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To assess independent and joint effects of pairs of vascular and cardiometabolic risk factors (VCMRFs) in relation to risk of all-cause dementia.
Population-based longitudinal cohort study of cognitive impairment. We used an algorithm to select pairs of VCMRFs and tested their joint effects in time-dependent Cox models. We used attributable proportions (AP) to measure the proportion of risk from interactions beyond any additive effect.
Economically depressed small-town population.
Adults age 65+ years with up to 10 yearly study visits (N=1701, median (Q1, Q3) age, 78 (71.0, 83.0), 62.3% female, 94.9% white).
Among 1701 participants free from prevalent dementia with at least one follow-up visit, 109 developed incident all-cause dementia. In pairings of APOE*4 with hypertension (HTN) and congestive heart failure (CHF), the variables contributed independently and additively to all-cause dementia risk. In pairings of APOE*4 with stroke and stroke with CHF, the variables demonstrated independent contributions to all-cause dementia risk; their joint effects showed excess detriment demonstrating synergistic interactions (joint HR [95% CI]: 28.33 [6.74, 119.01] and 50.30 [14.57, 173.57] respectively, fully adjusted models). Physical activity (PA) was independently associated with lower all-cause dementia risk when paired with APOE*4, stroke, and CHF in unadjusted models; these associations did not survive covariate adjustment. The joint effect of low PA and APOE*4 was associated with additively increased all-cause dementia risk (joint HR [95% CI]: 4.61 [2.07, 10.23], fully adjusted model).
Reduction of VCMRFs, including low PA, could be valuable for dementia prevention, especially among APOE*4 carriers.
The heat transfer properties of the organic molecular crystal α-RDX were studied using three phonon scattering based thermal conductivity models. It was found that the widely used Peierls-Boltzmann model for thermal transport in crystalline materials breaks down for α-RDX. We show this breakdown is due to a large degree of anharmonicity that leads to a dominance of diffusive-like carriers. Despite being developed for disordered systems, the Allen-Feldman theory for thermal conductivity actually gives the best description of thermal transport. This is likely because diffusive carriers contribute to over 95% of the thermal conductivity in α-RDX. The dominance of diffusive carriers is larger than previously observed in other fully ordered crystalline systems. These results indicate that van der Waals bonded organic crystalline solids conduct heat in a manner more akin to amorphous materials than simple atomic crystals.
Background: Previous post-hoc analysis of three 12-week, double-blind, placebo-controlled trials of adjunctive brivaracetam (BRV) in patients with focal seizures demonstrated similar efficacy over placebo regardless of previous carbamazepine (CBZ), lamotrigine (LTG), levetiracetam (LEV), or topiramate (TPM) failure. This analysis explored long-term retention of adjunctive BRV in patients with previous CBZ/LTG/LEV/TPM. Methods: Post-hoc analysis of double-blind, placebo-controlled trial (N01358 [NCT01261325]) and open-label extension (N01379 [NCT01339559]; cut-off 15-March-2017) of adjunctive BRV in patients (≥16 years) with focal seizures. Outcomes were assessed in patients randomized to BRV (100 or 200 mg/day) who had previous CBZ/LTG/LEV/TPM (stopped ≥90 days before BRV initiation). Results: 503 patients were analyzed. Baseline characteristics were generally similar in subgroups with previous CBZ/LTG/LEV/TPM (n=209/162/256/182). Overall, Kaplan-Meier-estimated BRV retention at 1-, 3-, and 5-years was 71.0%, 50.9%, and 32.4%. Across previous antiepileptic drug (AED) subgroups, Kaplan-Meier-estimated BRV retention (1-year: 64.8%–73.2%; 3-year: 41.9%–49.9%; 5-year: 31.5%–35.7%), BRV discontinuations (58.4%–63.0%), and most common reasons for discontinuation (lack of efficacy: 23.0%–25.3%; adverse event: 16.7%–22.2%) were generally similar. Conclusions: Post-hoc analysis demonstrated similar long-term retention rates and discontinuation reasons with adjunctive BRV in adults previously treated with CBZ/LTG/LEV/TPM. Adjunctive BRV provides long-term effectiveness in patients who failed common AED treatments, including LEV.
