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1.

Background

Polymorphisms in the promoter region of the serotonin transporter gene (5-HTTLPR) and exposure to early childhood adversities (CA) are independently associated with individual differences in cognitive and emotional processing. Whether these two factors interact to influence cognitive and emotional processing is not known.

Methodology and Principal Findings

We used a sample of 238 adolescents from a community study characterised by the presence of the short allele of 5-HTTLPR (LL, LS, SS) and the presence or absence of exposure to CA before 6 years of age. We measured cognitive and emotional processing using a set of neuropsychological tasks selected predominantly from the CANTAB® battery. We found that adolescents homozygous for the short allele (SS) of 5-HTTLPR and exposed to CA were worse at classifying negative and neutral stimuli and made more errors in response to ambiguous negative feedback. In addition, cognitive and emotional processing deficits were associated with diagnoses of anxiety and/or depressions.

Conclusion and Significance

Cognitive and emotional processing deficits may act as a transdiagnostic intermediate marker for anxiety and depressive disorders in genetically susceptible individuals exposed to CA.  相似文献   

2.

Introduction

Disability and Physical Function (PF) outcome assessment has had limited ability to measure functional status at the floor (very poor functional abilities) or the ceiling (very high functional abilities). We sought to identify, develop and evaluate new floor and ceiling items to enable broader and more precise assessment of PF outcomes for the NIH Patient-Reported-Outcomes Measurement Information System (PROMIS).

Methods

We conducted two cross-sectional studies using NIH PROMIS item improvement protocols with expert review, participant survey and focus group methods. In Study 1, respondents with low PF abilities evaluated new floor items, and those with high PF abilities evaluated new ceiling items for clarity, importance and relevance. In Study 2, we compared difficulty ratings of new floor items by low functioning respondents and ceiling items by high functioning respondents to reference PROMIS PF-10 items. We used frequencies, percentages, means and standard deviations to analyze the data.

Results

In Study 1, low (n = 84) and high (n = 90) functioning respondents were mostly White, women, 70 years old, with some college, and disability scores of 0.62 and 0.30. More than 90% of the 31 new floor and 31 new ceiling items were rated as clear, important and relevant, leaving 26 ceiling and 30 floor items for Study 2. Low (n = 246) and high (n = 637) functioning Study 2 respondents were mostly White, women, 70 years old, with some college, and Health Assessment Questionnaire (HAQ) scores of 1.62 and 0.003. Compared to difficulty ratings of reference items, ceiling items were rated to be 10% more to greater than 40% more difficult to do, and floor items were rated to be about 12% to nearly 90% less difficult to do.

Conclusions

These new floor and ceiling items considerably extend the measurable range of physical function at either extreme. They will help improve instrument performance in populations with broad functional ranges and those concentrated at one or the other extreme ends of functioning. Optimal use of these new items will be assisted by computerized adaptive testing (CAT), reducing questionnaire burden and insuring item administration to appropriate individuals.  相似文献   

3.

Background

A recent modeling study by the authors predicted that contextual information is poorly integrated into episodic representations in schizophrenia, and that this is a main cause of the retrieval deficits seen in schizophrenia.

Methodology/Principal Findings

We have tested this prediction in patients with first-episode schizophrenia and matched controls. The benefit from contextual cues in retrieval was strongly reduced in patients. On the other hand, retrieval based on item cues was spared.

Conclusions/Significance

These results suggest that reduced integration of context information into episodic representations is a core deficit in schizophrenia and one of the main causes of episodic memory impairment.  相似文献   

4.

Background

Classic work on visual short-term memory (VSTM) suggests that people store a limited amount of items for subsequent report. However, when human observers are cued to shift attention to one item in VSTM during retention, it seems as if there is a much larger representation, which keeps additional items in a more fragile VSTM store. Thus far, it is not clear whether the capacity of this fragile VSTM store indeed exceeds the traditional capacity limits of VSTM. The current experiments address this issue and explore the capacity, stability, and duration of fragile VSTM representations.

