi; Guan, Yanjun; Suzuki, Satoko

2016-01-01

The current study disentangled two different effects of wealth on psychological tendency toward independence: one is an effect exerted at the individual level (i.e., being rich) and the other one is a contextual effect (i.e., being surrounded by rich individuals). Past research has found a stronger tendency toward independence among people in economically developed societies. This association has often been explained as a result of a greater amount of choices, and thus more opportunities to express individuality that wealth affords individuals. In addition to this individual-level process, theories in cultural psychology imply that the wealth-independence link also reflects social processes—living in a rich society, regardless of one’s own wealth, promotes independence (contextual effect of wealth on independence). Through a large-scale survey in China, using multilevel analyses, we found that wealth had both the individual-level effect and contextual effect on independence as well as related psychological tendencies (influence orientation and generalized trust), suggesting that individuals are more likely to be independent with greater personal wealth and when surrounded by wealthy others. Possible processes through which independence is promoted by liing in a wealthy area are discussed. PMID:27014175

MAROON BELLS-SNOWMASS WILDERNESS AND ADDITIONS, COLORADO.

USGS Publications Warehouse

Freeman, Val L.; Weisner, Robert C.

1984-01-01

The Maroon Bells-Snowmass Wilderness and Additions, located in western Colorado, was examined for mineral potential. Evidence of mineralization is widespread and numerous areas have either probable or substantiated mineral-resource potential for one or more of the following metals: gold, silver, lead, zinc, copper, and molybdenum. In addition, part of the wilderness has substantiated coal resource potential. There is little promise for the occurrence of oil and gas or geothermal resources.

Evidence on health-promoting lifestyle practices and information and communication technologies: scoping review protocol.

PubMed

Joseph-Shehu, Elizabeth M; Ncama, Busisiwe P

2017-03-29

Information and communication technologies (ICTs) play a key role in improving health and maintaining health promoting behaviours. ICTs are therefore one potential solution for promoting healthy lifestyles. In addition, they can assist in the reduction and control of the menace of both communicable and non-communicable diseases. This study will map evidence of interventions that demonstrate the effect of ICTs on health-promoting lifestyle practices that can prevent and control diseases. It is anticipated that this study will help identify areas where there is need for primary research. The following electronic databases will be searched: PsycArticle (EBSCO), PsycINFO (EBSCO), Science direct, PubMed, Medline (EBSCO) and Google Scholar. The study will be conducted in two stages: the first stage will map out the studies descriptively while the second stage will map the additional inclusion criteria of quality assessment. Two independent reviewers will undertake the data extraction. Relevant outcomes of the studies will be analysed thematically using NVIvo computer software. The authors will code all evidence independently. Thereafter the authors will critically cross-examine the relationship of the research questions to the emerging themes from the selected articles. The authors hope to find a large number of studies on health-promoting lifestyles that encompass six-subscales of health-promoting activities (nutrition, stress management, interpersonal relation, self-actualisation, health responsibility, physical activity) and ICT. This study will be presented in conferences related to health promotion and health-promoting lifestyles. It will also be disseminated in print and electronically. CRD42016042568. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Independent Activation of Hepatitis B Virus Biosynthesis by Retinoids, Peroxisome Proliferators, and Bile Acids

PubMed Central

Reese, Vanessa C.; Oropeza, Claudia E.

2013-01-01

In the human hepatoma cell line HepG2, retinoic acid, clofibric acid, and bile acid treatment can only modestly increase hepatitis B virus (HBV) biosynthesis. Utilizing the human embryonic kidney cell line 293T, it was possible to demonstrate that the retinoid X receptor α (RXRα) plus its ligand can support viral biosynthesis independently of additional nuclear receptors. In addition, RXRα/peroxisome proliferator-activated receptor α (PPARα) and RXRα/farnesoid X receptor α (FXRα) heterodimeric nuclear receptors can also mediate ligand-dependent HBV transcription and replication when activated by clofibric acid and bile acid, respectively, independently of a requirement for the ligand-dependent activation of RXRα. These observations indicate that there are at least three possible modes of ligand-mediated activation of HBV transcription and replication existing within hepatocytes, suggesting that multiple independent mechanisms control viral production in the livers of infected individuals. PMID:23135717

Transitioning to employment with a rheumatic disease: the role of independence, overprotection, and social support.

PubMed

Jetha, Arif; Badley, Elizabeth; Beaton, Dorcas; Fortin, Paul R; Shiff, Natalie J; Rosenberg, Alan M; Tucker, Lori B; Mosher, Dianne P; Gignac, Monique A M

2014-12-01

To examine perceived independence, overprotection, and support, and their association with the employment participation of young adults with rheumatic disease. One hundred and forty-three young adults, ages 18 to 30 years, with systemic lupus erythematosus (54.5%) and juvenile arthritis (45.5%) completed a 30-min online questionnaire of their work and education experiences. Information collected was demographic, health (e.g., pain, fatigue, disease activity), work context (e.g., career satisfaction, helpfulness of job accommodation/benefits, and workplace activity limitations), and psychosocial (e.g., independence, social support, and overprotection). Log-Poisson regression analysis examined factors associated with employment status. Over half of respondents were employed (59%) and 26% were enrolled in school. Respondents reported moderate to high perceptions of independence and social support. However, 27% reported that "quite a bit" to "a great deal" of overprotection characterized their relationships with those closest to them. At the bivariate level, employed participants and those indicating greater perceived independence reported greater social support and less overprotection. Multivariable analysis revealed that being employed was associated with older age, more job accommodations/benefits perceived as being helpful, and greater perceived independence. This is one of the first studies examining the employment of young adults with rheumatic diseases. Findings highlight the importance of psychosocial perceptions such as independence and overprotection, in addition to support related to working. Additional research is needed to better understand the role of those close to young adults with rheumatic diseases in supporting independence and encouraging employment.

Analysis of Aircraft Clusters to Measure Sector-Independent Airspace Congestion

NASA Technical Reports Server (NTRS)

Bilimoria, Karl D.; Lee, Hilda Q.

2005-01-01

The Distributed Air/Ground Traffic Management (DAG-TM) concept of operations* permits appropriately equipped aircraft to conduct Free Maneuvering operations. These independent aircraft have the freedom to optimize their trajectories in real time according to user preferences; however, they also take on the responsibility to separate themselves from other aircraft while conforming to any local Traffic Flow Management (TFM) constraints imposed by the air traffic service provider (ATSP). Examples of local-TFM constraints include temporal constraints such as a required time of arrival (RTA), as well as spatial constraints such as regions of convective weather, special use airspace, and congested airspace. Under current operations, congested airspace typically refers to a sector(s) that cannot accept additional aircraft due to controller workload limitations; hence Dynamic Density (a metric that is indicative of controller workload) can be used to quantify airspace congestion. However, for Free Maneuvering operations under DAG-TM, an additional metric is needed to quantify the airspace congestion problem from the perspective of independent aircraft. Such a metric would enable the ATSP to prevent independent aircraft from entering any local areas of congestion in which the flight deck based systems and procedures may not be able to ensure separation. This new metric, called Gaggle Density, offers the ATSP a mode of control to regulate normal operations and to ensure safety and stability during rare-normal or off-normal situations (e.g., system failures). It may be difficult to certify Free Maneuvering systems for unrestricted operations, but it may be easier to certify systems and procedures for specified levels of Gaggle Density that could be monitored by the ATSP, and maintained through relatively minor flow-rate (RTA type) restrictions. Since flight deck based separation assurance is airspace independent, the challenge is to measure congestion independent of sector

Perceived effects of home renovation on independence of physically disabled Koreans living at home.

PubMed

Lee, Yeunsook; Park, Jiyoung; Jang, Miseon

2017-06-06

This study aims to identify the potential effects of home renovation on independence promotion of physically disabled Koreans living at home. The method of the study is a survey with a questionnaire; subjects are physically disabled people living at home in rural and urban areas in Korea. The Functional Independence Measure was used to measure changes in subjects' levels of independence. It was expected that if homes were renovated according to individual needs, disabled people's independence level would be increased by one or more level compared to their current daily independence level in their existing homes. In particular, independence levels concerning bathing and locomotion, which are low in existing conditions, were expected to increase significantly with renovation. Such effects on independence level were conspicuous for disabled people in rural area. The results prove the positive effects of home renovations of disabled people's independence, thus providing meaningful academic evidence on home renovations for disabled people. Implication for rehabilitation Korea had a culture where support measures to aid the life independence of disabled persons relied heavily on human services, leading to a lack of diversity in support measures. By closing the gap between the resident's disability and the inadequacy in their prevailing environment, house remodeling can be a crucial intervention for improving the independence of disabled persons in their daily lives. Depending on the nature of their disabilities and their residential arrangements, disabled persons have diverse needs regarding home remodeling. Implementing home remodeling in such a manner that suits the resident's needs is crucial to boosting their independence. Because of this, remodeling personnel must interact with residents prior to the renovation while also strengthening their expertise.

Causal evidence for retina dependent and independent visual motion computations in mouse cortex

PubMed Central

Hillier, Daniel; Fiscella, Michele; Drinnenberg, Antonia; Trenholm, Stuart; Rompani, Santiago B.; Raics, Zoltan; Katona, Gergely; Juettner, Josephine; Hierlemann, Andreas; Rozsa, Balazs; Roska, Botond

2017-01-01

How neuronal computations in the sensory periphery contribute to computations in the cortex is not well understood. We examined this question in the context of visual-motion processing in the retina and primary visual cortex (V1) of mice. We disrupted retinal direction selectivity – either exclusively along the horizontal axis using FRMD7 mutants or along all directions by ablating starburst amacrine cells – and monitored neuronal activity in layer 2/3 of V1 during stimulation with visual motion. In control mice, we found an overrepresentation of cortical cells preferring posterior visual motion, the dominant motion direction an animal experiences when it moves forward. In mice with disrupted retinal direction selectivity, the overrepresentation of posterior-motion-preferring cortical cells disappeared, and their response at higher stimulus speeds was reduced. This work reveals the existence of two functionally distinct, sensory-periphery-dependent and -independent computations of visual motion in the cortex. PMID:28530661

Differential recruitment of brain networks in single-digit addition and multiplication: Evidence from EEG oscillations in theta and lower alpha bands.

PubMed

Wang, Lihan; Gan, John Q; Zhang, Li; Wang, Haixian

2018-06-01

Previous neuroimaging research investigating dissociation between single-digit addition and multiplication has suggested that the former placed more reliance on the visuo-spatial processing whereas the latter on the verbal processing. However, there has been little exploration into the disassociation in spatio-temporal dynamics of the oscillatory brain activity in specific frequency bands during the two arithmetic operations. To address this issue, the electroencephalogram (EEG) data were recorded from 19 participants engaged in a delayed verification arithmetic task. By analyzing oscillatory EEG activity in theta (5-7 Hz) and lower alpha frequency (9-10 Hz) bands, we found different patterns of oscillatory brain activity between single-digit addition and multiplication during the early processing stage (0-400 ms post-operand onset). Experiment results in this study showed a larger phasic increase of theta-band power for addition than for multiplication in the midline and the right frontal and central regions during the operator and operands presentation intervals, which was extended to the right parietal and the right occipito-temporal regions during the interval immediately after the operands presentation. In contrast, during multiplication higher phase-locking in lower alpha band was evident in the centro-parietal regions during the operator presentation, which was extended to the left fronto-central and anterior regions during the operands presentation. Besides, we found stronger theta phase synchrony between the parietal areas and the right occipital areas for single-digit addition than for multiplication during operands encoding. These findings of oscillatory brain activity extend the previous observations on functional dissociation between the two arithmetic operations. Copyright © 2018 Elsevier B.V. All rights reserved.

Additional Evidence for the Accuracy of Biographical Data: Long-Term Retest and Observer Ratings.

ERIC Educational Resources Information Center

Shaffer, Garnett Stokes; And Others

1986-01-01

Investigated accuracy of responses to biodata questionnaire using a test-retest design and informed external observers for verification. Responses from 237 subjects and 200 observers provided evidence that many responses to biodata questionnaire were accurate. Assessed sources of inaccuracy, including social desirability effects, and noted…

External Standards or Standard Addition? Selecting and Validating a Method of Standardization

NASA Astrophysics Data System (ADS)

Harvey, David T.

2002-05-01

A common feature of many problem-based laboratories in analytical chemistry is a lengthy independent project involving the analysis of "real-world" samples. Students research the literature, adapting and developing a method suitable for their analyte, sample matrix, and problem scenario. Because these projects encompass the complete analytical process, students must consider issues such as obtaining a representative sample, selecting a method of analysis, developing a suitable standardization, validating results, and implementing appropriate quality assessment/quality control practices. Most textbooks and monographs suitable for an undergraduate course in analytical chemistry, however, provide only limited coverage of these important topics. The need for short laboratory experiments emphasizing important facets of method development, such as selecting a method of standardization, is evident. The experiment reported here, which is suitable for an introductory course in analytical chemistry, illustrates the importance of matrix effects when selecting a method of standardization. Students also learn how a spike recovery is used to validate an analytical method, and obtain a practical experience in the difference between performing an external standardization and a standard addition.

Independent Orbiter Assessment (IOA): Assessment of the extravehicular mobility unit, volume 1

NASA Technical Reports Server (NTRS)

Raffaelli, Gary G.

1988-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA effort performed an independent analysis of the Extravehicular Mobility Unit (EMU) hardware and system, generating draft failure modes criticalities and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The IOA results were than compared to the most recent proposed Post 51-L NASA FMEA/CIL baseline. A resolution of each discrepancy from the comparison was provided through additional analysis as required. This report documents the results of that comparison for the Orbiter EMU hardware.

User-Independent Motion State Recognition Using Smartphone Sensors

PubMed Central

Gu, Fuqiang; Kealy, Allison; Khoshelham, Kourosh; Shang, Jianga

2015-01-01

The recognition of locomotion activities (e.g., walking, running, still) is important for a wide range of applications like indoor positioning, navigation, location-based services, and health monitoring. Recently, there has been a growing interest in activity recognition using accelerometer data. However, when utilizing only acceleration-based features, it is difficult to differentiate varying vertical motion states from horizontal motion states especially when conducting user-independent classification. In this paper, we also make use of the newly emerging barometer built in modern smartphones, and propose a novel feature called pressure derivative from the barometer readings for user motion state recognition, which is proven to be effective for distinguishing vertical motion states and does not depend on specific users’ data. Seven types of motion states are defined and six commonly-used classifiers are compared. In addition, we utilize the motion state history and the characteristics of people’s motion to improve the classification accuracies of those classifiers. Experimental results show that by using the historical information and human’s motion characteristics, we can achieve user-independent motion state classification with an accuracy of up to 90.7%. In addition, we analyze the influence of the window size and smartphone pose on the accuracy. PMID:26690163

User-Independent Motion State Recognition Using Smartphone Sensors.

PubMed

Gu, Fuqiang; Kealy, Allison; Khoshelham, Kourosh; Shang, Jianga

2015-12-04

The recognition of locomotion activities (e.g., walking, running, still) is important for a wide range of applications like indoor positioning, navigation, location-based services, and health monitoring. Recently, there has been a growing interest in activity recognition using accelerometer data. However, when utilizing only acceleration-based features, it is difficult to differentiate varying vertical motion states from horizontal motion states especially when conducting user-independent classification. In this paper, we also make use of the newly emerging barometer built in modern smartphones, and propose a novel feature called pressure derivative from the barometer readings for user motion state recognition, which is proven to be effective for distinguishing vertical motion states and does not depend on specific users' data. Seven types of motion states are defined and six commonly-used classifiers are compared. In addition, we utilize the motion state history and the characteristics of people's motion to improve the classification accuracies of those classifiers. Experimental results show that by using the historical information and human's motion characteristics, we can achieve user-independent motion state classification with an accuracy of up to 90.7%. In addition, we analyze the influence of the window size and smartphone pose on the accuracy.

Independent and additive association of prenatal famine exposure and intermediary life conditions with adult mortality between age 18-63 years.

PubMed

Ekamper, P; van Poppel, F; Stein, A D; Lumey, L H

2014-10-01

To quantify the relation between prenatal famine exposure and adult mortality, taking into account mediating effects of intermediary life conditions. Historical follow-up study. The Dutch famine (Hunger Winter) of 1944-1945 which occurred towards the end of WWII in occupied Netherlands. From 408,015 Dutch male births born 1944-1947, examined for military service at age 18, we selected for follow-up all men born at the time of the famine in six affected cities in the Western Netherlands (n=25,283), and a sample of unexposed time (n=10,667) and place (n=9087) controls. These men were traced and followed for mortality through the national population and death record systems. All-cause mortality between ages 18 and 63 years using Cox proportional hazards models adjusted for intermediary life conditions. An increase in mortality was seen after famine exposure in early gestation (HR 1.12; 95% confidence interval (CI): 1.01-1.24) but not late gestation (HR 1.04; 95% CI: 0.96-1.13). Among intermediary life conditions at age 18 years, educational level was inversely associated with mortality and mortality was elevated in men with fathers with manual versus non-manual occupations (HR 1.08; CI: 1.02-1.16) and in men who were declared unfit for military service (HR 1.44; CI: 1.31-1.58). Associations of intermediate factors with mortality were independent of famine exposure in early life and associations between prenatal famine exposure and adult mortality were independent of social class and education at age 18. Timing of exposure in relation to the stage of pregnancy may be of critical importance for later health outcomes independent of intermediary life conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Metagenomics: The Next Culture-Independent Game Changer

PubMed Central

Forbes, Jessica D.; Knox, Natalie C.; Ronholm, Jennifer; Pagotto, Franco; Reimer, Aleisha

2017-01-01

A trend towards the abandonment of obtaining pure culture isolates in frontline laboratories is at a crossroads with the ability of public health agencies to perform their basic mandate of foodborne disease surveillance and response. The implementation of culture-independent diagnostic tests (CIDTs) including nucleic acid and antigen-based assays for acute gastroenteritis is leaving public health agencies without laboratory evidence to link clinical cases to each other and to food or environmental substances. This limits the efficacy of public health epidemiology and surveillance as well as outbreak detection and investigation. Foodborne outbreaks have the potential to remain undetected or have insufficient evidence to support source attribution and may inadvertently increase the incidence of foodborne diseases. Next-generation sequencing of pure culture isolates in clinical microbiology laboratories has the potential to revolutionize the fields of food safety and public health. Metagenomics and other ‘omics’ disciplines could provide the solution to a cultureless future in clinical microbiology, food safety and public health. Data mining of information obtained from metagenomics assays can be particularly useful for the identification of clinical causative agents or foodborne contamination, detection of AMR and/or virulence factors, in addition to providing high-resolution subtyping data. Thus, metagenomics assays may provide a universal test for clinical diagnostics, foodborne pathogen detection, subtyping and investigation. This information has the potential to reform the field of enteric disease diagnostics and surveillance and also infectious diseases as a whole. The aim of this review will be to present the current state of CIDTs in diagnostic and public health laboratories as they relate to foodborne illness and food safety. Moreover, we will also discuss the diagnostic and subtyping utility and concomitant bias limitations of metagenomics and comparable

Phylogenetic reconstruction by cross-species chromosome painting and G-banding in four species of Phyllostomini tribe (Chiroptera, Phyllostomidae) in the Brazilian Amazon: an independent evidence for monophyly.

PubMed

Ribas, Talita Fernanda Augusto; Rodrigues, Luis Reginaldo Ribeiro; Nagamachi, Cleusa Yoshiko; Gomes, Anderson José Baia; Rissino, Jorge das Dores; O'Brien, Patricia Caroline Mary; Yang, Fengtang; Ferguson-Smith, Malcolm Andrew; Pieczarka, Julio Cesar

2015-01-01

The subfamily Phyllostominae comprises taxa with a variety of feeding strategies. From the cytogenetic point of view, Phyllostominae shows different rates of chromosomal evolution between genera, with Phyllostomus hastatus probably retaining the ancestral karyotype for the subfamily. Since chromosomal rearrangements occur rarely in the genome and have great value as phylogenetic markers and in taxonomic characterization, we analyzed three species: Lophostoma silvicola (LSI), Phyllostomus discolor (PDI) and Tonatia saurophila (TSA), representing the tribe Phyllostomini, collected in the Amazon region, by classic and molecular cytogenetic techniques in order to reconstruct the phylogenetic relationships within this tribe. LSA has a karyotype of 2n=34 and FN=60, PDI has 2n=32 and FN=60 and TSA has 2n=16 and FN=20. Comparative analysis using G-banding and chromosome painting show that the karyotypic complement of TSA is highly rearranged relative to LSI and PHA, while LSI, PHA and PDI have similar karyotypes, differing by only three chromosome pairs. Nearly all chromosomes of PDI and PHA were conserved in toto, except for chromosome 15 that was changed by a pericentric inversion. A strongly supported phylogeny (bootstrap=100 and Bremer=10 steps), confirms the monophyly of Phyllostomini. In agreement with molecular topologies, TSA was in the basal position, while PHA and LSI formed sister taxa. A few ancestral syntenies are conserved without rearrangements and most associations are autapomorphic traits for Tonatia or plesiomorphic for the three genera analyzed here. The karyotype of TSA is highly derived in relation to that of other phyllostomid bats, differing from the supposed ancestral karyotype of Phyllostomidae by multiple rearrangements. Phylogenies based on chromosomal data are independent evidence for the monophyly of tribe Phyllostomini as determined by molecular topologies and provide additional support for the paraphyly of the genus Tonatia by the exclusion

Phylogenetic Reconstruction by Cross-Species Chromosome Painting and G-Banding in Four Species of Phyllostomini Tribe (Chiroptera, Phyllostomidae) in the Brazilian Amazon: An Independent Evidence for Monophyly

PubMed Central

Ribas, Talita Fernanda Augusto; Rodrigues, Luis Reginaldo Ribeiro; Nagamachi, Cleusa Yoshiko; Gomes, Anderson José Baia; Rissino, Jorge das Dores; O'Brien, Patricia Caroline Mary; Yang, Fengtang; Ferguson-Smith, Malcolm Andrew; Pieczarka, Julio Cesar

2015-01-01

The subfamily Phyllostominae comprises taxa with a variety of feeding strategies. From the cytogenetic point of view, Phyllostominae shows different rates of chromosomal evolution between genera, with Phyllostomus hastatus probably retaining the ancestral karyotype for the subfamily. Since chromosomal rearrangements occur rarely in the genome and have great value as phylogenetic markers and in taxonomic characterization, we analyzed three species: Lophostoma silvicola (LSI), Phyllostomus discolor (PDI) and Tonatia saurophila (TSA), representing the tribe Phyllostomini, collected in the Amazon region, by classic and molecular cytogenetic techniques in order to reconstruct the phylogenetic relationships within this tribe. LSA has a karyotype of 2n=34 and FN=60, PDI has 2n=32 and FN=60 and TSA has 2n=16 and FN=20. Comparative analysis using G-banding and chromosome painting show that the karyotypic complement of TSA is highly rearranged relative to LSI and PHA, while LSI, PHA and PDI have similar karyotypes, differing by only three chromosome pairs. Nearly all chromosomes of PDI and PHA were conserved in toto, except for chromosome 15 that was changed by a pericentric inversion. A strongly supported phylogeny (bootstrap=100 and Bremer=10 steps), confirms the monophyly of Phyllostomini. In agreement with molecular topologies, TSA was in the basal position, while PHA and LSI formed sister taxa. A few ancestral syntenies are conserved without rearrangements and most associations are autapomorphic traits for Tonatia or plesiomorphic for the three genera analyzed here. The karyotype of TSA is highly derived in relation to that of other phyllostomid bats, differing from the supposed ancestral karyotype of Phyllostomidae by multiple rearrangements. Phylogenies based on chromosomal data are independent evidence for the monophyly of tribe Phyllostomini as determined by molecular topologies and provide additional support for the paraphyly of the genus Tonatia by the exclusion

How evidence-based medicine is failing due to biased trials and selective publication.

PubMed

Every-Palmer, Susanna; Howick, Jeremy

2014-12-01

Evidence-based medicine (EBM) was announced in the early 1990s as a 'new paradigm' for improving patient care. Yet there is currently little evidence that EBM has achieved its aim. Since its introduction, health care costs have increased while there remains a lack of high-quality evidence suggesting EBM has resulted in substantial population-level health gains. In this paper we suggest that EBM's potential for improving patients' health care has been thwarted by bias in the choice of hypotheses tested, manipulation of study design and selective publication. Evidence for these flaws is clearest in industry-funded studies. We argue EBM's indiscriminate acceptance of industry-generated 'evidence' is akin to letting politicians count their own votes. Given that most intervention studies are industry funded, this is a serious problem for the overall evidence base. Clinical decisions based on such evidence are likely to be misinformed, with patients given less effective, harmful or more expensive treatments. More investment in independent research is urgently required. Independent bodies, informed democratically, need to set research priorities. We also propose that evidence rating schemes are formally modified so research with conflict of interest bias is explicitly downgraded in value. © 2014 John Wiley & Sons, Ltd.

Polarization-independent transparent effect in windmill-like metasurface

NASA Astrophysics Data System (ADS)

Zhu, Lei; Dong, Liang; Guo, Jing; Meng, Fan Yi; He, Xun Jun; Hao Wu, Tian

2018-07-01

A windmill-like metasurface featuring a polarization-independent electromagnetically induced transparency (EIT) at microwave frequencies is numerically and experimentally demonstrated. The unit cell of the metasurface consists of four rotated identical metal wires, with a 45° angle between the adjacent wires. Destructive coupling between the resonance modes of the metal wires results in the emergence of a transparent window. By combining the metal wires with different degrees of symmetry, EIT effects in the metasurface show polarization-independent properties to incident linear and circular polarization waves. In addition, it is numerically demonstrated that the metasurface possesses a low-loss slow wave property with a group index of 125 and sensing capability based on the refractive index with a figure of merit of 8.73. Such a scheme may lead to many potential applications in areas of slow light and sensing.

Generalizations of the subject-independent feature set for music-induced emotion recognition.

PubMed

Lin, Yuan-Pin; Chen, Jyh-Horng; Duann, Jeng-Ren; Lin, Chin-Teng; Jung, Tzyy-Ping

2011-01-01

Electroencephalogram (EEG)-based emotion recognition has been an intensely growing field. Yet, how to achieve acceptable accuracy on a practical system with as fewer electrodes as possible is less concerned. This study evaluates a set of subject-independent features, based on differential power asymmetry of symmetric electrode pairs [1], with emphasis on its applicability to subject variability in music-induced emotion classification problem. Results of this study have evidently validated the feasibility of using subject-independent EEG features to classify four emotional states with acceptable accuracy in second-scale temporal resolution. These features could be generalized across subjects to detect emotion induced by music excerpts not limited to the music database that was used to derive the emotion-specific features.

Estrogen receptor-independent catechol estrogen binding activity: protein binding studies in wild-type, Estrogen receptor-alpha KO, and aromatase KO mice tissues.

PubMed

Philips, Brian J; Ansell, Pete J; Newton, Leslie G; Harada, Nobuhiro; Honda, Shin-Ichiro; Ganjam, Venkataseshu K; Rottinghaus, George E; Welshons, Wade V; Lubahn, Dennis B

2004-06-01

Primary evidence for novel estrogen signaling pathways is based upon well-documented estrogenic responses not inhibited by estrogen receptor antagonists. In addition to 17beta-E2, the catechol estrogen 4-hydroxyestradiol (4OHE2) has been shown to elicit biological responses independent of classical estrogen receptors in estrogen receptor-alpha knockout (ERalphaKO) mice. Consequently, our research was designed to biochemically characterize the protein(s) that could be mediating the biological effects of catechol estrogens using enzymatically synthesized, radiolabeled 4-hydroxyestrone (4OHE1) and 4OHE2. Scatchard analyses identified a single class of high-affinity (K(d) approximately 1.6 nM), saturable cytosolic binding sites in several ERalphaKO estrogen-responsive tissues. Specific catechol estrogen binding was competitively inhibited by unlabeled catechol estrogens, but not by 17beta-E2 or the estrogen receptor antagonist ICI 182,780. Tissue distribution studies indicated significant binding differences both within and among various tissues in wild-type, ERalphaKO, and aromatase knockout female mice. Ligand metabolism experiments revealed extensive metabolism of labeled catechol estrogen, suggesting that catechol estrogen metabolites were responsible for the specific binding. Collectively, our data provide compelling evidence for the interaction of catechol estrogen metabolites with a novel binding protein that exhibits high affinity, specificity, and selective tissue distribution. The extensive biochemical characterization of this binding protein indicates that this protein may be a receptor, and thus may mediate ERalpha/beta-independent effects of catechol estrogens and their metabolites.

Linkage of Type 2 Diabetes on Chromosome 9p24 in Mexican Americans: Additional Evidence from the Veterans Administration Genetic Epidemiology Study (VAGES)

PubMed Central

Farook, Vidya S.; Coletta, Dawn K.; Puppala, Sobha; Schneider, Jennifer; Chittoor, Geetha; Hu, Shirley L.; Winnier, Deidre A.; Norton, Luke; Dyer, Thomas D.; Arya, Rector; Cole, Shelley A.; Carless, Melanie; Göring, Harald H.; Almasy, Laura; Mahaney, Michael C.; Comuzzie, Anthony G.; Curran, Joanne E.; Blangero, John; Duggirala, Ravindranath; Lehman, Donna M.; Jenkinson, Christopher P.; DeFronzo, Ralph A.

2014-01-01

Objective Type 2 diabetes (T2DM) is a complex metabolic disease and is more prevalent in certain ethnic groups such as the Mexican Americans. The goal of our study was to perform a genome-wide linkage analysis to localize T2DM susceptibility loci in Mexican Americans. Methods We used the phenotypic and genotypic data from 1,122 Mexican American individuals (307 families) who participated in the Veterans Administration Genetic Epidemiology Study (VAGES). Genome-wide linkage analysis was performed, using the variance components approach. Data from two additional Mexican American family studies, the San Antonio Family Heart Study (SAFHS) and the San Antonio Family Diabetes/Gallbladder Study (SAFDGS), were combined with the VAGES data to test for improved linkage evidence. Results After adjusting for covariate effects, T2DM was found to be under significant genetic influences (h2 = 0.62, P = 2.7 × 10−6). The strongest evidence for linkage of T2DM occurred between markers D9S1871 and D9S2169 on chromosome 9p24.2-p24.1 (LOD = 1.8). Given that we previously reported suggestive evidence for linkage of T2DM at this region in SAFDGS also, we found the significant and increased linkage evidence (LOD = 4.3, empirical P = 1.0 × 10−5, genome-wide P = 1.6 × 10−3) for T2DM at the same chromosomal region when we performed genome-wide linkage analysis of the VAGES data combined with SAFHS and SAFDGS data. Conclusion Significant T2DM linkage evidence was found on chromosome 9p24 in Mexican Americans. Importantly, the chromosomal region of interest in this study overlaps with several recent genome-wide association studies (GWASs) involving T2DM related traits. Given its overlap with such findings and our own initial T2DM association findings in the 9p24 chromosomal region, high throughput sequencing of the linked chromosomal region could identify the potential causal T2DM genes. PMID:24060607

Interpretation and use of evidence in state policymaking: a qualitative analysis.

PubMed

Apollonio, Dorie E; Bero, Lisa A

2017-02-20

Researchers advocating for evidence-informed policy have attempted to encourage policymakers to develop a greater understanding of research and researchers to develop a better understanding of the policymaking process. Our aim was to apply findings drawn from studies of the policymaking process, specifically the theory of policy windows, to identify strategies used to integrate evidence into policymaking and points in the policymaking process where evidence was more or less relevant. Our observational study relied on interviews conducted with 24 policymakers from the USA who had been trained to interpret scientific research in multiple iterations of an evidence-based workshop. Participants were asked to describe cases where they had been involved in making health policy and to provide examples in which research was used, either successfully or unsuccessfully. Interviews were transcribed, independently coded by multiple members of the study team and analysed for content using key words, concepts identified by participants and concepts arising from review of the texts. Our results suggest that policymakers who focused on health issues used multiple strategies to encourage evidence-informed policymaking. The respondents used a strict definition of what constituted evidence, and relied on their experience with research to discourage the use of less rigorous research. Their experience suggested that evidence was less useful in identifying problems, encouraging political action or ensuring feasibility and more useful in developing policy alternatives. Past research has suggested multiple strategies to increase the use of evidence in policymaking, including the development of rapid-response research and policy-oriented summaries of data. Our findings suggest that these strategies may be most relevant to the policymaking stream, which develops policy alternatives. In addition, we identify several strategies that policymakers and researchers can apply to encourage evidence

[The functional independence of lexical numeric knowledge and the representation of magnitude: evidence from one case].

PubMed

Salguero-Alcañiz, M P; Lorca-Marín, J A; Alameda-Bailén, J R

The ultimate purpose of cognitive neuropsychology is to find out how normal cognitive processes work. To this end, it studies subjects who have suffered brain damage but who, until their accident, were competent in the skills that are later to become the object of study. It is therefore necessary to study patients who have difficulty in processing numbers and in calculating in order to further our knowledge of these processes in the normal population. Our aim was to analyse the relationships between the different cognitive processes involved in numeric knowledge. We studied the case of a female patient who suffered an ischemic infarct in the perisylvian region, on both a superficial and deep level. She presented predominantly expressive mixed aphasia and predominantly brachial hemiparesis. Numeric processing and calculation were evaluated. The patient still had her lexical numeric knowledge but her quantitative numeric knowledge was impaired. These alterations in the quantitative numeric knowledge are evidenced by the difficulties the patient had in numeric comprehension tasks, as well as the severe impairments displayed in calculation. These findings allow us to conclude that quantitative numeric knowledge is functionally independent of lexical or non-quantitative numeric knowledge. From this functional autonomy, a possible structural independence can be inferred.

Modality independence of order coding in working memory: Evidence from cross-modal order interference at recall.

PubMed

Vandierendonck, André

2016-01-01

Working memory researchers do not agree on whether order in serial recall is encoded by dedicated modality-specific systems or by a more general modality-independent system. Although previous research supports the existence of autonomous modality-specific systems, it has been shown that serial recognition memory is prone to cross-modal order interference by concurrent tasks. The present study used a serial recall task, which was performed in a single-task condition and in a dual-task condition with an embedded memory task in the retention interval. The modality of the serial task was either verbal or visuospatial, and the embedded tasks were in the other modality and required either serial or item recall. Care was taken to avoid modality overlaps during presentation and recall. In Experiment 1, visuospatial but not verbal serial recall was more impaired when the embedded task was an order than when it was an item task. Using a more difficult verbal serial recall task, verbal serial recall was also more impaired by another order recall task in Experiment 2. These findings are consistent with the hypothesis of modality-independent order coding. The implications for views on short-term recall and the multicomponent view of working memory are discussed.

Chronic Recreational Physical Inactivity and Epithelial Ovarian Cancer Risk: Evidence from the Ovarian Cancer Association Consortium

PubMed Central

Cannioto, Rikki; LaMonte, Michael J.; Risch, Harvey A.; Hong, Chi-Chen; Sucheston-Campbell, Lara E.; Eng, Kevin H.; Szender, J. Brian; Chang-Claude, Jenny; Schmalfeldt, Barbara; Klapdor, Ruediger; Gower, Emily; Minlikeeva, Albina N.; Zirpoli, Gary; Bandera, Elisa V.; Berchuck, Andrew; Cramer, Daniel; Doherty, Jennifer A.; Edwards, Robert P.; Fridley, Brooke L.; Goode, Ellen L.; Goodman, Marc T.; Hogdall, Estrid; Hosono, Satoyo; Jensen, Allan; Jordan, Susan; Kjaer, Susanne K.; Matsuo, Keitaro; Ness, Roberta B.; Olsen, Catherine M.; Olson, Sara H.; Pearce, Celeste Leigh; Pike, Malcolm C.; Rossing, Mary Anne; Szamreta, Elizabeth A.; Thompson, Pamela J.; Tseng, Chiu-Chen; Vierkant, Robert A.; Webb, Penelope M.; Wentzensen, Nicolas; Wicklund, Kristine G.; Winham, Stacey J.; Wu, Anna H.; Modugno, Francesmary; Schildkraut, Joellen M.; Terry, Kathryn L.; Kelemen, Linda E.; Moysich, Kirsten B.

2016-01-01

Background Despite a large body of literature evaluating the association between recreational physical activity and epithelial ovarian cancer (EOC) risk, the extant evidence is inconclusive and little is known about the independent association between recreational physical inactivity and EOC risk. We conducted a pooled analysis of nine studies from the Ovarian Cancer Association Consortium (OCAC) to investigate the association between chronic recreational physical inactivity and EOC risk. Methods In accordance with the 2008 Physical Activity Guidelines for Americans, women reporting no regular, weekly recreational physical activity were classified as inactive. Multivariable logistic regression was utilized to estimate the odds ratios (OR) and 95% confidence intervals (CI) for the association between inactivity and EOC risk overall and by subgroups based upon histotype, menopausal status, race and body mass index (BMI). Results The current analysis included data from 8,309 EOC patients and 12,612 controls. We observed a significant positive association between inactivity and EOC risk (OR=1.34, 95% CI: 1.14-1.57) and similar associations were observed for each histotype. Conclusions In this large pooled analysis examining the association between recreational physical inactivity and EOC risk, we observed consistent evidence of an association between chronic inactivity and all EOC histotypes. Impact These data add to the growing body of evidence suggesting that inactivity is an independent risk factor for cancer. If the apparent association between inactivity and EOC risk is substantiated, additional work via targeted interventions should be pursued to characterize the dose of activity required to mitigate the risk of this highly fatal disease. PMID:27197285

Time-limited home-care reablement services for maintaining and improving the functional independence of older adults.