Consumption of certain berries appears to slow postprandial glucose absorption, attributable to polyphenols, which may benefit exercise and cognition, reduce appetite and/or oxidative stress. This randomised, crossover, placebo-controlled study determined whether polyphenol-rich fruits added to carbohydrate-based foods produce a dose-dependent moderation of postprandial glycaemic, glucoregulatory hormone, appetite and ex vivo oxidative stress responses. Twenty participants (eighteen males/two females; 24 (sd 5) years; BMI: 27 (sd 3) kg/m2) consumed one of five cereal bars (approximately 88 % carbohydrate) containing no fruit ingredients (reference), freeze-dried black raspberries (10 or 20 % total weight; LOW-Rasp and HIGH-Rasp, respectively) and cranberry extract (0·5 or 1 % total weight; LOW-Cran and HIGH-Cran), on trials separated by ≥5 d. Postprandial peak/nadir from baseline (Δmax) and incremental postprandial AUC over 60 and 180 min for glucose and other biochemistries were measured to examine the dose-dependent effects. Glucose AUC0–180 min trended towards being higher (43 %) after HIGH-Rasp v. LOW-Rasp (P=0·06), with no glucose differences between the raspberry and reference bars. Relative to reference, HIGH-Rasp resulted in a 17 % lower Δmax insulin, 3 % lower C-peptide (AUC0–60 min and 3 % lower glucose-dependent insulinotropic polypeptide (AUC0–180 min) P<0·05. No treatment effects were observed for the cranberry bars regarding glucose and glucoregulatory hormones, nor were there any treatment effects for either berry type regarding ex vivo oxidation, appetite-mediating hormones or appetite. Fortification with freeze-dried black raspberries (approximately 25 g, containing 1·2 g of polyphenols) seems to slightly improve the glucoregulatory hormone and glycaemic responses to a high-carbohydrate food item in young adults but did not affect appetite or oxidative stress responses at doses or with methods studied herein.
The Pain Catastrophizing Scale (PCS) measures three aspects of catastrophic cognitions about pain—rumination, magnification, and helplessness. To facilitate assessment and clinical application, we aimed to (a) develop a short version on the basis of its factorial structure and the items’ correlations with key pain-related outcomes, and (b) identify the threshold on the short form indicative of risk for depression.
Social centers for older people.
664 Chinese older adults with chronic pain.
Besides the PCS, pain intensity, pain disability, and depressive symptoms were assessed.
For the full scale, confirmatory factor analysis showed that the hypothesized 3-factor model fit the data moderately well. On the basis of the factor loadings, two items were selected from each of the three dimensions. An additional item significantly associated with pain disability and depressive symptoms, over and above these six items, was identified through regression analyses. A short-PCS composed of seven items was formed, which correlated at r=0.97 with the full scale. Subsequently, receiver operating characteristic (ROC) curves were plotted against clinically significant depressive symptoms, defined as a score of ≥12 on a 10-item version of the Center for Epidemiologic Studies-Depression Scale. This analysis showed a score of ≥7 to be the optimal cutoff for the short-PCS, with sensitivity = 81.6% and specificity = 78.3% when predicting clinically significant depressive symptoms.
The short-PCS may be used in lieu of the full scale and as a brief screen to identify individuals with serious catastrophizing.
Predictive analytics in health is a complex, transdisciplinary field requiring collaboration across diverse scientific and stakeholder groups. Pilot implementation of participatory research to foster team science in predictive analytics through a partnered-symposium and funding competition. In total, 85 stakeholders were engaged across diverse translational domains, with a significant increase in perceived importance of early inclusion of patients and communities in research. Participatory research approaches may be an effective model for engaging broad stakeholders in predictive analytics.