Methodology/Principal Findings

We presented cues in a change-detection task either just after off-set of the memory array (iconic-cue), 1,000 ms after off-set of the memory array (retro-cue) or after on-set of the probe array (post-cue). We observed three stages in visual information processing 1) iconic memory with unlimited capacity, 2) a four seconds lasting fragile VSTM store with a capacity that is at least a factor of two higher than 3) the robust and capacity-limited form of VSTM. Iconic memory seemed to depend on the strength of the positive after-image resulting from the memory display and was virtually absent under conditions of isoluminance or when intervening light masks were presented. This suggests that iconic memory is driven by prolonged retinal activation beyond stimulus duration. Fragile VSTM representations were not affected by light masks, but were completely overwritten by irrelevant pattern masks that spatially overlapped the memory array.

Conclusions/Significance

We find that immediately after a stimulus has disappeared from view, subjects can still access information from iconic memory because they can see an after-image of the display. After that period, human observers can still access a substantial, but somewhat more limited amount of information from a high-capacity, but fragile VSTM that is overwritten when new items are presented to the eyes. What is left after that is the traditional VSTM store, with a limit of about four objects. We conclude that human observers store more sustained representations than is evident from standard change detection tasks and that these representations can be accessed at will.  相似文献   

5.

Introduction

Patient-reported physical function is an established outcome domain in clinical studies in rheumatology. To overcome the limitations of the current generation of questionnaires, the Patient-Reported Outcomes Measurement Information System (PROMIS®) project in the USA has developed calibrated item banks for measuring several domains of health status in people with a wide range of chronic diseases. The aim of this study was to translate and cross-culturally adapt the PROMIS physical function item bank to the Dutch language and to pretest it in a sample of patients with arthritis.

Methods

The items of the PROMIS physical function item bank were translated using rigorous forward-backward protocols and the translated version was subsequently cognitively pretested in a sample of Dutch patients with rheumatoid arthritis.

Results

Few issues were encountered in the forward-backward translation. Only 5 of the 124 items to be translated had to be rewritten because of culturally inappropriate content. Subsequent pretesting showed that overall, questions of the Dutch version were understood as they were intended, while only one item required rewriting.

Conclusions

Results suggest that the translated version of the PROMIS physical function item bank is semantically and conceptually equivalent to the original. Future work will be directed at creating a Dutch-Flemish final version of the item bank to be used in research with Dutch speaking populations.  相似文献   

6.

Background

The quality of reporting in systematic reviews (SRs)/meta-analyses (MAs) of diagnostic tests published by authors in China has not been evaluated. The aims of present study are to evaluate the quality of reporting in diagnostic SRs/MAs using the PRISMA statement and determine the changes in the quality of reporting over time.

Methods

According to the inclusion and exclusion criteria, we searched five databases including Chinese Biomedical Literature Database, PubMed, EMBASE, the Cochrane Library, and Web of knowledge, to identify SRs/MAs on diagnostic tests. The searches were conducted on July 14, 2012 and the cut off for inclusion of the SRs/MAs was December 31st 2011. The PRISMA statement was used to assess the quality of reporting. Analysis was performed using Excel 2003, RevMan 5.

Results

A total of 312 studies were included. Fifteen diseases systems were covered. According to the PRISMA checklist, there had been serious reporting flaws in following items: structured summary (item 2, 22.4%), objectives (item 4, 18.9%), protocol and registration (item 5, 2.6%), risk of bias across studies (item 15, 26.3%), funding (item 27, 28.8%). The subgroup analysis showed that there had been some statistically significant improvement in total compliance for 9 PRISMA items after the PRISMA was released, 6 items were statistically improved regarding funded articles, 3 items were statistically improved for CSCD articles, and there was a statistically significant increase in the proportion of reviews reporting on 22 items for SCI articles (P<0.050).

Conclusion

The numbers of diagnostic SRs/MAs is increasing annually. The quality of reporting has measurably been improved over the previous years. Unfortunately, there are still many deficiencies in the reporting including protocol and registration, search, risk of bias across studies, and funding. Future Chinese reviewers should address issues on these aspects.  相似文献   

7.

Objectives

Center for Epidemiologic Studies Depression (CES-D) Scale scores in English- and French-speaking Canadian systemic sclerosis (SSc) patients are commonly pooled in analyses, but no studies have evaluated the metric equivalence of the English and French CES-D. The study objective was to examine the metric equivalence of the CES-D in English- and French-speaking SSc patients.