PubMed

Cochrane, Andy; Furlong, Mairead; McGilloway, Sinead; Molloy, David W; Stevenson, Michael; Donnelly, Michael

2016-10-11

Reablement, also known as restorative care, is one possible approach to home-care services for older adults at risk of functional decline. Unlike traditional home-care services, reablement is frequently time-limited (usually six to 12 weeks) and aims to maximise independence by offering an intensive multidisciplinary, person-centred and goal-directed intervention. To assess the effects of time-limited home-care reablement services (up to 12 weeks) for maintaining and improving the functional independence of older adults (aged 65 years or more) when compared to usual home-care or wait-list control group. We searched the following databases with no language restrictions during April to June 2015: the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (OvidSP); Embase (OvidSP); PsycINFO (OvidSP); ERIC; Sociological Abstracts; ProQuest Dissertations and Theses; CINAHL (EBSCOhost); SIGLE (OpenGrey); AgeLine and Social Care Online. We also searched the reference lists of relevant studies and reviews as well as contacting authors in the field. We included randomised controlled trials (RCTs), cluster randomised or quasi-randomised trials of time-limited reablement services for older adults (aged 65 years or more) delivered in their home; and incorporated a usual home-care or wait-list control group. Two authors independently assessed studies for inclusion, extracted data, assessed the risk of bias of individual studies and considered quality of the evidence using GRADE. We contacted study authors for additional information where needed. Two studies, comparing reablement with usual home-care services with 811 participants, met our eligibility criteria for inclusion; we also identified three potentially eligible studies, but findings were not yet available. One included study was conducted in Western Australia with 750 participants (mean age 82.29 years). The second study was conducted in Norway (61 participants; mean age 79 years).We are very uncertain as to

Human rpL3 induces G₁/S arrest or apoptosis by modulating p21waf1/cip1 levels in a p53-independent manner

PubMed Central

Russo, Annapina; Esposito, Davide; Catillo, Morena; Pietropaolo, Concetta; Crescenzi, Elvira; Russo, Giulia

2013-01-01

It is now largely accepted that ribosomal proteins may be implicated in a variety of biological functions besides that of components of the translation machinery. Many evidences show that a subset of ribosomal proteins are involved in the regulation of the cell cycle and apoptosis through modulation of p53 activity. In addition, p53-independent mechanisms of cell cycle arrest in response to alterations of ribosomal proteins availability have been described. Here, we identify human rpL3 as a new regulator of cell cycle and apoptosis through positive regulation of p21 expression in a p53-independent system. We demonstrate that the rpL3-mediated p21 upregulation requires the specific interaction between rpL3 and Sp1. Furthermore, in our experimental system, p21 overexpression leads to a dual outcome, activating the G₁/S arrest of the cell cycle or the apoptotic pathway through mitochondria, depending on its intracellular levels. It is noteworthy that depletion of p21 abrogates both effects. Taken together, our findings unravel a novel extraribosomal function of rpL3 and reinforce the proapoptotic role of p21 in addition to its widely reported ability as an inhibitor of cell proliferation. PMID:23255119

Motivated independence? Implicit party identity predicts political judgments among self-proclaimed Independents.

PubMed

Hawkins, Carlee Beth; Nosek, Brian A

2012-11-01

Reporting an Independent political identity does not guarantee the absence of partisanship. Independents demonstrated considerable variability in relative identification with Republicans versus Democrats as measured by an Implicit Association Test (IAT; M = 0.10, SD = 0.47). To test whether this variation predicted political judgment, participants read a newspaper article describing two competing welfare (Study 1) or special education (Study 2) policies. The authors manipulated which policy was proposed by which party. Among self-proclaimed Independents, those who were implicitly Democratic preferred the liberal welfare plan, and those who were implicitly Republican preferred the conservative welfare plan. Regardless of the policy details, these implicit partisans preferred the policy proposed by "their" party, and this effect occurred more strongly for implicit than explicit plan preference. The authors suggest that implicitly partisan Independents may consciously override some partisan influence when making explicit political judgments, and Independents may identify as such to appear objective even when they are not.

Integrating evidence based medicine into undergraduate medical education: combining online instruction with clinical clerkships.

PubMed

Aronoff, Stephen C; Evans, Barry; Fleece, David; Lyons, Paul; Kaplan, Lawrence; Rojas, Roberto

2010-07-01

Incorporation of evidence based medicine into the undergraduate curriculum varies from school to school. The purpose of this study was to determine if an online course in evidence based medicine run concurrently with the clinical clerkships in the 3rd year of undergraduate medical education provided effective instruction in evidence based medicine (EBM). During the first 18 weeks of the 3rd year, students completed 6 online, didactic modules. Over the next 24 weeks, students developed questions independently from patients seen during clerkships and then retrieved and appraised relevant evidence. Online, faculty mentors reviewed student assignments submitted throughout the course to monitor progress. Mastery of the skills of EBM was assessed prior to and at the conclusion of the course using the Fresno test of competency. Paired data were available from 139 students. Postcourse test scores (M= 77.7; 95% CI = 59-96.4) were significantly higher than precourse scores (M= 66.6; 95% CI = 46.5-86.7), p< .001. Paired evaluations demonstrated an average improvement of 11.1 +/- 20.0 points. All of the students submitted 4 independently derived questions and successfully retrieved and appraised evidence. Medical students successfully acquired and independently applied EBM skills following extended, online, faculty mentored instruction. This method of instruction provided uniform instruction across geographic sites and medical specialties and permitted efficient use of faculty time.

Induction and expression of GluA1 (GluR-A)-independent LTP in the hippocampus

PubMed Central

Romberg, Carola; Raffel, Joel; Martin, Lucy; Sprengel, Rolf; Seeburg, Peter H; Rawlins, J Nicholas P; Bannerman, David M; Paulsen, Ole

2009-01-01

Long-term potentiation (LTP) at hippocampal CA3–CA1 synapses is thought to be mediated, at least in part, by an increase in the postsynaptic surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) receptors induced by N-methyl-d-aspartate (NMDA) receptor activation. While this process was originally attributed to the regulated synaptic insertion of GluA1 (GluR-A) subunit-containing AMPA receptors, recent evidence suggests that regulated synaptic trafficking of GluA2 subunits might also contribute to one or several phases of potentiation. However, it has so far been difficult to separate these two mechanisms experimentally. Here we used genetically modified mice lacking the GluA1 subunit (Gria1−/− mice) to investigate GluA1-independent mechanisms of LTP at CA3–CA1 synapses in transverse hippocampal slices. An extracellular, paired theta-burst stimulation paradigm induced a robust GluA1-independent form of LTP lacking the early, rapidly decaying component characteristic of LTP in wild-type mice. This GluA1-independent form of LTP was attenuated by inhibitors of neuronal nitric oxide synthase and protein kinase C (PKC), two enzymes known to regulate GluA2 surface expression. Furthermore, the induction of GluA1-independent potentiation required the activation of GluN2B (NR2B) subunit-containing NMDA receptors. Our findings support and extend the evidence that LTP at hippocampal CA3–CA1 synapses comprises a rapidly decaying, GluA1-dependent component and a more sustained, GluA1-independent component, induced and expressed via a separate mechanism involving GluN2B-containing NMDA receptors, neuronal nitric oxide synthase and PKC. PMID:19302150

Stakeholder insights on the planning and development of an independent benchmark standard for responsible food marketing.

PubMed

Cairns, Georgina; Macdonald, Laura

2016-06-01

A mixed methods qualitative survey investigated stakeholder responses to the proposal to develop an independently defined, audited and certifiable set of benchmark standards for responsible food marketing. Its purpose was to inform the policy planning and development process. A majority of respondents were supportive of the proposal. A majority also viewed the engagement and collaboration of a broad base of stakeholders in its planning and development as potentially beneficial. Positive responses were associated with views that policy controls can and should be extended to include all form of marketing, that obesity and non-communicable diseases prevention and control was a shared responsibility and an urgent policy priority and prior experience of independent standardisation as a policy lever for good practice. Strong policy leadership, demonstrable utilisation of the evidence base in its development and deployment and a conceptually clear communications plan were identified as priority targets for future policy planning. Future research priorities include generating more evidence on the feasibility of developing an effective community of practice and theory of change, the strengths and limitations of these and developing an evidence-based step-wise communications strategy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mode-independent attenuation in evanescent-field sensors

NASA Astrophysics Data System (ADS)

Gnewuch, Harald; Renner, Hagen

1995-03-01

Generally, the total power attenuation in multimode evanescent-field sensor waveguides is nonproportional to the bulk absorbance because the modal attenuation constants differ. Hence a direct measurement is difficult and is additionally aggravated because the waveguide absorbance is highly sensitive to the specific launching conditions at the waveguide input. A general asymptotic formula for the modal power attenuation in strongly asymmetric inhomogeneous planar waveguides with arbitrarily distributed weak absorption in the low-index superstrate is derived. Explicit expressions for typical refractive-index profiles are given. Except when very close to the cutoff, the predicted asymptotic attenuation behavior agrees well with exact calculations. The ratio of TM versus TE absorption has been derived to be (2 - n0 2/nf2 ) for arbitrary profiles. Waveguides with a linear refractive-index profile show mode-independent attenuation coefficients within each polarization. Further, the asymptotic sensitivity is independent of the wavelength, so that it should be possible to directly measure the spectral variation of the bulk absorption. The mode independence of the attenuation has been verified experimentally for a second-order polynomial profile, which is close to a linear refractive-index distribution. In contrast, the attenuation in the step-profile waveguide has been found to depend strongly on the mode number, as predicted by theory. A strong spread of the modal attenuation coefficients is also predicted for the parabolic-profile waveguide sensor.

When is enough evidence enough? - Using systematic decision analysis and value-of-information analysis to determine the need for further evidence.

PubMed

Siebert, Uwe; Rochau, Ursula; Claxton, Karl

2013-01-01

Decision analysis (DA) and value-of-information (VOI) analysis provide a systematic, quantitative methodological framework that explicitly considers the uncertainty surrounding the currently available evidence to guide healthcare decisions. In medical decision making under uncertainty, there are two fundamental questions: 1) What decision should be made now given the best available evidence (and its uncertainty)?; 2) Subsequent to the current decision and given the magnitude of the remaining uncertainty, should we gather further evidence (i.e., perform additional studies), and if yes, which studies should be undertaken (e.g., efficacy, side effects, quality of life, costs), and what sample sizes are needed? Using the currently best available evidence, VoI analysis focuses on the likelihood of making a wrong decision if the new intervention is adopted. The value of performing further studies and gathering additional evidence is based on the extent to which the additional information will reduce this uncertainty. A quantitative framework allows for the valuation of the additional information that is generated by further research, and considers the decision maker's objectives and resource constraints. Claxton et al. summarise: "Value of information analysis can be used to inform a range of policy questions including whether a new technology should be approved based on existing evidence, whether it should be approved but additional research conducted or whether approval should be withheld until the additional evidence becomes available." [Claxton K. Value of information entry in Encyclopaedia of Health Economics, Elsevier, forthcoming 2014.] The purpose of this tutorial is to introduce the framework of systematic VoI analysis to guide further research. In our tutorial article, we explain the theoretical foundations and practical methods of decision analysis and value-of-information analysis. To illustrate, we use a simple case example of a foot ulcer (e.g., with

Independent Colimitation for Carbon Dioxide and Inorganic Phosphorus

PubMed Central

Spijkerman, Elly; de Castro, Francisco; Gaedke, Ursula

2011-01-01

Simultaneous limitation of plant growth by two or more nutrients is increasingly acknowledged as a common phenomenon in nature, but its cellular mechanisms are far from understood. We investigated the uptake kinetics of CO2 and phosphorus of the algae Chlamydomonas acidophila in response to growth at limiting conditions of CO2 and phosphorus. In addition, we fitted the data to four different Monod-type models: one assuming Liebigs Law of the minimum, one assuming that the affinity for the uptake of one nutrient is not influenced by the supply of the other (independent colimitation) and two where the uptake affinity for one nutrient depends on the supply of the other (dependent colimitation). In addition we asked whether the physiological response under colimitation differs from that under single nutrient limitation. We found no negative correlation between the affinities for uptake of the two nutrients, thereby rejecting a dependent colimitation. Kinetic data were supported by a better model fit assuming independent uptake of colimiting nutrients than when assuming Liebigs Law of the minimum or a dependent colimitation. Results show that cell nutrient homeostasis regulated nutrient acquisition which resulted in a trade-off in the maximum uptake rates of CO2 and phosphorus, possibly driven by space limitation on the cell membrane for porters for the different nutrients. Hence, the response to colimitation deviated from that to a single nutrient limitation. In conclusion, responses to single nutrient limitation cannot be extrapolated to situations where multiple nutrients are limiting, which calls for colimitation experiments and models to properly predict growth responses to a changing natural environment. These deviations from single nutrient limitation response under colimiting conditions and independent colimitation may also hold for other nutrients in algae and in higher plants. PMID:22145031

Independent Component Analysis applied to Ground-based observations

NASA Astrophysics Data System (ADS)

Martins-Filho, Walter; Griffith, Caitlin; Pearson, Kyle; Waldmann, Ingo; Alvarez-Candal, Alvaro; Zellem, Robert Thomas

2018-01-01

Transit measurements of Jovian-sized exoplanetary atmospheres allow one to study the composition of exoplanets, largely independent of the planet’s temperature profile. However, measurements of hot-Jupiter transits must archive a level of accuracy in the flux to determine the spectral modulation of the exoplanetary atmosphere. To accomplish this level of precision, we need to extract systematic errors, and, for ground-based measurements, the effects of Earth’s atmosphere, from signal due to the exoplanet, which is several orders of magnitude smaller. The effects of the terrestrial atmosphere and some of the time-dependent systematic errors of ground-based transit measurements are treated mainly by dividing the host star by a reference star at each wavelength and time step of the transit. Recently, Independent Component Analysis (ICA) have been used to remove systematics effects from the raw data of space-based observations (Waldmann, 2014, 2012; Morello et al., 2016, 2015). ICA is a statistical method born from the ideas of the blind-source separations studies, which can be used to de-trend several independent source signals of a data set (Hyvarinen and Oja, 2000). This technique requires no additional prior knowledge of the data set. In addition, this technique has the advantage of requiring no reference star. Here we apply the ICA to ground-based photometry of the exoplanet XO-2b recorded by the 61” Kuiper Telescope and compare the results of the ICA to those of a previous analysis from Zellem et al. (2015), which does not use ICA. We also simulate the effects of various conditions (concerning the systematic errors, noise and the stability of object on the detector) to determine the conditions under which an ICA can be used with high precision to extract the light curve of exoplanetary photometry measurements

Independent Component Analysis applied to Ground-based observations

NASA Astrophysics Data System (ADS)

Martins-Filho, Walter; Griffith, Caitlin Ann; Pearson, Kyle; Waldmann, Ingo; Alvarez-Candal, Alvaro; Zellem, Robert

2017-10-01

Transit measurements of Jovian-sized exoplanetary atmospheres allow one to study the composition of exoplanets, largely independent of the planet’s temperature profile. However, measurements of hot-Jupiter transits must archive a level of accuracy in the flux to determine the spectral modulations of the exoplanetary atmosphere. To accomplish this level of precision, we need to extract systematic errors, and, for ground-based measurements, the effects of Earth’s atmosphere, from signal due to the exoplanet, which is several orders of magnitudes smaller.The effects of the terrestrial atmosphere and some of the time dependent systematic errors of ground-based transit measurements are treated mainly by dividing the host star by a reference star at each wavelength and time step of the transit. Recently, Independent Component Analyses (ICA) have been used to remove systematics effects from the raw data of space-based observations (Waldmann, 2014, 2012; Morello et al., 2016, 2015). ICA is a statistical method born from the ideas of the blind-source separations studies, which can be used to de-trend several independent source signals of a data set (Hyvarinen and Oja, 2000). This technique requires no additional prior knowledge of the data set. In addition this technique has the advantage of requiring no reference star.Here we apply the ICA to ground-based photometry of the exoplanet XO-2b recorded by the 61” Kuiper Telescope and compare the results of the ICA to those of a previous analysis from Zellem et al. (2015), which does not use ICA. We also simulate the effects of various conditions (concerning the systematic errors, noise and the stability of object on the detector) to determine the conditions under which an ICA can be used with high precision to extract the light curve of exoplanetary photometry measurements.

Regulation of P2Y1 receptor traffic by sorting Nexin 1 is retromer independent.

PubMed

Nisar, Shaista; Kelly, Eamonn; Cullen, Pete J; Mundell, Stuart J

2010-04-01

The activity and traffic of G-protein coupled receptors (GPCRs) is tightly controlled. Recent work from our laboratory has shown that P2Y(1) and P2Y(12) responsiveness is rapidly and reversibly modulated in human platelets and that the underlying mechanism requires receptor trafficking as an essential part of this process. However, little is known about the molecular mechanisms underlying P2Y receptor traffic. Sorting nexin 1 (SNX1) has been shown to regulate the endosomal sorting of cell surface receptors either to lysosomes where they are downregulated or back to the cell surface. These functions may in part be due to interactions of SNX1 with the mammalian retromer complex. In this study, we investigated the role of SNX1 in P2Y receptor trafficking. We show that P2Y(1) receptors recycle via a slow recycling pathway that is regulated by SNX1, whereas P2Y(12) receptors return to the cell surface via a rapid route that is SNX1 independent. SNX1 inhibition caused a dramatic increase in the rate of P2Y(1) receptor recycling, whereas inhibition of Vps26 and Vps35 known to be present in retromer had no effect, indicating that SNX1 regulation of P2Y(1) receptor recycling is retromer independent. In addition, inhibition of SNX4, 6 and 17 proteins did not affect P2Y(1) receptor recycling. SNX1 has also been implicated in GPCR degradation; however, we provide evidence that P2Y receptor degradation is SNX1 independent. These data describe a novel function of SNX1 in the regulation of P2Y(1) receptor recycling and suggest that SNX1 plays multiple roles in endocytic trafficking of GPCRs.

Predictors of chain acquisition among independent dialysis facilities.

PubMed

Pozniak, Alyssa S; Hirth, Richard A; Banaszak-Holl, Jane; Wheeler, John R C

2010-04-01

To determine the predictors of chain acquisition among independent dialysis providers. Retrospective facility-level data combined from CMS Cost Reports, Medical Evidence Forms, Annual Facility Surveys, and claims for 1996-2003. Independent dialysis facilities' probability of acquisition by a dialysis chain (overall and by chain size) was estimated using a discrete time hazard rate model, controlling for financial and clinical performance, practice patterns, market factors, and other facility characteristics. The sample includes all U.S. freestanding dialysis facilities that report not being chain affiliated for at least 1 year between 1997 and 2003. Above-average costs and better quality outcomes are significant determinants of dialysis chain acquisition. Facilities in larger markets were more likely to be acquired by a chain. Furthermore, small dialysis chains have different acquisition strategies than large chains. Dialysis chains appear to employ a mix of turn-around and cream-skimming strategies. Poor financial health is a predictor of chain acquisition as in other health care sectors, but the increased likelihood of chain acquisition among higher quality facilities is unique to the dialysis industry. Significant differences among predictors of acquisition by small and large chains reinforce the importance of using a richer classification for chain status.

The Independence of James Rest's Components of Morality: Evidence from a Professional Ethics Curriculum Study

ERIC Educational Resources Information Center

You, Di; Bebeau, Muriel J.

2013-01-01

Rest's hypothesis that the components of morality (i.e., sensitivity, reasoning, motivation, and implementation) are distinct from one another was tested using evidence from a dental ethics curriculum that uses well-validated measures of each component. Archival data from five cohorts ("n" = 385) included the following: (1) transcribed…

Measurement-device-independent quantum cryptography

DOE PAGES

Xu, Feihu; Curty, Marcos; Qi, Bing; ...

2014-12-18

In theory, quantum key distribution (QKD) provides information-theoretic security based on the laws of physics. Owing to the imperfections of real-life implementations, however, there is a big gap between the theory and practice of QKD, which has been recently exploited by several quantum hacking activities. To fill this gap, a novel approach, called measurement-device-independent QKD (mdiQKD), has been proposed. In addition, it can remove all side-channels from the measurement unit, arguably the most vulnerable part in QKD systems, thus offering a clear avenue toward secure QKD realisations. In this study, we review the latest developments in the framework of mdiQKD,more » together with its assumptions, strengths, and weaknesses.« less

New evidence for global tectonic zones on Venus

NASA Technical Reports Server (NTRS)

Kozak, Richard C.; Schaber, Gerald G.

1989-01-01

Venera 15 and 16 spacecraft images show clear evidence of major crustal disruptions on Venus which have been interpreted to indicate crustal divergence. Complementary to the divergent zones are mountain belts that border the continent-like high terrains. The requisite transcurrent motions appear to be manifested as diffuse shear zones. The rift zones form an interconnected transpolar system which ties in with previously recognized equatorial disruption zones, suggesting a global tectonic network. Several independent lines of evidence suggest that the tectonism may be geologically young.

Melanoma Biomolecules: Independently Identified but Functionally Intertwined

PubMed Central

Dye, Danielle E.; Medic, Sandra; Ziman, Mel; Coombe, Deirdre R.

2013-01-01

The majority of patients diagnosed with melanoma present with thin lesions and generally these patients have a good prognosis. However, 5% of patients with early melanoma (<1 mm thick) will have recurrence and die within 10 years, despite no evidence of local or metastatic spread at the time of diagnosis. Thus, there is a need for additional prognostic markers to help identify those patients that may be at risk of recurrent disease. Many studies and several meta-analyses have compared gene and protein expression in melanocytes, naevi, primary, and metastatic melanoma in an attempt to find informative prognostic markers for these patients. However, although a large number of putative biomarkers have been described, few of these molecules are informative when used in isolation. The best approach is likely to involve a combination of molecules. We believe one approach could be to analyze the expression of a group of interacting proteins that regulate different aspects of the metastatic pathway. This is because a primary lesion expressing proteins involved in multiple stages of metastasis may be more likely to lead to secondary disease than one that does not. This review focuses on five putative biomarkers – melanoma cell adhesion molecule (MCAM), galectin-3 (gal-3), matrix metalloproteinase 2 (MMP-2), chondroitin sulfate proteoglycan 4 (CSPG4), and paired box 3 (PAX3). The goal is to provide context around what is known about the contribution of these biomarkers to melanoma biology and metastasis. Although each of these molecules have been independently identified as likely biomarkers, it is clear from our analyses that each are closely linked with each other, with intertwined roles in melanoma biology. PMID:24069584

Evidence-based medicine - an appropriate tool for evidence-based health policy? A case study from Norway.

PubMed

Malterud, Kirsti; Bjelland, Anne Karen; Elvbakken, Kari Tove

2016-03-05

Evidence-based policy (EBP), a concept modelled on the principles of evidence-based medicine (EBM), is widely used in different areas of policymaking. Systematic reviews (SRs) with meta-analyses gradually became the methods of choice for synthesizing research evidence about interventions and judgements about quality of evidence and strength of recommendations. Critics have argued that the relation between research evidence and service policies is weak, and that the notion of EBP rests on a misunderstanding of policy processes. Having explored EBM standards and knowledge requirements for health policy decision-making, we present an empirical point of departure for discussing the relationship between EBM and EBP. In a case study exploring the Norwegian Knowledge Centre for the Health Services (NOKC), an independent government unit, we first searched for information about the background and development of the NOKC to establish a research context. We then identified, selected and organized official NOKC publications as an empirical sample of typical top-of-the-line knowledge delivery adhering to EBM standards. Finally, we explored conclusions in this type of publication, specifically addressing their potential as policy decision tools. From a total sample of 151 SRs published by the NOKC in the period 2004-2013, a purposive subsample from 2012 (14 publications) advised major caution about their conclusions because of the quality or relevance of the underlying documentation. Although the case study did not include a systematic investigation of uptake and policy consequences, SRs were found to be inappropriate as universal tools for health policy decision-making. The case study demonstrates that EBM is not necessarily suited to knowledge provision for every kind of policy decision-making. Our analysis raises the question of whether the evidence-based movement, represented here by an independent government organization, undertakes too broad a range of commissions using

Evidence that impaired sleep recovery may complicate burnout improvement independently of depressive mood.

PubMed

Sonnenschein, Mieke; Sorbi, Marjolijn J; van Doornen, Lorenz J P; Schaufeli, Wilmar B; Maas, Cora J M

2007-04-01

This article examines recovery through sleep in relation to sleep quality, exhaustion, and depression in clinical burnout. We focus on actual recovery per night, given its relevance to burnout improvement. Sixty clinically burned-out participants and 40 healthy controls recorded symptoms with an electronic diary for 2 weeks at random times per day. Recovery through sleep was defined as the difference in fatigue between late evening and the next morning. In clinical burnout, sleep quality and recovery are impaired, and depression is elevated. Poor recovery through sleep is associated with poor same-night sleep quality, clarifying the mechanisms underlying poor recovery. Individual differences in recovery though sleep were related to differences in refreshed awakening, but not to other sleep problems. Impaired recovery was also related to severity of exhaustion, but not to severity of depressive mood, indicating that, in burnout, nonprofit from sleep is a symptom of energy depletion, not a sign of depression. Impaired recovery through sleep may hamper recovery from burnout independently of the influence of depression.

Independent representation of parts and the relations between them: evidence from integrative agnosia.

PubMed

Behrmann, Marlene; Peterson, Mary A; Moscovitch, Morris; Suzuki, Satoru

2006-10-01

Whether objects are represented as a collection of parts whose relations are coded independently remains a topic of ongoing discussion among theorists in the domain of shape perception. S. M., an individual with integrative agnosia, and neurologically intact ("normal") individuals learned initially to identify 4 target objects constructed of 2 simple volumetric parts. At test, the targets were mixed with distractors, some of which could be discriminated from the targets on the basis of a mismatching part, whereas the rest could be discriminated only on the basis of the altered spatial arrangements of parts. S. M. learned to identify the target objects, although at a rate slower than that of the normal participants. At test, he correctly rejected distractors on the basis of mismatching parts but was profoundly impaired at rejecting distractors made of the same local components but with mismatching spatial arrangements. These results suggest that encoding the spatial arrangements of parts of an object requires a mechanism that is different from that required for encoding the shape of individual parts, with the former selectively compromised in integrative agnosia. Copyright 2006 APA.

Modality-independent coding of spatial layout in the human brain

PubMed Central

Wolbers, Thomas; Klatzky, Roberta L.; Loomis, Jack M.; Wutte, Magdalena G.; Giudice, Nicholas A.

2011-01-01

Summary In many non-human species, neural computations of navigational information such as position and orientation are not tied to a specific sensory modality [1, 2]. Rather, spatial signals are integrated from multiple input sources, likely leading to abstract representations of space. In contrast, the potential for abstract spatial representations in humans is not known, as most neuroscientific experiments on human navigation have focused exclusively on visual cues. Here, we tested the modality independence hypothesis with two fMRI experiments that characterized computations in regions implicated in processing spatial layout [3]. According to the hypothesis, such regions should be recruited for spatial computation of 3-D geometric configuration, independent of a specific sensory modality. In support of this view, sighted participants showed strong activation of the parahippocampal place area (PPA) and the retrosplenial cortex (RSC) for visual and haptic exploration of information-matched scenes but not objects. Functional connectivity analyses suggested that these effects were not related to visual recoding, which was further supported by a similar preference for haptic scenes found with blind participants. Taken together, these findings establish the PPA/RSC network as critical in modality-independent spatial computations and provide important evidence for a theory of high-level abstract spatial information processing in the human brain. PMID:21620708

Sandra L. Shullman: Award for Distinguished Professional Contributions to Independent Practice.

PubMed

2012-11-01

Presents a short biography of the winner of the American psychological Association's Award for Distinguished Professional Contributions to Independent Practice. The 2012 winner is Sandra L. Shullman for her outstanding contributions and leadership as an independent practitioner in the fields of counseling and consulting psychology. Through her national scholarship on sexual harassment in the workplace, her development of the practice of organizational counseling psychology, her management of a leading behavioral health care practice, and her pioneering leadership development initiatives for national and international clients, Shullman has greatly enhanced the public's recognition of psychology. In addition, her involvement and leadership as a representative of independent practitioners in professional associations at the state and national levels have benefited the profession in immeasurable ways. Shullman's Award citation and a selected bibliography are also presented here. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Fragile X-associated primary ovarian insufficiency: evidence for additional genetic contributions to severity.

PubMed

Hunter, Jessica Ezzell; Epstein, Michael P; Tinker, Stuart W; Charen, Krista H; Sherman, Stephanie L

2008-09-01

The fragile X mental retardation gene (FMR1) contains a CGG repeat sequence in its 5' untranslated region that can become unstable and expand in length from generation to generation. Alleles with expanded repeats in the range of approximately 55-199, termed premutation alleles, are associated with an increased risk for fragile-X-associated primary ovarian insufficiency (FXPOI). However, not all women who carry the premutation develop FXPOI. To determine if additional genes could explain variability in onset and severity, we used a random-effects Cox proportional hazards model to analyze age at menopause on 680 women from 225 families who have a history of fragile X syndrome and 321 women from 219 families from the general population. We tested for the presence of a residual additive genetic effect after adjustment for FMR1 repeat length, race, smoking, body mass index, and method of ascertainment. Results showed significant familial aggregation of age at menopause with an estimated additive genetic variance of 0.55-0.96 depending on the parameterization of FMR1 repeat size and definition of age at menopause (P-values ranging between 0.0002 and 0.0027). This is the first study to analyze familial aggregation of FXPOI. This result is important for proper counseling of women who carry FMR1 premutation alleles and for guidance of future studies to identify additional genes that influence ovarian insufficiency. (c) 2008 Wiley-Liss, Inc.

Selection of early-occurring mutations dictates hormone-independent progression in mouse mammary tumor lines.

PubMed

Gattelli, Albana; Zimberlin, María N; Meiss, Roberto P; Castilla, Lucio H; Kordon, Edith C

2006-11-01

Mice harboring three mouse mammary tumor virus (MMTV) variants develop pregnancy-dependent (PD) tumors that progress to pregnancy-independent (PI) behavior through successive passages. Herein, we identified 10 predominant insertions in PI transplants from 8 independent tumor lines. These mutations were also detected in small cell populations in the early PD passages. In addition, we identified a new viral insertion upstream of the gene Rspo3, which is overexpressed in three of the eight independent tumor lines and codes for a protein very similar to the recently described protein encoded by Int7. This study suggests that during progression towards hormone independence, clonal expansion of cells with specific mutations might be more relevant than the occurrence of new MMTV insertions.

Selection of Early-Occurring Mutations Dictates Hormone-Independent Progression in Mouse Mammary Tumor Lines▿

PubMed Central

Gattelli, Albana; Zimberlin, María N.; Meiss, Roberto P.; Castilla, Lucio H.; Kordon, Edith C.

2006-01-01

Mice harboring three mouse mammary tumor virus (MMTV) variants develop pregnancy-dependent (PD) tumors that progress to pregnancy-independent (PI) behavior through successive passages. Herein, we identified 10 predominant insertions in PI transplants from 8 independent tumor lines. These mutations were also detected in small cell populations in the early PD passages. In addition, we identified a new viral insertion upstream of the gene Rspo3, which is overexpressed in three of the eight independent tumor lines and codes for a protein very similar to the recently described protein encoded by Int7. This study suggests that during progression towards hormone independence, clonal expansion of cells with specific mutations might be more relevant than the occurrence of new MMTV insertions. PMID:16971449

Early additional food and fluids for healthy breastfed full-term infants.

PubMed

Becker, Genevieve E; Remmington, Tracey

2014-11-25

Widespread recommendations from health organisations encourage exclusive breastfeeding for six months. However, the addition of other fluids or foods before six months is common in many countries and communities. This practice suggests perceived benefits of early supplementation or lack of awareness of the possible risks. To assess the benefits and harms of supplementation for full-term healthy breastfed infants and to examine the timing and type of supplementation. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (21 March 2014) and reference lists of all relevant retrieved papers. Randomised or quasi-randomised controlled trials in infants under six months of age comparing exclusive breastfeeding versus breastfeeding with any additional food or fluids. Two review authors independently selected the trials, extracted data and assessed risk of bias. We included eight trials (984 randomised infants/mothers). Six trials (n = 613 analysed) provided data on outcomes of interest to this review. The variation in outcome measures and time points made it difficult to pool results from trials. Data could only be combined in a meta-analysis for one secondary outcome (weight change). The trials that provided outcome data compared exclusively breastfed infants with breastfed infants who were allowed additional nutrients in the form of artificial milk, glucose, water or solid foods.In relation to the majority of the older trials, the description of study methods was inadequate to assess the risk of bias. The two more recent trials, were found to be at low risk of bias for selection and detection bias. The overall quality of the evidence for the main comparison was low.In one trial (170 infants) comparing exclusively breastfeeding infants with infants who were allowed additional glucose water, there was a significant difference favouring exclusive breastfeeding up to and including week 20 (risk ratio (RR) 1.45, 95% confidence interval (CI) 1.05 to 1

The double-deficit hypothesis: a comprehensive analysis of the evidence.

PubMed

Vukovic, Rose K; Siegel, Linda S

2006-01-01

The double-deficit hypothesis of developmental dyslexia proposes that deficits in phonological processing and naming speed represent independent sources of dysfunction in dyslexia. The present article is a review of the evidence for the double-deficit hypothesis, including a discussion of recent findings related to the hypothesis. Studies in this area have been characterized by variability in methodology--how dyslexia is defined and identified, and how dyslexia subtypes are classified. Such variability sets limitations on the extent to which conclusions may be drawn with respect to the double-deficit hypothesis. Furthermore, the literature is complicated by the persistent finding that measures of phonological processing and naming speed are significantly correlated, resulting in a statistical artifact that makes it difficult to disentangle the influence of naming speed from that of phonological processing. Longitudinal and intervention studies of the double-deficit hypothesis are needed to accumulate evidence that investigates a naming speed deficit that is independent of a phonological deficit for readers with dyslexia. The existing evidence does not support a persistent core deficit in naming speed for readers with dyslexia.

Syntactic Prediction in Language Comprehension: Evidence From Either…or

PubMed Central

Staub, Adrian; Clifton, Charles

2006-01-01

Readers’ eye movements were monitored as they read sentences in which two noun phrases or two independent clauses were connected by the word or (NP-coordination and S-coordination, respectively). The word either could be present or absent earlier in the sentence. When either was present, the material immediately following or was read more quickly, across both sentence types. In addition, there was evidence that readers misanalyzed the S-coordination structure as an NP-coordination structure only when either was absent. The authors interpret the results as indicating that the word either enabled readers to predict the arrival of a coordination structure; this predictive activation facilitated processing of this structure when it ultimately arrived, and in the case of S-coordination sentences, enabled readers to avoid the incorrect NP-coordination analysis. The authors argue that these results support parsing theories according to which the parser can build predictable syntactic structure before encountering the corresponding lexical input. PMID:16569157

Myth or Truth: Independence Day.

ERIC Educational Resources Information Center

Gardner, Traci

Most Americans think of the Fourth of July as Independence Day, but is it really the day the U.S. declared and celebrated independence? By exploring myths and truths surrounding Independence Day, this lesson asks students to think critically about commonly believed stories regarding the beginning of the Revolutionary War and the Independence Day…

Cary Potter on Independent Education

ERIC Educational Resources Information Center

Potter, Cary

1978-01-01

Cary Potter was President of the National Association of Independent Schools from 1964-1978. As he leaves NAIS he gives his views on education, on independence, on the independent school, on public responsibility, on choice in a free society, on educational change, and on the need for collective action by independent schools. (Author/RK)

Chaotic evolution of the long-period Milankovitch cycle during the early Mesozoic: independent evidences from the Newark lacustrine sequence (North America) and the pelagic bedded chert sequence (Japan)

NASA Astrophysics Data System (ADS)

Ikeda, M.; Olsen, P. E.; Tada, R.

2012-12-01

The correlation of Earth's orbital parameters with climatic variations has been used to generate astronomically calibrated geologic time scales of high accuracy. However, because of the chaotic behavior of the solar planets, the orbital models have a large uncertainty beyond several tens of million years in the past. This chaotic behavior also causes the long-period astronomical cycles (> 0.5 Myr periodicity) to modulate their frequency and amplitude. In other words, their modulation patterns could be potential constraints for the orbital models. Here we report the first geologic constraints on the timing of frequency transition and amplitude modulation of the ~ 2 Myr long eccentricity cycles during the early Mesozoic. We examined the lake level records of the early Mesozoic Newark lacustrine sequence in North America and the biogenic silica burial rate of the pelagic bedded chert sequence in the Inuyama area, Japan, which are proven to be reflect the astronomical cycle (Olsen, 1986; Olsen and Kent, 1996; Ikeda et al., 2010). The time scales of the two sequences were orbitally calibrated with the end-Triassic mass extinction interval as the age anchor, covering ~ 30 Myr and ~ 65 Myr, respectively (Olsen et al., 2011; Ikeda et al., 2010, in prep). We find that the frequency modulation of ~ 2 Myr cycle between 2.4 Myr to 1.6 Myr cycle have occurred at least the Middle to Late Triassic. In addition, the ~ 2 Myr cycle modulate its amplitude with ~ 10 Myr periodicity with in-phase relation between the two. Similar modulation patterns of ~ 2 Myr cycles from the two independent geologic records indicate convincing evidences for the chaotic behavior of the Solar planets. Because these modulation patterns are different from the results of the orbital models by Laskar et al. (2004, 2011), our records will provide the new and challenging constraints for the orbital models in terms of chaotic behavior of Solar planets.

Independence Compared and Contrasted: The United States and Mozambique [And] Whither the Struggle for Mozambique? Mini-Module.

ERIC Educational Resources Information Center

African-American Inst., New York, NY. School Services Div.

In addition to presenting background information on Mozambique's struggle for independence from Portugal, this module contains compare-and-contrast exercises and enrichment activities. The background discussion includes a historical sketch of political events prior to Mozambique's independence in 1975 and presents excerpts from the writings of two…

Further evidence for addition and numerical competence by a Grey parrot (Psittacus erithacus).

PubMed

Pepperberg, Irene M

2012-07-01

A Grey parrot (Psittacus erithacus), able to quantify sets of eight or fewer items (including heterogeneous subsets), to sum two sequentially presented sets of 0–6 items (up to 6), and to identify and serially order Arabic numerals (1–8), all by using English labels (Pepperberg in J Comp Psychol 108:36–44, 1994; J CompPsychol 120:1–11, 2006a; J Comp Psychol 120:205–216,2006b; Pepperberg and Carey submitted), was tested on addition of two Arabic numerals or three sequentially presented collections (e.g., of variously sized jelly beans or nuts). He was, without explicit training and in the absence of the previously viewed addends, asked, "How many total?" and required to answer with a vocal English number label. In a few trials on the Arabic numeral addition, he was also shown variously colored Arabic numerals while the addends were hidden and asked "What color number (is the) total?" Although his death precluded testing on all possible arrays, his accuracy was statistically significant and suggested addition abilities comparable with those of nonhuman primates.

Time-independent models of asset returns revisited

NASA Astrophysics Data System (ADS)

Gillemot, L.; Töyli, J.; Kertesz, J.; Kaski, K.

2000-07-01

In this study we investigate various well-known time-independent models of asset returns being simple normal distribution, Student t-distribution, Lévy, truncated Lévy, general stable distribution, mixed diffusion jump, and compound normal distribution. For this we use Standard and Poor's 500 index data of the New York Stock Exchange, Helsinki Stock Exchange index data describing a small volatile market, and artificial data. The results indicate that all models, excluding the simple normal distribution, are, at least, quite reasonable descriptions of the data. Furthermore, the use of differences instead of logarithmic returns tends to make the data looking visually more Lévy-type distributed than it is. This phenomenon is especially evident in the artificial data that has been generated by an inflated random walk process.