We investigated the clinical predictors of methicillin-resistance and their impact on mortality in 371 patients with Staphylococcus aureus bacteraemia identified from two prospective multi-centre studies. Methicillin resistant S. aureus (MRSA) accounted for 42.2% of community-onset and 74.5% of hospital-onset cases. No significant clinical difference was found between patients infected with MRSA vs. methicillin-sensitive S. aureus (MSSA), except that the former were more likely to have had hospital-onset bacteraemia and received antibiotics in the preceding 90 days. After stratifying according to the acquisition site, prior antibiotic use was the only independent predictor of having MRSA in both community-onset and hospital-onset cases. The frequency of inappropriate empirical antibiotic therapy was higher in patients with MRSA than in those with MSSA bacteraemia. However, methicillin resistance was not a predictor of mortality in patients and the clinical characteristics and outcomes of both MRSA and MSSA bacteraemia were similar. This study indicates that there are no definitive clinical or epidemiological risk factors which could distinguish MRSA from MSSA cases with the exception of the previous use of antibiotics for having MRSA bacteraemia, which emphasises the prudent use of glycopeptide treatment of patients at risk for invasive MRSA infections.
Many women experience both vasomotor menopausal symptoms (VMS) and depressed mood at midlife, but little is known regarding the prospective bi-directional relationships between VMS and depressed mood and the role of sleep difficulties in both directions.
A pooled analysis was conducted using data from 21 312 women (median: 50 years, interquartile range 49−51) in eight studies from the InterLACE consortium. The degree of VMS, sleep difficulties, and depressed mood was self-reported and categorised as never, rarely, sometimes, and often (if reporting frequency) or never, mild, moderate, and severe (if reporting severity). Multivariable logistic regression models were used to examine the bi-directional associations adjusted for within-study correlation.
At baseline, the prevalence of VMS (40%, range 13–62%) and depressed mood (26%, 8–41%) varied substantially across studies, and a strong dose-dependent association between VMS and likelihood of depressed mood was found. Over 3 years of follow-up, women with often/severe VMS at baseline were more likely to have subsequent depressed mood compared with those without VMS (odds ratios (OR) 1.56, 1.27–1.92). Women with often/severe depressed mood at baseline were also more likely to have subsequent VMS than those without depressed mood (OR 1.89, 1.47–2.44). With further adjustment for the degree of sleep difficulties at baseline, the OR of having a subsequent depressed mood associated with often/severe VMS was attenuated and no longer significant (OR 1.13, 0.90–1.40). Conversely, often/severe depressed mood remained significantly associated with subsequent VMS (OR 1.80, 1.38–2.34).
Difficulty in sleeping largely explained the relationship between VMS and subsequent depressed mood, but it had little impact on the relationship between depressed mood and subsequent VMS.
Evidence suggests that semantic interference may be a sensitive indicator of early dementia. We examined the utility of the Semantic Interference Test (SIT), a cognitive stress memory paradigm which taps proactive and retroactive semantic interference, for predicting progression from mild cognitive impairment (MCI) to dementia in both a clinical and a population-based sample.
Participants with MCI in the clinical (n = 184) and population-based (n = 435) samples were followed for up to four years. We employed receiver operating characteristic (ROC) methods to establish optimal thresholds for four different SIT indices. Threshold performance was compared in the two samples using logistic and Cox proportional hazard regression models.
Within four years, 42 (22.8%) MCI individuals in the clinical sample and 45 (10.3%) individuals in the population-based sample progressed to dementia. Overall classification accuracy of SIT thresholds ranged from 61.4% to 84.8%. Different subtests of the SIT had slightly different performance characteristics in the two samples. However, regression models showed that thresholds established in the clinical sample performed similarly in the population sample before and after adjusting for demographics and other baseline neuropsychological test scores.
