Syntactic processing as a marker for cognitive impairment in amyotrophic lateral sclerosis

Despite recent interest in cognitive changes in patients with amyotrophic lateral sclerosis (ALS), investigations of language function looking at the level of word, sentence and discourse processing are relatively scarce. Data were obtained from 26 patients with sporadic ALS and 26 healthy controls matched for age, education, gender, anxiety, depression and executive function performance. Standardized language tasks included confrontation naming, semantic access, and syntactic comprehension. Quantitative production analysis (QPA) was used to analyse connected speech samples of the Cookie Theft picture description task. Results showed that the ALS patients were impaired on standardized measures of grammatical comprehension and action/verb semantics. At the level of discourse, ALS patients were impaired on measures of syntactic complexity and fluency; however, the latter could be better explained by disease related factors. Discriminant analysis revealed that syntactic measures differentiated ALS patients from controls. In conclusion, patients with ALS exhibit deficits in receptive and expressive language on tasks of comprehension and connected speech production, respectively. Our findings suggest that syntactic processing deficits seem to be the predominant feature of language impairment in ALS and that these deficits can be detected by relatively simple language tests

Neighborhood Influences on Perceived Social Support Among Parents: Findings from the Project on Human Development in Chicago Neighborhoods

Background: Social support is frequently linked to positive parenting behavior. Similarly, studies increasingly show a link between neighborhood residential environment and positive parenting behavior. However, less is known about how the residential environment influences parental social support. To address this gap, we examine the relationship between neighborhood concentrated disadvantage and collective efficacy and the level and change in parental caregiver perceptions of non-familial social support. Methodology/Principal Findings: The data for this study came from three data sources, the Project on Human Development in Chicago Neighborhoods (PHDCN) Study's Longitudinal Cohort Survey of caregivers and their offspring, a Community Survey of adult residents in these same neighborhoods and the 1990 Census. Social support is measured at Wave 1 and Wave 3 and neighborhood characteristics are measured at Wave 1. Multilevel linear regression models are fit. The results show that neighborhood collective efficacy is a significant ($\beta$ = .04; SE = .02; p = .03), predictor of the positive change in perceived social support over a 7 year period, however, not of the level of social support, adjusting for key compositional variables and neighborhood concentrated disadvantage. In contrast concentrated neighborhood disadvantage is not a significant predictor of either the level or change in social support. Conclusion: Our finding suggests that neighborhood collective efficacy may be important for inducing the perception of support from friends in parental caregivers over time

A prospective study of serum insulin-like growth factor-I (IGF-I), IGF-II, IGF-binding protein-3 and breast cancer risk.

The associations between serum concentrations of insulin-like growth factor-I (IGF-I), IGF-II and IGF-binding proteins (IGFBP)-3 and risk of breast cancer were investigated in a nested case-control study involving 117 cases (70 premenopausal and 47 postmenopausal at blood collection) and 350 matched controls within a cohort of women from the island of Guernsey, UK. Women using exogenous hormones at the time of blood collection were excluded. Premenopausal women in the top vs bottom third of serum IGF-I concentration had a nonsignificantly increased risk for breast cancer after adjustment for IGFBP-3 (odds ratio (OR) 1.71; 95% confidence interval (CI): 0.74-3.95; test for linear trend, P=0.21). Serum IGFBP-3 was associated with a reduction in risk in premenopausal women after adjustment for IGF-I (top third vs the bottom third: OR 0.49; 95% CI: 0.21-1.12, P for trend=0.07). Neither IGF-I nor IGFBP-3 was associated with risk in postmenopausal women and serum IGF-II concentration was not associated with risk in pre- or postmenopausal women. These data are compatible with the hypothesis that premenopausal women with a relatively high circulating concentration of IGF-I and low IGFBP-3 are at an increased risk of developing breast cancer

Socio-economic status, racial composition and the affordability of fresh fruits and vegetables in neighborhoods of a large rural region in Texas