A systematic review of selected evidence on developing nursing students' critical thinking through problem-based learning.

PubMed

Yuan, Haobin; Williams, Beverly A; Fan, Lin

2008-08-01

Rapidly changing developments and expanding roles in healthcare environment requires professional nurses to develop critical thinking. Nursing education strives to facilitate students' critical thinking through the appropriate instructional approaches. Problem-based learning (PBL) is a student-centered approach to learning which enables the students to work cooperatively in small groups for seeking solutions to situations/problems. The systematic review was conducted to provide the available evidence on developing nursing students' critical thinking through PBL. The computerized searches from 1990-2006 in CINAHL, Proquest, Cochrane library, Pubmed etc were performed. All studies which addressed the differences in critical thinking among nursing students in PBL were considered. Two independent reviewers assessed the eligibility of each study, its level of evidence and the methodological quality. As a result, only ten studies were retrieved, they were: one RCT with a Jadad quality score of 3, one nonrandomized control study, two quasi-experimental studies with non-controlled pretest-posttest design, and six descriptive studies. The available evidence in this review did not provide supportive evidence on developing nursing students' critical thinking through PBL. Clearly, there is a need for additional research with larger sample size and high quality to clarify the effects of PBL on critical thinking development within nursing educational context.

Quantitative Relationships Involving Additive Differences: Numerical Resilience

ERIC Educational Resources Information Center

Ramful, Ajay; Ho, Siew Yin

2014-01-01

This case study describes the ways in which problems involving additive differences with unknown starting quantities, constrain the problem solver in articulating the inherent quantitative relationship. It gives empirical evidence to show how numerical reasoning takes over as a Grade 6 student instantiates the quantitative relation by resorting to…

MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4

PubMed Central

Walsh, James T.; Hendrix, Sven; Boato, Francesco; Smirnov, Igor; Zheng, Jingjing; Lukens, John R.; Gadani, Sachin; Hechler, Daniel; Gölz, Greta; Rosenberger, Karen; Kammertöns, Thomas; Vogt, Johannes; Vogelaar, Christina; Siffrin, Volker; Radjavi, Ali; Fernandez-Castaneda, Anthony; Gaultier, Alban; Gold, Ralf; Kanneganti, Thirumala-Devi; Nitsch, Robert; Zipp, Frauke; Kipnis, Jonathan

2015-01-01

A body of experimental evidence suggests that T cells mediate neuroprotection following CNS injury; however, the antigen specificity of these T cells and how they mediate neuroprotection are unknown. Here, we have provided evidence that T cell–mediated neuroprotection after CNS injury can occur independently of major histocompatibility class II (MHCII) signaling to T cell receptors (TCRs). Using two murine models of CNS injury, we determined that damage-associated molecular mediators that originate from injured CNS tissue induce a population of neuroprotective, IL-4–producing T cells in an antigen-independent fashion. Compared with wild-type mice, IL-4–deficient animals had decreased functional recovery following CNS injury; however, transfer of CD4+ T cells from wild-type mice, but not from IL-4–deficient mice, enhanced neuronal survival. Using a culture-based system, we determined that T cell–derived IL-4 protects and induces recovery of injured neurons by activation of neuronal IL-4 receptors, which potentiated neurotrophin signaling via the AKT and MAPK pathways. Together, these findings demonstrate that damage-associated molecules from the injured CNS induce a neuroprotective T cell response that is independent of MHCII/TCR interactions and is MyD88 dependent. Moreover, our results indicate that IL-4 mediates neuroprotection and recovery of the injured CNS and suggest that strategies to enhance IL-4–producing CD4+ T cells have potential to attenuate axonal damage in the course of CNS injury in trauma, inflammation, or neurodegeneration. PMID:25607842

Cognitive Contributions to Gait and Falls: Evidence and Implications

PubMed Central

Amboni, Marianna; Barone, Paolo; Hausdorff, Jeffrey M.

2014-01-01

Dementia and gait impairments often coexist in older adults and patients with neurodegenerative disease. Both conditions represent independent risk factors for falls. The relationship between cognitive function and gait has recently received increasing attention. Gait is no longer considered merely automated motor activity but rather an activity that requires executive function and attention as well as judgment of external and internal cues. In this review, we intend to: (1) summarize and synthesize the experimental, neuropsychological, and neuroimaging evidence that supports the role played by cognition in the control of gait; and (2) briefly discuss the implications deriving from the interplay between cognition and gait. In recent years, the dual task paradigm has been widely used as an experimental method to explore the interplay between gait and cognition. Several neuropsychological investigations have also demonstrated that walking relies on the use of several cognitive domains, including executive-attentional function, visuospatial abilities, and even memory resources. A number of morphological and functional neuroimaging studies have offered additional evidence supporting the relationship between gait and cognitive resources. Based on the findings from 3 lines of studies, it appears that a growing body of evidence indicates a pivotal role of cognition in gait control and fall prevention. The interplay between higher-order neural function and gait has a number of clinical implications, ranging from integrated assessment tools to possible innovative lines of interventions, including cognitive therapy for falls prevention on one hand and walking program for reducing dementia risk on the other. PMID:24132840

Independent Contributions of the Central Executive, Intelligence, and In-Class Attentive Behavior to Developmental Change in the Strategies Used to Solve Addition Problems

PubMed Central

Geary, David C.; Hoard, Mary K.; Nugent, Lara

2012-01-01

Children’s (n = 275) use of retrieval, decomposition (e.g., 7 = 4+3, and thus 6+7=6+4+3), and counting to solve additional problems was longitudinally assessed from first to fourth grade, and intelligence, working memory, and in-class attentive behavior was assessed in one or several grades. The goal was to assess the relation between capacity of the central executive component of working memory, controlling for intelligence and in-class attentive behavior, and grade-related changes in children’s use of these strategies. The predictor on intercept effects from multilevel models revealed that children with higher central executive capacity correctly retrieved more facts and used the most sophisticated counting procedure more frequently and accurately than did their lower capacity peers at the beginning of first grade, but the predictor on slope effects indicated that this advantage disappeared (retrieval) or declined in importance (counting) from first to fourth grade. The predictor on slope effects also revealed that from first through fourth grade, children with higher capacity adopted the decomposition strategy more quickly than did other children. The results remained robust with controls for children’s sex, race, school site, speed of encoding Arabic numerals and articulating number words, and mathematics achievement in kindergarten. The results also revealed that intelligence and in-class attentive behavior independently contributed to children’s strategy development. PMID:22698947

Independent contributions of the central executive, intelligence, and in-class attentive behavior to developmental change in the strategies used to solve addition problems.

PubMed

Geary, David C; Hoard, Mary K; Nugent, Lara

2012-09-01

Children's (N=275) use of retrieval, decomposition (e.g., 7=4+3 and thus 6+7=6+4+3), and counting to solve additional problems was longitudinally assessed from first grade to fourth grade, and intelligence, working memory, and in-class attentive behavior was assessed in one or several grades. The goal was to assess the relation between capacity of the central executive component of working memory, controlling for intelligence and in-class attentive behavior, and grade-related changes in children's use of these strategies. The predictor on intercept effects from multilevel models revealed that children with higher central executive capacity correctly retrieved more facts and used the most sophisticated counting procedure more frequently and accurately than their lower capacity peers at the beginning of first grade, but the predictor on slope effects indicated that this advantage disappeared (retrieval) or declined in importance (counting) from first grade to fourth grade. The predictor on slope effects also revealed that from first grade to fourth grade, children with higher capacity adopted the decomposition strategy more quickly than other children. The results remained robust with controls for children's sex, race, school site, speed of encoding Arabic numerals and articulating number words, and mathematics achievement in kindergarten. The results also revealed that intelligence and in-class attentive behavior independently contributed to children's strategy development. Copyright © 2012 Elsevier Inc. All rights reserved.

Silver oxysalts promote cutaneous wound healing independent of infection.

PubMed

Thomason, Helen A; Lovett, Jodie M; Spina, Carla J; Stephenson, Christian; McBain, Andrew J; Hardman, Matthew J

2018-03-12

Chronic wounds often exist in a heightened state of inflammation whereby excessive inflammatory cells release high levels of proteases and reactive oxygen species (ROS). While low levels of ROS play a fundamental role in the regulation of normal wound healing, their levels need to be tightly regulated to prevent a hostile wound environment resulting from excessive levels of ROS. Infection amplifies the inflammatory response, augmenting levels of ROS which creates additional tissue damage that supports microbial growth. Antimicrobial dressings are used to combat infection; however, the effects of these dressing on the wound environment and healing independent of infection are rarely assessed. Cytotoxic or adverse effects on healing may exacerbate the hostile wound environment and prolong healing. Here we assessed the effect on healing independent of infection of silver oxysalts which produce higher oxidative states of silver (Ag 2+ /Ag 3+ ). Silver oxysalts had no adverse effect on fibroblast scratch wound closure whilst significantly promoting closure of keratinocyte scratch wounds (34% increase compared with control). Furthermore, dressings containing silver oxysalts accelerated healing of full-thickness incisional wounds in wild-type mice, reducing wound area, promoting reepithelialization, and dampening inflammation. We explored the mechanisms by which silver oxysalts promote healing and found that unlike other silver dressings tested, silver oxysalt dressings catalyze the breakdown of hydrogen peroxide to water and oxygen. In addition, we found that silver oxysalts directly released oxygen when exposed to water. Collectively, these data provide the first indication that silver oxysalts promote healing independent of infection and may regulate oxidative stress within a wound through catalysis of hydrogen peroxide. © 2018 by the Wound Healing Society.

Empirical validation of the triple-code model of numerical processing for complex math operations using functional MRI and group Independent Component Analysis of the mental addition and subtraction of fractions.

PubMed

Schmithorst, Vincent J; Brown, Rhonda Douglas

2004-07-01

The suitability of a previously hypothesized triple-code model of numerical processing, involving analog magnitude, auditory verbal, and visual Arabic codes of representation, was investigated for the complex mathematical task of the mental addition and subtraction of fractions. Functional magnetic resonance imaging (fMRI) data from 15 normal adult subjects were processed using exploratory group Independent Component Analysis (ICA). Separate task-related components were found with activation in bilateral inferior parietal, left perisylvian, and ventral occipitotemporal areas. These results support the hypothesized triple-code model corresponding to the activated regions found in the individual components and indicate that the triple-code model may be a suitable framework for analyzing the neuropsychological bases of the performance of complex mathematical tasks. Copyright 2004 Elsevier Inc.

Fathers’ Leave and Fathers’ Involvement: Evidence from Four OECD Countries

PubMed Central

Huerta, Maria C.; Adema, Willem; Baxter, Jennifer; Han, Wen-Jui; Lausten, Mette; Lee, RaeHyuck; Waldfogel, Jane

2016-01-01

In recent years, several OECD countries have taken steps to promote policies encouraging fathers to spend more time caring for young children, thereby promoting a more gender equal division of care work. Evidence, mainly for the United States and United Kingdom, has shown fathers taking some time off work around childbirth are more likely to be involved in childcare related activities than fathers who do not take time off. This paper conducts a first cross-national analysis on the association between fathers’ leave taking and fathers’ involvement when children are young. It uses birth cohort data of children born around 2000 from four OECD countries: Australia, Denmark, the United Kingdom and the United States. Results show that the majority of fathers take time off around childbirth independent of the leave policies in place. In all countries, except Denmark, important socio-economic differences between fathers who take leave and those who do not are observed. In addition, fathers who take leave, especially those taking two weeks or more, are more likely to carry out childcare related activities when children are young. This study adds to the evidence that suggests that parental leave for fathers is positively associated with subsequent paternal involvement. PMID:28479865

Independent Orbiter Assessment (IOA): Assessment of the nose wheel steering subsystem

NASA Technical Reports Server (NTRS)

Mediavilla, Anthony Scott

1988-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA effort first completed an analysis of the Nose Wheel Steering (NWS) hardware, generating draft failure modes and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The IOA results were then compared to the proposed NASA post 51-L FMEA/CIL baseline. A resolution of each discrepancy from the comparison is provided through additional analysis as required. This report documents the results of that comparison for the Orbiter NWS hardware.

25 CFR 215.17 - Additional information required.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false Additional information required. 215.17 Section 215.17 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEAD AND ZINC MINING... application, must file one certified copy of articles of incorporation and, if a foreign corporation, evidence...

Statistical independence of the initial conditions in chaotic mixing.

PubMed

García de la Cruz, J M; Vassilicos, J C; Rossi, L

2017-11-01

Experimental evidence of the scalar convergence towards a global strange eigenmode independent of the scalar initial condition in chaotic mixing is provided. This convergence, underpinning the independent nature of chaotic mixing in any passive scalar, is presented by scalar fields with different initial conditions casting statistically similar shapes when advected by periodic unsteady flows. As the scalar patterns converge towards a global strange eigenmode, the scalar filaments, locally aligned with the direction of maximum stretching, as described by the Lagrangian stretching theory, stack together in an inhomogeneous pattern at distances smaller than their asymptotic minimum widths. The scalar variance decay becomes then exponential and independent of the scalar diffusivity or initial condition. In this work, mixing is achieved by advecting the scalar using a set of laminar flows with unsteady periodic topology. These flows, that resemble the tendril-whorl map, are obtained by morphing the forcing geometry in an electromagnetic free surface 2D mixing experiment. This forcing generates a velocity field which periodically switches between two concentric hyperbolic and elliptic stagnation points. In agreement with previous literature, the velocity fields obtained produce a chaotic mixer with two regions: a central mixing and an external extensional area. These two regions are interconnected through two pairs of fluid conduits which transfer clean and dyed fluid from the extensional area towards the mixing region and a homogenized mixture from the mixing area towards the extensional region.

Addition of milk to tea infusions: Helpful or harmful? Evidence from in vitro and in vivo studies on antioxidant properties.

PubMed

Rashidinejad, Ali; Birch, E John; Sun-Waterhouse, Dongxiao; Everett, David W

2017-10-13

Tea consumption is practised as a tradition, and has shown potential to improve human health. Maximal uptake of tea antioxidants and milk proteins without a negative impact on tea flavor is highly desired by consumers. There is a conflicting evidence of the effect of milk addition to tea on antioxidant activity. Differences in the type of tea, the composition, type and amount of milk, preparation method of tea-milk infusions, the assays used to measure antioxidant activity, and sampling size likely account for different findings. Interactions between tea polyphenols and milk proteins, especially between catechins and caseins, could account for a decrease in antioxidant activity, although other mechanisms are also possible, given the similar effects between soy and bovine milk. The role of milk fat globules and the milk fat globule membrane surface is also important when considering interactions and loss of polyphenolic antioxidant activity, which has not been addressed in the literature.

Evidence-based Medicine--How to Teach Critical Scientific Thinking to Medical Undergraduates.

ERIC Educational Resources Information Center

Pitkala, K.; Mantyranta, T.; Strandberg, T. E.; Makela, M.; Vanhanen, H.; Varonen, H.

2000-01-01

Discusses an evidence-based course which activates students' critical thinking, enhances social learning and group processes, and promotes attitudes towards independent information retrieval and critical appraisal. (Author/CCM)

Standardized description of scientific evidence using the Evidence Ontology (ECO)

PubMed Central

Chibucos, Marcus C.; Mungall, Christopher J.; Balakrishnan, Rama; Christie, Karen R.; Huntley, Rachael P.; White, Owen; Blake, Judith A.; Lewis, Suzanna E.; Giglio, Michelle

2014-01-01

The Evidence Ontology (ECO) is a structured, controlled vocabulary for capturing evidence in biological research. ECO includes diverse terms for categorizing evidence that supports annotation assertions including experimental types, computational methods, author statements and curator inferences. Using ECO, annotation assertions can be distinguished according to the evidence they are based on such as those made by curators versus those automatically computed or those made via high-throughput data review versus single test experiments. Originally created for capturing evidence associated with Gene Ontology annotations, ECO is now used in other capacities by many additional annotation resources including UniProt, Mouse Genome Informatics, Saccharomyces Genome Database, PomBase, the Protein Information Resource and others. Information on the development and use of ECO can be found at http://evidenceontology.org. The ontology is freely available under Creative Commons license (CC BY-SA 3.0), and can be downloaded in both Open Biological Ontologies and Web Ontology Language formats at http://code.google.com/p/evidenceontology. Also at this site is a tracker for user submission of term requests and questions. ECO remains under active development in response to user-requested terms and in collaborations with other ontologies and database resources. Database URL: Evidence Ontology Web site: http://evidenceontology.org PMID:25052702

Transit Timing Variation Measurements of WASP-12b and Qatar-1b: No Evidence Of Additional Planets

NASA Astrophysics Data System (ADS)

Collins, Karen A.; Kielkopf, John F.; Stassun, Keivan G.

2017-02-01

WASP-12b and Qatar-1b are transiting hot Jupiters for which previous works have suggested the presence of transit timing variations (TTVs) indicative of additional bodies in these systems—an Earth-mass planet in WASP-12 and a brown-dwarf mass object in Qatar-1. Here, we present 23 new WASP-12b and 18 new Qatar-1b complete (or nearly complete) transit observations. We perform global system fits to all of our light curves for each system, as well as RV and stellar spectroscopic parameters from the literature. The global fits provide refined system parameters and uncertainties for each system, including precise transit center times for each transit. The transit model residuals of the combined and five minute binned light curves have an rms of 183 and 255 parts per million (ppm) for WASP-12b and Qatar-1b, respectively. Most of the WASP-12b system parameter values from this work are consistent with values from previous studies, but have ˜40%-50% smaller uncertainties. Most of the Qatar-1b system parameter values and uncertainties from this work are consistent with values recently reported in the literature. We find no convincing evidence for sinusoidal TTVs with a semi-amplitude of more than ˜35 and ˜25 s in the WASP-12b and Qatar-1b systems, respectively.

Relationship between theory of mind and functional independence is mediated by executive function.

PubMed

Ahmed, Fayeza S; Miller, L Stephen

2013-06-01

Theory of mind (ToM) is the ability to comprehend another person's perspective. Although there is much literature of ToM in children, there is a limited and somewhat inconclusive amount of studies examining ToM in a geriatric population. This study examined ToM's relationship to functional independence. Two tests of ToM, tests of executive function, and a measure of functional ability were administered to cognitively intact older adults. Results showed that 1 test of ToM (Strange Stories test) significantly accounted for variance in functional ability, whereas the other did not (Faux Pas test). In addition, Strange Stories test performance was partially driven by a verbal abstraction-based executive function: proverb interpretation. A multiple mediation model was employed to examine whether executive functions explained the relationship between the Strange Stories test and functional ability. Results showed that both the combined and individual indirect effects of the executive function measures mediated the relationship. We argue that, although components of ToM are associated with functional independence, ToM does not appear to account for additional variance in functional independence beyond executive function measures. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Chronic Recreational Physical Inactivity and Epithelial Ovarian Cancer Risk: Evidence from the Ovarian Cancer Association Consortium.

PubMed

Cannioto, Rikki; LaMonte, Michael J; Risch, Harvey A; Hong, Chi-Chen; Sucheston-Campbell, Lara E; Eng, Kevin H; Brian Szender, J; Chang-Claude, Jenny; Schmalfeldt, Barbara; Klapdor, Ruediger; Gower, Emily; Minlikeeva, Albina N; Zirpoli, Gary R; Bandera, Elisa V; Berchuck, Andrew; Cramer, Daniel; Doherty, Jennifer A; Edwards, Robert P; Fridley, Brooke L; Goode, Ellen L; Goodman, Marc T; Hogdall, Estrid; Hosono, Satoyo; Jensen, Allan; Jordan, Susan; Kjaer, Susanne K; Matsuo, Keitaro; Ness, Roberta B; Olsen, Catherine M; Olson, Sara H; Leigh Pearce, Celeste; Pike, Malcolm C; Anne Rossing, Mary; Szamreta, Elizabeth A; Thompson, Pamela J; Tseng, Chiu-Chen; Vierkant, Robert A; Webb, Penelope M; Wentzensen, Nicolas; Wicklund, Kristine G; Winham, Stacey J; Wu, Anna H; Modugno, Francesmary; Schildkraut, Joellen M; Terry, Kathryn L; Kelemen, Linda E; Moysich, Kirsten B

2016-07-01

Despite a large body of literature evaluating the association between recreational physical activity and epithelial ovarian cancer (EOC) risk, the extant evidence is inconclusive, and little is known about the independent association between recreational physical inactivity and EOC risk. We conducted a pooled analysis of nine studies from the Ovarian Cancer Association Consortium to investigate the association between chronic recreational physical inactivity and EOC risk. In accordance with the 2008 Physical Activity Guidelines for Americans, women reporting no regular, weekly recreational physical activity were classified as inactive. Multivariable logistic regression was utilized to estimate the ORs and 95% confidence intervals (CI) for the association between inactivity and EOC risk overall and by subgroups based upon histotype, menopausal status, race, and body mass index. The current analysis included data from 8,309 EOC patients and 12,612 controls. We observed a significant positive association between inactivity and EOC risk (OR = 1.34; 95% CI, 1.14-1.57), and similar associations were observed for each histotype. In this large pooled analysis examining the association between recreational physical inactivity and EOC risk, we observed consistent evidence of an association between chronic inactivity and all EOC histotypes. These data add to the growing body of evidence suggesting that inactivity is an independent risk factor for cancer. If the apparent association between inactivity and EOC risk is substantiated, additional work via targeted interventions should be pursued to characterize the dose of activity required to mitigate the risk of this highly fatal disease. Cancer Epidemiol Biomarkers Prev; 25(7); 1114-24. ©2016 AACR. ©2016 American Association for Cancer Research.

French Intervention: British Failure To Anticipate Transition In The American War of Independence

DTIC Science & Technology

2016-05-26

between Louis XVI and Charles Gravier, Comte de Vergennes, the French Foreign Minister, offer evidence of the French interest in an independent...New York: St. Martin’s Press, 1991), 9. 30 George Germain to General Irwin, 10 August 1968, Historical Manuscripts Commission, Report on the...France and by early 1776 Comte de Vergennes, the French Foreign Minister, informed Arthur Lee, an American diplomat in France, the French intended

Students in Australian Catholic and Independent Schools Have More Positive Learning Environments: Evidence from the 2012 PISA Study

ERIC Educational Resources Information Center

Marks, Gary N.

2017-01-01

Critics of Catholic and independent (nongovernment) schools in Australia contend that the higher levels of performance of students in nongovernment schools can be dismissed as simply a function of student- and especially school-level socioeconomic status (school-SES). A recent article extends this critique to school-sector differences in students'…

Nerve-independent and ectopically additional induction of taste buds in organ culture of fetal tongues.

PubMed

Honda, Kotaro; Tomooka, Yasuhiro

2016-10-01

An improved organ culture system allowed to observe morphogenesis of mouse lingual papillae and taste buds relatively for longer period, in which fetal tongues were analyzed for 6 d. Taste cells were defined as eosinophobic epithelial cells expressing CK8 and Sox2 within lingual epithelium. Addition of glycogen synthase kinase 3 beta inhibitor CHIR99021 induced many taste cells and buds in non-gustatory and gustatory stratified lingual epithelium. The present study clearly demonstrated induction of taste cells and buds ectopically and without innervation.

Adequate proverb interpretation is associated with performance on the independent living scales.

PubMed

Ahmed, Fayeza S; Miller, L Stephen

2015-01-01

The purpose of this study was to examine proverb interpretation performance and functional independence in older adults. From the limited literature on proverb interpretation in aging and its conceptualization as an executive function, it was hypothesized that proverb interpretation would be related to functional independence similar to other executive functions. Tests of proverb interpretation, additional executive functions, and functional ability were administered to nondemented older adults. Results showed that proverb interpretation accounted for a significant amount of unique variance of functional ability scores. This supports including a measure of proverb interpretation to the assessment of older adults.

Mid-Space-Independent Deformable Image Registration

PubMed Central

Aganj, Iman; Iglesias, Juan Eugenio; Reuter, Martin; Sabuncu, Mert Rory; Fischl, Bruce

2017-01-01

Aligning images in a mid-space is a common approach to ensuring that deformable image registration is symmetric – that it does not depend on the arbitrary ordering of the input images. The results are, however, generally dependent on the mathematical definition of the mid-space. In particular, the set of possible solutions is typically restricted by the constraints that are enforced on the transformations to prevent the mid-space from drifting too far from the native image spaces. The use of an implicit atlas has been proposed as an approach to mid-space image registration. In this work, we show that when the atlas is aligned to each image in the native image space, the data term of implicit-atlas-based deformable registration is inherently independent of the mid-space. In addition, we show that the regularization term can be reformulated independently of the mid-space as well. We derive a new symmetric cost function that only depends on the transformation morphing the images to each other, rather than to the atlas. This eliminates the need for anti-drift constraints, thereby expanding the space of allowable deformations. We provide an implementation scheme for the proposed framework, and validate it through diffeomorphic registration experiments on brain magnetic resonance images. PMID:28242316

Predictors of Chain Acquisition among Independent Dialysis Facilities

PubMed Central

Pozniak, Alyssa S; Hirth, Richard A; Banaszak-Holl, Jane; Wheeler, John R C

2010-01-01

Objective To determine the predictors of chain acquisition among independent dialysis providers. Data Sources Retrospective facility-level data combined from CMS Cost Reports, Medical Evidence Forms, Annual Facility Surveys, and claims for 1996–2003. Study Design Independent dialysis facilities' probability of acquisition by a dialysis chain (overall and by chain size) was estimated using a discrete time hazard rate model, controlling for financial and clinical performance, practice patterns, market factors, and other facility characteristics. Data Collection The sample includes all U.S. freestanding dialysis facilities that report not being chain affiliated for at least 1 year between 1997 and 2003. Principal Findings Above-average costs and better quality outcomes are significant determinants of dialysis chain acquisition. Facilities in larger markets were more likely to be acquired by a chain. Furthermore, small dialysis chains have different acquisition strategies than large chains. Conclusions Dialysis chains appear to employ a mix of turn-around and cream-skimming strategies. Poor financial health is a predictor of chain acquisition as in other health care sectors, but the increased likelihood of chain acquisition among higher quality facilities is unique to the dialysis industry. Significant differences among predictors of acquisition by small and large chains reinforce the importance of using a richer classification for chain status. PMID:20148985

Capturing Functional Independence Measure (FIM®) Ratings.

PubMed

Torres, Audrey

The aim of the study was to identify interventions to capture admission functional independence measure (FIM®) ratings on the day of admission to an inpatient rehabilitation facility. A quantitative evidence-based practice quality improvement study utilizing descriptive statistics. Admission FIM® ratings from patients discharged in June 2012 (retrospective review) were compared to admission FIM® ratings from patients discharged in June 2014 (prospective review). The logic model was utilized to determine the project inputs, outputs, and outcomes. Interventions to capture admission FIM® ratings on the day of admission are essential to accurately predict the patient's burden of care, length of stay, and reimbursement. Waiting until Day 2 or Day 3 after admission to capture the admission FIM® assessment resulted in inflated admission FIM® ratings and suboptimal quality outcomes. Interventions to capture admission FIM® ratings on the day of admission were successful at improving the quality of care, length of stay efficiency, and accurately recording admission FIM® ratings to determine the patient's burden of care.

Affected States soft independent modeling by class analogy from the relation between independent variables, number of independent variables and sample size.

PubMed

Kanık, Emine Arzu; Temel, Gülhan Orekici; Erdoğan, Semra; Kaya, Irem Ersöz

2013-03-01

The aim of study is to introduce method of Soft Independent Modeling of Class Analogy (SIMCA), and to express whether the method is affected from the number of independent variables, the relationship between variables and sample size. Simulation study. SIMCA model is performed in two stages. In order to determine whether the method is influenced by the number of independent variables, the relationship between variables and sample size, simulations were done. Conditions in which sample sizes in both groups are equal, and where there are 30, 100 and 1000 samples; where the number of variables is 2, 3, 5, 10, 50 and 100; moreover where the relationship between variables are quite high, in medium level and quite low were mentioned. Average classification accuracy of simulation results which were carried out 1000 times for each possible condition of trial plan were given as tables. It is seen that diagnostic accuracy results increase as the number of independent variables increase. SIMCA method is a method in which the relationship between variables are quite high, the number of independent variables are many in number and where there are outlier values in the data that can be used in conditions having outlier values.

Length-independent structural similarities enrich the antibody CDR canonical class model.

PubMed

Nowak, Jaroslaw; Baker, Terry; Georges, Guy; Kelm, Sebastian; Klostermann, Stefan; Shi, Jiye; Sridharan, Sudharsan; Deane, Charlotte M

2016-01-01

Complementarity-determining regions (CDRs) are antibody loops that make up the antigen binding site. Here, we show that all CDR types have structurally similar loops of different lengths. Based on these findings, we created length-independent canonical classes for the non-H3 CDRs. Our length variable structural clusters show strong sequence patterns suggesting either that they evolved from the same original structure or result from some form of convergence. We find that our length-independent method not only clusters a larger number of CDRs, but also predicts canonical class from sequence better than the standard length-dependent approach. To demonstrate the usefulness of our findings, we predicted cluster membership of CDR-L3 sequences from 3 next-generation sequencing datasets of the antibody repertoire (over 1,000,000 sequences). Using the length-independent clusters, we can structurally classify an additional 135,000 sequences, which represents a ∼20% improvement over the standard approach. This suggests that our length-independent canonical classes might be a highly prevalent feature of antibody space, and could substantially improve our ability to accurately predict the structure of novel CDRs identified by next-generation sequencing.

Evaluating Evidence Regarding Relationships with Criteria

ERIC Educational Resources Information Center

Balkin, Richard S.

2017-01-01

An overview of standards related to demonstrating evidence regarding relationships with criteria as it pertains to instrument development was presented, along with heuristic examples. Additional measures and a comprehensive design are necessary to establish evidence related to the use and interpretation of test scores for the validation of a…

A pathway-based analysis provides additional support for an immune-related genetic susceptibility to Parkinson's disease

PubMed Central

Holmans, Peter; Moskvina, Valentina; Jones, Lesley; Sharma, Manu; Vedernikov, Alexey; Buchel, Finja; Sadd, Mohamad; Bras, Jose M.; Bettella, Francesco; Nicolaou, Nayia; Simón-Sánchez, Javier; Mittag, Florian; Gibbs, J. Raphael; Schulte, Claudia; Durr, Alexandra; Guerreiro, Rita; Hernandez, Dena; Brice, Alexis; Stefánsson, Hreinn; Majamaa, Kari; Gasser, Thomas; Heutink, Peter; Wood, Nicholas W.; Martinez, Maria; Singleton, Andrew B.; Nalls, Michael A.; Hardy, John; Morris, Huw R.; Williams, Nigel M.; Arepalli, Sampath; Barker, Roger; Barrett, Jeffrey; Ben-Shlomo, Yoav; Berendse, Henk W.; Berg, Daniela; Bhatia, Kailash; de Bie, Rob M.A.; Biffi, Alessandro; Bloem, Bas; Brice, Alexis; Bochdanovits, Zoltan; Bonin, Michael; Bras, Jose M.; Brockmann, Kathrin; Brooks, Janet; Burn, David J.; Charlesworth, Gavin; Chen, Honglei; Chinnery, Patrick F.; Chong, Sean; Clarke, Carl E.; Cookson, Mark R.; Cooper, Jonathan M.; Corvol, Jen-Christophe; Counsell, Carl; Damier, Philippe; Dartigues, Jean Francois; Deloukas, Panagiotis; Deuschl, Günther; Dexter, David T.; van Dijk, Karin D.; Dillman, Allissa; Durif, Frank; Durr, Alexandra; Edkins, Sarah; Evans, Jonathan R.; Foltynie, Thomas; Gao, Jianjun; Gardner, Michelle; Gasser, Thomas; Gibbs, J. Raphael; Goate, Alison; Gray, Emma; Guerreiro, Rita; Gústafsson, Ómar; Hardy, John; Harris, Clare; Hernandez, Dena G.; Heutink, Peter; van Hilten, Jacobus J.; Hofman, Albert; Hollenbeck, Albert; Holmans, Peter; Holton, Janice; Hu, Michele; Huber, Heiko; Hudson, Gavin; Hunt, Sarah E.; Huttenlocher, Johanna; Illig, Thomas; Langford, Cordelia; Lees, Andrew; Lesage, Suzanne; Lichtner, Peter; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; Martinez, Maria; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morris, Huw; Morrison, Karen E.; Moskvina, Valentina; Mudanohwo, Ese; Nalls, Michael A.; Pearson, Justin; Perlmutter, Joel S.; Pétursson, Hjörvar; Plagnol, Vincent; Pollak, Pierre; Post, Bart; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Saad, Mohamad; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Sharma, Manu; Shaw, Karen; Sheerin, Una-Marie; Shoulson, Ira; Schulte, Claudia; Sidransky, Ellen; Simón-Sánchez, Javier; Singleton, Andrew B.; Smith, Colin; Stefánsson, Hreinn; Stefánsson, Kári; Steinberg, Stacy; Stockton, Joanna D.; Sveinbjornsdottir, Sigurlaug; Talbot, Kevin; Tanner, Carlie M.; Tashakkori-Ghanbaria, Avazeh; Tison, François; Trabzuni, Daniah; Traynor, Bryan J.; Uitterlinden, André G.; Velseboer, Daan; Vidailhet, Marie; Walker, Robert; van de Warrenburg, Bart; Wickremaratchi, Mirdhu; Williams, Nigel; Williams-Gray, Caroline H.; Winder-Rhodes, Sophie; Wood, Nicholas

2013-01-01

Parkinson's disease (PD) is the second most common neurodegenerative disease affecting 1–2% in people >60 and 3–4% in people >80. Genome-wide association (GWA) studies have now implicated significant evidence for association in at least 18 genomic regions. We have studied a large PD-meta analysis and identified a significant excess of SNPs (P < 1 × 10−16) that are associated with PD but fall short of the genome-wide significance threshold. This result was independent of variants at the 18 previously implicated regions and implies the presence of additional polygenic risk alleles. To understand how these loci increase risk of PD, we applied a pathway-based analysis, testing for biological functions that were significantly enriched for genes containing variants associated with PD. Analysing two independent GWA studies, we identified that both had a significant excess in the number of functional categories enriched for PD-associated genes (minimum P = 0.014 and P = 0.006, respectively). Moreover, 58 categories were significantly enriched for associated genes in both GWA studies (P < 0.001), implicating genes involved in the ‘regulation of leucocyte/lymphocyte activity’ and also ‘cytokine-mediated signalling’ as conferring an increased susceptibility to PD. These results were unaltered by the exclusion of all 178 genes that were present at the 18 genomic regions previously reported to be strongly associated with PD (including the HLA locus). Our findings, therefore, provide independent support to the strong association signal at the HLA locus and imply that the immune-related genetic susceptibility to PD is likely to be more widespread in the genome than previously appreciated. PMID:23223016

Synchronous Endometrial and Ovarian Carcinomas: Evidence of Clonality.

PubMed

Anglesio, Michael S; Wang, Yi Kan; Maassen, Madlen; Horlings, Hugo M; Bashashati, Ali; Senz, Janine; Mackenzie, Robertson; Grewal, Diljot S; Li-Chang, Hector; Karnezis, Anthony N; Sheffield, Brandon S; McConechy, Melissa K; Kommoss, Friedrich; Taran, Florin A; Staebler, Annette; Shah, Sohrab P; Wallwiener, Diethelm; Brucker, Sara; Gilks, C Blake; Kommoss, Stefan; Huntsman, David G

2016-06-01

Many women with ovarian endometrioid carcinoma present with concurrent endometrial carcinoma. Organ-confined and low-grade synchronous endometrial and ovarian tumors (SEOs) clinically behave as independent primary tumors rather than a single advanced-stage carcinoma. We used 18 SEOs to investigate the ancestral relationship between the endometrial and ovarian components. Based on both targeted and exome sequencing, 17 of 18 patient cases of simultaneous cancer of the endometrium and ovary from our series showed evidence of a clonal relationship, ie, primary tumor and metastasis. Eleven patient cases fulfilled clinicopathological criteria that would lead to classification as independent endometrial and ovarian primary carcinomas, including being of FIGO stage T1a/1A, with organ-restricted growth and without surface involvement; 10 of 11 of these cases showed evidence of clonality. Our observations suggest that the disseminating cells amongst SEOs are restricted to physically accessible and microenvironment-compatible sites yet remain indolent, without the capacity for further dissemination. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Experimental evidence of a pathogen invasion threshold

PubMed Central

Krkošek, Martin

2018-01-01

Host density thresholds to pathogen invasion separate regions of parameter space corresponding to endemic and disease-free states. The host density threshold is a central concept in theoretical epidemiology and a common target of human and wildlife disease control programmes, but there is mixed evidence supporting the existence of thresholds, especially in wildlife populations or for pathogens with complex transmission modes (e.g. environmental transmission). Here, we demonstrate the existence of a host density threshold for an environmentally transmitted pathogen by combining an epidemiological model with a microcosm experiment. Experimental epidemics consisted of replicate populations of naive crustacean zooplankton (Daphnia dentifera) hosts across a range of host densities (20–640 hosts l−1) that were exposed to an environmentally transmitted fungal pathogen (Metschnikowia bicuspidata). Epidemiological model simulations, parametrized independently of the experiment, qualitatively predicted experimental pathogen invasion thresholds. Variability in parameter estimates did not strongly influence outcomes, though systematic changes to key parameters have the potential to shift pathogen invasion thresholds. In summary, we provide one of the first clear experimental demonstrations of pathogen invasion thresholds in a replicated experimental system, and provide evidence that such thresholds may be predictable using independently constructed epidemiological models. PMID:29410876

Independent Orbiter Assessment (IOA): Assessment of the extravehicular mobility unit, volume 2

NASA Technical Reports Server (NTRS)

Raffaelli, Gary G.

1988-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA effort performed an independent analysis of the Extravehicular Mobility Unit (EMU) hardware and system, generating draft failure modes criticalities and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The IOA results were then compared to the most recent proposed Post 51-L NASA FMEA/CIL baseline. A resolution of each discrepancy from the comparison was provided through additional analysis as required. This report documents the results of that comparison for the Orbiter EMU hardware. Volume 2 continues the presentation of IOA analysis worksheets and contains the potential critical items list and NASA FMEA to IOA worksheet cross references and recommendations.

Challenges to the transition to independent investigator in geriatric mental health.