Methods

The CES-D was completed by 1007 English-speaking and 248 French-speaking patients from the Canadian Scleroderma Research Group Registry. Confirmatory factor analysis (CFA) was used to assess the factor structure in both samples. The Multiple-Indicator Multiple-Cause (MIMIC) model was utilized to assess differential item functioning (DIF).

Results

A two-factor model (Positive and Negative affect) showed excellent fit in both samples. Statistically significant, but small-magnitude, DIF was found for 3 of 20 CES-D items, including items 3 (Blues), 10 (Fearful), and 11 (Sleep). Prior to accounting for DIF, French-speaking patients had 0.08 of a standard deviation (SD) lower latent scores for the Positive factor (95% confidence interval [CI]−0.25 to 0.08) and 0.09 SD higher scores (95% CI−0.07 to 0.24) for the Negative factor than English-speaking patients. After DIF correction, there was no change on the Positive factor and a non-significant increase of 0.04 SD on the Negative factor for French-speaking patients (difference = 0.13 SD, 95% CI−0.03 to 0.28).

Conclusions

The English and French versions of the CES-D, despite minor DIF on several items, are substantively equivalent and can be used in studies that combine data from English- and French-speaking Canadian SSc patients.  相似文献   

8.
Chen W  Liu CH  Nakabayashi K 《PloS one》2012,7(2):e32897

Background

Recent research has shown that the presence of a task-irrelevant attractive face can induce a transient diversion of attention from a perceptual task that requires covert deployment of attention to one of the two locations. However, it is not known whether this spontaneous appraisal for facial beauty also modulates attention in change detection among multiple locations, where a slower, and more controlled search process is simultaneously affected by the magnitude of a change and the facial distinctiveness. Using the flicker paradigm, this study examines how spontaneous appraisal for facial beauty affects the detection of identity change among multiple faces.

Methodology/Principal Findings

Participants viewed a display consisting of two alternating frames of four faces separated by a blank frame. In half of the trials, one of the faces (target face) changed to a different person. The task of the participant was to indicate whether a change of face identity had occurred. The results showed that (1) observers were less efficient at detecting identity change among multiple attractive faces relative to unattractive faces when the target and distractor faces were not highly distinctive from one another; and (2) it is difficult to detect a change if the new face is similar to the old.

Conclusions/Significance

The findings suggest that attractive faces may interfere with the attention-switch process in change detection. The results also show that attention in change detection was strongly modulated by physical similarity between the alternating faces. Although facial beauty is a powerful stimulus that has well-demonstrated priority, its influence on change detection is easily superseded by low-level image similarity. The visual system appears to take a different approach to facial beauty when a task requires resource-demanding feature comparisons.  相似文献   

9.

Background

Can hearing a word change what one sees? Although visual sensitivity is known to be enhanced by attending to the location of the target, perceptual enhancements of following cues to the identity of an object have been difficult to find. Here, we show that perceptual sensitivity is enhanced by verbal, but not visual cues.

Methodology/Principal Findings

Participants completed an object detection task in which they made an object-presence or -absence decision to briefly-presented letters. Hearing the letter name prior to the detection task increased perceptual sensitivity (d′). A visual cue in the form of a preview of the to-be-detected letter did not. Follow-up experiments found that the auditory cuing effect was specific to validly cued stimuli. The magnitude of the cuing effect positively correlated with an individual measure of vividness of mental imagery; introducing uncertainty into the position of the stimulus did not reduce the magnitude of the cuing effect, but eliminated the correlation with mental imagery.

Conclusions/Significance

Hearing a word made otherwise invisible objects visible. Interestingly, seeing a preview of the target stimulus did not similarly enhance detection of the target. These results are compatible with an account in which auditory verbal labels modulate lower-level visual processing. The findings show that a verbal cue in the form of hearing a word can influence even the most elementary visual processing and inform our understanding of how language affects perception.  相似文献   

10.

Purpose

To develop and validate a Chinese version of the Catquest-9SF questionnaire in a cataract population.