<p>Abstract</p> <p>Background</p> <p>Little is known about how affordability of healthy food varies with community characteristics in rural settings. We examined how the cost of fresh fruit and vegetables varies with the economic and demographic characteristics in six rural counties of Texas.</p> <p>Methods</p> <p>Ground-truthed data from the Brazos Valley Food Environment Project were used to identify all food stores in the rural region and the availability and lowest price of fresh whole fruit and vegetables in the food stores. Socioeconomic characteristics were extracted from the 2000 U.S. Census Summary Files 3 at the level of the census block group. We used an imputation strategy to calculate two types of price indices for both fresh fruit and fresh vegetables: a <it>high variety </it>and a <it>basic </it>index; and evaluated the relationship between neighborhood economic and demographic characteristics and affordability of fresh produce, using linear regression models.</p> <p>Results</p> <p>The mean cost of meeting the USDA recommendation of fruit consumption from a high variety basket of fruit types in our sample of stores was just over $27.50 per week. Relying on the three most common fruits lowered the weekly expense to under$17.25 per week, a reduction of 37.6%. The effect of moving from a high variety to a low variety basket was much less when considering vegetable consumption: a 4.3% decline from $29.23 to$27.97 per week. Univariate regression analysis revealed that the cost of fresh produce is not associated with the racial/ethnic composition of the local community. However, multivariate regression showed that holding median income constant, stores in neighborhoods with higher percentages of Black residents paid more for fresh fruits and vegetables. The proportion of Hispanic residents was not associated with cost in either the univariate or multivariate analysis.</p> <p>Conclusion</p> <p>This study extends prior work by examining the affordability of fresh fruit and vegetables from food stores in a large rural area; and how access to an affordable supply of fresh fruit and vegetables differs by neighborhood inequalities. The approach and findings of this study are relevant and have important research and policy implications for understanding access and availability of affordable, healthy foods.</p

Predicting dementia from primary care records: a systematic review and meta-analysis

Introduction Possible dementia is usually identified in primary care by general practitioners (GPs) who refer to specialists for diagnosis. Only two-thirds of dementia cases are currently recorded in primary care, so increasing the proportion of cases diagnosed is a strategic priority for the UK and internationally. Clinical entities in the primary care record may indicate risk of developing dementia, and could be combined in a predictive model to help find patients who are missing a diagnosis. We conducted a meta-analysis to identify clinical entities with potential for use in such a predictive model for dementia in primary care. Methods and Findings We conducted a systematic search in PubMed, Web of Science and primary care database bibliographies. We included cohort or case-control studies which used routinely collected primary care data, to measure the association between any clinical entity and dementia. Meta-analyses were performed to pool odds ratios. A sensitivity analysis assessed the impact of non-independence of cases between studies. From a sift of 3836 papers, 20 studies, all European, were eligible for inclusion, comprising >1 million patients. 75 clinical entities were assessed as risk factors for all cause dementia, Alzheimer’s (AD) and Vascular dementia (VaD). Data included were unexpectedly heterogeneous, and assumptions were made about definitions of clinical entities and timing as these were not all well described. Meta-analysis showed that neuropsychiatric symptoms including depression, anxiety, and seizures, cognitive symptoms, and history of stroke, were positively associated with dementia. Cardiovascular risk factors such as hypertension, heart disease, dyslipidaemia and diabetes were positively associated with VaD and negatively with AD. Sensitivity analyses showed similar results. Conclusions These findings are of potential value in guiding feature selection for a risk prediction tool for dementia in primary care. Limitations include findings being UK-focussed. Further predictive entities ascertainable from primary care data, such as changes in consulting patterns, were absent from the literature and should be explored in future studies

Group-based memory rehabilitation for people with multiple sclerosis: subgroup analysis of the ReMiND trial

Background/Aim: Memory problems are frequently reported in people with multiple sclerosis (MS). These can be debilitating and affect individuals and their families. This sub-group analysis focused on the effectiveness of memory rehabilitation in patients with MS. Methods: Data were extracted from a single blind randomised controlled trial, the ReMiND trial, which also included participants with traumatic brain injury and stroke. Participants were randomly allocated to compensation or restitution treatment programmes, or a self-help control. The programmes were manual-based and comprised two individual and ten group sessions. Outcome measures included assessments of memory, mood and activities of daily living. A total of 39 patients with MS participated in this study (ten males (26%), 29 females (74%); mean±SD age: 48.3±10.8 years). Results: Comparison of groups showed no significant effect of treatment on memory, but there were significant differences between compensation and restitution on self-report symptoms of emotional distress at both 5- (p=0.04) and 7-month (p=0.05) follow-up sessions. The compensation group showed less distress than the restitution group. Conclusions: Individuals with MS who received compensation memory rehabilitation reported significantly less emotional distress than those who received restitution. Further research is needed to explore why self-reported memory problems did not differ between groups

Evaluation of midkine and anterior gradient 2 in a multimarker panel for the detection of ovarian cancer