PubMed

Bruce, Martha L

2003-01-01

The author reports on the extent to which junior investigators in geriatric mental health successfully make the transition to independent scientists. The NIH CRISP database identified all NIMH Level-1 career awards (K01/K07/K08/K23/ R29) in geriatric mental health completed from 1992 to 2001. Of 46 awardees, 14 (30.4%) achieved R01 funding within 1 year of completion. An additional six investigators subsequently achieved R01s in the remaining follow-up period (ranging from 2 to 10 years), for a total of 43.5% (20/46). These data underscore the relatively small number of junior investigators who successfully make the transition to independent scientist. Their numbers underscore the importance of efforts by the field of geriatric mental health aimed at both increasing the flow into this career as well as ensuring the retention and success of junior investigators at the critical transition to independent investigators.

Caenorhabditis elegans reveals a FxNPxY-independent low-density lipoprotein receptor internalization mechanism mediated by epsin1

PubMed Central

Kang, Yuan-Lin; Yochem, John; Bell, Leslie; Sorensen, Erika B.; Chen, Lihsia; Conner, Sean D.

2013-01-01

Low-density lipoprotein receptor (LDLR) internalization clears cholesterol-laden LDL particles from circulation in humans. Defects in clathrin-dependent LDLR endocytosis promote elevated serum cholesterol levels and can lead to atherosclerosis. However, our understanding of the mechanisms that control LDLR uptake remains incomplete. To identify factors critical to LDLR uptake, we pursued a genome-wide RNA interference screen using Caenorhabditis elegans LRP-1/megalin as a model for LDLR transport. In doing so, we discovered an unanticipated requirement for the clathrin-binding endocytic adaptor epsin1 in LDLR endocytosis. Epsin1 depletion reduced LDLR internalization rates in mammalian cells, similar to the reduction observed following clathrin depletion. Genetic and biochemical analyses of epsin in C. elegans and mammalian cells uncovered a requirement for the ubiquitin-interaction motif (UIM) as critical for receptor transport. As the epsin UIM promotes the internalization of some ubiquitinated receptors, we predicted LDLR ubiquitination as necessary for endocytosis. However, engineered ubiquitination-impaired LDLR mutants showed modest internalization defects that were further enhanced with epsin1 depletion, demonstrating epsin1-mediated LDLR endocytosis is independent of receptor ubiquitination. Finally, we provide evidence that epsin1-mediated LDLR uptake occurs independently of either of the two documented internalization motifs (FxNPxY or HIC) encoded within the LDLR cytoplasmic tail, indicating an additional internalization mechanism for LDLR. PMID:23242996

Flowpath independent monitoring of reductive dechlorination potential in a fractured rock aquifer

USGS Publications Warehouse

Bradley, P.M.; Lacombe, P.J.; Imbrigiotta, T.E.; Chapelle, F.H.; Goode, D.J.

2009-01-01

The flowpath dependent approaches that are typically employed to assess biodegradation of chloroethene contaminants in unconsolidated aquifers are problematic in fractured rock settings, due to difficulties defining discrete groundwater flowpaths in such systems. In this study, the variation in the potential for chloroethene biodegradation with depth was evaluated in a fractured rock aquifer using two flowpath independent lines of field evidence: (1) the presence of the three biochemical prerequisites [electron donor(s), chloroethene electron acceptor(s), and chlororespiring microorganism(s)] for efficient chloroethene chlororespiration and (2) the in situ accumulation of chloroethene reductive dechlorination daughter products. The validity of this approach was assessed by comparing field results with the results of [1, 2- 14C] cis-DCE microcosm experiments. Microcosms were prepared with depth-specific core material, which was crushed and emplaced in discrete packer intervals for 1 year to allow colonization by the indigenous microbial community. Packer intervals characterized by significant electron donor concentrations, elevated numbers of chlororespiring microorganisms, and high reductive dechlorination product to parent contaminant ratios correlated well with the production of 14C-labeled reductive dechlorination products in the microcosm experiments. These results indicate that, in the absence of information on discrete groundwater flowpaths, a modified approach emphasizing flowpath independent lines of evidence can provide insight into the temporal and spatial variability of contaminant biodegradation in fractured rock systems. ?? 2009 National Ground Water Association.

Changes in infants' affect related to the onset of independent locomotion.

PubMed

Whitney, Pamela G; Green, James A

2011-06-01

Previous research suggests that after gaining several weeks of independent locomotor experience, infants may show both more negative and more positive affect toward parents. However, this prior work has been based largely on parent report, and no studies have used longitudinal or naturalistic methods to chart changes in infants' affective expressions as they gain locomotor ability. Fifteen infants were observed at home before, during, and after learning to crawl in two naturalistic contexts, free play and dyadic play. Expressions of negative affect during free play decreased after the onset of crawling, but there was no change in expressions of positive affect. At the same time, however, mothers reported an increase in both negative and positive reactivity. These results are discussed in terms of the contexts typically assessed during observations and the different sensitivities of mothers to infants' expressions of affect. Several lines of evidence point to a potential role for independent locomotion in the reorganization of affective expressions. Copyright © 2011 Elsevier Inc. All rights reserved.

The Effect of the Social and Physical Environment on Children's Independent Mobility to Neighborhood Destinations.

PubMed

Christian, Hayley E; Klinker, Charlotte D; Villanueva, Karen; Knuiman, Matthew W; Foster, Sarah A; Zubrick, Stephan R; Divitini, Mark; Wood, Lisa; Giles-Corti, Billie

2015-06-16

Relationships between context-specific measures of the physical and social environment and children's independent mobility to neighborhood destination types were examined. Parents in RESIDE's fourth survey reported whether their child (8-15 years; n = 181) was allowed to travel without an adult to school, friend's house, park and local shop. Objective physical environment measures were matched to each of these destinations. Social environment measures included neighborhood perceptions and items specific to local independent mobility. Independent mobility to local destinations ranged from 30% to 48%. Independent mobility to a local park was less likely as the distance to the closest park (small and large size) increased and less likely with additional school grounds (P < .05). Independent mobility to school was less likely as the distance to the closest large park increased and if the neighborhood was perceived as unsafe (P < .05). Independent mobility to a park or shops decreased if parenting social norms were unsupportive of children's local independent movement (P < .05). Independent mobility appears dependent upon the specific destination being visited and the impact of neighborhood features varies according to the destination examined. Findings highlight the importance of access to different types and sizes of urban green space for children's independent mobility to parks.

Independent NOAA considered

NASA Astrophysics Data System (ADS)

Richman, Barbara T.

A proposal to pull the National Oceanic and Atmospheric Administration (NOAA) out of the Department of Commerce and make it an independent agency was the subject of a recent congressional hearing. Supporters within the science community and in Congress said that an independent NOAA will benefit by being more visible and by not being tied to a cabinet-level department whose main concerns lie elsewhere. The proposal's critics, however, cautioned that making NOAA independent could make it even more vulnerable to the budget axe and would sever the agency's direct access to the President.The separation of NOAA from Commerce was contained in a June 1 proposal by President Ronald Reagan that also called for all federal trade functions under the Department of Commerce to be reorganized into a new Department of International Trade and Industry (DITI).

Association Analysis of the Extended MHC Region in Celiac Disease Implicates Multiple Independent Susceptibility Loci

PubMed Central

Ahn, Richard; Ding, Yuan Chun; Murray, Joseph; Fasano, Alessio; Green, Peter H. R.; Neuhausen, Susan L.; Garner, Chad

2012-01-01

Celiac disease is a common autoimmune disease caused by sensitivity to the dietary protein gluten. Forty loci have been implicated in the disease. All disease loci have been characterized as low-penetrance, with the exception of the high-risk genotypes in the HLA-DQA1 and HLA-DQB1 genes, which are necessary but not sufficient to cause the disease. The very strong effects from the known HLA loci and the genetically complex nature of the major histocompatibility complex (MHC) have precluded a thorough investigation of the region. The purpose of this study was to test the hypothesis that additional celiac disease loci exist within the extended MHC (xMHC). A set of 1898 SNPs was analyzed for association across the 7.6 Mb xMHC region in 1668 confirmed celiac disease cases and 517 unaffected controls. Conditional recursive partitioning was used to create an informative indicator of the known HLA-DQA1 and HLA-DQB1 high-risk genotypes that was included in the association analysis to account for their effects. A linkage disequilibrium-based grouping procedure was utilized to estimate the number of independent celiac disease loci present in the xMHC after accounting for the known effects. There was significant statistical evidence for four new independent celiac disease loci within the classic MHC region. This study is the first comprehensive association analysis of the xMHC in celiac disease that specifically accounts for the known HLA disease genotypes and the genetic complexity of the region. PMID:22615847

Affected States Soft Independent Modeling by Class Analogy from the Relation Between Independent Variables, Number of Independent Variables and Sample Size

PubMed Central

Kanık, Emine Arzu; Temel, Gülhan Orekici; Erdoğan, Semra; Kaya, İrem Ersöz

2013-01-01

Objective: The aim of study is to introduce method of Soft Independent Modeling of Class Analogy (SIMCA), and to express whether the method is affected from the number of independent variables, the relationship between variables and sample size. Study Design: Simulation study. Material and Methods: SIMCA model is performed in two stages. In order to determine whether the method is influenced by the number of independent variables, the relationship between variables and sample size, simulations were done. Conditions in which sample sizes in both groups are equal, and where there are 30, 100 and 1000 samples; where the number of variables is 2, 3, 5, 10, 50 and 100; moreover where the relationship between variables are quite high, in medium level and quite low were mentioned. Results: Average classification accuracy of simulation results which were carried out 1000 times for each possible condition of trial plan were given as tables. Conclusion: It is seen that diagnostic accuracy results increase as the number of independent variables increase. SIMCA method is a method in which the relationship between variables are quite high, the number of independent variables are many in number and where there are outlier values in the data that can be used in conditions having outlier values. PMID:25207065

Understanding 'independence': perspectives of occupational therapists.

PubMed

Tamaru, Akiko; McColl, Mary Ann; Yamasaki, Setsuko

2007-07-15

The purpose of this study was to understand how the term independence is used in rehabilitation. In particular, we asked occupational therapists in Canada and Japan to interpret the term independence in terms of people with disabilities. In rehabilitation, independence has long been a key concept. A review of the literature shows that the term's meaning has shifted throughout the past century. However, despite its significance, the word's meaning has never been deeply analysed, and it is left to the interpretation of the individual practitioner; consequently, there is a conceptual confusion surrounding the term. Furthermore, no studies have been conducted from an inter-cultural viewpoint that included non-Western societies. A qualitative interpretive study was conducted, based on semi-structured interviews with 18 occupational therapists. Nine Canadian and nine Japanese therapists were interviewed in depth and their perspectives analysed for themes and categories corresponding to their working definition of independence. Therapists' interpretation of the term independence consisted of three perspectives: "Independence as competence,"Independence as autonomy," and "Independence as psychological qualities". These perspectives were typically combined into two patterns of dealing with independence in practice. Differences between Canadian and Japanese perspectives were explored. The study's findings confirm some ideas about independence that have been pointed out in the professional literature, but they also add several important ideas - the idea of psychological characteristics as key to independence, and the notion of a cultural overlay on the definition and application of the concept independence. This study's findings should contribute to the ongoing discussion in the professional literature about the virtues and limitations of pursuing independence as the ultimate goal in rehabilitation.

An evidence map of yoga for low back pain.

PubMed

Goode, Adam P; Coeytaux, Remy R; McDuffie, Jennifer; Duan-Porter, Wei; Sharma, Poonam; Mennella, Hillary; Nagi, Avishek; Williams, John W

2016-04-01

Yoga is being increasingly studied as a treatment strategy for a variety of different clinical conditions, including low back pain (LBP). We set out to conduct an evidence map of yoga for the treatment, prevention and recurrence of acute or chronic low back pain (cLBP). We searched Medline, Cochrane Database of Systematic Reviews, EMBASE, Allied and Complementary Medicine Database and ClinicalTrials.gov for randomized controlled trials (RCT), systematic reviews or planned studies on the treatment or prevention of acute back pain or cLBP. Two independent reviewers screened papers for inclusion, extracted data and assessed the quality of included studies. Three eligible systematic reviews were identified that included 10 RCTs (n=956) that evaluated yoga for non-specific cLBP. We did not identify additional RCTs beyond those included in the systematic reviews. Our search of ClinicalTrials.gov identified one small (n=10) unpublished trial and one large (n=320) planned clinical trial. The most recent good quality systematic review indicated significant effects for short- and long-term pain reduction (n=6 trials; standardized mean difference [SMD] -0.48; 95% CI, -0.65 to -0.31; I(2)=0% and n=5; SMD -0.33; 95% CI, -0.59 to -0.07; I(2)=48%, respectively). Long-term effects for back specific disability were also identified (n=5; SMD -0.35; 95% CI, -0.55 to -0.15; I(2)=20%). No studies were identified evaluating yoga for prevention or treatment of acute LBP. Evidence suggests benefit of yoga in midlife adults with non-specific cLBP for short- and long-term pain and back-specific disability, but the effects of yoga for health-related quality of life, well- being and acute LBP are uncertain. Without additional studies, further systematic reviews are unlikely to be informative. Copyright © 2016 Elsevier Ltd. All rights reserved.

Magnesium inhibition of ryanodine-receptor calcium channels: evidence for two independent mechanisms.

PubMed

Laver, D R; Baynes, T M; Dulhunty, A F

1997-04-01

The gating of ryanodine receptor calcium release channels (RyRs) depends on myoplasmic Ca2+ and Mg2+ concentrations. RyRs from skeletal and cardiac muscle are activated by microm Ca2+ and inhibited by mm Ca2+ and Mg2+. 45Ca2+ release from skeletal SR vesicles suggests two mechanisms for Mg2+-inhibition (Meissner, Darling & Eveleth, 1986, Biochemistry 25:236-244). The present study investigates the nature of these mechanisms using measurements of single-channel activity from cardiac- and skeletal RyRs incorporated into planar lipid bilayers. Our measurements of Mg2+- and Ca2+-dependent gating kinetics confirm that there are two mechanisms for Mg2+ inhibition (Type I and II inhibition) in skeletal and cardiac RyRs. The mechanisms operate concurrently, are independent and are associated with different parts of the channel protein. Mg2+ reduces Po by competing with Ca2+ for the activation site (Type-I) or binding to more than one, and probably two low affinity inhibition sites which do not discriminate between Ca2+ and Mg2+ (Type-II). The relative contributions of the two inhibition mechanisms to the total Mg2+ effect depend on cytoplasmic [Ca2+] in such a way that Mg2+ inhibition has the properties of Types-I and II inhibition at low and high [Ca2+] respectively. Both mechanisms are equally important when [Ca2+] = 10 microm in cardiac RyRs or 1 microm in skeletal RyRs. We show that Type-I inhibition is not the sole mechanism responsible for Mg2+ inhibition, as is often assumed, and we discuss the physiological implications of this finding.

Object detection in natural scenes: Independent effects of spatial and category-based attention.

PubMed

Stein, Timo; Peelen, Marius V

2017-04-01

Humans are remarkably efficient in detecting highly familiar object categories in natural scenes, with evidence suggesting that such object detection can be performed in the (near) absence of attention. Here we systematically explored the influences of both spatial attention and category-based attention on the accuracy of object detection in natural scenes. Manipulating both types of attention additionally allowed for addressing how these factors interact: whether the requirement for spatial attention depends on the extent to which observers are prepared to detect a specific object category-that is, on category-based attention. The results showed that the detection of targets from one category (animals or vehicles) was better than the detection of targets from two categories (animals and vehicles), demonstrating the beneficial effect of category-based attention. This effect did not depend on the semantic congruency of the target object and the background scene, indicating that observers attended to visual features diagnostic of the foreground target objects from the cued category. Importantly, in three experiments the detection of objects in scenes presented in the periphery was significantly impaired when observers simultaneously performed an attentionally demanding task at fixation, showing that spatial attention affects natural scene perception. In all experiments, the effects of category-based attention and spatial attention on object detection performance were additive rather than interactive. Finally, neither spatial nor category-based attention influenced metacognitive ability for object detection performance. These findings demonstrate that efficient object detection in natural scenes is independently facilitated by spatial and category-based attention.

Sensorimotor-Independent Prefrontal Activity During Response Inhibition

PubMed Central

Cai, Weidong; Cannistraci, Christopher J.; Gore, John C.; Leung, Hoi-Chung

2015-01-01

A network of brain regions involving the ventral inferior frontal gyrus/anterior insula (vIFG/AI), presupplementary motor area (pre-SMA) and basal ganglia has been implicated in stopping impulsive, unwanted responses. However, whether this network plays an equal role in response inhibition under different sensorimotor contexts has not been tested systematically. Here, we conducted an fMRI experiment using the stop signal task, a sensorimotor task requiring occasional withholding of the planned response upon the presentation of a stop signal. We manipulated both the sensory modality of the stop signal (visual versus auditory) and the motor response modality (hand versus eye). Results showed that the vIFG/AI and the preSMA along with the right middle frontal gyrus were commonly activated in response inhibition across the various sensorimotor conditions. Our findings provide direct evidence for a common role of these frontal areas, but not striatal areas in response inhibition independent of the sensorimotor contexts. Nevertheless, these three frontal regions exhibited different activation patterns during successful and unsuccessful stopping. Together with the existing evidence, we suggest that the vIFG/AI is involved in the early stages of stopping such as triggering the stop process while the preSMA may play a role in regulating other cortical and subcortical regions involved in stopping. PMID:23798325

NASA 2010 Pharmacology Evidence Review

NASA Technical Reports Server (NTRS)

Steinberg, Susan

2011-01-01

In 2008, the Institute of Medicine reviewed NASA's Human Research Program Evidence in assessing the Pharmacology risk identified in NASA's Human Research Program Requirements Document (PRD). Since this review there was a major reorganization of the Pharmacology discipline within the HRP, as well as a re-evaluation of the Pharmacology evidence. This panel is being asked to review the latest version of the Pharmacology Evidence Report. Specifically, this panel will: (1) Appraise the descriptions of the human health-related risk in the HRP PRD. (2) Assess the relevance and comprehensiveness of the evidence in identifying potential threats to long-term space missions. (3) Assess the associated gaps in knowledge and identify additional areas for research as necessary.

Lack of association between alcohol-dependence and D3 dopamine receptor gene in three independent samples

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

Gorwood, P.; Feingold, J.; Ades, J.

1995-12-18

Numerous studies on the involvement of dopamine receptors in the genetics of alcoholism focused on associations between a polymorphism of the D2 dopamine receptor (DRD2) gene and alcohol dependence. However, the results of these studies are conflicting. Another receptor, the D3 dopamine receptor (DRD3), may be of additional interest since it is specifically located in the limbic area, and in particular in the nucleus accumbens which plays a significant role in the reward process of addiction behavior. We thus tested the association in three independent samples of alcoholic patients, with different origins and various inclusion criteria. No difference in themore » DRD3 gene polymorphism emerged between controls and alcoholic patients, regardless of their origin, inclusion criteria, or presence or absence of the DRD2 TaqI A1-allele. Despite the fact that more information could have been considered and that association studies provide limited information, there is good evidence that this DRD3 polymorphism does not play a major role in the genetic component of alcoholism. 17 refs., 2 tabs.« less

Serum testosterone levels in males are not associated with entrepreneurial behavior in two independent observational studies.

PubMed

van der Loos, Matthijs J H M; Haring, Robin; Rietveld, Cornelius A; Baumeister, Sebastian E; Groenen, Patrick J F; Hofman, Albert; de Jong, Frank H; Koellinger, Philipp D; Kohlmann, Thomas; Nauck, Matthias A; Rivadeneira, Fernando; Uitterlinden, André G; van Rooij, Frank J A; Wallaschofski, Henri; Thurik, A Roy

2013-07-02

Previous research has suggested a positive association between testosterone (T) and entrepreneurial behavior in males. However, this evidence was found in a study with a small sample size and has not been replicated. In the present study, we aimed to verify this association using two large, independent, population-based samples of males. We tested the association of T with entrepreneurial behavior, operationalized as self-employment, using data from the Rotterdam Study (N=587) and the Study of Health in Pomerania (N=1697). Total testosterone (TT) and sex hormone-binding globulin (SHBG) were measured in the serum. Free testosterone (FT), non-SHBG-bound T (non-SHBG-T), and the TT/SHBG ratio were calculated and used as measures of bioactive serum T, in addition to TT adjusted for SHBG. Using logistic regression models, we found no significant associations between any of the serum T measures and self-employment in either of the samples. To our knowledge, this is the first large-scale study on the relationship between serum T and entrepreneurial behavior. Copyright © 2013 Elsevier Inc. All rights reserved.

Independence May Feel Strange

ERIC Educational Resources Information Center

Meyer, Joerg M.

2017-01-01

Stochastic independence is not an easy notion. Because it is part of the probability structure, it can have some surprising non-properties, which is beneficial for teachers and students to see illustrated. Neither is the relationship to causal independence an easy one.

Biochemical evidence for Ku-independent backup pathways of NHEJ.

PubMed

Wang, Huichen; Perrault, Ange Ronel; Takeda, Yoshihiko; Qin, Wei; Wang, Hongyan; Iliakis, George

2003-09-15

Cells of higher eukaryotes process within minutes double strand breaks (DSBs) in their genome using a non-homologous end joining (NHEJ) apparatus that engages DNA-PKcs, Ku, DNA ligase IV, XRCC4 and other as of yet unidentified factors. Although chemical inhibition, or mutation, in any of these factors delays processing, cells ultimately remove the majority of DNA DSBs using an alternative pathway operating with an order of magnitude slower kinetics. This alternative pathway is active in mutants deficient in genes of the RAD52 epistasis group and frequently joins incorrect ends. We proposed, therefore, that it reflects an alternative form of NHEJ that operates as a backup (B-NHEJ) to the DNA-PK-dependent (D-NHEJ) pathway, rather than homology directed repair of DSBs. The present study investigates the role of Ku in the coordination of these pathways using as a model end joining of restriction endonuclease linearized plasmid DNA in whole cell extracts. Efficient, error-free, end joining observed in such in vitro reactions is strongly inhibited by anti-Ku antibodies. The inhibition requires DNA-PKcs, despite the fact that Ku efficiently binds DNA ends in the presence of antibodies, or in the absence of DNA-PKcs. Strong inhibition of DNA end joining is also mediated by wortmannin, an inhibitor of DNA-PKcs, in the presence but not in the absence of Ku, and this inhibition can be rescued by pre-incubating the reaction with double stranded oligonucleotides. The results are compatible with a role of Ku in directing end joining to a DNA-PK dependent pathway, mediated by efficient end binding and productive interactions with DNA-PKcs. On the other hand, efficient end joining is observed in extracts of cells lacking DNA-PKcs, as well as in Ku-depleted extracts in line with the operation of alternative pathways. Extracts depleted of Ku and DNA-PKcs rejoin blunt ends, as well as homologous ends with 3' or 5' protruding single strands with similar efficiency, but addition of Ku

Biochemical evidence for Ku-independent backup pathways of NHEJ

PubMed Central

Wang, Huichen; Perrault, Ange Ronel; Takeda, Yoshihiko; Qin, Wei; Wang, Hongyan; Iliakis, George

2003-01-01

Cells of higher eukaryotes process within minutes double strand breaks (DSBs) in their genome using a non-homologous end joining (NHEJ) apparatus that engages DNA-PKcs, Ku, DNA ligase IV, XRCC4 and other as of yet unidentified factors. Although chemical inhibition, or mutation, in any of these factors delays processing, cells ultimately remove the majority of DNA DSBs using an alternative pathway operating with an order of magnitude slower kinetics. This alternative pathway is active in mutants deficient in genes of the RAD52 epistasis group and frequently joins incorrect ends. We proposed, therefore, that it reflects an alternative form of NHEJ that operates as a backup (B-NHEJ) to the DNA-PK-dependent (D-NHEJ) pathway, rather than homology directed repair of DSBs. The present study investigates the role of Ku in the coordination of these pathways using as a model end joining of restriction endonuclease linearized plasmid DNA in whole cell extracts. Efficient, error-free, end joining observed in such in vitro reactions is strongly inhibited by anti-Ku antibodies. The inhibition requires DNA-PKcs, despite the fact that Ku efficiently binds DNA ends in the presence of antibodies, or in the absence of DNA-PKcs. Strong inhibition of DNA end joining is also mediated by wortmannin, an inhibitor of DNA-PKcs, in the presence but not in the absence of Ku, and this inhibition can be rescued by pre-incubating the reaction with double stranded oligonucleotides. The results are compatible with a role of Ku in directing end joining to a DNA-PK dependent pathway, mediated by efficient end binding and productive interactions with DNA-PKcs. On the other hand, efficient end joining is observed in extracts of cells lacking DNA-PKcs, as well as in Ku-depleted extracts in line with the operation of alternative pathways. Extracts depleted of Ku and DNA-PKcs rejoin blunt ends, as well as homologous ends with 3′ or 5′ protruding single strands with similar efficiency, but addition of

TRANSIT TIMING VARIATION MEASUREMENTS OF WASP-12b AND QATAR-1b: NO EVIDENCE OF ADDITIONAL PLANETS

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

Collins, Karen A.; Stassun, Keivan G.; Kielkopf, John F.

WASP-12b and Qatar-1b are transiting hot Jupiters for which previous works have suggested the presence of transit timing variations (TTVs) indicative of additional bodies in these systems—an Earth-mass planet in WASP-12 and a brown-dwarf mass object in Qatar-1. Here, we present 23 new WASP-12b and 18 new Qatar-1b complete (or nearly complete) transit observations. We perform global system fits to all of our light curves for each system, as well as RV and stellar spectroscopic parameters from the literature. The global fits provide refined system parameters and uncertainties for each system, including precise transit center times for each transit. Themore » transit model residuals of the combined and five minute binned light curves have an rms of 183 and 255 parts per million (ppm) for WASP-12b and Qatar-1b, respectively. Most of the WASP-12b system parameter values from this work are consistent with values from previous studies, but have ∼40%–50% smaller uncertainties. Most of the Qatar-1b system parameter values and uncertainties from this work are consistent with values recently reported in the literature. We find no convincing evidence for sinusoidal TTVs with a semi-amplitude of more than ∼35 and ∼25 s in the WASP-12b and Qatar-1b systems, respectively.« less

Effectiveness of the Touch Math Technique in Teaching Basic Addition to Children with Autism

ERIC Educational Resources Information Center

Yikmis, Ahmet

2016-01-01

This study aims to reveal whether the touch math technique is effective in teaching basic addition to children with autism. The dependent variable of this study is the children's skills to solve addition problems correctly, whereas teaching with the touch math technique is the independent variable. Among the single-subject research models, a…

Evidence, temperature, and the laws of thermodynamics.

PubMed

Vieland, Veronica J

2014-01-01

A primary purpose of statistical analysis in genetics is the measurement of the strength of evidence for or against hypotheses. As with any type of measurement, a properly calibrated measurement scale is necessary if we want to be able to meaningfully compare degrees of evidence across genetic data sets, across different types of genetic studies and/or across distinct experimental modalities. In previous papers in this journal and elsewhere, my colleagues and I have argued that geneticists ought to care about the scale on which statistical evidence is measured, and we have proposed the Kelvin temperature scale as a template for a context-independent measurement scale for statistical evidence. Moreover, we have claimed that, mathematically speaking, evidence and temperature may be one and the same thing. On first blush, this might seem absurd. Temperature is a property of systems following certain laws of nature (in particular, the 1st and 2nd Law of Thermodynamics) involving very physical quantities (e.g., energy) and processes (e.g., mechanical work). But what do the laws of thermodynamics have to do with statistical systems? Here I address that question. © 2014 S. Karger AG, Basel.

A comparison of factors associated with substance-induced versus independent depressions.

PubMed

Schuckit, Marc A; Smith, Tom L; Danko, George P; Pierson, Juliann; Trim, Ryan; Nurnberger, John I; Kramer, John; Kuperman, Samuel; Bierut, Laura J; Hesselbrock, Victor

2007-11-01

This article expands on the results from a 1997 report from the Collaborative Study on the Genetics of Alcoholism (COGA), using a new phase of the protocol to evaluate the prevalence and characteristics of substance-induced and independent major depressive episodes (MDEs) in a population of alcoholics and nonalcoholics. Data were evaluated from Phase II of the six-center-wide COGA investigation using information gathered beginning in January 1997. Data were generated through face-to-face evaluations using the updated version of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA-II) interview, with distinctions between substanceinduced and independent MDEs based on the chronology of development of full depressive syndromes. The analyses focused on the 2,548 men and women who were divided into 351 individuals who had only an independent MDE (Group 1), 238 subjects who experienced only substance-induced MDEs, and 1,959 individuals with no MDE history. The two MDE groups were similar in age, marital status, and religion; but those with substance-induced depressions (Group 2) were more likely to be original alcoholic probands, be males, be nonwhite, and have less education. They were also more likely to have alcohol, drug, or antisocial personality diagnoses and to report higher maximum drinks. In addition, only Group 2 subjects reported an elevated family history of alcohol diagnoses compared with the nondepressed Group 3. Subjects with independent MDEs were different from the comparison Group 3 regarding the family histories of independent MDEs. However, symptoms during the worst depressive episode were quite similar across Groups 1 and 2. This study corroborates a high rate of substance-induced MDEs among alcoholics, with these disorders explaining about half of the lifetime depressive episodes. The results also support the validity of the distinction between substance-induced and independent depressions regarding external validators of gender

Understanding independence

NASA Astrophysics Data System (ADS)

Annan, James; Hargreaves, Julia

2016-04-01

In order to perform any Bayesian processing of a model ensemble, we need a prior over the ensemble members. In the case of multimodel ensembles such as CMIP, the historical approach of ``model democracy'' (i.e. equal weight for all models in the sample) is no longer credible (if it ever was) due to model duplication and inbreeding. The question of ``model independence'' is central to the question of prior weights. However, although this question has been repeatedly raised, it has not yet been satisfactorily addressed. Here I will discuss the issue of independence and present a theoretical foundation for understanding and analysing the ensemble in this context. I will also present some simple examples showing how these ideas may be applied and developed.

Independent Orbiter Assessment (IOA): Assessment of the data processing system FMEA/CIL

NASA Technical Reports Server (NTRS)

Lowery, H. J.; Haufler, W. A.

1986-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA effort first completed an analysis of the Data Processing System (DPS) hardware, generating draft failure modes and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The IOA results were then compared to the NASA FMEA/CIL baseline with proposed Post 51-L updates included. A resolution of each discrepancy from the comparison is provided through additional analysis as required. The results of that comparison is documented for the Orbiter DPS hardware.

Successional changes in the chicken cecal microbiome during 42 days of growth are independent of organic acid feed additives

USDA-ARS?s Scientific Manuscript database

Poultry remains a major source of foodborne infections in the U.S. and globally. A variety of additives with presumed anti-microbial and/or growth-promoting effects are commonly added to poultry feed, yet the effects of these additives on the ecology of the gastro-intestinal microbial community (th...

The earliest fossil evidence for sexual dimorphism in primates

NASA Technical Reports Server (NTRS)

Krishtalka, Leonard; Stucky, Richard K.; Beard, K. C.

1990-01-01

Recently obtained material of the early Eocene primate Notharctus venticolus, including two partial skulls from a single stratigraphic horizon, provides the geologically earliest evidence of sexual dimorphism in canine size and shape in primates and the only unequivocal evidence for such dimorphism in strepsirhines. By analogy with living platyrrhines, these data suggest that Notharctus venticolus may have lived in polygynous social groups characterized by a relatively high level of intermale competition for mates and other limited resources. The anatomy of the upper incisors and related evidence imply that Notharctus is not as closely related to extant lemuriform primates as has been recently proposed. The early Eocene evidence for canine sexual dimorphism reported here, and its occurrence in a nonanthropoid, indicates that in the order Primates such a condition is either primitive or evolved independently more than once.

Independent cellular effects of cold ischemia and reperfusion: experimental molecular study.

PubMed

Lledó-García, E; Humanes-Sánchez, B; Mojena-Sánchez, M; Rodrígez, J C J; Hernández-Fernández, C; Tejedor-Jorge, A; Fernández, A L

2013-04-01

There is less information available on cell cultures on the exclusive effects of either duration of cold ischemia (CI) or rewarming-reperfusion in the kidney subjected to initial warm ischemia (WI). Therefore, the goals of our work were: (1) to evaluate the consequences on tubular cellular viability of different durations of CI on a kidney after an initial period of WI, and (2) to analyze the additional effect on tubular cell viability of rewarming of the same kidney. Sixteen mini-pig were used. All the animals were performed a right nephrectomy after 45-minute occlusion of the vascular pedicle. The kidneys were then divided into 2 groups (phase 1): cold storage in university of wisconsin (UW) solution for 3 hours (group A, n = 8) at 4°C, or cold storage in UW for 12 hours (group B, n = 8) at 4°C. Four organs of group A and four organs of group B were autotrasplanted (AT) and reperfused for 1 hour (phase 2). Nephrectomy was finally done. Biopsies were taken from all groups to perform cultures of proximal tubule epithelium cells. The biopsies were subjected to studies of cellular morphological viability (contrast phase microscopy [CPM]) and quantitative (confluence cell [CC]) parameters. Phase of pure CI effects (phase 1): Both CC rate and CPM parameters were significantly lower in group B compared with group A, where cell activity reached almost normal results. Phase of CI + AT (phase 2): At produced additional harmful effects in cell cultures compared with those obtained in phase 1, more evident in group B cells. The presence of cold storage followed by rewarming-reperfusion induces independent and cumulative detrimental effects in viability of renal proximal tubule cells. CI periods ≤ 3 hours may ameliorate the injuries secondary to reperfusion in comparison with longer CI periods. Copyright © 2013 Elsevier Inc. All rights reserved.

High anaplastic lymphoma kinase immunohistochemical staining in neuroblastoma and ganglioneuroblastoma is an independent predictor of poor outcome.

PubMed

Duijkers, Floor A M; Gaal, José; Meijerink, Jules P P; Admiraal, Pieter; Pieters, Rob; de Krijger, Ronald R; van Noesel, Max M

2012-03-01

Anaplastic lymphoma kinase (ALK) mutations occur in 3% to 11% of neuroblastoma (NBL) cases and are associated with high ALK levels. However, high ALK levels appear to be a mutation-independent hallmark of NBL. Evidence about the prognostic relevance of ALK mutations and ALK tumor positivity in patients with NBL has been inconclusive. In this study, we investigated the prognostic relevance of ALK positivity by IHC and ALK mutation status by PCR sequencing in 71 NBL, 12 ganglioneuroblastoma (GNBL), and 20 ganglioneuroma samples in a multivariate model. ALK mutations were present in 2 of 72 NBL and 2 of 12 GNBL samples, which all contained many ALK-positive cells (>50%). In addition, half of all NBL samples showed ALK positivity in most (>50%) of tumor cells, whereas half of the GNBL showed staining in <20% of the tumor cells. In most ganglioneuroma samples, a low percentage of tumor cells stained positive for ALK, which mainly involved ganglion cells. Higher percentages of ALK-positive cells in NBL and GNBL patient samples correlated with inferior survival in univariate and multivariate analyses with established prognostic factors, such as stage, age, and MYCN status. In conclusion, ALK positivity by IHC is an independent, poor prognostic factor in patients with GNBL and NBL. ALK IHC is an easy test suitable for future risk stratification in patients with NBL and GNBL. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

The right hemisphere is independent from the left hemisphere in allocating visuospatial attention.

PubMed

Zuanazzi, Arianna; Cattaneo, Luigi

2017-07-28

The capacity to allocate visuospatial attention is traditionally considered right-lateralized according to the effects of unilateral cerebral lesions. Contralateral hemi-spatial neglect occurs much more frequently after lesions of the right hemisphere, which has therefore been dubbed as 'dominant'. This pattern of symptoms is supported by functional models that postulate either independence or reciprocal influences between the two hemispheres. Here we specifically explored the dependency of the right hemisphere (RH) from the left hemisphere (LH) in spatial attention. We capitalized on the well-known effect of online transcranial magnetic stimulation (TMS) on the RH in healthy individuals, consisting in transient neglect-like manifestations in the left hemi-space. We assessed whether prior stimulation of the left posterior parietal cortex with a long-lasting neuromodulatory procedure (transcranial direct current stimulation - tDCS) affected the acute effects of TMS on the right posterior parietal cortex. We performed a within-subjects factorial study with two factors: LH tDCS (sham or real) and RH TMS (sham or real), resulting in a 2×2 design. The effects on spatial attention were examined separately for the two hemi-spaces by means of a modified line-bisection task. The results indicated that TMS over the RH produced a spatial attention deficit in the left hemi-space alone and the behavioural effects of TMS were not modulated by prior stimulation of the LH. Interestingly, additional analyses showed that tDCS over the LH alone produced a deficit in spatial attention to the right hemi-space. We interpret the current results as evidence for a largely independent contribution of each hemisphere to the allocation of visuospatial attention limited to the contralateral hemi-space. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effector-independent motor sequence representations exist in extrinsic and intrinsic reference frames.

PubMed

Wiestler, Tobias; Waters-Metenier, Sheena; Diedrichsen, Jörn

2014-04-02

Many daily activities rely on the ability to produce meaningful sequences of movements. Motor sequences can be learned in an effector-specific fashion (such that benefits of training are restricted to the trained hand) or an effector-independent manner (meaning that learning also facilitates performance with the untrained hand). Effector-independent knowledge can be represented in extrinsic/world-centered or in intrinsic/body-centered coordinates. Here, we used functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis to determine the distribution of intrinsic and extrinsic finger sequence representations across the human neocortex. Participants practiced four sequences with one hand for 4 d, and then performed these sequences during fMRI with both left and right hand. Between hands, these sequences were equivalent in extrinsic or intrinsic space, or were unrelated. In dorsal premotor cortex (PMd), we found that sequence-specific activity patterns correlated higher for extrinsic than for unrelated pairs, providing evidence for an extrinsic sequence representation. In contrast, primary sensory and motor cortices showed effector-independent representations in intrinsic space, with considerable overlap of the two reference frames in caudal PMd. These results suggest that effector-independent representations exist not only in world-centered, but also in body-centered coordinates, and that PMd may be involved in transforming sequential knowledge between the two. Moreover, although effector-independent sequence representations were found bilaterally, they were stronger in the hemisphere contralateral to the trained hand. This indicates that intermanual transfer relies on motor memories that are laid down during training in both hemispheres, but preferentially draws upon sequential knowledge represented in the trained hemisphere.