Methods

The Catquest-9SF Questionnaire was translated and back translated into Chinese. Preoperative patients were recruited at a tertiary eye hospital and their demographic information and visual acuity were documented. Psychometric properties of the Catquest-9SF, including ordered thresholds, the ability to distinguish between different strata of person ability, absence of misfitting items, unidimentionality, differential item functioning (DIF) and construct validity were tested, using Rasch analysis.

Results

A total of 102 patients (100% response rate) were enrolled. The participants''mean age was 70.2 year (SD = 12.1) and 46.9% were female. Rasch analysis showed that this version of the questionnaire had ordered response thresholds and was free of DIF. The items fit a single overall construct and unidimensional by principal components analysis of the residuals. Patients with visual impairment had significantly poorer Rasch scores on the Catquest-9SF (mean change, -2.5, p = 0.035, compared with non-visually impaired patients).

Conclusion

The Chinese version of Catquest-9SF is a valid and reliable questionnaire for assessing the visual disability outcomes of Chinese patients with cataract, and it may be recommended for routine clinical use.  相似文献   

11.

Background

Abnormalities of the intracellular metabolism of the hydrophobic surfactant proteins SP-B and SP-C and their precursors may be causally linked to chronic childhood diffuse lung diseases. The profile of these proteins in the alveolar space is unknown in such subjects.

Methods

We analyzed bronchoalveolar lavage fluid by Western blotting for SP-B, SP-C and their proforms in children with pulmonary alveolar proteinosis (PAP, n = 15), children with no SP-B (n = 6), children with chronic respiratory distress of unknown cause (cRD, n = 7), in comparison to children without lung disease (n = 15) or chronic obstructive bronchitis (n = 19).

Results

Pro-SP-B of 25–26 kD was commonly abundant in all groups of subjects, suggesting that their presence is not of diagnostic value for processing defects. In contrast, pro-SP-B peptides cleaved off during intracellular processing of SP-B and smaller than 19–21 kD, were exclusively found in PAP and cRD. In 4 of 6 children with no SP-B, mutations of SFTPB or SPTPC genes were found. Pro-SP-C forms were identified at very low frequency. Their presence was clearly, but not exclusively associated with mutations of the SFTPB and SPTPC genes, impeding their usage as candidates for diagnostic screening.

Conclusion

Immuno-analysis of the hydrophobic surfactant proteins and their precursor forms in bronchoalveolar lavage is minimally invasive and can give valuable clues for the involvement of processing abnormalities in pediatric pulmonary disorders.  相似文献   

12.

Background

Suicide has been linked to intense negative affect. However, little is known about the range of affects experienced by suicidal persons, or the separate effects of affect valence and intensity. We examine a novel self-report scale, the 17-item Affective Intensity Rating Scale (AIRS), and its relation to suicidality in a high-risk sample.

Methodology/Principal Findings

Patients presenting with suicidality were recruited from the Emergency Department in a large urban hospital, and completed a battery of assessments there. Structure of the AIRS was assessed using Maximum Likelihood Factor Analysis with Oblimin rotation. Convergent and divergent validity were assessed by regressing AIRS subscales against Brief Symptom Inventory subscales. Relation to suicidality was assessed by regression of suicide attempt status against scale and subscale scores, and individual items and two-way item interactions, along with significant clinical and demographic factors. 176 subjects were included in analyses. Three reliable subscales were identified within the AIRS measure: positive feelings towards self, negative feelings towards self, and negative feelings towards other. Only individual AIRS items associated significantly with suicide attempt status; strong ‘feelings of love’ associated positively with actual suicide attempt, while ‘feelings of calm’ and ‘positive feelings towards self’ associated negatively. Interaction analyses suggest ‘calm’ moderates the association of ‘love’ with suicide attempt.

Conclusions/Significance

Factor analysis of the AIRS is consistent with a circumplex model of affect. Affective dimensions did not predict suicidal behavior, but intense feelings of love, particularly in the absence of protective feelings of calm or positive self-view associated with current attempt.  相似文献   

13.

Background

One of the most debated issues in the cognitive neuroscience of language is whether distinct semantic domains are differentially represented in the brain. Clinical studies described several anomic dissociations with no clear neuroanatomical correlate. Neuroimaging studies have shown that memory retrieval is more demanding for proper than common nouns in that the former are purely arbitrary referential expressions. In this study a semantic relatedness paradigm was devised to investigate neural processing of proper and common nouns.