The aims of this study were: to characterise and compare plasma concentrations of midkine (MDK) in normal healthy women with concentrations observed in women with ovarian cancer; and to establish and compare the performance of MDK with that of anterior gradient 2 protein (AGR2) and CA125 in the development of multi-analyte classification algorithms for ovarian cancer. Median plasma concentrations of immunoreactive MDK, AGR2 and CA125 were significantly greater in the case cohort (909 pg/ml, 765 pg/ml and 502 U/ml, respectively n = 46) than in the control cohort (383 pg/ml, 188 pg/ml and 13 U/ml, respectively n = 61) (p < 0.001). The area under the receiver operator characteristic curve (AUC) for MDK and AGR2 was not significantly different (0.734 ± 0.046 and 0.784 ± 0.049, respectively, mean ± SE) but were both significantly less than the AUC for CA125 (0.934 ± 0.030, p < 0.003). When subjected to stochastic gradient boosted logistic regression modelling, the AUC of the multi-analyte panel (MDK, AGR2 and CA125, 0.988 ± 0.010) was significantly greater than that of CA125 alone (0.934 ± 0.030, p = 0.035). The sensitivity and specificity of the multi-analyte algorithm were 95.2 and 97.7%, respectively. Within the study cohort, CA125 displayed a sensitivity and specificity of 87.0 and 94.6%, respectively. The data obtained in this study confirm that both MDK and AGR2 individually display utility as biomarkers for ovarian cancer and that in a multi-analyte panel significantly improve the diagnostic utility of CA125 in symptomatic women

A Single Nucleotide in Stem Loop II of 5′-Untranslated Region Contributes to Virulence of Enterovirus 71 in Mice

BACKGROUND: Enterovirus 71 (EV71) has emerged as a neuroinvasive virus responsible for several large outbreaks in the Asia-Pacific region while virulence determinant remains unexplored. PRINCIPAL FINDINGS: In this report, we investigated increased virulence of unadapted EV71 clinical isolate 237 as compared with isolate 4643 in mice. A fragment 12 nucleotides in length in stem loop (SL) II of 237 5'-untranslated region (UTR) visibly reduced survival time and rate in mice was identified by constructing a series of infectious clones harboring chimeric 5'-UTR. In cells transfected with bicistronic plasmids, and replicon RNAs, the 12-nt fragment of isolate 237 enhanced translational activities and accelerated replication of subgenomic EV71. Finally, single nucleotide change from cytosine to uridine at base 158 in this short fragment of 5'-UTR was proven to reduce viral translation and EV71 virulence in mice. Results collectively indicated a pivotal role of novel virulence determinant C158 on virus translation in vitro and EV71 virulence in vivo. CONCLUSIONS: These results presented the first reported virulence determinant in EV71 5'-UTR and first position discovered from unadapted isolates

How to find simple and accurate rules for viral protease cleavage specificities

<p>Abstract</p> <p>Background</p> <p>Proteases of human pathogens are becoming increasingly important drug targets, hence it is necessary to understand their substrate specificity and to interpret this knowledge in practically useful ways. New methods are being developed that produce large amounts of cleavage information for individual proteases and some have been applied to extract cleavage rules from data. However, the hitherto proposed methods for extracting rules have been neither easy to understand nor very accurate. To be practically useful, cleavage rules should be accurate, compact, and expressed in an easily understandable way.</p> <p>Results</p> <p>A new method is presented for producing cleavage rules for viral proteases with seemingly complex cleavage profiles. The method is based on orthogonal search-based rule extraction (OSRE) combined with spectral clustering. It is demonstrated on substrate data sets for human immunodeficiency virus type 1 (HIV-1) protease and hepatitis C (HCV) NS3/4A protease, showing excellent prediction performance for both HIV-1 cleavage and HCV NS3/4A cleavage, agreeing with observed HCV genotype differences. New cleavage rules (consensus sequences) are suggested for HIV-1 and HCV NS3/4A cleavages. The practical usability of the method is also demonstrated by using it to predict the location of an internal cleavage site in the HCV NS3 protease and to correct the location of a previously reported internal cleavage site in the HCV NS3 protease. The method is fast to converge and yields accurate rules, on par with previous results for HIV-1 protease and better than previous state-of-the-art for HCV NS3/4A protease. Moreover, the rules are fewer and simpler than previously obtained with rule extraction methods.</p> <p>Conclusion</p> <p>A rule extraction methodology by searching for multivariate low-order predicates yields results that significantly outperform existing rule bases on out-of-sample data, but are more transparent to expert users. The approach yields rules that are easy to use and useful for interpreting experimental data.</p