Effector-Independent Motor Sequence Representations Exist in Extrinsic and Intrinsic Reference Frames

PubMed Central

Wiestler, Tobias; Waters-Metenier, Sheena

2014-01-01

Many daily activities rely on the ability to produce meaningful sequences of movements. Motor sequences can be learned in an effector-specific fashion (such that benefits of training are restricted to the trained hand) or an effector-independent manner (meaning that learning also facilitates performance with the untrained hand). Effector-independent knowledge can be represented in extrinsic/world-centered or in intrinsic/body-centered coordinates. Here, we used functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis to determine the distribution of intrinsic and extrinsic finger sequence representations across the human neocortex. Participants practiced four sequences with one hand for 4 d, and then performed these sequences during fMRI with both left and right hand. Between hands, these sequences were equivalent in extrinsic or intrinsic space, or were unrelated. In dorsal premotor cortex (PMd), we found that sequence-specific activity patterns correlated higher for extrinsic than for unrelated pairs, providing evidence for an extrinsic sequence representation. In contrast, primary sensory and motor cortices showed effector-independent representations in intrinsic space, with considerable overlap of the two reference frames in caudal PMd. These results suggest that effector-independent representations exist not only in world-centered, but also in body-centered coordinates, and that PMd may be involved in transforming sequential knowledge between the two. Moreover, although effector-independent sequence representations were found bilaterally, they were stronger in the hemisphere contralateral to the trained hand. This indicates that intermanual transfer relies on motor memories that are laid down during training in both hemispheres, but preferentially draws upon sequential knowledge represented in the trained hemisphere. PMID:24695723

Evidence-based clinical policy: case report of a reproducible process to encourage understanding and evaluation of evidence.

PubMed

Rikard-Bell, G; Waters, E; Ward, J

2006-07-01

We report within a case study a reproducible process to facilitate the explicit incorporation of evidence by a multidisciplinary group into clinical policy development. To support the decision-making of a multidisciplinary Intersectoral Advisory Group (IAG) convened by the Royal Australasian College of Physicians Health Policy Unit, a systematic review of randomized controlled trials about environmental tobacco smoke and smoking cessation interventions in paediatric settings was first undertaken. As reported in detail here, IAG members were then formally engaged in a transparent and replicable process to understand and interpret the synthesized evidence and to proffer their independent reactions regarding policy, practice and research. Our intention was to ensure that all IAG members were democratically engaged and made aware of the available evidence. As clinical policy must engage stakeholder representatives from diverse backgrounds, a process to equalize understanding of the evidence and 'democratize' judgment about its implications is needed. Future research must then examine the benefits of such explicit steps when guidelines, in turn, are implemented. We hypothesize that changes to future practice will be more likely if processes undertaken to develop guidelines are transparent to clinicians and other target groups.

Are Interactions between cis-Regulatory Variants Evidence for Biological Epistasis or Statistical Artifacts?

PubMed

Fish, Alexandra E; Capra, John A; Bush, William S

2016-10-06

The importance of epistasis-or statistical interactions between genetic variants-to the development of complex disease in humans has been controversial. Genome-wide association studies of statistical interactions influencing human traits have recently become computationally feasible and have identified many putative interactions. However, statistical models used to detect interactions can be confounded, which makes it difficult to be certain that observed statistical interactions are evidence for true molecular epistasis. In this study, we investigate whether there is evidence for epistatic interactions between genetic variants within the cis-regulatory region that influence gene expression after accounting for technical, statistical, and biological confounding factors. We identified 1,119 (FDR = 5%) interactions that appear to regulate gene expression in human lymphoblastoid cell lines, a tightly controlled, largely genetically determined phenotype. Many of these interactions replicated in an independent dataset (90 of 803 tested, Bonferroni threshold). We then performed an exhaustive analysis of both known and novel confounders, including ceiling/floor effects, missing genotype combinations, haplotype effects, single variants tagged through linkage disequilibrium, and population stratification. Every interaction could be explained by at least one of these confounders, and replication in independent datasets did not protect against some confounders. Assuming that the confounding factors provide a more parsimonious explanation for each interaction, we find it unlikely that cis-regulatory interactions contribute strongly to human gene expression, which calls into question the relevance of cis-regulatory interactions for other human phenotypes. We additionally propose several best practices for epistasis testing to protect future studies from confounding. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Achievements and Limitations of Evidence-Based Medicine.

PubMed

Sheridan, Desmond J; Julian, Desmond G

2016-07-12

Evidence-based medicine (EBM) has a long history, but was revived in the early 1990s by a campaign mounted by a movement that took its name. The EBM movement focused attention on the need for greater objectivity in medical decision-making and led to the Cochrane Collaboration, which provides reviews of evidence on the basis of comparative research. Important limitations of EBM's effect on medicine have also emerged. Failure to acknowledge the limitations of clinical trials and systematic reviews has limited their applicability to individual patients' circumstances. An almost exclusive focus on drugs and devices has left vast areas of health care in an evidence vacuum. An overdependence on commissions for its research may have limited its independence in selecting what it investigates. EBM needs to widen its scope beyond drugs and devices to address many areas that often lack evidence at present, notably, health policy, management, and reforms. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Precipitation and Latent Heating Distributions from Satellite Passive Microwave Radiometry. Part II: Evaluation of Estimates Using Independent Data

NASA Technical Reports Server (NTRS)

Yang, Song; Olson, William S.; Wang, Jian-Jian; Bell, Thomas L.; Smith, Eric A.; Kummerow, Christian D.

2006-01-01

Rainfall rate estimates from spaceborne microwave radiometers are generally accepted as reliable by a majority of the atmospheric science community. One of the Tropical Rainfall Measuring Mission (TRMM) facility rain-rate algorithms is based upon passive microwave observations from the TRMM Microwave Imager (TMI). In Part I of this series, improvements of the TMI algorithm that are required to introduce latent heating as an additional algorithm product are described. Here, estimates of surface rain rate, convective proportion, and latent heating are evaluated using independent ground-based estimates and satellite products. Instantaneous, 0.5 deg. -resolution estimates of surface rain rate over ocean from the improved TMI algorithm are well correlated with independent radar estimates (r approx. 0.88 over the Tropics), but bias reduction is the most significant improvement over earlier algorithms. The bias reduction is attributed to the greater breadth of cloud-resolving model simulations that support the improved algorithm and the more consistent and specific convective/stratiform rain separation method utilized. The bias of monthly 2.5 -resolution estimates is similarly reduced, with comparable correlations to radar estimates. Although the amount of independent latent heating data is limited, TMI-estimated latent heating profiles compare favorably with instantaneous estimates based upon dual-Doppler radar observations, and time series of surface rain-rate and heating profiles are generally consistent with those derived from rawinsonde analyses. Still, some biases in profile shape are evident, and these may be resolved with (a) additional contextual information brought to the estimation problem and/or (b) physically consistent and representative databases supporting the algorithm. A model of the random error in instantaneous 0.5 deg. -resolution rain-rate estimates appears to be consistent with the levels of error determined from TMI comparisons with collocated

Precipitation and Latent Heating Distributions from Satellite Passive Microwave Radiometry. Part 2; Evaluation of Estimates Using Independent Data

NASA Technical Reports Server (NTRS)

Yang, Song; Olson, William S.; Wang, Jian-Jian; Bell, Thomas L.; Smith, Eric A.; Kummerow, Christian D.

2004-01-01

Rainfall rate estimates from space-borne k&ents are generally accepted as reliable by a majority of the atmospheric science commu&y. One-of the Tropical Rainfall Measuring Mission (TRh4M) facility rain rate algorithms is based upon passive microwave observations fiom the TRMM Microwave Imager (TMI). Part I of this study describes improvements in the TMI algorithm that are required to introduce cloud latent heating and drying as additional algorithm products. Here, estimates of surface rain rate, convective proportion, and latent heating are evaluated using independent ground-based estimates and satellite products. Instantaneous, OP5resolution estimates of surface rain rate over ocean fiom the improved TMI algorithm are well correlated with independent radar estimates (r approx. 0.88 over the Tropics), but bias reduction is the most significant improvement over forerunning algorithms. The bias reduction is attributed to the greater breadth of cloud-resolving model simulations that support the improved algorithm, and the more consistent and specific convective/stratiform rain separation method utilized. The bias of monthly, 2.5 deg. -resolution estimates is similarly reduced, with comparable correlations to radar estimates. Although the amount of independent latent heating data are limited, TMI estimated latent heating profiles compare favorably with instantaneous estimates based upon dual-Doppler radar observations, and time series of surface rain rate and heating profiles are generally consistent with those derived from rawinsonde analyses. Still, some biases in profile shape are evident, and these may be resolved with: (a) additional contextual information brought to the estimation problem, and/or; (b) physically-consistent and representative databases supporting the algorithm. A model of the random error in instantaneous, 0.5 deg-resolution rain rate estimates appears to be consistent with the levels of error determined from TMI comparisons to collocated radar

46 CFR 535.801 - Independent action.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 9 2010-10-01 2010-10-01 false Independent action. 535.801 Section 535.801 Shipping... Provisions § 535.801 Independent action. (a) Each conference agreement shall specify the independent action... independent action on any rate or service item upon not more than 5 calendar days' notice to the conference...

A Continuum of Renin-Independent Aldosteronism in Normotension

PubMed Central

Baudrand, Rene; Guarda, Francisco J.; Fardella, Carlos; Hundemer, Gregory; Brown, Jenifer; Williams, Gordon; Vaidya, Anand

2017-01-01

Primary aldosteronism (PA) is a severe form of autonomous aldosteronism. Milder forms of autonomous and renin-independent aldosteronism may be common, even in normotension. We characterized aldosterone secretion in 210 normotensives who had suppressed plasma renin activity (PRA<1.0 ng/mL/h), completed an oral sodium suppression test, received an infusion of angiotensin II (AngII), and had measurements of blood pressure (BP) and renal plasma flow (RPF). Continuous associations between urinary aldosterone excretion rate (AER), renin, and potassium handling were investigated. Severe autonomous aldosterone secretion that was consistent with confirmed PA was defined based on accepted criteria of an AER >12 mcg/24h with urinary sodium excretion >200 mmol/24h. Across the population, there were strong and significant associations between higher AER and higher urinary potassium excretion, higher AngII-stimulated aldosterone, and lower PRA, suggesting a continuum of renin-independent aldosteronism and mineralocorticoid receptor activity. Autonomous aldosterone secretion that fulfilled confirmatory criteria for PA was detected in 29 participants (14%). Normotensives with evidence suggestive of confirmed PA had higher 24h urinary AER (20.2±12.2 vs. 6.2±2.9 mcg/24h, P<0.001) as expected, but also higher AngII-stimulated aldosterone (12.4±8.6 vs. 6.6±4.3 ng/dL, P<0.001) and lower 24h urinary sodium-to-potassium excretion (2.69±0.65 vs. 3.69±1.50 mmol/mmol, P=0.001); however, there were no differences in age, aldosterone-to-renin ratio, BP, or RPF between the two groups. These findings indicate a continuum of renin-independent aldosteronism and mineralocorticoid receptor activity in normotension that ranges from subtle to overtly dysregulated and autonomous. Longitudinal studies are needed to determine whether this spectrum of autonomous aldosterone secretion contributes to hypertension and cardiovascular disease. PMID:28289182

Mid-space-independent deformable image registration.

PubMed

Aganj, Iman; Iglesias, Juan Eugenio; Reuter, Martin; Sabuncu, Mert Rory; Fischl, Bruce

2017-05-15

Aligning images in a mid-space is a common approach to ensuring that deformable image registration is symmetric - that it does not depend on the arbitrary ordering of the input images. The results are, however, generally dependent on the mathematical definition of the mid-space. In particular, the set of possible solutions is typically restricted by the constraints that are enforced on the transformations to prevent the mid-space from drifting too far from the native image spaces. The use of an implicit atlas has been proposed as an approach to mid-space image registration. In this work, we show that when the atlas is aligned to each image in the native image space, the data term of implicit-atlas-based deformable registration is inherently independent of the mid-space. In addition, we show that the regularization term can be reformulated independently of the mid-space as well. We derive a new symmetric cost function that only depends on the transformation morphing the images to each other, rather than to the atlas. This eliminates the need for anti-drift constraints, thereby expanding the space of allowable deformations. We provide an implementation scheme for the proposed framework, and validate it through diffeomorphic registration experiments on brain magnetic resonance images. Copyright © 2017 Elsevier Inc. All rights reserved.

Maintaining Independence.

ERIC Educational Resources Information Center

Upah-Bant, Marilyn

1978-01-01

Describes the over-all business and production operation of the "Daily Illini" at the University of Illinois to show how this college publication has assumed the burdens and responsibilities of true independence. (GW)

Accounting for Independent Schools.

ERIC Educational Resources Information Center

Sonenstein, Burton

The diversity of independent schools in size, function, and mode of operation has resulted in a considerable variety of accounting principles and practices. This lack of uniformity has tended to make understanding, evaluation, and comparison of independent schools' financial statements a difficult and sometimes impossible task. This manual has…

Finding and applying evidence during clinical rounds: the "evidence cart".

PubMed

Sackett, D L; Straus, S E

1998-10-21

Physicians need easy access to evidence for clinical decisions while they care for patients but, to our knowledge, no investigators have assessed use of evidence during rounds with house staff. To determine if it was feasible to find and apply evidence during clinical rounds, using an "evidence cart" that contains multiple sources of evidence and the means for projecting and printing them. Descriptive feasibility study of use of evidence during 1 month (April 1997) and anonymous questionnaire (May 1997). General medicine inpatient service. Medical students, house staff, fellows, and attending consultant. Evidence cart that included 2 secondary sources developed by the department (critically appraised topics [CATs] and Redbook), Best Evidence, JAMA Rational Clinical Examination series, the Cochrane Library, MEDLINE, a physical examination textbook, a radiology anatomy textbook, and a Simulscope, which allows several people to listen simultaneously to the same signs on physical examination. Number of times sources were used, type of sources searched and success of searches, time needed to search, and whether the search affected patient care. The evidence cart was used 98 times, but could not be taken on bedside rounds because of its bulk; hard copies of several sources were taken instead. When the evidence cart was used during team rounds and student rounds, some sources could be accessed quickly enough (10.2-25.4 seconds) to be practical on our service. Of 98 searches, 79 (81%) sought evidence that could affect diagnostic and/or treatment decisions. Seventy-one (90%) of 79 searches regarding patient management were successful, and when assessed from the perspective of the most junior team members responsible for each patient's evaluation and management, 37 (52%) of the 71 successful searches confirmed their current or tentative diagnostic or treatment plans, 18 (25%) led to a new diagnostic skill, an additional test, or a new management decision, and 16 (23

Consistency between direct and indirect trial evidence: is direct evidence always more reliable?

PubMed

Madan, Jason; Stevenson, Matt D; Cooper, Katy L; Ades, A E; Whyte, Sophie; Akehurst, Ron

2011-01-01

To present a case study involving the reduction in incidence of febrile neutropenia (FN) after chemotherapy with granulocyte colony-stimulating factors (G-CSFs), illustrating difficulties that may arise when following the common preference for direct evidence over indirect evidence. Evidence of the efficacy of treatments was identified from two previous systematic reviews. We used Bayesian evidence synthesis to estimate relative treatment effects based on direct evidence, indirect evidence, and both pooled together. We checked for inconsistency between direct and indirect evidence and explored the role of one specific trial using cross-validation. A subsequent review identified further studies not available at the time of the original analysis. We repeated the analyses on the enlarged evidence base. We found substantial inconsistency in the original evidence base. The median odds ratio of FN for primary pegfilgrastim versus no primary G-CSF was 0.06 (95% credible interval: 0.02-0.19) based on direct evidence, but 0.27 (95% credible interval: 0.13-0.53) based on indirect evidence (P value for consistency hypothesis 0.027). The additional trials were consistent with the earlier indirect, rather than the direct, evidence, and there was no inconsistency between direct and indirect estimates in the updated evidence. The earlier inconsistency was due to one trial comparing primary pegfilgrastim with no primary G-CSF. Predictive cross-validation showed that this study was inconsistent with the evidence as a whole and with other trials making this comparison. Both the Cochrane Handbook and the NICE Methods Guide express a preference for direct evidence. A more robust strategy, which is in line with the accepted principles of evidence synthesis, would be to combine all relevant and appropriate information, whether direct or indirect. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Modulation of additive and interactive effects in lexical decision by trial history.

PubMed

Masson, Michael E J; Kliegl, Reinhold

2013-05-01

Additive and interactive effects of word frequency, stimulus quality, and semantic priming have been used to test theoretical claims about the cognitive architecture of word-reading processes. Additive effects among these factors have been taken as evidence for discrete-stage models of word reading. We present evidence from linear mixed-model analyses applied to 2 lexical decision experiments indicating that apparent additive effects can be the product of aggregating over- and underadditive interaction effects that are modulated by recent trial history, particularly the lexical status and stimulus quality of the previous trial's target. Even a simple practice effect expressed as improved response speed across trials was powerfully modulated by the nature of the previous target item. These results suggest that additivity and interaction between factors may reflect trial-to-trial variation in stimulus representations and decision processes rather than fundamental differences in processing architecture.

Evidence-Based Psychotherapy: Advantages and Challenges.

PubMed

Cook, Sarah C; Schwartz, Ann C; Kaslow, Nadine J

2017-07-01

Evidence-based psychotherapies have been shown to be efficacious and cost-effective for a wide range of psychiatric conditions. Psychiatric disorders are prevalent worldwide and associated with high rates of disease burden, as well as elevated rates of co-occurrence with medical disorders, which has led to an increased focus on the need for evidence-based psychotherapies. This chapter focuses on the current state of evidence-based psychotherapy. The strengths and challenges of evidence-based psychotherapy are discussed, as well as misperceptions regarding the approach that may discourage and limit its use. In addition, we review various factors associated with the optimal implementation and application of evidence-based psychotherapies. Lastly, suggestions are provided on ways to advance the evidence-based psychotherapy movement to become truly integrated into practice.

Ranking and averaging independent component analysis by reproducibility (RAICAR).

PubMed

Yang, Zhi; LaConte, Stephen; Weng, Xuchu; Hu, Xiaoping

2008-06-01

Independent component analysis (ICA) is a data-driven approach that has exhibited great utility for functional magnetic resonance imaging (fMRI). Standard ICA implementations, however, do not provide the number and relative importance of the resulting components. In addition, ICA algorithms utilizing gradient-based optimization give decompositions that are dependent on initialization values, which can lead to dramatically different results. In this work, a new method, RAICAR (Ranking and Averaging Independent Component Analysis by Reproducibility), is introduced to address these issues for spatial ICA applied to fMRI. RAICAR utilizes repeated ICA realizations and relies on the reproducibility between them to rank and select components. Different realizations are aligned based on correlations, leading to aligned components. Each component is ranked and thresholded based on between-realization correlations. Furthermore, different realizations of each aligned component are selectively averaged to generate the final estimate of the given component. Reliability and accuracy of this method are demonstrated with both simulated and experimental fMRI data. Copyright 2007 Wiley-Liss, Inc.

Evidence in Support of the Independent Channel Model Describing the Sensorimotor Control of Human Stance Using a Humanoid Robot

PubMed Central

Pasma, Jantsje H.; Assländer, Lorenz; van Kordelaar, Joost; de Kam, Digna; Mergner, Thomas; Schouten, Alfred C.

2018-01-01

The Independent Channel (IC) model is a commonly used linear balance control model in the frequency domain to analyze human balance control using system identification and parameter estimation. The IC model is a rudimentary and noise-free description of balance behavior in the frequency domain, where a stable model representation is not guaranteed. In this study, we conducted firstly time-domain simulations with added noise, and secondly robot experiments by implementing the IC model in a real-world robot (PostuRob II) to test the validity and stability of the model in the time domain and for real world situations. Balance behavior of seven healthy participants was measured during upright stance by applying pseudorandom continuous support surface rotations. System identification and parameter estimation were used to describe the balance behavior with the IC model in the frequency domain. The IC model with the estimated parameters from human experiments was implemented in Simulink for computer simulations including noise in the time domain and robot experiments using the humanoid robot PostuRob II. Again, system identification and parameter estimation were used to describe the simulated balance behavior. Time series, Frequency Response Functions, and estimated parameters from human experiments, computer simulations, and robot experiments were compared with each other. The computer simulations showed similar balance behavior and estimated control parameters compared to the human experiments, in the time and frequency domain. Also, the IC model was able to control the humanoid robot by keeping it upright, but showed small differences compared to the human experiments in the time and frequency domain, especially at high frequencies. We conclude that the IC model, a descriptive model in the frequency domain, can imitate human balance behavior also in the time domain, both in computer simulations with added noise and real world situations with a humanoid robot. This

Evidence in Support of the Independent Channel Model Describing the Sensorimotor Control of Human Stance Using a Humanoid Robot.

PubMed

Pasma, Jantsje H; Assländer, Lorenz; van Kordelaar, Joost; de Kam, Digna; Mergner, Thomas; Schouten, Alfred C

2018-01-01

The Independent Channel (IC) model is a commonly used linear balance control model in the frequency domain to analyze human balance control using system identification and parameter estimation. The IC model is a rudimentary and noise-free description of balance behavior in the frequency domain, where a stable model representation is not guaranteed. In this study, we conducted firstly time-domain simulations with added noise, and secondly robot experiments by implementing the IC model in a real-world robot (PostuRob II) to test the validity and stability of the model in the time domain and for real world situations. Balance behavior of seven healthy participants was measured during upright stance by applying pseudorandom continuous support surface rotations. System identification and parameter estimation were used to describe the balance behavior with the IC model in the frequency domain. The IC model with the estimated parameters from human experiments was implemented in Simulink for computer simulations including noise in the time domain and robot experiments using the humanoid robot PostuRob II. Again, system identification and parameter estimation were used to describe the simulated balance behavior. Time series, Frequency Response Functions, and estimated parameters from human experiments, computer simulations, and robot experiments were compared with each other. The computer simulations showed similar balance behavior and estimated control parameters compared to the human experiments, in the time and frequency domain. Also, the IC model was able to control the humanoid robot by keeping it upright, but showed small differences compared to the human experiments in the time and frequency domain, especially at high frequencies. We conclude that the IC model, a descriptive model in the frequency domain, can imitate human balance behavior also in the time domain, both in computer simulations with added noise and real world situations with a humanoid robot. This

Bacillus anthracis lethal toxin induces TNF-α–independent hypoxia-mediated toxicity in mice

PubMed Central

Moayeri, Mahtab; Haines, Diana; Young, Howard A.; Leppla, Stephen H.

2003-01-01

Bacillus anthracis lethal toxin (LT) is the major virulence factor of anthrax and reproduces most of the laboratory manifestations of the disease in animals. We studied LT toxicity in BALB/cJ and C57BL/6J mice. BALB/cJ mice became terminally ill earlier and with higher frequency than C57BL/6J mice. Timed histopathological analysis identified bone marrow, spleen, and liver as major affected organs in both mouse strains. LT induced extensive hypoxia. Crisis was due to extensive liver necrosis accompanied by pleural edema. There was no evidence of disseminated intravascular coagulation or renal dysfunction. Instead, analyses revealed hepatic dysfunction, hypoalbuminemia, and vascular/oxygenation insufficiency. Of 50 cytokines analyzed, BALB/cJ mice showed rapid but transitory increases in specific factors including KC, MCP-1/JE, IL-6, MIP-2, G-CSF, GM-CSF, eotaxin, FasL, and IL-1β. No changes in TNF-α occurred. The C57BL/6J mice did not mount a similar cytokine response. These factors were not induced in vitro by LT treatment of toxin-sensitive macrophages. The evidence presented shows that LT kills mice through a TNF-α–independent, FasL-independent, noninflammatory mechanism that involves hypoxic tissue injury but does not require macrophage sensitivity to toxin. PMID:12952916

Making the Long Tail Visible: Social Networking Sites and Independent Music Discovery

ERIC Educational Resources Information Center

Gaffney, Michael; Rafferty, Pauline

2009-01-01

Purpose: The purpose of this paper is to investigate users' knowledge and use of social networking sites and folksonomies to discover if social tagging and folksonomies, within the area of independent music, aid in its information retrieval and discovery. The sites examined in this project are MySpace, Lastfm, Pandora and Allmusic. In addition,…

Independent Molecular Basis of Convergent Highland Adaptation in Maize

PubMed Central

Takuno, Shohei; Ralph, Peter; Swarts, Kelly; Elshire, Rob J.; Glaubitz, Jeffrey C.; Buckler, Edward S.; Hufford, Matthew B.; Ross-Ibarra, Jeffrey

2015-01-01

Convergent evolution is the independent evolution of similar traits in different species or lineages of the same species; this often is a result of adaptation to similar environments, a process referred to as convergent adaptation. We investigate here the molecular basis of convergent adaptation in maize to highland climates in Mesoamerica and South America, using genome-wide SNP data. Taking advantage of archaeological data on the arrival of maize to the highlands, we infer demographic models for both populations, identifying evidence of a strong bottleneck and rapid expansion in South America. We use these models to then identify loci showing an excess of differentiation as a means of identifying putative targets of natural selection and compare our results to expectations from recently developed theory on convergent adaptation. Consistent with predictions across a wide parameter space, we see limited evidence for convergent evolution at the nucleotide level in spite of strong similarities in overall phenotypes. Instead, we show that selection appears to have predominantly acted on standing genetic variation and that introgression from wild teosinte populations appears to have played a role in highland adaptation in Mexican maize. PMID:26078279

Novel Active Learning Experiences for Students to Identify Barriers to Independent Living for People with Disabilities.

PubMed

McArthur, Polly; Burch, Lillian; Moore, Katherine; Hodges, Mary Sue

2016-07-01

This article describes interactive learning about independent living for people with disabilities and features the partnership of the College of Nursing and a Center for Independent Living (CIL). Using qualitative descriptive approach, students' written reflections were analyzed. Through "Xtreme Challenge," 82 undergraduate nursing students participated in aspects of independent living as well as identifying barriers. Students were engaged and learned to consider the person before the disability. Moreover, students valued the activity leaders' openness, which facilitated understanding the point of view of a person with disability. The value of partnership was evident as it allowed students to participate in active learning, which led to growth in the affective domain. Students became aware of potential education resources through the CIL. This article will guide educators in designing experiences that teach nursing care at the individual, family, and community level for people living with disabilities. © 2015 Association of Rehabilitation Nurses.

Phosphate Additive Avoidance in Chronic Kidney Disease.

PubMed

St-Jules, David E; Goldfarb, David S; Pompeii, Mary Lou; Sevick, Mary Ann

2017-05-01

IN BRIEF Dietary guidelines for patients with diabetes extend beyond glycemic management to include recommendations for mitigating chronic disease risk. This review summarizes the literature suggesting that excess dietary phosphorus intake may increase the risk of skeletal and cardiovascular disease in patients who are in the early stages of chronic kidney disease (CKD) despite having normal serum phosphorus concentrations. It explores strategies for limiting dietary phosphorus, emphasizing that food additives, as a major source of highly bioavailable dietary phosphorus, may be a suitable target. Although the evidence for restricting phosphorus-based food additives in early CKD is limited, diabetes clinicians should monitor ongoing research aimed at assessing its efficacy.

Phosphate Additive Avoidance in Chronic Kidney Disease

PubMed Central

Goldfarb, David S.; Pompeii, Mary Lou; Sevick, Mary Ann

2017-01-01

IN BRIEF Dietary guidelines for patients with diabetes extend beyond glycemic management to include recommendations for mitigating chronic disease risk. This review summarizes the literature suggesting that excess dietary phosphorus intake may increase the risk of skeletal and cardiovascular disease in patients who are in the early stages of chronic kidney disease (CKD) despite having normal serum phosphorus concentrations. It explores strategies for limiting dietary phosphorus, emphasizing that food additives, as a major source of highly bioavailable dietary phosphorus, may be a suitable target. Although the evidence for restricting phosphorus-based food additives in early CKD is limited, diabetes clinicians should monitor ongoing research aimed at assessing its efficacy. PMID:28588376

Strengthening the framework for independence of science in policymaking

NASA Astrophysics Data System (ADS)

Rosenberg, A.; Phartiyal, P.; Halpern, M.; Goldman, G. T.; Reed, G.

2016-12-01

The "independence" of scientific advice—shorthand for the safeguards that are needed to ensure that scientific evidence that informs policy proposals stems from a valid and credible scientific process—is crucial to better policy decisions and public faith in public policy decisions. To the public, and often policy-makers, the process of developing, refereeing, and synthesizing science is often opaque, confusing, and underappreciated. At the same time, calls for disclosure of real or perceived conflicts of interest and for greater public access to scientific information and data are increasing. Further, vested interests routinely produce their own analyses, which often do not meet acceptable standards, to justify their own ends or a particular pre-determined policy position for economic, political, ideological, or other gains. These are not speculative concerns. For example, conflict of interest disclosure is often incomplete and inconsistently enforced. Peer review, even in the academic community, has been compromised or circumvented in too many cases. Scientific misconduct and research integrity in several fields have become high-profile scandals. Scientific integrity policies in government agencies are not fully implemented. A decline in public funding of research makes private-public partnerships more commonplace, and sometimes, those partnerships allow funders to unduly influence faculty appointment, curricula, and research. In this complicated landscape, a coherent, publicly credible and acceptable framework to assure that scientific advice is independent is sorely needed. Such a framework must incorporate best practices such as peer review; disclosure of conflicts; public availability of research findings, methodology and data; reproducibility of results; scientific freedom to publish; and deterrents against scientific misconduct. The framework would be broadly applicable across many technical fields and sectors. Here we delve into each of these elements

Soil microbial communities influence seedling growth of a rare conifer independent of plant-soil feedback.

PubMed

Rigg, Jessica L; Offord, Cathy A; Singh, Brajesh K; Anderson, Ian; Clarke, Steve; Powell, Jeff R

2016-12-01

Plant-soil feedback, the reciprocal relationship between a plant and its associated microbial communities, has been proposed to be an important driver of plant populations and community dynamics. While rarely considered, understanding how plant-soil feedback contributes to plant rarity may have implications for conservation and management of rare species. Wollemi pine (Wollemia nobilis) is a critically endangered species, of which fewer than 100 trees are known to exist in the wild. Seedling survival within the first year after germination and subsequent recruitment of Wollemi pine is limited in the wild. We used a plant-soil feedback approach to investigate the functional effect of species-specific differences previously observed in the microbial communities underneath adult Wollemi pine and a neighboring species, coachwood (Ceratopetalum apetalum), and also whether additional variation in microbial communities in the wild could impact seedling growth. There was no evidence for seedling growth being affected by tree species associated with soil inocula, suggesting that plant-soil feedbacks are not limiting recruitment in the natural population. However, there was evidence of fungal, but not bacterial, community variation impacting seedling growth independently of plant-soil feedbacks. Chemical (pH) and physical (porosity) soil characteristics were identified as potential drivers of the functional outcomes of these fungal communities. The empirical approach described here may provide opportunities to identify the importance of soil microbes to conservation efforts targeting other rare plant species and is also relevant to understanding the importance of soil microbes and plant-soil feedbacks for plant community dynamics more broadly. © 2016 by the Ecological Society of America.

Garlic-derived S-allylmercaptocysteine is a novel in vivo antimetastatic agent for androgen-independent prostate cancer.

PubMed

Howard, Edward W; Ling, Ming-Tat; Chua, Chee Wai; Cheung, Hiu Wing; Wang, Xianghong; Wong, Yong Chuan

2007-03-15

There is epidemiologic evidence that high garlic consumption decreases the incidence of prostate cancer, and compounds isolated from garlic have been shown to have cancer-preventive and tumor-suppressive effects. Recent in vitro studies in our laboratory have shown that garlic-derived organosulfur compound S-allylmercaptocysteine suppresses invasion and cell motility of androgen-independent prostate cancer cells via the up-regulation of cell-adhesion molecule E-cadherin. S-allylmercaptocysteine is therefore a potential antimetastatic drug with broad clinical applications that we tested in vivo for the first time in this study. We used a newly established fluorescent orthotopic androgen-independent prostate cancer mouse model to assess the ability of S-allylmercaptocysteine to inhibit tumor growth and dissemination. We showed that oral S-allylmercaptocysteine not only inhibited the growth of primary tumors by up to 71% (P < 0.001) but also reduced the number of lung and adrenal metastases by as much as 85.5% (P = 0.001) without causing notable toxicity. This metastatic suppression was accompanied by a 91% reduction of viable circulating tumor cells (P = 0.041), suggesting that S-allylmercaptocysteine prevents dissemination by decreasing tumor cell intravasation. Our results provide in vivo evidence supporting the potential use of S-allylmercaptocysteine as an E-cadherin up-regulating antimetastatic agent for the treatment of androgen-independent prostate cancer. This is the first report of the in vivo antimetastatic properties of garlic, which may also apply to other cancer types.

An adenosine triphosphate-independent proteasome activator contributes to the virulence of Mycobacterium tuberculosis

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

Jastrab, Jordan B.; Wang, Tong; Murphy, J. Patrick

Mycobacterium tuberculosis encodes a proteasome that is highly similar to eukaryotic proteasomes and is required to cause lethal infections in animals. The only pathway known to target proteins for proteasomal degradation in bacteria is pupylation, which is functionally analogous to eukaryotic ubiquitylation. However, evidence suggests that the M. tuberculosis proteasome contributes to pupylation-independent pathways as well. To identify new proteasome cofactors that might contribute to such pathways, we isolated proteins that bound to proteasomes overproduced in M. tuberculosis and found a previously uncharacterized protein, Rv3780, which formed rings and capped M. tuberculosis proteasome core particles. Rv3780 enhanced peptide and proteinmore » degradation by proteasomes in an adenosine triphosphate (ATP)-independent manner. We identified putative Rv3780-dependent proteasome substrates and found that Rv3780 promoted robust degradation of the heat shock protein repressor, HspR. Importantly, an M. tuberculosis Rv3780 mutant had a general growth defect, was sensitive to heat stress, and was attenuated for growth in mice. Collectively, these data demonstrate that ATP-independent proteasome activators are not confined to eukaryotes and can contribute to the virulence of one the world’s most devastating pathogens.« less

An adenosine triphosphate-independent proteasome activator contributes to the virulence of Mycobacterium tuberculosis

DOE PAGES

Jastrab, Jordan B.; Wang, Tong; Murphy, J. Patrick; ...

2015-03-23

Mycobacterium tuberculosis encodes a proteasome that is highly similar to eukaryotic proteasomes and is required to cause lethal infections in animals. The only pathway known to target proteins for proteasomal degradation in bacteria is pupylation, which is functionally analogous to eukaryotic ubiquitylation. However, evidence suggests that the M. tuberculosis proteasome contributes to pupylation-independent pathways as well. To identify new proteasome cofactors that might contribute to such pathways, we isolated proteins that bound to proteasomes overproduced in M. tuberculosis and found a previously uncharacterized protein, Rv3780, which formed rings and capped M. tuberculosis proteasome core particles. Rv3780 enhanced peptide and proteinmore » degradation by proteasomes in an adenosine triphosphate (ATP)-independent manner. We identified putative Rv3780-dependent proteasome substrates and found that Rv3780 promoted robust degradation of the heat shock protein repressor, HspR. Importantly, an M. tuberculosis Rv3780 mutant had a general growth defect, was sensitive to heat stress, and was attenuated for growth in mice. Collectively, these data demonstrate that ATP-independent proteasome activators are not confined to eukaryotes and can contribute to the virulence of one the world’s most devastating pathogens.« less

Independent extended and supplementary nurse prescribing practice in the UK: a national questionnaire survey.

PubMed

Courtenay, Molly; Carey, Nicola; Burke, Joanna

2007-09-01

Nurses are able to prescribe independently from a list of nearly 250 prescription only medicines for a range of over 100 medical conditions or, from the whole British National Formulary as a supplementary prescriber. There is some evidence available on the prescribing practices of district nurses and health visitors and early independent extended prescribers. Little or no attention has focussed on supplementary nurse prescribing. To provide an overview of the prescribing practices of independent extended/supplementary nurse prescribers and the factors that facilitate or inhibit prescribing. National questionnaire survey. United Kingdom. A convenience sample of 868 qualified independent extended/supplementary nurse prescribers self-completed a written questionnaire. A total of 756 (87%) used independent extended prescribing; 304 (35%) used supplementary prescribing to treat a range of chronic conditions (including asthma, diabetes and hypertension); 710 (82%) nurses worked in primary care. Nurses in general practice reported the largest number of reasons preventing prescribing. Reasons included the inability to computer generate prescriptions and to implement the Clinical Management Plan. Nurses in primary care reported more continuing professional development needs. These needs included update on prescribing policy and the treatment management of conditions. A total of 277 (32%) nurses were unable to access continuing professional development. Independent extended/supplementary nurse prescribers work predominantly in primary care and do prescribe medicines. These nurses are highly qualified and have many years clinical experience. Supplementary prescribing is used by a minority of nurses. Implementing the Clinical Management Plan is a barrier preventing the use of this mode of prescribing. The continuing professional development needs of independent extended/supplementary nurse prescribers are frequently unmet. It will become increasingly important that these needs

Are sleep and depression independent or overlapping risk factors for cardiometabolic disease?

PubMed

Mezick, Elizabeth J; Hall, Martica; Matthews, Karen A

2011-02-01

Sleep duration, sleep continuity, and depression are associated with cardiovascular disease and metabolic disorders. Despite the well-established relationship between sleep and depression, few studies examine these characteristics simultaneously in the development of cardiometabolic disease. Here, we review available studies that include measures of both sleep and depression in relation to cardiometabolic outcomes (cardiovascular disease, diabetes, and the metabolic syndrome). In general, data show that independent of depression, sleep continuity is a risk factor for cardiovascular disease, and short or long sleep duration is a risk factor for diabetes and the metabolic syndrome. Results for associations between sleep duration and cardiovascular disease, and associations between sleep continuity and metabolic disease, are more mixed. Regarding depression, there is preliminary evidence that depression increases risk for cardiovascular disease, independent of sleep continuity. However, there are insufficient data to address whether relationships between depression and cardiovascular and metabolic disease are independent of sleep duration. A number of biobehavioral mechanisms, including inflammation, hypothalamic and sympathetic dysregulation, and obesity and health behaviors, may account for the relationships among sleep, depression, and cardiometabolic disease. After summarizing these mechanisms, we discuss limitations of the extant literature and suggest directions for future research. © 2010 Elsevier Ltd. All rights reserved.

New addition curing polyimides

NASA Technical Reports Server (NTRS)

Frimer, Aryeh A.; Cavano, Paul

1991-01-01

In an attempt to improve the thermal-oxidative stability (TOS) of PMR-type polymers, the use of 1,4-phenylenebis (phenylmaleic anhydride) PPMA, was evaluated. Two series of nadic end-capped addition curing polyimides were prepared by imidizing PPMA with either 4,4'-methylene dianiline or p-phenylenediamine. The first resulted in improved solubility and increased resin flow while the latter yielded a compression molded neat resin sample with a T(sub g) of 408 C, close to 70 C higher than PME-15. The performance of these materials in long term weight loss studies was below that of PMR-15, independent of post-cure conditions. These results can be rationalized in terms of the thermal lability of the pendant phenyl groups and the incomplete imidization of the sterically congested PPMA. The preparation of model compounds as well as future research directions are discussed.