Despite differences in demographic composition and progression rates, baseline SIT scores predicted progression from MCI to dementia similarly in both samples. Thresholds that best predicted progression were slightly below thresholds established for distinguishing between amnestic MCI and cognitively normal subjects in clinical practice. This confirms the utility of the SIT in both clinical and population-based samples and establishes thresholds most predictive of progression of individuals with MCI.
Depression is one of the most common mental disorders and identifying effective treatment strategies is crucial for the control of depression. Well-conducted systematic reviews (SRs) and meta-analyses can provide the best evidence for supporting treatment decision-making. Nevertheless, the trustworthiness of conclusions can be limited by lack of methodological rigour. This study aims to assess the methodological quality of a representative sample of SRs on depression treatments.
A cross-sectional study on the bibliographical and methodological characteristics of SRs published on depression treatments trials was conducted. Two electronic databases (the Cochrane Database of Systematic Reviews and the Database of Abstracts of Reviews of Effects) were searched for potential SRs. SRs with at least one meta-analysis on the effects of depression treatments were considered eligible. The methodological quality of included SRs was assessed using the validated AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool. The associations between bibliographical characteristics and scoring on AMSTAR items were analysed using logistic regression analysis.
A total of 358 SRs were included and appraised. Over half of included SRs (n = 195) focused on non-pharmacological treatments and harms were reported in 45.5% (n = 163) of all studies. Studies varied in methods and reporting practices: only 112 (31.3%) took the risk of bias among primary studies into account when formulating conclusions; 245 (68.4%) did not fully declare conflict of interests; 93 (26.0%) reported an ‘a priori’ design and 104 (29.1%) provided lists of both included and excluded studies. Results from regression analyses showed: more recent publications were more likely to report ‘a priori’ designs [adjusted odds ratio (AOR) 1.31, 95% confidence interval (CI) 1.09–1.57], to describe study characteristics fully (AOR 1.16, 95% CI 1.06–1.28), and to assess presence of publication bias (AOR 1.13, 95% CI 1.06–1.19), but were less likely to list both included and excluded studies (AOR 0.86, 95% CI 0.81–0.92). SRs published in journals with higher impact factor (AOR 1.14, 95% CI 1.04–1.25), completed by more review authors (AOR 1.12, 95% CI 1.01–1.24) and SRs on non-pharmacological treatments (AOR 1.62, 95% CI 1.01–2.59) were associated with better performance in publication bias assessment.
The methodological quality of included SRs is disappointing. Future SRs should strive to improve rigour by considering of risk of bias when formulating conclusions, reporting conflict of interests and authors should explicitly describe harms. SR authors should also use appropriate methods to combine the results, prevent language and publication biases, and ensure timely updates.
Plant defence systems can be induced by biotic and abiotic stress. Experiments were undertaken to explore the feasibility of different fungal proteins for the reduction of vegetable diseases. Total proteins purified from three soil-borne and five foliar fungal pathogens had no fungistatic effects nor did they trigger hypersensitive reactions on test plants. The abilities to promote plant growth and to reduce disease severity varied among test proteins and plants. Depending on test proteins, experiments have demonstrated that exogenous application of fungal proteins could reduce Alternaria brassicicola-induced black spot severity on cabbage, Colletotrichum spp.-induced anthracnose on Chinese cabbage and cucumber, Rhizoctonia solani-induced damping-off on sweet pepper and Chinese cabbage, and powdery mildew on cucumber seedlings. An Alternariaprotein effector 1 (Ape1)-coding gene was cloned from two Alternaria spp. and expressed in Escherichia coli. The expressed Ape1 reduced anthracnose incidence on cucumber leaves, indicating that Ape1 was the primary activator in the crude protein extracts responsible for disease reduction. Application of Alternaria proteins onto Chinese cabbage seedlings caused an increase of phenylalanine ammonia lyase and peroxidase activities in treated seedlings, which may have played a role in host defence.