Methodology/Principal Findings

780 words (arranged in pairs of Italian nouns/adjectives and the first/last names of well known persons) were presented. Half pairs were semantically related (“Woody Allen” or “social security”), while the others were not (“Sigmund Parodi” or “judicial cream”). All items were balanced for length, frequency, familiarity and semantic relatedness. Participants were to decide about the semantic relatedness of the two items in a pair. RTs and N400 data suggest that the task was more demanding for common nouns. The LORETA neural generators for the related-unrelated contrast (for proper names) included the left fusiform gyrus, right medial temporal gyrus, limbic and parahippocampal regions, inferior parietal and inferior frontal areas, which are thought to be involved in the conjoined processing a familiar face with the relevant episodic information. Person name was more emotional and sensory vivid than common noun semantic access.

Conclusions/Significance

When memory retrieval is not required, proper name access (conspecifics knowledge) is not more demanding. The neural generators of N400 to unrelated items (unknown persons and things) did not differ as a function of lexical class, thus suggesting that proper and common nouns are not treated differently as belonging to different grammatical classes.  相似文献   

14.

Background

Caenorhabditis elegans locomotion is a simple behavior that has been widely used to dissect genetic components of behavior, synaptic transmission, and muscle function. Many of the paradigms that have been created to study C. elegans locomotion rely on qualitative experimenter observation. Here we report the implementation of an automated tracking system developed to quantify the locomotion of multiple individual worms in parallel.

Methodology/Principal Findings

Our tracking system generates a consistent measurement of locomotion that allows direct comparison of results across experiments and experimenters and provides a standard method to share data between laboratories. The tracker utilizes a video camera attached to a zoom lens and a software package implemented in MATLAB®. We demonstrate several proof-of-principle applications for the tracker including measuring speed in the absence and presence of food and in the presence of serotonin. We further use the tracker to automatically quantify the time course of paralysis of worms exposed to aldicarb and levamisole and show that tracker performance compares favorably to data generated using a hand-scored metric.

Conclusions/Signficance

Although this is not the first automated tracking system developed to measure C. elegans locomotion, our tracking software package is freely available and provides a simple interface that includes tools for rapid data collection and analysis. By contrast with other tools, it is not dependent on a specific set of hardware. We propose that the tracker may be used for a broad range of additional worm locomotion applications including genetic and chemical screening.  相似文献   

15.

Background

Discovering causal genetic variants from large genetic association studies poses many difficult challenges. Assessing which genetic markers are involved in determining trait status is a computationally demanding task, especially in the presence of gene-gene interactions.

Results

A non-parametric Bayesian approach in the form of a Bayesian neural network is proposed for use in analyzing genetic association studies. Demonstrations on synthetic and real data reveal they are able to efficiently and accurately determine which variants are involved in determining case-control status. By using graphics processing units (GPUs) the time needed to build these models is decreased by several orders of magnitude. In comparison with commonly used approaches for detecting interactions, Bayesian neural networks perform very well across a broad spectrum of possible genetic relationships.

Conclusions

The proposed framework is shown to be a powerful method for detecting causal SNPs while being computationally efficient enough to handle large datasets.

Electronic supplementary material

The online version of this article (doi:10.1186/s12859-014-0368-0) contains supplementary material, which is available to authorized users.  相似文献   

16.

Introduction

Human personality is described preferentially in terms of factors (dimensions) found using factor analysis. An alternative and highly related method is network analysis, which may have several advantages over factor analytic methods.

Aim

To directly compare the ability of network community detection (NCD) and principal component factor analysis (PCA) to examine modularity in multidimensional datasets such as the neuroticism-extraversion-openness personality inventory revised (NEO-PI-R).

Methods

434 healthy subjects were tested on the NEO-PI-R. PCA was performed to extract factor structures (FS) of the current dataset using both item scores and facet scores. Correlational network graphs were constructed from univariate correlation matrices of interactions between both items and facets. These networks were pruned in a link-by-link fashion while calculating the network community structure (NCS) of each resulting network using the Wakita Tsurumi clustering algorithm. NCSs were matched against FS and networks of best matches were kept for further analysis.