30 CFR 45.4 - Independent contractor register.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Independent contractor register. 45.4 Section... ADMINISTRATIVE REQUIREMENTS INDEPENDENT CONTRACTORS § 45.4 Independent contractor register. (a) Each independent contractor shall provide the production-operator in writing the following information: (1) The independent...

Exogenous attentional capture by subliminal abrupt-onset cues: evidence from contrast-polarity independent cueing effects.

PubMed

Fuchs, Isabella; Theeuwes, Jan; Ansorge, Ulrich

2013-08-01

In the present study, we tested whether subliminal abrupt-onset cues capture attention in a bottom-up or top-down controlled manner. For our tests, we varied the searched-for target-contrast polarity (i.e., dark or light targets against a gray background) over four experiments. In line with the bottom-up hypothesis, our results indicate that subliminal-onset cues capture attention independently of the searched-for target-contrast polarity (Experiment 1), and this effect is not stronger for targets that matched the searched-for target-contrast polarity (Experiment 2). In fact, even to-be-ignored cues associated with a no-go response captured attention in a salience-driven way (Experiment 3). For supraliminal cues, we found attentional capture only by cues with a matching contrast polarity, reflecting contingent capture (Experiment 4). The results point toward a specific role of subliminal abrupt onsets for attentional capture. 2013 APA, all rights reserved

The independent association between diet quality and body composition.

PubMed

Drenowatz, Clemens; Shook, Robin P; Hand, Gregory A; Hébert, James R; Blair, Steven N

2014-05-12

Excess body weight is associated with an imbalance between energy expenditure and dietary intake but evidence on the association between diet quality and body composition remains equivocal. Rather than relying on differences in diet quality between overweight/obese and normal weight adults, this study examined the association between the Healthy Eating Index 2010 (HEI-2010) and body fatness on a continuous scale, independent of physical activity (PA). Further the association between components of the HEI-2010 and risk for overweight/obesity was explored. 407 adults (27.6 ± 3.7 years) provided at least two 24-hour diet recalls over a period of 14 days, which were used to calculate the HEI-2010. Percent body fat (BF) was assessed via dual X-ray absorptiometry and PA was determined via a multi-sensor device, worn over a period of 10 days. PA was a stronger contributor to the variability in BF than the HEI-2010 and the association between HEI-2010 and BF was significant only in men. Particularly a high consumption of protein, sodium and empty calories increased the risk for overweight/obesity. Adherence to dietary guidelines positively affects body fatness in men, independent of PA. In contrast to current dietary recommendations, the risk for overweight/obesity was increased with a higher protein intake.

Characterization of Puma-Dependent and Puma-Independent Neuronal Cell Death Pathways following Prolonged Proteasomal Inhibition▿

PubMed Central

Tuffy, Liam P.; Concannon, Caoimhín G.; D'Orsi, Beatrice; King, Matthew A.; Woods, Ina; Huber, Heinrich J.; Ward, Manus W.; Prehn, Jochen H. M.

2010-01-01

Proteasomal stress and the accumulation of polyubiquitinated proteins are key features of numerous neurodegenerative disorders. Previously we demonstrated that stabilization of p53 and activation of its target gene, puma (p53-upregulated mediator of apoptosis), mediated proteasome inhibitor-induced apoptosis in cancer cells. Here we demonstrated that Puma also contributed to proteasome inhibitor-induced apoptosis in mouse neocortical neurons. Although protection afforded by puma gene deletion was incomplete, we found little evidence indicating contributions from other proapoptotic BH3-only proteins. Attenuation of bax expression did not further reduce Puma-independent apoptosis, suggesting that pathways other than the mitochondrial apoptosis pathway were activated. Real-time imaging experiments in wild-type and puma-deficient neurons using a fluorescence resonance energy transfer (FRET)-based caspase sensor confirmed the involvement of a second cell death pathway characterized by caspase activation prior to mitochondrial permeabilization and, more prominently, a third, caspase-independent and Puma-independent pathway characterized by rapid cell shrinkage and nuclear condensation. This pathway involved lysosomal permeabilization in the absence of autophagy activation and was sensitive to cathepsin but not autophagy inhibition. Our data demonstrate that proteasomal stress activates distinct cell death pathways in neurons, leading to both caspase-dependent and caspase-independent apoptosis, and demonstrate independent roles for Puma and lysosomal permeabilization in this model. PMID:20921277

Multiscale Analysis of Independent Alzheimer's Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus.

PubMed

Readhead, Ben; Haure-Mirande, Jean-Vianney; Funk, Cory C; Richards, Matthew A; Shannon, Paul; Haroutunian, Vahram; Sano, Mary; Liang, Winnie S; Beckmann, Noam D; Price, Nathan D; Reiman, Eric M; Schadt, Eric E; Ehrlich, Michelle E; Gandy, Sam; Dudley, Joel T

2018-06-21

Investigators have long suspected that pathogenic microbes might contribute to the onset and progression of Alzheimer's disease (AD) although definitive evidence has not been presented. Whether such findings represent a causal contribution, or reflect opportunistic passengers of neurodegeneration, is also difficult to resolve. We constructed multiscale networks of the late-onset AD-associated virome, integrating genomic, transcriptomic, proteomic, and histopathological data across four brain regions from human post-mortem tissue. We observed increased human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV-7) from subjects with AD compared with controls. These results were replicated in two additional, independent and geographically dispersed cohorts. We observed regulatory relationships linking viral abundance and modulators of APP metabolism, including induction of APBB2, APPBP2, BIN1, BACE1, CLU, PICALM, and PSEN1 by HHV-6A. This study elucidates networks linking molecular, clinical, and neuropathological features with viral activity and is consistent with viral activity constituting a general feature of AD. Copyright © 2018 Elsevier Inc. All rights reserved.

Polarization-independent electromagnetically induced transparency-like metasurface

NASA Astrophysics Data System (ADS)

Jia, Xiuli; Wang, Xiaoou

2018-01-01

A classical electromagnetically induced transparency-like (EIT-like) metasurface is numerically simulated. This metasurface is composed of two identical and orthogonal double-end semitoroidals (DESTs) metal resonators. Under the excitation of the normal incidence waves, each of the two DESTs structure exhibits electromagnetic dipole responses at different frequencies, which leads to the polarization-independent EIT-like effect. The features of the EIT-like effect are qualitatively analyzed based on the surface current and magnetic field distribution. In addition, the large index is extracted to verify the slow-light property within the transmission window. The EIT-like metasurface structure with the above-mentioned characteristics may have potential applications in some areas, such as sensing, slow light, and filtering devices.

New French Coverage with Evidence Development for Innovative Medical Devices: Improvements and Unresolved Issues.

PubMed

Martelli, Nicolas; van den Brink, Hélène; Borget, Isabelle

2016-01-01

We describe here recent modifications to the French Coverage with Evidence Development (CED) scheme for innovative medical devices. CED can be defined as temporary coverage for a novel health product during collection of the additional evidence required to determine whether definitive coverage is possible. The principle refinements to the scheme include a more precise definition of what may be considered an innovative product, the possibility for device manufacturers to request CED either independently or in partnership with hospitals, and the establishment of processing deadlines for health authorities. In the long term, these modifications may increase the number of applications to the CED scheme, which could lead to unsustainable funding for future projects. It will also be necessary to ensure that the study conditions required by national health authorities are suitable for medical devices and that processing deadlines are met for the scheme to be fully operational. Overall, the modifications recently applied to the French CED scheme for innovative medical devices should increase the transparency of the process, and therefore be more appealing to medical device manufacturers. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Stretch-induced Ca2+ independent ATP release in hippocampal astrocytes.

PubMed

Xiong, Yingfei; Teng, Sasa; Zheng, Lianghong; Sun, Suhua; Li, Jie; Guo, Ning; Li, Mingli; Wang, Li; Zhu, Feipeng; Wang, Changhe; Rao, Zhiren; Zhou, Zhuan

2018-02-28

Similar to neurons, astrocytes actively participate in synaptic transmission via releasing gliotransmitters. The Ca 2+ -dependent release of gliotransmitters includes glutamate and ATP. Following an 'on-cell-like' mechanical stimulus to a single astrocyte, Ca 2+ independent single, large, non-quantal, ATP release occurs. Astrocytic ATP release is inhibited by either selective antagonist treatment or genetic knockdown of P2X7 receptor channels. Our work suggests that ATP can be released from astrocytes via two independent pathways in hippocampal astrocytes; in addition to the known Ca 2+ -dependent vesicular release, larger non-quantal ATP release depends on P2X7 channels following mechanical stretch. Astrocytic ATP release is essential for brain functions such as synaptic long-term potentiation for learning and memory. However, whether and how ATP is released via exocytosis remains hotly debated. All previous studies of non-vesicular ATP release have used indirect assays. By contrast, two recent studies report vesicular ATP release using more direct assays. In the present study, using patch clamped 'ATP-sniffer cells', we re-investigated astrocytic ATP release at single-vesicle resolution in hippocampal astrocytes. Following an 'on-cell-like' mechanical stimulus of a single astrocyte, a Ca 2+ independent single large non-quantal ATP release occurred, in contrast to the Ca 2+ -dependent multiple small quantal ATP release in a chromaffin cell. The mechanical stimulation-induced ATP release from an astrocyte was inhibited by either exposure to a selective antagonist or genetic knockdown of P2X7 receptor channels. Functional P2X7 channels were expressed in astrocytes in hippocampal brain slices. Thus, in addition to small quantal ATP release, larger non-quantal ATP release depends on P2X7 channels in astrocytes. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

AICAR induces AMPK-independent programmed necrosis in prostate cancer cells.

PubMed

Guo, Feng; Liu, Shuang-Qing; Gao, Xing-Hua; Zhang, Long-Yang

2016-05-27

AICAR (5-Aminoimidazole-4-carboxamide riboside or acadesine) is an AMP-activated protein kinase (AMPK) agonist, which induces cytotoxic effect to several cancer cells. Its potential activity in prostate cancer cells and the underlying signaling mechanisms have not been extensively studied. Here, we showed that AICAR primarily induced programmed necrosis, but not apoptosis, in prostate cancer cells (LNCaP, PC-3 and PC-82 lines). AICAR's cytotoxicity to prostate cancer cells was largely attenuated by the necrosis inhibitor necrostatin-1. Mitochondrial protein cyclophilin-D (CYPD) is required for AICAR-induced programmed necrosis. CYPD inhibitors (cyclosporin A and sanglifehrin A) as well as CYPD shRNAs dramatically attenuated AICAR-induced prostate cancer cell necrosis and cytotoxicity. Notably, AICAR-induced cell necrosis appeared independent of AMPK, yet requiring reactive oxygen species (ROS) production. ROS scavengers (N-acetylcysteine and MnTBAP), but not AMPKα shRNAs, largely inhibited prostate cancer cell necrosis and cytotoxicity by AICAR. In summary, the results of the present study demonstrate mechanistic evidences that AMPK-independent programmed necrosis contributes to AICAR's cytotoxicity in prostate cancer cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Evidence for Agile Policy Makers: The Contribution of Transformative Realism

ERIC Educational Resources Information Center

Room, Graham

2013-01-01

Advocates of evidence-based policy making (EBPM) are typically concerned with the impact of particular interventions. This implicit ontology of the policy world, as disaggregated into a variety of independent interventions, has been challenged by Pawson (2006), in terms of the contingencies that activate, inhibit or reshape the impact of any…

The Double-Deficit Hypothesis: A Comprehensive Analysis of the Evidence

ERIC Educational Resources Information Center

Vukovic, Rose K.; Siegel, Linda S.

2006-01-01

The double-deficit hypothesis of developmental dyslexia proposes that deficits in phonological processing and naming speed represent independent sources of dysfunction in dyslexia. The present article is a review of the evidence for the double-deficit hypothesis, including a discussion of recent findings related to the hypothesis. Studies in this…

Common Core Standards: The Emperor Has No Clothes, or Evidence

ERIC Educational Resources Information Center

Tienken, Christopher H.

2011-01-01

The Common Core State Standards (CCSS) initiative continues to gather strength. But the evidence presented by its developers--the National Governors Association (NGA) and the Council of Chief State School Officers (CCSSO)--seems lacking compared to the independent reviews and the available research on the topic that suggest otherwise. In this…

PIP₂ hydrolysis is responsible for voltage independent inhibition of CaV2.2 channels in sympathetic neurons.

PubMed

Vivas, Oscar; Castro, Hector; Arenas, Isabel; Elías-Viñas, David; García, David E

2013-03-08

GPCRs regulate Ca(V)2.2 channels through both voltage dependent and independent inhibition pathways. The aim of the present work was to assess the phosphatidylinositol-4,5-bisphosphate (PIP2) as the molecule underlying the voltage independent inhibition of Ca(V)2.2 channels in SCG neurons. We used a double pulse protocol to study the voltage independent inhibition and changed the PIP(2) concentration by means of blocking the enzyme PLC, filling the cell with a PIP(2) analogue and preventing the PIP(2) resynthesis with wortmannin. We found that voltage independent inhibition requires the activation of PLC and can be hampered by internal dialysis of exogenous PIP(2). In addition, the recovery from voltage independent inhibition is blocked by inhibition of the enzymes involved in the resynthesis of PIP(2). These results support that the hydrolysis of PIP(2) is responsible for the voltage independent inhibition of Ca(V)2.2 channels. Copyright © 2013 Elsevier Inc. All rights reserved.

Grouping individual independent BOLD effects: a new way to ICA group analysis

NASA Astrophysics Data System (ADS)

Duann, Jeng-Ren; Jung, Tzyy-Ping; Sejnowski, Terrence J.; Makeig, Scott

2009-04-01

A new group analysis method to summarize the task-related BOLD responses based on independent component analysis (ICA) was presented. As opposite to the previously proposed group ICA (gICA) method, which first combined multi-subject fMRI data in either temporal or spatial domain and applied ICA decomposition only once to the combined fMRI data to extract the task-related BOLD effects, the method presented here applied ICA decomposition to the individual subjects' fMRI data to first find the independent BOLD effects specifically for each individual subject. Then, the task-related independent BOLD component was selected among the resulting independent components from the single-subject ICA decomposition and hence grouped across subjects to derive the group inference. In this new ICA group analysis (ICAga) method, one does not need to assume that the task-related BOLD time courses are identical across brain areas and subjects as used in the grand ICA decomposition on the spatially concatenated fMRI data. Neither does one need to assume that after spatial normalization, the voxels at the same coordinates represent exactly the same functional or structural brain anatomies across different subjects. These two assumptions have been problematic given the recent BOLD activation evidences. Further, since the independent BOLD effects were obtained from each individual subject, the ICAga method can better account for the individual differences in the task-related BOLD effects. Unlike the gICA approach whereby the task-related BOLD effects could only be accounted for by a single unified BOLD model across multiple subjects. As a result, the newly proposed method, ICAga, was able to better fit the task-related BOLD effects at individual level and thus allow grouping more appropriate multisubject BOLD effects in the group analysis.

Simon and Garner effects with color and location: Evidence for two independent routes by which irrelevant location influences performance.

PubMed

Fitousi, Daniel

2016-11-01

Classic theories of attention assume that the processing of a target's featural dimension (e.g., color) is contingent on the processing of its spatial location. The present study challenges this maxim. Three experiments evaluated the dimensional independence of spatial location and color using a combined Simon (Simon & Rudell Journal of Applied Psychology: 51, 300-304, 1967) and Garner (Garner, 1974) design. The results showed that when the stimulus's spatial location was rendered more discriminable than its color (Experiment 1 and 2), both Simon and Garner effects were obtained, and location interfered with color judgments to a larger extent than color intruded on location. However, when baseline discriminabilities of location and color were matched (Experiment 3), no Garner interference was obtained from location to color, yet Simon effects still emerged, proving resilient to manipulations of discriminability. Further correlational and distributional analyses showed that Garner and Simon effects have dissociable effects. A triple-route model is proposed to account for the results, according to which irrelevant location can influence performance via two independent location routes/codes.

Evidence That Environmental and Familial Risks for Psychosis Additively Impact a Multidimensional Subthreshold Psychosis Syndrome.

PubMed

Pries, Lotta-Katrin; Guloksuz, Sinan; Ten Have, Margreet; de Graaf, Ron; van Dorsselaer, Saskia; Gunther, Nicole; Rauschenberg, Christian; Reininghaus, Ulrich; Radhakrishnan, Rajiv; Bak, Maarten; Rutten, Bart P F; van Os, Jim

2018-06-06

The observed link between positive psychotic experiences (PE) and psychosis spectrum disorder (PSD) may be stronger depending on concomitant presence of PE with other dimensions of psychopathology. We examined whether the effect of common risk factors for PSD on PE is additive and whether the impact of risk factors on the occurrence of PE depends on the co-occurrence of other symptom dimensions (affective dysregulation, negative symptoms, and cognitive alteration). Data from the Netherlands Mental Health Survey and Incidence Study 2 were used. Risk factors included childhood adversity, cannabis use, urbanicity, foreign born, hearing impairment, and family history of affective disorders. Logistic regression models were applied to test (1) the additive effect of risk factors (4 levels) on PE and (2) the moderating effects of symptom dimensions on the association between risk factors (present/absent) and PE, using additive interaction, expressed as the interaction contrast ratio. Risk factors were additive: the greater the number of risk factors, the greater the odds of PE. Furthermore, concomitant presence of the other symptom dimensions all increased the impact of risk factors on PE. After controlling for age, sex, and education, only affective dysregulation and negative symptoms remained significant moderators; only affective dysregulation remained a significant moderator if all dimensions were adjusted for each other. Risk factors may not be directly associated with PE but additively give rise to a multidimensional subthreshold state anticipating the multidimensional clinical syndrome. Early motivational and cognitive impairments in the context of PE may be reducible to affective dysregulation.

34 CFR 365.22 - What additional IL services may the State provide?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 2 2010-07-01 2010-07-01 false What additional IL services may the State provide? 365.22 Section 365.22 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION STATE INDEPENDENT LIVING...

34 CFR 365.22 - What additional IL services may the State provide?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 2 2011-07-01 2010-07-01 true What additional IL services may the State provide? 365.22 Section 365.22 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION STATE INDEPENDENT LIVING...

Independent Orbiter Assessment (IOA): Assessment of the Orbiter Experiment (OEX) subsystem

NASA Technical Reports Server (NTRS)

Compton, J. M.

1988-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA effort first completed an analysis of the Orbiter Experiments (OEX) hardware, generating draft failure modes and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The IOA results were then compared to the NASA FMEA/CIL baseline with proposed Post 51-L updates included. A resolution of each discrepancy from the comparison is provided through additional analysis as required. The results of that comparison for the Orbiter OEX hardware are documented. The IOA product for the OEX analysis consisted of 82 failure mode worksheets that resulted in two potential critical items being identified.

Antibiotics for PANDAS? Limited Evidence: Review and Putative Mechanisms of Action.

PubMed

Burchi, Elisabetta; Pallanti, Stefano

2018-05-03

Antibiotics have been used extensively by clinicians to treat patients with PANDAS or PANS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and pediatric acute-onset neuropsychiatric syndrome, respectively). This review examines the best-quality evidence supporting the practice-based use of antibiotics in these psychiatric conditions. PubMed was searched for English-language articles published between January 1994 and July 2017 using the search terms [PANDAS OR PANS OR new-onset pediatric OCD] AND [antibiotics OR macrolides OR beta-lactams]. Randomized clinical trials, observational studies, and case reports concerning antibiotic use in PANDAS/PANS were reviewed. Four publications were included in the quantitative synthesis. The evidence was rated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) method. Although the single studies conveyed no statistically significant results, there is some evidence for efficacy of antibiotic therapy in reducing neuropsychiatric symptoms in the PANDAS/PANS population. Whereas the use of eradicating antibiotic therapy during active infections in PANDAS/PANS is well established, there is still a need for studies that improve the quality of evidence supporting use of antibiotics in this population independent of ongoing infections. Studies that compare antibiotics with other therapies, as well as studies that assess safety and efficacy of long-term use of antibiotic therapy in PANDAS/PANS, are still lacking. However, the available research supports evidence of a subgroup in the pediatric OCD population that is sensitive to antibiotic treatment and immunomodulatory therapy, independent of ongoing infectious conditions. Thus, more studies are warranted in the overall OCD spectrum. © Copyright 2018 Physicians Postgraduate Press, Inc.

Lenalidomide in multiple myeloma: an evidence-based review of its role in therapy

PubMed Central

Richardson, Paul; Mitsiades, Constantine; Laubach, Jacob; Schlossman, Robert; Ghobrial, Irene; Hideshima, Teru; Munshi, Nikhil; Anderson, Kenneth

2010-01-01

Introduction: Multiple myeloma (MM) is a relatively common and incurable hematological malignancy. Currently, there is no single standard therapy, with choice of treatment dependent on individual patient factors. Lenalidomide is an immunomodulatory drug with potent antitumor, antiangiogenic, immunomodulatory, and proapoptotic activity in MM. Aims: To evaluate the evidence for the use of lenalidomide in its current indication in relapsed or refractory MM, and additionally its investigational use for the treatment of newly diagnosed MM. Evidence review: In patients with relapsed and refractory MM, adding lenalidomide to high-dose dexamethasone significantly improves response rates and time-to-progression, relative to high-dose dexamethasone alone. This translates into a significant extension of overall survival (with a median extension of 9.1 months in a pivotal phase III study). Outcome is independent of patient age, number of previous therapies, type of previous therapy (including thalidomide or autologous stem cell transplantation), renal impairment, and β2-microglobulin level. Evidence suggests that combining lenalidomide with low-dose dexamethasone improves outcomes in patients with newly diagnosed disease and is superior to lenalidomide combined with high-dose dexamethasone. Myelosuppression is the predominant toxicity observed, although some studies have shown high incidences of venous thromboembolism in the absence of prophylactic antithrombotic anticoagulation therapy. There is currently only limited evidence regarding the health economics of lenalidomide. Role in therapy: The encouraging results obtained with lenalidomide alone and in combination with dexamethasone in patients with relapsed or refractory MM have led to its adoption as a recommended therapy in patients who have received at least one prior treatment. Emerging evidence supports the ongoing investigation of lenalidomide in combination with low-dose dexamethasone, and in other combinations

A Systematic Review of the Economic Evidence for Home Support Interventions in Dementia.

PubMed

Clarkson, Paul; Davies, Linda; Jasper, Rowan; Loynes, Niklas; Challis, David

2017-09-01

Recent evidence signals the need for effective forms of home support to people with dementia and their carers. The cost-effectiveness evidence of different approaches to support is scant. To appraise economic evidence on the cost-effectiveness of home support interventions for dementia to inform future evaluation. A systematic literature review of full and partial economic evaluations was performed using the British National Health Service Economic Evaluation Database supplemented by additional references. Study characteristics and findings, including incremental cost-effectiveness ratios, when available, were summarized narratively. Study quality was appraised using the National Health Service Economic Evaluation Database critical appraisal criteria and independent ratings, agreed by two reviewers. Studies were located on a permutation matrix describing their mix of incremental costs/effects to aid decision making. Of the 151 articles retrieved, 14 studies met the inclusion criteria: 8 concerning support to people with dementia and 6 to carers. Five studies were incremental cost-utility analyses, seven were cost-effectiveness analyses, and two were cost consequences analyses. Five studies expressed incremental cost-effectiveness ratios as cost per quality-adjusted life-year (£6,696-£207,942 per quality-adjusted life-year). In four studies, interventions were dominant over usual care. Two interventions were more costly but more beneficial and were favorable against current acceptability thresholds. Occupational therapy, home-based exercise, and a carers' coping intervention emerged as cost-effective approaches for which there was better evidence. These interventions used environmental modifications, behavior management, physical activity, and emotional support as active components. More robust evidence is needed to judge the value of these and other interventions across the dementia care pathway. Copyright © 2017 International Society for Pharmacoeconomics and

An Ultra-wideband and Polarization-independent Metasurface for RCS Reduction.

PubMed

Su, Pei; Zhao, Yongjiu; Jia, Shengli; Shi, Wenwen; Wang, Hongli

2016-02-11

In this paper, an ultra-wideband and polarization-independent metasurface for radar cross section (RCS) reduction is proposed. The unit cell of the metasurface operates in a linear cross-polarization scheme in a broad band. The phase and amplitude of cross-polarized reflection can be separately controlled by its geometry and rotation angle. Based on the diffuse reflection theory, a 3-bit coding metasurface is designed to reduce the RCS in an ultra-wide band. The wideband property of the metasurface benefits from the wideband cross polarization conversion and flexible phase modulation. In addition, the polarization-independent feature of the metasurface is achieved by tailoring the rotation angle of each element. Both the simulated and measured results demonstrate that the proposed metasurface can reduce the RCS significantly in an ultra-wide frequency band for both normal and oblique incidences, which makes it promising in the applications such as electromagnetic cloaking.

Independent Orbiter Assessment (IOA): Assessment of the crew equipment subsystem

NASA Technical Reports Server (NTRS)

Saxon, H.; Richard, Bill; Sinclair, S. K.

1988-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA effort first completed an analysis of the Crew Equipment hardware, generating draft failure modes and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The IOA results were then compared to the NASA FMEA/CIL baseline with proposed Post 51-L updates included. A resolution of each discrepancy from the comparison is provided through additional analysis as required. This report documents the results of that comparison for the Orbiter Crew Equipment hardware. The IOA product for the Crew Equipment analysis consisted of 352 failure mode worksheets that resulted in 78 potential critical items being identified. Comparison was made to the NASA baseline which consisted of 351 FMEAs and 82 CIL items.

Cultural orientations, parental beliefs and practices, and latino adolescents' autonomy and independence.

PubMed

Roche, Kathleen M; Caughy, Margaret O; Schuster, Mark A; Bogart, Laura M; Dittus, Patricia J; Franzini, Luisa

2014-08-01

Despite the salience of behavioral autonomy and independence to parent-child interactions during middle adolescence, little is known about parenting processes pertinent to youth autonomy development for Latino families. Among a diverse sample of 684 Latino-origin parent-adolescent dyads in Houston, Texas, this study examines how parents' cultural orientations are associated directly and indirectly, through parental beliefs, with parenting practices giving youth behavioral autonomy and independence. Informed by social domain theory, the study's parenting constructs pertain to youth behaviors in an "ambiguously personal" domain-activities that adolescents believe are up to youth to decide, but which parents might argue require parents' supervision, knowledge, and/or decision-making. Results for latent profile analyses of parents' cultural identity across various facets of acculturation indicate considerable cultural heterogeneity among Latino parents. Although 43% of parents have a Latino cultural orientation, others represent Spanish-speaking/bicultural (21%), bilingual/bicultural (15%), English-speaking/bicultural (15%), or US (6%) cultural orientations. Structural equation modeling results indicate that bilingual/bicultural, English-speaking/bicultural, and US-oriented parents report less emphasis on the legitimacy of parental authority and younger age expectations for youth to engage in independent behaviors than do Latino-oriented parents. Parental beliefs endorsing youth's behavioral independence and autonomy, in turn, are associated with less stringent parental rules (parental report), less parental supervision (parental and youth report), and more youth autonomy in decision-making (parental and youth report). Evidence thus supports the idea that the diverse cultural orientations of Latino parents in the US may result in considerable variations in parenting processes pertinent to Latino adolescents' development.

Proliferative responses in the local lymph node assay associated with concomitant exposure to 1,4-phenylenediamine and methyldibromo glutaronitrile: evidence for synergy?

PubMed

Jowsey, Ian R; Basketter, David A; Irwin, Anita

2008-08-01

A key consideration when undertaking risk assessments should be the potential for synergy between contact allergens. Previously, this concept has only been investigated during elicitation in contact allergic individuals. To determine whether there exists evidence for synergy between contact allergens during the induction phase of skin sensitization using the mouse local lymph node assay (LLNA) as a model system. Proliferative responses in draining lymph nodes were assessed with increasing concentrations of 1,4-phenylenediamine (PPD), methyldibromo glutaronitrile (MDBGN), and a combination of PPD and MDBGN. Data from each of two independent experiments show that lymph node cell proliferation associated with combined exposure to PPD and MDBGN was, in general, only modestly increased relative to that predicted from a simple summation of their individual responses. Although the increase in response is very modest, it does imply a relationship between this combination of sensitizers that may not be simply additive in terms of their ability to stimulate proliferative responses in draining lymph nodes. The reproducibility of this observation should be confirmed in future studies with additional pairs of contact allergens to ascertain whether or not this represents evidence of synergy.

Applications of Metal Additive Manufacturing in Veterinary Orthopedic Surgery

NASA Astrophysics Data System (ADS)

Harrysson, Ola L. A.; Marcellin-Little, Denis J.; Horn, Timothy J.

2015-03-01

Veterinary medicine has undergone a rapid increase in specialization over the last three decades. Veterinarians now routinely perform joint replacement, neurosurgery, limb-sparing surgery, interventional radiology, radiation therapy, and other complex medical procedures. Many procedures involve advanced imaging and surgical planning. Evidence-based medicine has also become part of the modus operandi of veterinary clinicians. Modeling and additive manufacturing can provide individualized or customized therapeutic solutions to support the management of companion animals with complex medical problems. The use of metal additive manufacturing is increasing in veterinary orthopedic surgery. This review describes and discusses current and potential applications of metal additive manufacturing in veterinary orthopedic surgery.

Factors associated with independent pharmacy owners' satisfaction with Medicare Part D contracts.

PubMed

Zhang, Su; Doucette, William R; Urmie, Julie M; Xie, Yang; Brooks, John M

2010-06-01

As Medicare Part D contracts apply pressure on the profitability of independent pharmacies, there is concern about their owners' willingness to sign such contracts. Identifying factors affecting independent pharmacy owners' satisfaction with Medicare Part D contracts could inform policy makers in managing Medicare Part D. (1) To identify influences on independent pharmacy owners' satisfaction with Medicare Part D contracts and (2) to characterize comments made by independent pharmacy owners about Medicare Part D. This cross-sectional study used a mail survey of independent pharmacy owners in 15 states comprising 6 Medicare regions to collect information on their most- and least-favorable Medicare Part D contracts, including satisfaction, contract management activities, market position, pharmacy operation, and specific payment levels on brand and generic drugs. Of the 1649 surveys mailed, 296 surveys were analyzed. The regression models for satisfaction with both the least and the most-favorable Part D contracts were significant (P<0.05). A different set of significant influences on satisfaction was identified for each regression model. For the most-favorable contract, influences were contending and equity. For the least-favorable contract, influences were negotiation, equity, generic rate bonus, and medication therapy management (MTM) payment. About one-third of the survey respondents made at least 1 comment. The most frequent themes in the comments were that Medicare Part D reimbursement rate is too low (28%) and that contracts are offered without negotiation in a "take it or leave it" manner (20%). Equity, contending, negotiation, generic rate bonus, and MTM payments were identified as the influences of independent pharmacy owners' satisfaction toward Medicare Part D contracts. Generic rate bonus and MTM payment provide additional financial incentives to less financially favorable contracts and, in turn, contribute to independent pharmacy owner's satisfaction

Understanding evidence-based diagnosis.

PubMed

Kohn, Michael A

2014-01-01

The real meaning of the word "diagnosis" is naming the disease that is causing a patient's illness. The cognitive process of assigning this name is a mysterious combination of pattern recognition and the hypothetico-deductive approach that is only remotely related to the mathematical process of using test results to update the probability of a disease. What I refer to as "evidence-based diagnosis" is really evidence-based use of medical tests to guide treatment decisions. Understanding how to use test results to update the probability of disease can help us interpret test results more rationally. Also, evidence-based diagnosis reminds us to consider the costs and risks of testing and the dangers of over-diagnosis and over-treatment, in addition to the costs and risks of missing serious disease.

Orientation independence of single-vacancy and single-ion permeability ratios.

PubMed Central

McGill, P; Schumaker, M F

1995-01-01

Single-vacancy models have been proposed as open channel permeation mechanisms for K+ channels. Single-ion models have been used to describe permeation through Na+ channels. This paper demonstrates that these models have a distinctive symmetry property. Their permeability ratios, measured under biionic conditions, are independent of channel orientation when the reversal potential is zero. This symmetry is a property of general m-site single-vacancy channels, m-site shaking-stack channels, as well as m-site single-ion channels. An experimental finding that the permeability ratios of a channel did not have this symmetry would provide evidence that a single-vacancy or single-ion model is an incorrect or incomplete description of permeation. Images FIGURE 1 PMID:7669913

Eye-gaze independent EEG-based brain-computer interfaces for communication.

PubMed

Riccio, A; Mattia, D; Simione, L; Olivetti, M; Cincotti, F

2012-08-01

The present review systematically examines the literature reporting gaze independent interaction modalities in non-invasive brain-computer interfaces (BCIs) for communication. BCIs measure signals related to specific brain activity and translate them into device control signals. This technology can be used to provide users with severe motor disability (e.g. late stage amyotrophic lateral sclerosis (ALS); acquired brain injury) with an assistive device that does not rely on muscular contraction. Most of the studies on BCIs explored mental tasks and paradigms using visual modality. Considering that in ALS patients the oculomotor control can deteriorate and also other potential users could have impaired visual function, tactile and auditory modalities have been investigated over the past years to seek alternative BCI systems which are independent from vision. In addition, various attentional mechanisms, such as covert attention and feature-directed attention, have been investigated to develop gaze independent visual-based BCI paradigms. Three areas of research were considered in the present review: (i) auditory BCIs, (ii) tactile BCIs and (iii) independent visual BCIs. Out of a total of 130 search results, 34 articles were selected on the basis of pre-defined exclusion criteria. Thirteen articles dealt with independent visual BCIs, 15 reported on auditory BCIs and the last six on tactile BCIs, respectively. From the review of the available literature, it can be concluded that a crucial point is represented by the trade-off between BCI systems/paradigms with high accuracy and speed, but highly demanding in terms of attention and memory load, and systems requiring lower cognitive effort but with a limited amount of communicable information. These issues should be considered as priorities to be explored in future studies to meet users' requirements in a real-life scenario.

Eye-gaze independent EEG-based brain-computer interfaces for communication

NASA Astrophysics Data System (ADS)

Riccio, A.; Mattia, D.; Simione, L.; Olivetti, M.; Cincotti, F.

2012-08-01

The present review systematically examines the literature reporting gaze independent interaction modalities in non-invasive brain-computer interfaces (BCIs) for communication. BCIs measure signals related to specific brain activity and translate them into device control signals. This technology can be used to provide users with severe motor disability (e.g. late stage amyotrophic lateral sclerosis (ALS); acquired brain injury) with an assistive device that does not rely on muscular contraction. Most of the studies on BCIs explored mental tasks and paradigms using visual modality. Considering that in ALS patients the oculomotor control can deteriorate and also other potential users could have impaired visual function, tactile and auditory modalities have been investigated over the past years to seek alternative BCI systems which are independent from vision. In addition, various attentional mechanisms, such as covert attention and feature-directed attention, have been investigated to develop gaze independent visual-based BCI paradigms. Three areas of research were considered in the present review: (i) auditory BCIs, (ii) tactile BCIs and (iii) independent visual BCIs. Out of a total of 130 search results, 34 articles were selected on the basis of pre-defined exclusion criteria. Thirteen articles dealt with independent visual BCIs, 15 reported on auditory BCIs and the last six on tactile BCIs, respectively. From the review of the available literature, it can be concluded that a crucial point is represented by the trade-off between BCI systems/paradigms with high accuracy and speed, but highly demanding in terms of attention and memory load, and systems requiring lower cognitive effort but with a limited amount of communicable information. These issues should be considered as priorities to be explored in future studies to meet users’ requirements in a real-life scenario.

Research on the Fusion of Dependent Evidence Based on Rank Correlation Coefficient.

PubMed

Shi, Fengjian; Su, Xiaoyan; Qian, Hong; Yang, Ning; Han, Wenhua

2017-10-16

In order to meet the higher accuracy and system reliability requirements, the information fusion for multi-sensor systems is an increasing concern. Dempster-Shafer evidence theory (D-S theory) has been investigated for many applications in multi-sensor information fusion due to its flexibility in uncertainty modeling. However, classical evidence theory assumes that the evidence is independent of each other, which is often unrealistic. Ignoring the relationship between the evidence may lead to unreasonable fusion results, and even lead to wrong decisions. This assumption severely prevents D-S evidence theory from practical application and further development. In this paper, an innovative evidence fusion model to deal with dependent evidence based on rank correlation coefficient is proposed. The model first uses rank correlation coefficient to measure the dependence degree between different evidence. Then, total discount coefficient is obtained based on the dependence degree, which also considers the impact of the reliability of evidence. Finally, the discount evidence fusion model is presented. An example is illustrated to show the use and effectiveness of the proposed method.

Research on the Fusion of Dependent Evidence Based on Rank Correlation Coefficient

PubMed Central

Su, Xiaoyan; Qian, Hong; Yang, Ning; Han, Wenhua

2017-01-01

In order to meet the higher accuracy and system reliability requirements, the information fusion for multi-sensor systems is an increasing concern. Dempster–Shafer evidence theory (D–S theory) has been investigated for many applications in multi-sensor information fusion due to its flexibility in uncertainty modeling. However, classical evidence theory assumes that the evidence is independent of each other, which is often unrealistic. Ignoring the relationship between the evidence may lead to unreasonable fusion results, and even lead to wrong decisions. This assumption severely prevents D–S evidence theory from practical application and further development. In this paper, an innovative evidence fusion model to deal with dependent evidence based on rank correlation coefficient is proposed. The model first uses rank correlation coefficient to measure the dependence degree between different evidence. Then, total discount coefficient is obtained based on the dependence degree, which also considers the impact of the reliability of evidence. Finally, the discount evidence fusion model is presented. An example is illustrated to show the use and effectiveness of the proposed method. PMID:29035341

Speech-independent production of communicative gestures: evidence from patients with complete callosal disconnection.

PubMed

Lausberg, Hedda; Zaidel, Eran; Cruz, Robyn F; Ptito, Alain

2007-10-01

Recent neuropsychological, psycholinguistic, and evolutionary theories on language and gesture associate communicative gesture production exclusively with left hemisphere language production. An argument for this approach is the finding that right-handers with left hemisphere language dominance prefer the right hand for communicative gestures. However, several studies have reported distinct patterns of hand preferences for different gesture types, such as deictics, batons, or physiographs, and this calls for an alternative hypothesis. We investigated hand preference and gesture types in spontaneous gesticulation during three semi-standardized interviews of three right-handed patients and one left-handed patient with complete callosal disconnection, all with left hemisphere dominance for praxis. Three of them, with left hemisphere language dominance, exhibited a reliable left-hand preference for spontaneous communicative gestures despite their left hand agraphia and apraxia. The fourth patient, with presumed bihemispheric language representation, revealed a consistent right-hand preference for gestures. All four patients displayed batons, tosses, and shrugs more often with the left hand/shoulder, but exhibited a right hand preference for pantomime gestures. We conclude that the hand preference for certain gesture types cannot be predicted by hemispheric dominance for language or by handedness. We found distinct hand preferences for specific gesture types. This suggests a conceptual specificity of the left and right hand gestures. We propose that left hand gestures are related to specialized right hemisphere functions, such as prosody or emotion, and that they are generated independently of left hemisphere language production. Our findings challenge the traditional neuropsychological and psycholinguistic view on communicative gesture production.

Loss of cell invasiveness through PKC-mediated syndecan-1 downregulation in melanoma cells under anchorage independency.

PubMed

Wang, ChiaChen; Tseng, TingTing; Jhang, Yaoyun; Tseng, JenChih; Hsieh, ChiaoHui; Wu, Wen-guey; Lee, ShaoChen

2014-11-01

Anchorage-independent survival is one of the key features for malignant tumor cells. Whether specific gene alterations contributed by anchorage independency would further affect metastatic phenotypes of melanoma cells was unclear. We adapted suspension culture of melanoma cells to establish anchorage independency. The suspended melanoma cells lost their invasive abilities in vitro. Specific loss of laminin-binding ability in suspended melanoma cells was observed, which was correlated with downregulation of syndecan-1 as revealed by microarray and validated by qPCR and Western blot. Modulation of syndecan-1 expression level affected laminin binding, transwell migration and matrix metalloproteinase-2 secretion in melanoma cells. SDC1 expression and transwell migration were correlated with activity or level of protein kinase Cδ as evidence by specific inhibitors and shRNA transfection. In this study, we compared metastatic phenotypes and gene expressions of adherent and suspended melanoma cells. The anchorage independency led to protein kinase Cδ-mediated syndecan-1 downregulation, which contributed to loss of laminin-binding ability, reduced metalloproteinase-2 secretion and loss of invasiveness. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evidence and evidence gaps - an introduction.

PubMed

Dreier, Gabriele; Löhler, Jan

2016-01-01

, databases, information portals with processed evidence as well as specific journals and finally teaching are appropriate vehicles. One problem is the multitude of information so that knowledge gaps may affect the clinical routine despite actually existing evidence. Generally, it still takes several years until new knowledge is implemented in daily routine. Tasks: The German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (Deutsche Gesellschaft für Hals-, Nasen- und Ohren-Heilkunde, Kopf- und Hals-Chirurgie e.V., DGHNOKHC) and the Professional Association of Otolaryngologists (Deutscher Berufsverband der HNO-Ärzte e.V., BVHNO) have fundamental interest in supporting their members in generating, processing, and providing evidence as well as accompanying knowledge transfer. It encompasses the fields of diagnostics, therapy, and prognosis in the same way as prevention and applies to medicinal products as well as to medical devices or surgical procedures. The base for this is the regular assessment of evidence gaps, also in the area of established procedures, that has to be followed by a prioritization of research questions and the subsequent initiation of clinical research. In addition, large trials verifying therapies and diagnostics, for example in the context of daily conditions after approval, can only be conducted combining all resources in the ENT community. Method, results, and outlook: Together, the executive committees of the DGHNOKHC and the BVHNO founded the German Study Center of Oto-Rhino-Laryngology, Head and Neck Surgery (Deutsches Studienzentrum für Hals-, Nasen- und Ohren-Heilkunde, Kopf- und Hals-Chirurgie, DSZ-HNO). First projects have been initiated, among those a clinical trial on the therapy of sudden hearing loss supported by the BMBF and a survey on evidence gaps in oto-rhino-laryngology. It seems to be both reasonable and feasible to make available methodological expertise via such an infrastructure of a study center for physicians in

Dimension reduction: additional benefit of an optimal filter for independent component analysis to extract event-related potentials.

PubMed

Cong, Fengyu; Leppänen, Paavo H T; Astikainen, Piia; Hämäläinen, Jarmo; Hietanen, Jari K; Ristaniemi, Tapani

2011-09-30

The present study addresses benefits of a linear optimal filter (OF) for independent component analysis (ICA) in extracting brain event-related potentials (ERPs). A filter such as the digital filter is usually considered as a denoising tool. Actually, in filtering ERP recordings by an OF, the ERP' topography should not be changed by the filter, and the output should also be able to be modeled by the linear transformation. Moreover, an OF designed for a specific ERP source or component may remove noise, as well as reduce the overlap of sources and even reject some non-targeted sources in the ERP recordings. The OF can thus accomplish both the denoising and dimension reduction (reducing the number of sources) simultaneously. We demonstrated these effects using two datasets, one containing visual and the other auditory ERPs. The results showed that the method including OF and ICA extracted much more reliable components than the sole ICA without OF did, and that OF removed some non-targeted sources and made the underdetermined model of EEG recordings approach to the determined one. Thus, we suggest designing an OF based on the properties of an ERP to filter recordings before using ICA decomposition to extract the targeted ERP component. Copyright © 2011 Elsevier B.V. All rights reserved.

Lubricants or lubricant additives composed of ionic liquids containing ammonium cations

DOEpatents

Qu, Jun [Knoxville, TN; Truhan, Jr; John, J [Cookeville, TN; Dai, Sheng [Knoxville, TN; Luo, Huimin [Knoxville, TN; Blau, Peter J [Knoxville, TN

2010-07-13

A lubricant or lubricant additive is an ionic liquid alkylammonium salt. The alkylammonium salt has the structure R.sub.xNH.sub.(4-x).sup.+,[F.sub.3C(CF.sub.2).sub.yS(O).sub.2].sub.2N.sup- .- where x is 1 to 3, R is independently C.sub.1 to C.sub.12 straight chain alkyl, branched chain alkyl, cycloalkyl, alkyl substituted cycloalkyl, cycloalkyl substituted alkyl, or, optionally, when x is greater than 1, two R groups comprise a cyclic structure including the nitrogen atom and 4 to 12 carbon atoms, and y is independently 0 to 11. The lubricant is effective for the lubrication of many surfaces including aluminum and ceramics surfaces.

Predictors of victim disclosure in child sexual abuse: Additional evidence from a sample of incarcerated adult sex offenders.

PubMed

Leclerc, Benoit; Wortley, Richard

2015-05-01

The under-reporting of child sexual abuse by victims is a serious problem that may prolong the suffering of victims and leave perpetrators free to continue offending. Yet empirical evidence indicates that victim disclosure rates are low. In this study, we perform regression analysis with a sample of 369 adult child sexual offenders to examine potential predictors of victim disclosure. Specifically, we extend the range of previously examined potential predictors of victim disclosure and investigate interaction effects in order to better capture under which circumstances victim disclosure is more likely. The current study differs from previous studies in that it examines the impact of victim and offense variables on victim disclosure from the perspective of the offender. In line with previous studies, we found that disclosure increased with the age of the victim and if penetration had occurred. In addition, we found that disclosure increased when the victim came from a non-dysfunctional family and resisted the abuse. The presence of an interaction effect highlighted the impact of the situation on victim disclosure. This effect indicated that as victims get older, they are more likely to disclose the abuse when they are not living with the offender at the time of abuse, but less likely to do so when they are living with the offender at the time of abuse. These findings are discussed in relation to previous studies and the need to facilitate victim disclosure. Copyright © 2015 Elsevier Ltd. All rights reserved.

Independent Evaluation: Insights from Public Accounting

ERIC Educational Resources Information Center

Brown, Abigail B.; Klerman, Jacob Alex

2012-01-01

Background: Maintaining the independence of contract government program evaluation presents significant contracting challenges. The ideal outcome for an agency is often both the impression of an independent evaluation "and" a glowing report. In this, independent evaluation is like financial statement audits: firm management wants both a public…

Effectiveness of virtual reality rehabilitation for children and adolescents with cerebral palsy: an updated evidence-based systematic review.

PubMed

Ravi, D K; Kumar, N; Singhi, P

2017-09-01

The use of virtual reality systems in the motor rehabilitation of children with cerebral palsy is new, and thus the scientific evidence for its effectiveness needs to be evaluated through a systematic review. To provide updated evidence-based guidance for virtual reality rehabilitation in sensory and functional motor skills of children and adolescents with cerebral palsy. PubMed, PEDro, Web of Science, OTseeker, PsycINFO and Cochrane Library were searched from their earliest records up to 1 June, 2016. Two reviewers applied the population intervention comparison outcome (PICO) question to screen the studies for this review. Information on study design, subjects, intervention, outcome measures and efficacy results were extracted into a pilot-tested form. Method quality was assessed independently by two reviewers using the Downs and Black checklist. Thirty-one studies included 369 participants in total. Best evidence synthesis was applied to summarize the outcomes, which were grouped according to International Classification of Functioning, Disability and Health. Moderate evidence was found for balance and overall motor development. The evidence is still limited for other motor skills. This review uncovered additional literature showing moderate evidence that virtual reality rehabilitation is a promising intervention to improve balance and motor skills in children and adolescents with cerebral palsy. The technique is growing, so long-term follow-up and further research are required to determine its exact place in the management of cerebral palsy. Systematic review registration number PROSPERO 2015:CRD42015026048. Copyright © 2016 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

SATB2 expression increased anchorage-independent growth and cell migration in human bronchial epithelial cells

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

Wu, Feng; Jordan, Ashley; Kluz, Thomas

The special AT-rich sequence-binding protein 2 (SATB2) is a protein that binds to the nuclear matrix attachment region of the cell and regulates gene expression by altering chromatin structure. In our previous study, we reported that SATB2 gene expression was induced in human bronchial epithelial BEAS-2B cells transformed by arsenic, chromium, nickel and vanadium. In this study, we show that ectopic expression of SATB2 in the normal human bronchial epithelial cell-line BEAS-2B increased anchorage-independent growth and cell migration, meanwhile, shRNA-mediated knockdown of SATB2 significantly decreased anchorage-independent growth in Ni transformed BEAS-2B cells. RNA sequencing analyses of SATB2 regulated genes revealedmore » the enrichment of those involved in cytoskeleton, cell adhesion and cell-movement pathways. Our evidence supports the hypothesis that SATB2 plays an important role in BEAS-2B cell transformation. - Highlights: • We performed SATB2 overexpression in the BEAS-2B cell line. • We performed SATB2 knockdown in a Ni transformed BEAS-2B cell line. • SATB2 induced anchorage-independent growth and increased cell migration. • SATB2 knockdown significantly decreased anchorage-independent growth. • We identified alterations in gene involved in cytoskeleton, cell adhesion.« less

Measurement-device-independent semiquantum key distribution

NASA Astrophysics Data System (ADS)

He, Jinjun; Li, Qin; Wu, Chunhui; Chan, Wai Hong; Zhang, Shengyu

Semiquantum key distribution (SQKD) allows two parties to share a common string when one of them is quantum and the other has rather limited quantum capability. Almost all existing SQKD protocols have been proved to be robust in theory, namely that if an eavesdropper tries to gain information, he will inevitably induce some detectable errors. However, ideal devices do not exist in reality and their imperfection may result in side-channel attacks, which can be used by an adversary to get some information on the secret key string. In this paper, we design a measurement-device-independent SQKD protocol for the first time, which can remove the threat of all detector side-channel attacks and show that it is also robust. In addition, we discuss the possible use of the proposed protocol in real-world applications and in QKD networks.

[Gait, balance and independence rehabilitation program in elderly adults in a primary care unit].

PubMed

Espinosa-Cuervo, Gisela; López-Roldán, Verónica Miriam; Escobar-Rodríguez, David Alvaro; Conde-Embarcadero, Margarita; Trejo-León, Gerardo; González-Carmona, Beatriz

2013-01-01

to evaluate the effect of a supervised rehabilitation program to improve gait, balance and independence in elderly patients attending a family medicine unit. we conducted a quasi-experimental study over a period of four weeks in a group of 72 patients older than 65 years. a supervised program regarding the risk factors for falling, and balance, gait, coordination and oculovestibular system, the modalities to be done two or three times a week in the primary care unit or at home. An analysis of both tests was performed by "up and go," Tinetti scale and the Katz index. "intention to treat" and "by protocol." mean age was 72 ± 5 years, 67.8% were female and 81.9% of the patients completed the program. A significant clinical improvement with statistical level were evident for gait and balance (p = 0.001), independence showed only clinical improvement (p = 0.083). The efficacy for periodicity (two or three times/week) and performance place showed same clinical improvement and statistical level for gait and balance (p = 0.001 to 0.003) and independence showed only clinical improvement (p = 0.317 to 0.991). an integral rehabilitation program improved gait, balance and clinical independence significantly. The supervised program is applicable and can be reproduced at primary care unit or home for geriatric care and preventive actions.

Processing of the Escherichia coli leuX tRNA transcript, encoding tRNA(Leu5), requires either the 3'-->5' exoribonuclease polynucleotide phosphorylase or RNase P to remove the Rho-independent transcription terminator.

PubMed

Mohanty, Bijoy K; Kushner, Sidney R

2010-01-01

Here we report a unique processing pathway in Escherichia coli for tRNA(Leu5) in which the exoribonuclease polynucleotide phosphorylase (PNPase) removes the Rho-independent transcription terminator from the leuX transcript without requiring the RhlB RNA helicase. Our data demonstrate for the first time that PNPase can efficiently degrade an RNA substrate containing secondary structures in vivo. Furthermore, RNase P, an endoribonuclease that normally generates the mature 5'-ends of tRNAs, removes the leuX terminator inefficiently independent of PNPase activity. RNase P cleaves 4-7 nt downstream of the CCA determinant generating a substrate for RNase II, which removes an additional 3-4 nt. Subsequently, RNase T completes the 3' maturation process by removing the remaining 1-3 nt downstream of the CCA determinant. RNase E, G and Z are not involved in terminator removal. These results provide further evidence that the E. coli tRNA processing machinery is far more diverse than previously envisioned.

Evidence in the learning organization

PubMed Central

Crites, Gerald E; McNamara, Megan C; Akl, Elie A; Richardson, W Scott; Umscheid, Craig A; Nishikawa, James

2009-01-01

Background Organizational leaders in business and medicine have been experiencing a similar dilemma: how to ensure that their organizational members are adopting work innovations in a timely fashion. Organizational leaders in healthcare have attempted to resolve this dilemma by offering specific solutions, such as evidence-based medicine (EBM), but organizations are still not systematically adopting evidence-based practice innovations as rapidly as expected by policy-makers (the knowing-doing gap problem). Some business leaders have adopted a systems-based perspective, called the learning organization (LO), to address a similar dilemma. Three years ago, the Society of General Internal Medicine's Evidence-based Medicine Task Force began an inquiry to integrate the EBM and LO concepts into one model to address the knowing-doing gap problem. Methods During the model development process, the authors searched several databases for relevant LO frameworks and their related concepts by using a broad search strategy. To identify the key LO frameworks and consolidate them into one model, the authors used consensus-based decision-making and a narrative thematic synthesis guided by several qualitative criteria. The authors subjected the model to external, independent review and improved upon its design with this feedback. Results The authors found seven LO frameworks particularly relevant to evidence-based practice innovations in organizations. The authors describe their interpretations of these frameworks for healthcare organizations, the process they used to integrate the LO frameworks with EBM principles, and the resulting Evidence in the Learning Organization (ELO) model. They also provide a health organization scenario to illustrate ELO concepts in application. Conclusion The authors intend, by sharing the LO frameworks and the ELO model, to help organizations identify their capacities to learn and share knowledge about evidence-based practice innovations. The ELO model

Central leptin gene therapy ameliorates diabetes type 1 and 2 through two independent hypothalamic relays

PubMed Central

Kalra, Satya P.

2009-01-01

Although its role in energy homeostasis is firmly established, the evidence accumulated over a decade linking the adipocyte leptin -hypothalamus axis in the pathogenesis of diabetes mellitus has received little attention in the contemporary thinking. In this context various lines of evidence are collated here to show that (1) under the direction of leptin two independent relays emanating from the hypothalamus restrain insulin secretion from the pancreas and mobilize peripheral organs - liver, skeletal muscle and brown adipose tissue - to upregulate glucose disposal, and (2), leptin insufficiency in the hypothalamus produced by either leptinopenia or restriction of leptin transport across the blood brain barrier due to hyperleptinemia of obesity and aging, initiate antecedent pathophysiological sequalae of diabetes type 1 and 2. Further, we document here the efficacy of leptin replenishment in vivo, especially by supplying it to the hypothalamus with the aid of gene therapy, in preventing the antecedent pathophysiological sequalae-hyperinsulinemia, insulin resistance and hyperglycemia - in various animal models and clinical paradigms of diabetes type 1 and 2 with or without attendant obesity. Overall, the new insights on the long-lasting antidiabetic potential of two independent hypothalamic relays engendered by central leptin gene therapy and the preclinical safety indicators in rodents warrant further validation in subhuman primates and humans. PMID:19647774

47 CFR 64.904 - Independent audits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... independent auditor every two years, covering the prior two year period, or have a financial audit performed by an independent auditor every two years, covering the prior two year period. In either case, the... the auditor's report. At least 30 days prior to beginning the attestation engagement, the independent...

Culture and neuroscience: additive or synergistic?

PubMed Central

Dapretto, Mirella; Iacoboni, Marco

2010-01-01

The investigation of cultural phenomena using neuroscientific methods—cultural neuroscience (CN)—is receiving increasing attention. Yet it is unclear whether the integration of cultural study and neuroscience is merely additive, providing additional evidence of neural plasticity in the human brain, or truly synergistic, yielding discoveries that neither discipline could have achieved alone. We discuss how the parent fields to CN: cross-cultural psychology, psychological anthropology and cognitive neuroscience inform the investigation of the role of cultural experience in shaping the brain. Drawing on well-established methodologies from cross-cultural psychology and cognitive neuroscience, we outline a set of guidelines for CN, evaluate 17 CN studies in terms of these guidelines, and provide a summary table of our results. We conclude that the combination of culture and neuroscience is both additive and synergistic; while some CN methodologies and findings will represent the direct union of information from parent fields, CN studies employing the methodological rigor required by this logistically challenging new field have the potential to transform existing methodologies and produce unique findings. PMID:20083533

Resolution-independent surface rendering using programmable graphics hardware

DOEpatents

Loop, Charles T.; Blinn, James Frederick

2008-12-16

Surfaces defined by a Bezier tetrahedron, and in particular quadric surfaces, are rendered on programmable graphics hardware. Pixels are rendered through triangular sides of the tetrahedra and locations on the shapes, as well as surface normals for lighting evaluations, are computed using pixel shader computations. Additionally, vertex shaders are used to aid interpolation over a small number of values as input to the pixel shaders. Through this, rendering of the surfaces is performed independently of viewing resolution, allowing for advanced level-of-detail management. By individually rendering tetrahedrally-defined surfaces which together form complex shapes, the complex shapes can be rendered in their entirety.

Severe Acute Respiratory Syndrome Coronavirus Replication Is Severely Impaired by MG132 due to Proteasome-Independent Inhibition of M-Calpain

PubMed Central

Schneider, Martha; Ackermann, Kerstin; Stuart, Melissa; Wex, Claudia; Protzer, Ulrike; Schätzl, Hermann M.

2012-01-01

The ubiquitin-proteasome system (UPS) is involved in the replication of a broad range of viruses. Since replication of the murine hepatitis virus (MHV) is impaired upon proteasomal inhibition, the relevance of the UPS for the replication of the severe acute respiratory syndrome coronavirus (SARS-CoV) was investigated in this study. We demonstrate that the proteasomal inhibitor MG132 strongly inhibits SARS-CoV replication by interfering with early steps of the viral life cycle. Surprisingly, other proteasomal inhibitors (e.g., lactacystin and bortezomib) only marginally affected viral replication, indicating that the effect of MG132 is independent of proteasomal impairment. Induction of autophagy by MG132 treatment was excluded from playing a role, and no changes in SARS-CoV titers were observed during infection of wild-type or autophagy-deficient ATG5−/− mouse embryonic fibroblasts overexpressing the human SARS-CoV receptor, angiotensin-converting enzyme 2 (ACE2). Since MG132 also inhibits the cysteine protease m-calpain, we addressed the role of calpains in the early SARS-CoV life cycle using calpain inhibitors III (MDL28170) and VI (SJA6017). In fact, m-calpain inhibition with MDL28170 resulted in an even more pronounced inhibition of SARS-CoV replication (>7 orders of magnitude) than did MG132. Additional m-calpain knockdown experiments confirmed the dependence of SARS-CoV replication on the activity of the cysteine protease m-calpain. Taken together, we provide strong experimental evidence that SARS-CoV has unique replication requirements which are independent of functional UPS or autophagy pathways compared to other coronaviruses. Additionally, this work highlights an important role for m-calpain during early steps of the SARS-CoV life cycle. PMID:22787216

Independent Review Support for Phoenix Mars Mission Robotic Arm Brush Motor Failure

NASA Technical Reports Server (NTRS)

McManamen, John P.; Pellicciotti, Joseph; DeKramer, Cornelis; Dube, Michael J.; Peeler, Deborah; Muirhead, Brian K.; Sevilla, Donald R.; Sabahi, Dara; Knopp, Michael D.

2007-01-01

The Phoenix Project requested the NASA Engineering and Safety Center (NESC) perform an independent peer review of the Robotic Arm (RA) Direct Current (DC) motor brush anomalies that originated during the Mars Exploration Rover (MER) Project and recurred during the Phoenix Project. The request was to evaluate the Phoenix Project investigation efforts and provide an independent risk assessment. This includes a recommendation for additional work and assessment of the flight worthiness of the RA DC motors. Based on the investigation and findings contained within this report, the IRT concurs with the risk assessment Failure Cause / Corrective Action (FC/CA) by the project, "Failure Effect Rating "3"; Major Degradation or Total Loss of Function, Failure Cause/Corrective Action Rating Currently "4"; Unknown Cause, Uncertainty in Corrective Action."

Dietary fat intake promotes the development of hepatic steatosis independently from excess caloric consumption in a murine model.

PubMed

de Meijer, Vincent E; Le, Hau D; Meisel, Jonathan A; Akhavan Sharif, M Reza; Pan, Amy; Nosé, Vânia; Puder, Mark

2010-08-01

Nonalcoholic fatty liver disease results from overconsumption and is a significant and increasing cause of liver failure. The type of diet that is conducive to the development of this disease has not been established, and evidence-based treatment options are currently lacking. We hypothesized that the onset of hepatic steatosis is linked to the consumption of a diet with a high fat content, rather than related to excess caloric intake. In addition, we also hypothesized that fully manifested hepatic steatosis could be reversed by reducing the fat percentage in the diet of obese mice. C57BL/6J male mice were fed either a purified rodent diet containing 10% fat or a diet with 60% of calories derived from fat. A pair-feeding design was used to distinguish the effects of dietary fat content and caloric intake on dietary-induced hepatic lipid accumulation and associated injury. Livers were analyzed by quantitative reverse transcriptase polymerase chain reaction for lipid metabolism-related gene expression. After 9 weeks, mice on the 60%-fat diet exhibited more weight gain, insulin resistance, and hepatic steatosis compared with mice on a 10%-fat diet with equal caloric intake. Furthermore, mice with established metabolic syndrome at 9 weeks showed reversal of hepatic steatosis, insulin resistance, and obesity when switched to a 10%-fat diet for an additional 9 weeks, independent of caloric intake. Quantitative reverse transcriptase polymerase chain reaction revealed that transcripts related to both de novo lipogenesis and increased uptake of free fatty acids were significantly up-regulated in mice pair-fed a 60%-fat diet compared with 10%-fat-fed animals. Dietary fat content, independent from caloric intake, is a crucial factor in the development of hepatic steatosis, obesity, and insulin resistance in the C57BL/6J diet-induced obesity model caused by increased uptake of free fatty acids and de novo lipogenesis. In addition, once established, all these features of the

Neurophysiology of spontaneous facial expressions: I. Motor control of the upper and lower face is behaviorally independent in adults.

PubMed

Ross, Elliott D; Gupta, Smita S; Adnan, Asif M; Holden, Thomas L; Havlicek, Joseph; Radhakrishnan, Sridhar

2016-03-01

Facial expressions are described traditionally as monolithic entities. However, humans have the capacity to produce facial blends, in which the upper and lower face simultaneously display different emotional expressions. This, in turn, has led to the Component Theory of facial expressions. Recent neuroanatomical studies in monkeys have demonstrated that there are separate cortical motor areas for controlling the upper and lower face that, presumably, also occur in humans. The lower face is represented on the posterior ventrolateral surface of the frontal lobes in the primary motor and premotor cortices and the upper face is represented on the medial surface of the posterior frontal lobes in the supplementary motor and anterior cingulate cortices. Our laboratory has been engaged in a series of studies exploring the perception and production of facial blends. Using high-speed videography, we began measuring the temporal aspects of facial expressions to develop a more complete understanding of the neurophysiology underlying facial expressions and facial blends. The goal of the research presented here was to determine if spontaneous facial expressions in adults are predominantly monolithic or exhibit independent motor control of the upper and lower face. We found that spontaneous facial expressions are very complex and that the motor control of the upper and lower face is overwhelmingly independent, thus robustly supporting the Component Theory of facial expressions. Seemingly monolithic expressions, be they full facial or facial blends, are most likely the result of a timing coincident rather than a synchronous coordination between the ventrolateral and medial cortical motor areas responsible for controlling the lower and upper face, respectively. In addition, we found evidence that the right and left face may also exhibit independent motor control, thus supporting the concept that spontaneous facial expressions are organized predominantly across the horizontal facial

Serum phosphorus is related to left ventricular remodeling independent of renal function in hospitalized patients with chronic kidney disease.

PubMed

Zou, Jun; Yu, Yi; Wu, Ping; Lin, Fu-Jun; Yao, Yao; Xie, Yun; Jiang, Geng-Ru

2016-10-15

Increasing evidence indicated that phosphorus emerged as an important cardiovascular risk factor in patients with chronic kidney disease (CKD). The fact that serum phosphorus was closely linked to vascular and valvar calcification may account for one important reason. However, left ventricular remodeling may also serve as another potential mechanism of the cardiac toxicity of phosphorus. In the present study, we evaluated the association of serum phosphorus with left ventricular remodeling. We investigated consecutive hospitalized patients with pre-dialysis CKD, who did not have symptomatic heart failure or take any phosphorus binder or calcitriol medications. Transthoracic echocardiography was applied to assess their left ventricular remodeling indices, both structural and functional. The 296 study subjects (mean age 56.4years) included 169 (57.1%) men, 203 (68.6%) hypertensive patients. In addition to gender, systolic blood pressure, and estimated glomerular filtration rate, serum phosphorus was an independent determinant of left ventricular mass index (LVMI, P=0.001). Similarly, serum phosphorus was also a determinant of left ventricular end diastolic dimension (P=0.0003), but not of relative wall thickness. In multivariate logistic analyses, serum phosphorus was significantly and independently associated with the prevalence of left ventricular hypertrophy (LVH, odds ratio [OR] 2.38 for each 1mmol/L increase, 95% CI 1.20-4.75, P=0.01). Moreover, the association was only confirmatory in eccentric LVH (OR 3.01, 95% CI 1.43-6.32, P=0.003) but not in concentric LVH (1.38, 95% CI, 0.54-3.49, P=0.50). Serum phosphorus was significantly and independently associated with LVMI and the prevalence of eccentric LVH in hospitalized patients with CKD. Copyright © 2016. Published by Elsevier Ireland Ltd.

Characteristics of Rural Communities with a Sole, Independently Owned Pharmacy.

PubMed

Nattinger, Matthew; Ullrich, Fred; Mueller, Keith J

2015-04-01

Prior RUPRI Center policy briefs have described the role of rural pharmacies in providing many essential clinical services (in addition to prescription and nonprescription medications), such as blood pressure monitoring, immunizations, and diabetes counseling, and the adverse effects of Medicare Part D negotiated networks on the financial viability of rural pharmacies.1 Because rural pharmacies play such a broad role in health care delivery, pharmacy closures can sharply reduce access to essential health care services in rural and underserved communities. These closures are of particular concern in rural areas served by a sole, independently owned pharmacy (i.e., a pharmacy unaffiliated with a chain or franchise). This policy brief characterizes the population of rural areas served by a sole, independently owned pharmacy. Dependent on a sole pharmacy, these areas are at highest risk to lose access to many essential clinical services. Key Findings. (1) In 2014 over 2.7 million people lived in 663 rural communities served by a sole, independently owned pharmacy. (2) More than one-quarter of these residents (27.9 percent) were living below 150 percent of the federal poverty level. (3) Based on estimates from 2012, a substantial portion of the residents of these areas were dependent on public insurance (i.e., Medicare and/or Medicaid, 20.5 percent) or were uninsured (15.0 percent). (4) If the sole, independent retail pharmacy in these communities were to close, the next closest retail pharmacy would be over 10 miles away for a majority of rural communities (69.7 percent).

Vestibular Rehabilitation for Peripheral Vestibular Hypofunction: An Evidence-Based Clinical Practice Guideline

PubMed Central

Herdman, Susan J.; Whitney, Susan L.; Cass, Stephen P.; Clendaniel, Richard A.; Fife, Terry D.; Furman, Joseph M.; Getchius, Thomas S. D.; Goebel, Joel A.; Shepard, Neil T.; Woodhouse, Sheelah N.

2016-01-01

Background: Uncompensated vestibular hypofunction results in postural instability, visual blurring with head movement, and subjective complaints of dizziness and/or imbalance. We sought to answer the question, “Is vestibular exercise effective at enhancing recovery of function in people with peripheral (unilateral or bilateral) vestibular hypofunction?” Methods: A systematic review of the literature was performed in 5 databases published after 1985 and 5 additional sources for relevant publications were searched. Article types included meta-analyses, systematic reviews, randomized controlled trials, cohort studies, case control series, and case series for human subjects, published in English. One hundred thirty-five articles were identified as relevant to this clinical practice guideline. Results/Discussion: Based on strong evidence and a preponderance of benefit over harm, clinicians should offer vestibular rehabilitation to persons with unilateral and bilateral vestibular hypofunction with impairments and functional limitations related to the vestibular deficit. Based on strong evidence and a preponderance of harm over benefit, clinicians should not include voluntary saccadic or smooth-pursuit eye movements in isolation (ie, without head movement) as specific exercises for gaze stability. Based on moderate evidence, clinicians may offer specific exercise techniques to target identified impairments or functional limitations. Based on moderate evidence and in consideration of patient preference, clinicians may provide supervised vestibular rehabilitation. Based on expert opinion extrapolated from the evidence, clinicians may prescribe a minimum of 3 times per day for the performance of gaze stability exercises as 1 component of a home exercise program. Based on expert opinion extrapolated from the evidence (range of supervised visits: 2-38 weeks, mean = 10 weeks), clinicians may consider providing adequate supervised vestibular rehabilitation sessions for the

Evidence and evidence gaps of laryngeal cancer surgery

PubMed Central

Wiegand, Susanne

2016-01-01

Surgical treatment of laryngeal cancer has been established for decades. In addition to total laryngectomy, which was first performed in 1873, a large number or organ preservation surgical techniques, like open partial laryngectomy, transoral laser microsurgery, and transoral robotic surgery have been developed. Studies on laryngeal cancer surgery are mainly retrospective case series and cohort studies. The evolution of chemoradiation protocols and their analysis in prospective randomized trials have led to an increasing acceptance of non-surgical treatment procedures. In addition to an improvement of prognosis, in recent years the preservation of function and maintenance of life quality after primary therapy of laryngeal cancer has increasingly become the focus of therapy planning. Significant late toxicity after chemoradiation has been identified as an important issue. This leads to a reassessment of surgical concepts and initiation of studies on laryngeal cancer surgery which was additionally stimulated by the advent of transoral robotic surgery in the US. Improving the evidence base of laryngeal cancer surgery by successful establishment of surgical trials should be the future goal. PMID:28025603

ULK1 Regulates Melanin Levels in MNT-1 Cells Independently of mTORC1

PubMed Central

Tooze, Sharon A.

2013-01-01

Melanosomes are lysosome-related organelles that serve as specialized sites of melanin synthesis and storage in melanocytes. The progression of melanosomes through the different stages of their formation requires trafficking of specific proteins and membrane constituents in a sequential manner, which is likely to deploy ubiquitous cellular machinery along with melanocyte-specific proteins. Recent evidence revealed a connection between melanogenesis and the autophagy machinery, suggesting a novel role for members of the latter in melanocytes. Here we focused on ULK1, a key autophagy protein which is negatively regulated by mTORC1, to assess its potential role in melanogenesis in MNT-1 cells. We found that ULK1 depletion causes an increase in melanin levels, suggesting an inhibitory function for this protein in melanogenesis. Furthermore, this increase was accompanied by increased transcription of MITF (microphthalmia-associated transcription factor) and tyrosinase and by elevated protein levels of tyrosinase, the rate-limiting factor in melanin biogenesis. We also provide evidence to show that ULK1 function in this context is independent of the canonical ULK1 autophagy partners, ATG13 and FIP200. Furthermore we show that regulation of melanogenesis by ULK1 is independent of mTORC1 inhibition. Our data thus provide intriguing insights regarding the involvement of the key regulatory autophagy machinery in melanogenesis. PMID:24066173

ULK1 regulates melanin levels in MNT-1 cells independently of mTORC1.

PubMed

Kalie, Eyal; Razi, Minoo; Tooze, Sharon A

2013-01-01

Melanosomes are lysosome-related organelles that serve as specialized sites of melanin synthesis and storage in melanocytes. The progression of melanosomes through the different stages of their formation requires trafficking of specific proteins and membrane constituents in a sequential manner, which is likely to deploy ubiquitous cellular machinery along with melanocyte-specific proteins. Recent evidence revealed a connection between melanogenesis and the autophagy machinery, suggesting a novel role for members of the latter in melanocytes. Here we focused on ULK1, a key autophagy protein which is negatively regulated by mTORC1, to assess its potential role in melanogenesis in MNT-1 cells. We found that ULK1 depletion causes an increase in melanin levels, suggesting an inhibitory function for this protein in melanogenesis. Furthermore, this increase was accompanied by increased transcription of MITF (microphthalmia-associated transcription factor) and tyrosinase and by elevated protein levels of tyrosinase, the rate-limiting factor in melanin biogenesis. We also provide evidence to show that ULK1 function in this context is independent of the canonical ULK1 autophagy partners, ATG13 and FIP200. Furthermore we show that regulation of melanogenesis by ULK1 is independent of mTORC1 inhibition. Our data thus provide intriguing insights regarding the involvement of the key regulatory autophagy machinery in melanogenesis.

Reference-Frame-Independent and Measurement-Device-Independent Quantum Key Distribution Using One Single Source

NASA Astrophysics Data System (ADS)

Li, Qian; Zhu, Changhua; Ma, Shuquan; Wei, Kejin; Pei, Changxing

2018-04-01

Measurement-device-independent quantum key distribution (MDI-QKD) is immune to all detector side-channel attacks. However, practical implementations of MDI-QKD, which require two-photon interferences from separated independent single-photon sources and a nontrivial reference alignment procedure, are still challenging with current technologies. Here, we propose a scheme that significantly reduces the experimental complexity of two-photon interferences and eliminates reference frame alignment by the combination of plug-and-play and reference frame independent MDI-QKD. Simulation results show that the secure communication distance can be up to 219 km in the finite-data case and the scheme has good potential for practical MDI-QKD systems.

Moving the Journey Towards Independence: Adolescents Transitioning to Successful Diabetes Self-Management.

PubMed

Babler, Elizabeth; Strickland, Carolyn June

2015-01-01

To gain a greater understanding of adolescent's experiences living with Type 1 diabetes mellitus (T1DM) and create a theoretical paradigm. Grounded theory as described by Glaser was used. Fifteen in-depth interviews were conducted with adolescent's ages 11-15 with T1DM. Symbolic interactionism is the theoretical framework for grounded theory. Data were collected; transcribed, coded, and analyzed simultaneously using constant comparative analysis and findings were grounded in the words of participants. A theoretical model was created with the concept of "normalizing". Normalizing was defined as the ability to integrate diabetes into one's daily life to make diabetes 'part of me'. Phase four of the model, and the focus of this manuscript was "Moving the Journey towards Independence" and included: 1) taking over care, 2) experiencing conflict with parents, and 3) realizing diabetes is hard. The major task for adolescents in this phase was separating from parents to independently manage diabetes. The normalizing task for this phase was: "taking on the burden of care". Adolescents described challenges with independent care and increased parental conflict including: fearing needles, forgetting insulin, feeling embarrassed and believing that diabetes was a burden in their life. Additionally, juggling the multiple responsibilities of home, school and work along with managing a chronic illness during adolescence is challenging. Transitioning to diabetes self-management is a challenge for adolescents. This model advances understanding of the moving processes in adolescents transitioning; additionally, hypotheses are presented that may be used for developing interventions to promote success in self-management. Copyright © 2015 Elsevier Inc. All rights reserved.

Measure of functional independence dominates discharge outcome prediction after inpatient rehabilitation for stroke.

PubMed

Brown, Allen W; Therneau, Terry M; Schultz, Billie A; Niewczyk, Paulette M; Granger, Carl V

2015-04-01

Identifying clinical data acquired at inpatient rehabilitation admission for stroke that accurately predict key outcomes at discharge could inform the development of customized plans of care to achieve favorable outcomes. The purpose of this analysis was to use a large comprehensive national data set to consider a wide range of clinical elements known at admission to identify those that predict key outcomes at rehabilitation discharge. Sample data were obtained from the Uniform Data System for Medical Rehabilitation data set with the diagnosis of stroke for the years 2005 through 2007. This data set includes demographic, administrative, and medical variables collected at admission and discharge and uses the FIM (functional independence measure) instrument to assess functional independence. Primary outcomes of interest were functional independence measure gain, length of stay, and discharge to home. The sample included 148,367 people (75% white; mean age, 70.6±13.1 years; 97% with ischemic stroke) admitted to inpatient rehabilitation a mean of 8.2±12 days after symptom onset. The total functional independence measure score, the functional independence measure motor subscore, and the case-mix group were equally the strongest predictors for any of the primary outcomes. The most clinically relevant 3-variable model used the functional independence measure motor subscore, age, and walking distance at admission (r(2)=0.107). No important additional effect for any other variable was detected when added to this model. This analysis shows that a measure of functional independence in motor performance and age at rehabilitation hospital admission for stroke are predominant predictors of outcome at discharge in a uniquely large US national data set. © 2015 American Heart Association, Inc.

Immunological properties of the primer-independent glucosyltransferase of Streptococcus mutans serotypes d and g.