Results

At facet level, NCS showed a best match (96.2%) with a ‘confirmatory’ 5-FS. At item level, NCS showed a best match (80%) with the standard 5-FS and involved a total of 6 network clusters. Lesser matches were found with ‘confirmatory’ 5-FS and ‘exploratory’ 6-FS of the current dataset. Network analysis did not identify facets as a separate level of organization in between items and clusters. A small-world network structure was found in both item- and facet level networks.

Conclusion

We present the first optimized network graph of personality traits according to the NEO-PI-R: a ‘Personality Web’. Such a web may represent the possible routes that subjects can take during personality development. NCD outperforms PCA by producing plausible modularity at item level in non-standard datasets, and can identify the key roles of individual items and clusters in the network.  相似文献   

17.
18.

Background

The NBN gene codes for the protein nibrin, which is involved in the detection and repair of DNA double strand breaks (DSBs). The NBN gene is essential in mammals.

Methodology/Principal Findings

We have used a conditional null mutant mouse model in a proteomics approach to identify proteins with modified expression levels after 4 Gy ionizing irradiation in the absence of nibrin in vivo. Altogether, amongst ∼8,000 resolved proteins, 209 were differentially expressed in homozygous null mutant mice in comparison to control animals. One group of proteins significantly altered in null mutant mice were those involved in oxidative stress and cellular redox homeostasis (p<0.0001). In substantiation of this finding, analysis of Nbn null mutant fibroblasts indicated an increased production of reactive oxygen species following induction of DSBs.

Conclusions/Significance

In humans, biallelic hypomorphic mutations in NBN lead to Nijmegen breakage syndrome (NBS), an autosomal recessive genetic disease characterised by extreme radiosensitivity coupled with growth retardation, immunoinsufficiency and a very high risk of malignancy. This particularly high cancer risk in NBS may be attributable to the compound effect of a DSB repair defect and oxidative stress.  相似文献   

19.

Background

The inducible Cre-lox system is a valuable tool to study gene function in a spatial and time restricted fashion in mouse models. This strategy relies on the limited background activity of the modified Cre recombinase (CreER) in the absence of its inducer, the competitive estrogen receptor ligand, tamoxifen. The RIP-CreER mouse (Tg (Ins2-cre/Esr1) 1Dam) is among the few available β-cell specific CreER mouse lines and thus it has been often used to manipulate gene expression in the insulin-producing cells of the endocrine pancreas.

Principal Findings

Here, we report the detection of tamoxifen-independent Cre activity as early as 2 months of age in RIP-CreER mice crossed with three distinct reporter strains.

Significance

Evidence of Cre-mediated recombination of floxed alleles even in the absence of tamoxifen administration should warrant cautious use of this mouse for the study of pancreatic β-cells.  相似文献   

20.

Context

We aimed to develop a new tool for assessing and depicting the applicability of the results of surgical randomized controlled trials (RCTs) from the trial investigators'' perspective.

Methods

We identified all items related to applicability by a systematic methodological review, and then a sample of surgeons used these items in a web-based survey to evaluate the applicability of their own trial results. For each applicability item, participants had to indicate on a numerical scale that was simplified as a three-item scale: 1) items essential to consider, 2) items requiring attention, and 3) items inconsequential to the applicability of the results of their own RCT to clinical practice. For the final tool, we selected only items that were rated as being essential or requiring attention for at least 25% of the trials evaluated. We propose a specific process to construct the tool and to depict applicability in a graph. We identified all investigators of published and registered ongoing RCTs assessing surgery and invited them to participate in the web-based survey.

Results

148 surgeons assessed applicability for their own trial and participated in the process of item selection. The final tool contains 22 items (4 dedicated to patients, 5 to centers, 5 to surgeons and 8 to the intervention). We proposed a straightforward process of constructing the graphical tool: 1) a multidisciplinary team of investigators or other care providers participating in the trial could independently assess each item, 2) a consensus method could be used, and 3) the investigators could depict their assessment of the applicability of the trial results in 4 graphs related to patients, centers, surgeons and the intervention.

Conclusions

This investigator-reported assessment tool could help readers define under what conditions they could reasonably apply the results of a surgical RCT to their clinical practice.  相似文献   

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