PubMed

Yamashita, Y; Shigeoka, T; Hanada, N; Takehara, T

1988-05-01

Streptococcus mutans serotype g secretes at least three kinds of glucosyltransferase with different enzymological and immunological properties. One of them is a primer-independent enzyme and seems to be the source of primer for the others, both of which are primer-dependent enzymes. Recently, we purified the primer-independent enzyme, the third glucosyltransferase in this group from S. mutans strain AHT-k serotype g. In the present study, we examined the specificity of the antiserum against the primer-independent glucosyltransferase using extracellular culture-conditioned fluids of many strains of the various serotypes of S. mutans. The antiserum cross-reacted with the extracellular culture fluids from strains of serotypes d and a, in addition to serotype g, but not with those of other serotypes, indicating that the primer-independent glucosyltransferase is secreted by the S. sobrinus and S. cricetus, but not by S. mutans and S. rattus. The antiserum did not completely inhibit the activity of the enzyme, even at more than twofold antibody excess, determined by indirect precipitation with immobilized staphylococcal protein A.

Public Policy and Independent Higher Education.

ERIC Educational Resources Information Center

Foster, Marilyn K.

The relationship of public policy and independent higher education is examined, and the antecedents of an intentional public policy are traced. A comprehensive public policy for the independent sector, which was issued in 1974 by the National Council of Independent Colleges and Universities (NCICU) is discussed in the context of social ideals and…

45 CFR 1309.44 - Independent analysis.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Independent analysis. 1309.44 Section 1309.44... § 1309.44 Independent analysis. (a) The responsible HHS official may direct the grantee applying for funds to acquire or make major renovations to a facility to obtain an independent analysis of the cost...

45 CFR 1309.44 - Independent analysis.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 4 2011-10-01 2011-10-01 false Independent analysis. 1309.44 Section 1309.44... § 1309.44 Independent analysis. (a) The responsible HHS official may direct the grantee applying for funds to acquire or make major renovations to a facility to obtain an independent analysis of the cost...

Renin Angiotensin Aldosterone System Inhibitors in Hypertension: Is There Evidence for Benefit Independent of Blood Pressure Reduction?

PubMed

Bavishi, Chirag; Bangalore, Sripal; Messerli, Franz H

The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in the pathogenesis of hypertension (HTN). Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are first line anti-HTN drug classes that are potent, effective and largely safe. Direct renin inhibitors (DRIs) have shown similar blood pressure (BP) reduction but more side effects. The efficacy of ACEIs and ARBs (for cardiovascular, cerebrovascular and renal protection) has been promoted to extend beyond what could be explained by BP reduction alone. In the current review, we will briefly discuss the (1) pathophysiology of renin-angiotensin-aldosterone system (RAAS) system, (2) clinical evidence for ACEIs, ARBs and DRIs in HTN, (3) comparison of ACEIs vs. ARBs and combination therapy, (4) role of RAAS inhibitors in specific patient populations, (5) safety profile of RAAS inhibitors, and (6) guideline recommendations and future perspectives. Closer scrutiny of outcome data shows little, if any, evidence that the efficacy of RAAS blockers in HTN extends beyond BP reduction. Copyright © 2016 Elsevier Inc. All rights reserved.

The interdependence of perceived confession voluntariness and case evidence.

PubMed

Greenspan, Rachel; Scurich, Nicholas

2016-12-01

The current research investigated the mechanisms by which perceptions of confession evidence both influence and are influenced by perceptions of other case evidence using the theoretical framework of coherence-based reasoning (CBR). CBR posits that ambiguity and uncertainty are eschewed by artificially imposing consistency between pieces of evidence through bidirectional reasoning: Inferences about evidence lead to a preferred verdict, which in turn radiates backward to influence the perception of evidence. Two studies tested the CBR account with regard to confessions. An online sample of participants evaluated confession and nonconfession evidence at pretest and posttest. Study 1 revealed that, during pretest, participants (N = 119) deemed the evidence independent and nonprobative and the confession to be voluntary. However, at posttest, in the context of a criminal trial, participants considered the same evidence interrelated and highly inculpatory or exculpatory, depending on their verdict. Moreover, participants who voted to convict deemed the confession substantially voluntary, whereas participants who voted to acquit deemed it involuntary. Study 2 experimentally manipulated the strength of the nonconfession evidence in an effort to push participants (N = 127) toward a particular verdict. The same patterns of results emerged but were conditional on the strength of the nonconfession evidence: Strong case evidence caused the confession to be perceived as more voluntary, despite the fact that the confession was held constant. These findings replicate the coherence effect in a new domain and suggest that judges conducting harmless error analysis or making admissibility decisions might underappreciate the impact of confession evidence on jurors' verdicts. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Identification of ER-000444793, a Cyclophilin D-independent inhibitor of mitochondrial permeability transition, using a high-throughput screen in cryopreserved mitochondria

PubMed Central

Briston, Thomas; Lewis, Sian; Koglin, Mumta; Mistry, Kavita; Shen, Yongchun; Hartopp, Naomi; Katsumata, Ryosuke; Fukumoto, Hironori; Duchen, Michael R.; Szabadkai, Gyorgy; Staddon, James M.; Roberts, Malcolm; Powney, Ben

2016-01-01

Growing evidence suggests persistent mitochondrial permeability transition pore (mPTP) opening is a key pathophysiological event in cell death underlying a variety of diseases. While it has long been clear the mPTP is a druggable target, current agents are limited by off-target effects and low therapeutic efficacy. Therefore identification and development of novel inhibitors is necessary. To rapidly screen large compound libraries for novel mPTP modulators, a method was exploited to cryopreserve large batches of functionally active mitochondria from cells and tissues. The cryopreserved mitochondria maintained respiratory coupling and ATP synthesis, Ca2+ uptake and transmembrane potential. A high-throughput screen (HTS), using an assay of Ca2+-induced mitochondrial swelling in the cryopreserved mitochondria identified ER-000444793, a potent inhibitor of mPTP opening. Further evaluation using assays of Ca2+-induced membrane depolarisation and Ca2+ retention capacity also indicated that ER-000444793 acted as an inhibitor of the mPTP. ER-000444793 neither affected cyclophilin D (CypD) enzymatic activity, nor displaced of CsA from CypD protein, suggesting a mechanism independent of CypD inhibition. Here we identified a novel, CypD-independent inhibitor of the mPTP. The screening approach and compound described provides a workflow and additional tool to aid the search for novel mPTP modulators and to help understand its molecular nature. PMID:27886240

Fibrates upregulate TRB3 in lymphocytes independent of PPAR alpha by augmenting CCAAT/enhancer-binding protein beta (C/EBP beta) expression.

PubMed

Selim, Erin; Frkanec, Julie T; Cunard, Robyn

2007-02-01

Fibrates, which function by binding and activating peroxisome proliferator-activated receptor alpha (PPARalpha), have been used successfully to treat hyperlipidemia and atherosclerosis. Increasing evidence suggests that in addition to their lipid lowering activities these medications also function as immunosuppressive agents. Tribbles is a Drosophila protein that slows cell cycle progression, and its mammalian homolog, TRB3 interferes with insulin-induced activation of AKT. In these studies we demonstrate that fibrates upregulate TRB3 expression in mitogen-activated lymphocytes. Interestingly, in lymphocytes fibrates augment TRB3 expression in both PPARalpha wildtype and knockout mice, suggesting that upregulation of this protein occurs in a PPARalpha-independent manner. Fibrates activate a proximal TRB3 promoter construct and mutation or partial deletion of a potential PPAR response element does not alter the ability of fibrates to drive TRB3 expression. Subsequent studies reveal that fibrates upregulate C/EBPbeta and CHOP in lymphocytes and mutation of potential C/EBPbeta and CHOP consensus sequences abrogates the ability of fibrates to upregulate TRB3 promoter activity. Accordingly, fibrates enhance the recruitment of C/EBPbeta and CHOP to the proximal TRB3 promoter. Finally, TRB3 expression in lymphocytes induces G2 cell cycle delay and cellular depletion. These studies outline a novel PPARalpha-independent mechanism of action of fibrates and document for the first time the expression of TRB3 in activated lymphocytes.

Switch-Independent Task Representations in Frontal and Parietal Cortex.

PubMed

Loose, Lasse S; Wisniewski, David; Rusconi, Marco; Goschke, Thomas; Haynes, John-Dylan

2017-08-16

Alternating between two tasks is effortful and impairs performance. Previous fMRI studies have found increased activity in frontoparietal cortex when task switching is required. One possibility is that the additional control demands for switch trials are met by strengthening task representations in the human brain. Alternatively, on switch trials, the residual representation of the previous task might impede the buildup of a neural task representation. This would predict weaker task representations on switch trials, thus also explaining the performance costs. To test this, male and female participants were cued to perform one of two similar tasks, with the task being repeated or switched between successive trials. Multivoxel pattern analysis was used to test which regions encode the tasks and whether this encoding differs between switch and repeat trials. As expected, we found information about task representations in frontal and parietal cortex, but there was no difference in the decoding accuracy of task-related information between switch and repeat trials. Using cross-classification, we found that the frontoparietal cortex encodes tasks using a generalizable spatial pattern in switch and repeat trials. Therefore, task representations in frontal and parietal cortex are largely switch independent. We found no evidence that neural information about task representations in these regions can explain behavioral costs usually associated with task switching. SIGNIFICANCE STATEMENT Alternating between two tasks is effortful and slows down performance. One possible explanation is that the representations in the human brain need time to build up and are thus weaker on switch trials, explaining performance costs. Alternatively, task representations might even be enhanced to overcome the previous task. Here, we used a combination of fMRI and a brain classifier to test whether the additional control demands under switching conditions lead to an increased or decreased strength

Constrained independent component analysis approach to nonobtrusive pulse rate measurements

NASA Astrophysics Data System (ADS)

Tsouri, Gill R.; Kyal, Survi; Dianat, Sohail; Mestha, Lalit K.

2012-07-01

Nonobtrusive pulse rate measurement using a webcam is considered. We demonstrate how state-of-the-art algorithms based on independent component analysis suffer from a sorting problem which hinders their performance, and propose a novel algorithm based on constrained independent component analysis to improve performance. We present how the proposed algorithm extracts a photoplethysmography signal and resolves the sorting problem. In addition, we perform a comparative study between the proposed algorithm and state-of-the-art algorithms over 45 video streams using a finger probe oxymeter for reference measurements. The proposed algorithm provides improved accuracy: the root mean square error is decreased from 20.6 and 9.5 beats per minute (bpm) for existing algorithms to 3.5 bpm for the proposed algorithm. An error of 3.5 bpm is within the inaccuracy expected from the reference measurements. This implies that the proposed algorithm provided performance of equal accuracy to the finger probe oximeter.

An Ultra-wideband and Polarization-independent Metasurface for RCS Reduction

PubMed Central

Su, Pei; Zhao, Yongjiu; Jia, Shengli; Shi, Wenwen; Wang, Hongli

2016-01-01

In this paper, an ultra-wideband and polarization-independent metasurface for radar cross section (RCS) reduction is proposed. The unit cell of the metasurface operates in a linear cross-polarization scheme in a broad band. The phase and amplitude of cross-polarized reflection can be separately controlled by its geometry and rotation angle. Based on the diffuse reflection theory, a 3-bit coding metasurface is designed to reduce the RCS in an ultra-wide band. The wideband property of the metasurface benefits from the wideband cross polarization conversion and flexible phase modulation. In addition, the polarization-independent feature of the metasurface is achieved by tailoring the rotation angle of each element. Both the simulated and measured results demonstrate that the proposed metasurface can reduce the RCS significantly in an ultra-wide frequency band for both normal and oblique incidences, which makes it promising in the applications such as electromagnetic cloaking. PMID:26864084

System-independent characterization of materials using dual-energy computed tomography

DOE PAGES

Azevedo, Stephen G.; Martz, Jr., Harry E.; Aufderheide, III, Maurice B.; ...

2016-02-01

In this study, we present a new decomposition approach for dual-energy computed tomography (DECT) called SIRZ that provides precise and accurate material description, independent of the scanner, over diagnostic energy ranges (30 to 200 keV). System independence is achieved by explicitly including a scanner-specific spectral description in the decomposition method, and a new X-ray-relevant feature space. The feature space consists of electron density, ρ e, and a new effective atomic number, Z e, which is based on published X-ray cross sections. Reference materials are used in conjunction with the system spectral response so that additional beam-hardening correction is not necessary.more » The technique is tested against other methods on DECT data of known specimens scanned by diverse spectra and systems. Uncertainties in accuracy and precision are less than 3% and 2% respectively for the (ρ e, Z e) results compared to prior methods that are inaccurate and imprecise (over 9%).« less

Independent Community Pharmacists' Perspectives on Compounding in Contemporary Pharmacy Education

PubMed Central

McPherson, Timothy B.; Fontane, Patrick E.; Berry, Tricia; Chereson, Rasma; Bilger, Rhonda

2009-01-01

Objectives To identify compounding practices of independent community pharmacy practitioners in order to make recommendations for the development of curricular objectives for doctor of pharmacy (PharmD) programs. Methods Independent community practitioners were asked about compounding regarding their motivations, common activities, educational exposures, and recommendations for PharmD education. Results Most respondents (69%) accepted compounding as a component of pharmaceutical care and compounded dermatological preparations for local effects, oral solutions, and suspensions at least once a week. Ninety-five percent were exposed to compounding in required pharmacy school courses and most (98%) who identified compounding as a professional service offered in their pharmacy sought additional postgraduate compounding education. Regardless of the extent of compounding emphasis in the practices surveyed, 84% stated that PharmD curricula should include compounding. Conclusions Pharmacy schools should define compounding curricular objectives and develop compounding abilities in a required laboratory course to prepare graduates for pharmaceutical care practice. PMID:19564997

Constrained independent component analysis approach to nonobtrusive pulse rate measurements.

PubMed

Tsouri, Gill R; Kyal, Survi; Dianat, Sohail; Mestha, Lalit K

2012-07-01

Nonobtrusive pulse rate measurement using a webcam is considered. We demonstrate how state-of-the-art algorithms based on independent component analysis suffer from a sorting problem which hinders their performance, and propose a novel algorithm based on constrained independent component analysis to improve performance. We present how the proposed algorithm extracts a photoplethysmography signal and resolves the sorting problem. In addition, we perform a comparative study between the proposed algorithm and state-of-the-art algorithms over 45 video streams using a finger probe oxymeter for reference measurements. The proposed algorithm provides improved accuracy: the root mean square error is decreased from 20.6 and 9.5 beats per minute (bpm) for existing algorithms to 3.5 bpm for the proposed algorithm. An error of 3.5 bpm is within the inaccuracy expected from the reference measurements. This implies that the proposed algorithm provided performance of equal accuracy to the finger probe oximeter.

A Gaze Independent Brain-Computer Interface Based on Visual Stimulation through Closed Eyelids

NASA Astrophysics Data System (ADS)

Hwang, Han-Jeong; Ferreria, Valeria Y.; Ulrich, Daniel; Kilic, Tayfun; Chatziliadis, Xenofon; Blankertz, Benjamin; Treder, Matthias

2015-10-01

A classical brain-computer interface (BCI) based on visual event-related potentials (ERPs) is of limited application value for paralyzed patients with severe oculomotor impairments. In this study, we introduce a novel gaze independent BCI paradigm that can be potentially used for such end-users because visual stimuli are administered on closed eyelids. The paradigm involved verbally presented questions with 3 possible answers. Online BCI experiments were conducted with twelve healthy subjects, where they selected one option by attending to one of three different visual stimuli. It was confirmed that typical cognitive ERPs can be evidently modulated by the attention of a target stimulus in eyes-closed and gaze independent condition, and further classified with high accuracy during online operation (74.58% ± 17.85 s.d.; chance level 33.33%), demonstrating the effectiveness of the proposed novel visual ERP paradigm. Also, stimulus-specific eye movements observed during stimulation were verified as reflex responses to light stimuli, and they did not contribute to classification. To the best of our knowledge, this study is the first to show the possibility of using a gaze independent visual ERP paradigm in an eyes-closed condition, thereby providing another communication option for severely locked-in patients suffering from complex ocular dysfunctions.

Evidence flowers: An innovative, visual method of presenting "best evidence" summaries to health professional and lay audiences.

PubMed

Babatunde, O O; Tan, V; Jordan, J L; Dziedzic, K; Chew-Graham, C A; Jinks, C; Protheroe, J; van der Windt, D A

2018-06-01

Barriers to dissemination and engagement with evidence pose a threat to implementing evidence-based medicine. Understanding, retention, and recall can be enhanced by visual presentation of information. The aim of this exploratory research was to develop and evaluate the accessibility and acceptability of visual summaries for presenting evidence syntheses with multiple exposures or outcomes to professional and lay audiences. "Evidence flowers" were developed as a visual method of presenting data from 4 case scenarios: 2 complex evidence syntheses with multiple outcomes, Cochrane reviews, and clinical guidelines. Petals of evidence flowers were coloured according to the GRADE evidence rating system to display key findings and recommendations from the evidence summaries. Application of evidence flowers was observed during stakeholder workshops. Evaluation and feedback were conducted via questionnaires and informal interviews. Feedback from stakeholders on the evidence flowers collected from workshops, questionnaires, and interviews was encouraging and helpful for refining the design of the flowers. Comments were made on the content and design of the flowers, as well as the usability and potential for displaying different types of evidence. Evidence flowers are a novel and visually stimulating method for presenting research evidence from evidence syntheses with multiple exposures or outcomes, Cochrane reviews, and clinical guidelines. To promote access and engagement with research evidence, evidence flowers may be used in conjunction with other evidence synthesis products, such as (lay) summaries, evidence inventories, rapid reviews, and clinical guidelines. Additional research on potential adaptations and applications of the evidence flowers may further bridge the gap between research evidence and clinical practice. Copyright © 2018 John Wiley & Sons, Ltd.

78 FR 29364 - Independent Power Producers of New York, Inc. v. New York Independent System Operator, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-20

... Power Producers of New York, Inc. v. New York Independent System Operator, Inc. Notice of Complaint Take notice that on May 10, 2013, Independent Power Producers of New York, Inc. (IPPNY or Complainant) filed a complaint against New York Independent System Operator, Inc. (NYISO or Respondent), pursuant to [[Page 29365...

Sentence-Based Attentional Mechanisms in Word Learning: Evidence from a Computational Model

PubMed Central

Alishahi, Afra; Fazly, Afsaneh; Koehne, Judith; Crocker, Matthew W.

2012-01-01

When looking for the referents of novel nouns, adults and young children are sensitive to cross-situational statistics (Yu and Smith, 2007; Smith and Yu, 2008). In addition, the linguistic context that a word appears in has been shown to act as a powerful attention mechanism for guiding sentence processing and word learning (Landau and Gleitman, 1985; Altmann and Kamide, 1999; Kako and Trueswell, 2000). Koehne and Crocker (2010, 2011) investigate the interaction between cross-situational evidence and guidance from the sentential context in an adult language learning scenario. Their studies reveal that these learning mechanisms interact in a complex manner: they can be used in a complementary way when context helps reduce referential uncertainty; they influence word learning about equally strongly when cross-situational and contextual evidence are in conflict; and contextual cues block aspects of cross-situational learning when both mechanisms are independently applicable. To address this complex pattern of findings, we present a probabilistic computational model of word learning which extends a previous cross-situational model (Fazly et al., 2010) with an attention mechanism based on sentential cues. Our model uses a framework that seamlessly combines the two sources of evidence in order to study their emerging pattern of interaction during the process of word learning. Simulations of the experiments of (Koehne and Crocker, 2010, 2011) reveal an overall pattern of results that are in line with their findings. Importantly, we demonstrate that our model does not need to explicitly assign priority to either source of evidence in order to produce these results: learning patterns emerge as a result of a probabilistic interaction between the two clue types. Moreover, using a computational model allows us to examine the developmental trajectory of the differential roles of cross-situational and sentential cues in word learning. PMID:22783211

Effectiveness of mifamurtide in addition to standard chemotherapy for high-grade osteosarcoma: a systematic review.

PubMed

Jimmy, Rincy; Stern, Cindy; Lisy, Karolina; White, Sarahlouise

2017-08-01

Osteosarcoma mostly occurs during the period of rapid bone growth in children and adolescents as high-grade osteosarcomas. Current treatment recommended for high-grade non-metastatic and metastatic and/or relapsed osteosarcoma involves neoadjuvant multiagent conventional chemotherapy, followed by surgical resection of macroscopically detected tumor and postoperative adjuvant chemotherapy. However, residual micrometastatic deposits that develop following surgery have shown resistance to postoperative/adjuvant chemotherapy. Therefore, there is a critical need for more effective and innovative therapeutic approaches such as immune stimulatory agents. The most extensively studied immune stimulatory agent in the treatment of osteosarcoma is mifamurtide. The aim of this systematic review was to identify and synthesize the evidence on the effectiveness of mifamurtide in addition to standard chemotherapy on survival outcomes. To present the best available evidence on the treatment of high-grade non-metastatic and metastatic osteosarcoma with mifamurtide in addition to standard chemotherapy. All populations of patients regardless of age, gender or ethnicity with high-grade, resectable, non-metastatic and metastatic osteosarcoma based on histological diagnosis. This review focused on intravenous infusion of either of the pharmaceutical formulations of mifamurtide (MTP-PE or L-MTP-PE) in addition to standard chemotherapy, and the comparator was chemotherapy alone. This review considered any experimental study design including randomized controlled trials, non-randomized trials and quasi-experimental studies. The primary outcomes of interest were event-free survival, overall survival and recurrence of osteosarcoma. Secondary outcomes that were considered included health-related quality of life and any mifamurtide-related adverse events. A search for published and unpublished literature in English was undertaken (seven published literature databases, four unpublished literature

77 FR 60482 - Yankee Atomic Electric Company; Yankee Rowe Independent Spent Fuel Storage Installation, Staff...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-03

... Company; Yankee Rowe Independent Spent Fuel Storage Installation, Staff Evaluation; Exemption 1.0... exemption requests, the NRC staff believes that YAEC should be granted exemptions from the following.... Additional information regarding the NRC (staff) evaluation is documented in a Safety Evaluation Report that...

Independent Orbiter Assessment (IOA): Analysis of the instrumentation subsystem

NASA Technical Reports Server (NTRS)

Howard, B. S.

1986-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The independent analysis results for the Instrumentation Subsystem are documented. The Instrumentation Subsystem (SS) consists of transducers, signal conditioning equipment, pulse code modulation (PCM) encoding equipment, tape recorders, frequency division multiplexers, and timing equipment. For this analysis, the SS is broken into two major groupings: Operational Instrumentation (OI) equipment and Modular Auxiliary Data System (MADS) equipment. The OI equipment is required to acquire, condition, scale, digitize, interleave/multiplex, format, and distribute operational Orbiter and payload data and voice for display, recording, telemetry, and checkout. It also must provide accurate timing for time critical functions for crew and payload specialist use. The MADS provides additional instrumentation to measure and record selected pressure, temperature, strain, vibration, and event data for post-flight playback and analysis. MADS data is used to assess vehicle responses to the flight environment and to permit correlation of such data from flight to flight. The IOA analysis utilized available SS hardware drawings and schematics for identifying hardware assemblies and components and their interfaces. Criticality for each item was assigned on the basis of the worst-case effect of the failure modes identified.

Sequence independent amplification of DNA

DOEpatents

Bohlander, S.K.

1998-03-24

The present invention is a rapid sequence-independent amplification procedure (SIA). Even minute amounts of DNA from various sources can be amplified independent of any sequence requirements of the DNA or any a priori knowledge of any sequence characteristics of the DNA to be amplified. This method allows, for example, the sequence independent amplification of microdissected chromosomal material and the reliable construction of high quality fluorescent in situ hybridization (FISH) probes from YACs or from other sources. These probes can be used to localize YACs on metaphase chromosomes but also--with high efficiency--in interphase nuclei. 25 figs.

Sequence independent amplification of DNA

DOEpatents

Bohlander, Stefan K.

1998-01-01

The present invention is a rapid sequence-independent amplification procedure (SIA). Even minute amounts of DNA from various sources can be amplified independent of any sequence requirements of the DNA or any a priori knowledge of any sequence characteristics of the DNA to be amplified. This method allows, for example the sequence independent amplification of microdissected chromosomal material and the reliable construction of high quality fluorescent in situ hybridization (FISH) probes from YACs or from other sources. These probes can be used to localize YACs on metaphase chromosomes but also--with high efficiency--in interphase nuclei.

A UV-independent pathway to melanoma carcinogenesis in the redhair-fairskin background

PubMed Central

Mitra, Devarati; Luo, Xi; Morgan, Ann; Wang, Jin; Hoang, Mai P.; Lo, Jennifer; Guerrero, Candace R.; Lennerz, Jochen K.; Mihm, Martin C.; Wargo, Jennifer A.; Robinson, Kathleen C.; Devi, Suprabha P.; Vanover, Jillian C.; D’Orazio, John A.; McMahon, Martin; Bosenberg, Marcus W.; Haigis, Kevin M.; Haber, Daniel A.; Wang, Yinsheng; Fisher, David E.

2012-01-01

People with pale skin, red hair, freckles, and an inability to tan—the “redhair/fairskin” phenotype— are at highest risk of developing melanoma, compared to all other pigmentation types1. Genetically, this phenotype is frequently the product of inactivating polymorphisms in the Melanocortin 1 receptor (MC1R) gene. MC1R encodes a cAMP stimulating G-protein coupled receptor that controls pigment production. Minimal receptor activity, as in redhair/fairskin polymorphisms, produces red/yellow pheomelanin pigment, while increasing MC1R activity stimulates production of black/brown eumelanin2. Pheomelanin has weak UV shielding capacity relative to eumelanin and has been shown to amplify UVA-induced reactive oxygen species (ROS) 3–5. Several observations, however, complicate the assumption that melanoma risk is completely UV dependent. For example, unlike non-melanoma skin cancers, melanoma is not restricted to sun-exposed skin and UV signature mutations are infrequently oncogenic drivers6. While linkage of melanoma risk to UV exposure is beyond doubt, UV-independent events are also likely to play a significant role1,7. Here, we introduced into mice carrying an inactivating mutation in the Mc1r gene (who exhibit a phenotype analogous to redhair/fairskin humans), a conditional, melanocyte-targeted allele of the most commonly mutated melanoma oncogene, BRafV600E. We observed a high incidence of invasive melanomas without providing additional gene aberrations or UV exposure. To investigate the mechanism of UV-independent carcinogenesis, we introduced an albino allele, which ablates all pigment production on the Mc1r e/e background. Selective absence of pheomelanin synthesis was protective against melanoma development. In addition, normal Mc1re/e mouse skin was found to have significantly greater oxidative DNA and lipid damage than albino-Mc1re/e mouse skin. These data suggest that the pheomelanin pigment pathway produces UV-independent carcinogenic contributions to

FIA: An Open Forensic Integration Architecture for Composing Digital Evidence

NASA Astrophysics Data System (ADS)

Raghavan, Sriram; Clark, Andrew; Mohay, George

The analysis and value of digital evidence in an investigation has been the domain of discourse in the digital forensic community for several years. While many works have considered different approaches to model digital evidence, a comprehensive understanding of the process of merging different evidence items recovered during a forensic analysis is still a distant dream. With the advent of modern technologies, pro-active measures are integral to keeping abreast of all forms of cyber crimes and attacks. This paper motivates the need to formalize the process of analyzing digital evidence from multiple sources simultaneously. In this paper, we present the forensic integration architecture (FIA) which provides a framework for abstracting the evidence source and storage format information from digital evidence and explores the concept of integrating evidence information from multiple sources. The FIA architecture identifies evidence information from multiple sources that enables an investigator to build theories to reconstruct the past. FIA is hierarchically composed of multiple layers and adopts a technology independent approach. FIA is also open and extensible making it simple to adapt to technological changes. We present a case study using a hypothetical car theft case to demonstrate the concepts and illustrate the value it brings into the field.

Independent technical review, handbook

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

Not Available

Purpose Provide an independent engineering review of the major projects being funded by the Department of Energy, Office of Environmental Restoration and Waste Management. The independent engineering review will address questions of whether the engineering practice is sufficiently developed to a point where a major project can be executed without significant technical problems. The independent review will focus on questions related to: (1) Adequacy of development of the technical base of understanding; (2) Status of development and availability of technology among the various alternatives; (3) Status and availability of the industrial infrastructure to support project design, equipment fabrication, facility construction,more » and process and program/project operation; (4) Adequacy of the design effort to provide a sound foundation to support execution of project; (5) Ability of the organization to fully integrate the system, and direct, manage, and control the execution of a complex major project.« less

Evidence & Gap Maps: A tool for promoting evidence informed policy and strategic research agendas.

PubMed

Snilstveit, Birte; Vojtkova, Martina; Bhavsar, Ami; Stevenson, Jennifer; Gaarder, Marie

2016-11-01

A range of organizations are engaged in the production of evidence on the effects of health, social, and economic development programs on human welfare outcomes. However, evidence is often scattered around different databases, web sites, and the gray literature and is often presented in inaccessible formats. Lack of overview of the evidence in a specific field can be a barrier to the use of existing research and prevent efficient use of limited resources for new research. Evidence & Gap Maps (EGMs) aim to address these issues and complement existing synthesis and mapping approaches. EGMs are a new addition to the tools available to support evidence-informed policymaking. To provide an accessible resource for researchers, commissioners, and decision makers, EGMs provide thematic collections of evidence structured around a framework which schematically represents the types of interventions and outcomes of relevance to a particular sector. By mapping the existing evidence using this framework, EGMs provide a visual overview of what we know and do not know about the effects of different programs. They make existing evidence available, and by providing links to user-friendly summaries of relevant studies, EGMs can facilitate the use of existing evidence for decision making. They identify key "gaps" where little or no evidence from impact evaluations and systematic reviews is available and can be a valuable resource to inform a strategic approach to building the evidence base in a particular sector. The article will introduce readers to the concept and methods of EGMs and present a demonstration of the EGM tool using existing examples. Copyright © 2016 Elsevier Inc. All rights reserved.

Coesite Assemblages in Deep Continental Lithosphere: Additional Evidence for a Protolith from Subduction of Oceanic Crust

NASA Astrophysics Data System (ADS)

Sobolev, N.

2005-12-01

Inclusions in diamonds (DIs) represent an important source of information about the composition of continental lithospheric mantle. The isolated coesite inclusions in two diamonds (Harris, 1968) and a full set of eclogitic minerals (coesite (Cs), garnet (Ga), omphacite Cpx)) in two Yakutian diamonds (Sobolev et al., 1976), followed by finds of Cs-eclogite xenoliths (Smyth and Hatton, 1977; Ponomarenko et al., 1977) testify to the importance of coesite as a constituent of eclogitic rocks in deep lithospheric environment. Since these earlier times, coesite has been documented in more than 250 natural diamonds from 25 localities worldwide. Some 40 xenoliths of Cs-eclogites were found both in South African and Yakutian kimberlites. However, >50% of DIs of coesite are related to only four (4) diamond localities, including Guaniamo, Venezuela (Sobolev et al., 1998, 2003), Argyle (Jaques et al., 1989; Sobolev et al., 1989), New South Wales, all Australia (Sobolev et al., 1984; Meyer et al., 1997), and North Yakutian alluvials (Sobolev et al., 1999). All described DIs with coesite are from a wide range of assemblages: websterites to kyanite eclogites; grospydites and calcsilicate assemblages, with a large range in Gt [3.7-28.7 wt.% CaO] and Cpx [ 0.9-8.8 wt.% Na2O] compositions. In spite of these occurrences in diamonds, to the present, no coesite has been detected within the assemblage of minerals making up some 400 diamondiferous-eclogite xenoliths; similarly, no diamonds have been found in any Cs-eclogite xenoliths. This apparent paradox may be caused by coesite alteration in the diamondiferous eclogites, whereas coesite eclogites may have formed only outside of the diamond stability field. Indeed, coesite eclogites (without diamonds) may occupy a shallower position within continental lithosphere compared with the normal E-type diamond source. This indicates a broadly basaltic chemistry of the deep eclogitic environment, additional evidence for a protolith from the

Addressing unwarranted clinical variation: A rapid review of current evidence.

PubMed

Harrison, Reema; Manias, Elizabeth; Mears, Stephen; Heslop, David; Hinchcliff, Reece; Hay, Liz

2018-05-15

Unwarranted clinical variation (UCV) can be described as variation that can only be explained by differences in health system performance. There is a lack of clarity regarding how to define and identify UCV and, once identified, to determine whether it is sufficiently problematic to warrant action. As such, the implementation of systemic approaches to reducing UCV is challenging. A review of approaches to understand, identify, and address UCV was undertaken to determine how conceptual and theoretical frameworks currently attempt to define UCV, the approaches used to identify UCV, and the evidence of their effectiveness. Rapid evidence assessment (REA) methodology was used. A range of text words, synonyms, and subject headings were developed for the major concepts of unwarranted clinical variation, standards (and deviation from these standards), and health care environment. Two electronic databases (Medline and Pubmed) were searched from January 2006 to April 2017, in addition to hand searching of relevant journals, reference lists, and grey literature. Results were merged using reference-management software (Endnote) and duplicates removed. Inclusion criteria were independently applied to potentially relevant articles by 3 reviewers. Findings were presented in a narrative synthesis to highlight key concepts addressed in the published literature. A total of 48 relevant publications were included in the review; 21 articles were identified as eligible from the database search, 4 from hand searching published work and 23 from the grey literature. The search process highlighted the voluminous literature reporting clinical variation internationally; yet, there is a dearth of evidence regarding systematic approaches to identifying or addressing UCV. Wennberg's classification framework is commonly cited in relation to classifying variation, but no single approach is agreed upon to systematically explore and address UCV. The instances of UCV that warrant investigation and

Casein Kinase 2 Reverses Tail-Independent Inactivation of Kinesin-1

NASA Astrophysics Data System (ADS)

Xu, Jing

2013-03-01

Kinesin-1 is a plus-end microtubule-based motor, and defects in kinesin-based transport are linked to diseases including neurodegeneration. Kinesin can auto-inhibit via a head-tail interaction, but is believed to be active otherwise. Here we report a tail-independent inactivation of kinesin, reversible by the disease-relevant signalling protein, casein kinase 2 (CK2). The majority of initially active kinesin (native or tail-less) loses its ability to interact with microtubules in vitro, and CK2 reverses this inactivation (approximately fourfold) without altering kinesin's single motor properties. This activation pathway does not require motor phosphorylation, and is independent of head-tail auto-inhibition. In cultured mammalian cells, reducing CK2 expression, but not its kinase activity, decreases the force required to stall lipid droplet transport, consistent with a decreased number of active kinesin motors. Our results (Nat. Commun., 3:754, 2012) provide the first direct evidence of a protein kinase upregulating kinesin-based transport, and suggest a novel pathway for regulating the activity of cargo-bound kinesin. Work supported by NIGMS grants GM64624 to SPG, GM74830-06A1 to LH, GM76516 to LB, NS048501 to SJK, and AHA grant 825278F to JX.

The dopamine D4 receptor gene (DRD4) moderates cultural difference in independent versus interdependent social orientation.

PubMed

Kitayama, Shinobu; King, Anthony; Yoon, Carolyn; Tompson, Steve; Huff, Sarah; Liberzon, Israel

2014-06-01

Prior research suggests that cultural groups vary on an overarching dimension of independent versus interdependent social orientation, with European Americans being more independent, or less interdependent, than Asians. Drawing on recent evidence suggesting that the dopamine D4 receptor gene (DRD4) plays a role in modulating cultural learning, we predicted that carriers of DRD4 polymorphisms linked to increased dopamine signaling (7- or 2-repeat alleles) would show higher levels of culturally dominant social orientations, compared with noncarriers. European Americans and Asian-born Asians (total N = 398) reported their social orientation on multiple scales. They were also genotyped for DRD4. As in earlier work, European Americans were more independent, and Asian-born Asians more interdependent. This cultural difference was significantly more pronounced for carriers of the 7- or 2-repeat alleles than for noncarriers. Indeed, no cultural difference was apparent among the noncarriers. Implications for potential coevolution of genes and culture are discussed. © The Author(s) 2014.

Ipilimumab for Previously Untreated Unresectable Malignant Melanoma: A Critique of the Evidence.

PubMed

Giannopoulou, Christina; Sideris, Eleftherios; Wade, Ros; Moe-Byrne, Thirimon; Eastwood, Alison; McKenna, Claire

2015-12-01

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of ipilimumab (Bristol-Myers Squibb Pharmaceuticals Limited) to submit clinical and cost-effectiveness evidence for previously untreated advanced (unresectable or metastatic) melanoma as part of the Institute's Single Technology Appraisal process. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article presents a summary of the manufacturer's submission of ipilimumab, the ERG review and the resulting NICE guidance TA319, issued in July 2014. Ipilimumab at a recommended dose of 3 mg/kg monotherapy was previously granted marketing authorisation by the European Medicines Agency in adult patients who had received prior therapy and was recommended by NICE in guidance TA268. In October 2013, the EMA approved the extension of this indication to previously untreated advanced melanoma patients. NICE decisions are bound by the marketing authorisation; therefore, the decision problem faced by the NICE Appraisal Committee was whether ipilimumab at a recommended dose of 3 mg/kg monotherapy was effective and cost effective compared with first-line standard of care involving dacarbazine (DTIC) and vemurafenib (for BRAF V600 mutation-positive patients). The CA184-024 trial was the primary source of clinical evidence for ipilimumab. However, this was based on a dose of 10 mg/kg with concomitant DTIC. The results over a 5-year period indicated that ipilimumab 10 mg/kg plus DTIC demonstrated a significant increase in median overall survival (OS) of 2.1 months compared with DTIC plus placebo (11.2 vs. 9.1 months). The BRIM-3 trial, which was an open-label randomised controlled trial (RCT) in BRAF V600 mutation-positive patients, was the primary source of evidence for an indirect comparison with vemurafenib. The results showed that vemurafenib increased median OS by 3

Non-additive dissipation in open quantum networks out of equilibrium

NASA Astrophysics Data System (ADS)

Mitchison, Mark T.; Plenio, Martin B.

2018-03-01

We theoretically study a simple non-equilibrium quantum network whose dynamics can be expressed and exactly solved in terms of a time-local master equation. Specifically, we consider a pair of coupled fermionic modes, each one locally exchanging energy and particles with an independent, macroscopic thermal reservoir. We show that the generator of the asymptotic master equation is not additive, i.e. it cannot be expressed as a sum of contributions describing the action of each reservoir alone. Instead, we identify an additional interference term that generates coherences in the energy eigenbasis, associated with the current of conserved particles flowing in the steady state. Notably, non-additivity arises even for wide-band reservoirs coupled arbitrarily weakly to the system. Our results shed light on the non-trivial interplay between multiple thermal noise sources in modular open quantum systems.