Extended-spectrum β-lactamase (ESBL) production has been very rare in serotype K1 Klebsiella pneumoniae ST23 strains, which are well-known invasive community strains. Among 92 ESBL-producing strains identified in 218 isolates from nine Asian countries, serotype K1 K. pneumoniae strains were screened. Two ESBL-producing K. pneumoniae isolates from Singapore and Indonesia were determined to be serotype K1 and ST23. Their plasmids, which contain CTX-M-15 genes, are transferable rendering the effective transfer of ESBL resistance plasmids to other organisms.
Improving neurocognitive outcomes following treatment for brain metastases have become increasingly important. We propose that a brief telephone-based neurocognitive assessment may improve follow-up cognitive assessments in this palliative population. Aim: To prospectively assess the feasibility and reliability of a telephone based brief neurocognitive assessment compared to the same tests delivered face-to-face. Methods: Brain metastases patients to be treated with whole brain radiotherapy (WBRT) were assessed using a brief validated neurocognitive battery at baseline, at 1 month and 3 months following WBRT (in person and over the phone). The primary outcome was feasibility and inter-procedural (in person versus telephone) reliability. The secondary objective was to evaluate the change in neurocognitive function before and after WBRT. Results: Out of 39 patients enrolled, 82% of patients completed the baseline in-person and telephone neurocognitive assessments. However, at 1 month, only 41% of enrolled patients completed the in-person and telephone cognitive assessments and at 3 months, only 10% of patients completed them. Results pertaining to reliability and change in neurocognitive function will be updated. Conclusion: The pre-defined definition of feasibility (at least 80% completion for face to face and telephone neurocognitive assessments) was met at baseline. However, a large proportion of participants did not complete either telephone or in person neurocognitive follow-up at 1 month and at 3 months post-WBRT. Attrition remained a challenge for neurocognitive testing in this population even when a telephone-based brief assessment was used.
Background: Post concussion syndrome (PCS) can affect up to 30% of patients with concussion. Biomarkers of this condition would be beneficial for diagnosis and management. We hypothesized that eye tracking parameters would correlate with microstructural changes of white matter integrity, as measured by diffusion tensor imaging (DTI), in patients with PCS. Methods: Sixty patients with PCS and at least 2 concussions participated in our prospective study. Attention and executive function were tested using Visual Attention Scanning Technology (VAST). In a matching task, the normalized number of visits to master image before making the first selection is used as a surrogate of working memory. We related performance on VAST to white matter integrity using Tract-Based Spatial Statistics of diffusion tensor imaging data. Results: 60 participants (mean age 34.3 years, SD 13.8) had a mean of 4 concussions. There were negative correlations between fractional anisotropy (FA) of the genu, body, and splenium of the corpus callosum and normalized number of visits to master image before first selection (r=-0.432, p=0.001; r=-0.504, p<0.001; and r=-0.388, p=0.002; respectively). A negative correlation was also seen between right cingulum FA and the global processing index (r=-0.349, p=0.006). Conclusions: Impaired performance on eye tracking measures of attention and executive function may reflect alterations in white matter tracts.
This study aimed to evaluate the association of chronic rhinosinusitis with sudden sensorineural hearing loss using a population-based database.
Sampled subject data were obtained from the Taiwan Longitudinal Health Insurance Database 2000. A total of 3325 patients with sudden sensorineural hearing loss were identified and 9975 controls were randomly selected. A conditional logistic regression was used to calculate the odds ratio for having been previously diagnosed with chronic rhinosinusitis, for cases and controls.
Results and conclusion:
The adjusted odds ratio of having prior chronic rhinosinusitis among cases compared to controls was 1.36 (95 per cent confidence interval = 1.16–1.60). The significant relationship between sudden sensorineural hearing loss and chronic rhinosinusitis was most pronounced among those patients aged 44 years or less (compared to controls) (odds ratio = 2.18; 95 per cent confidence interval = 1.63–2.92). However, the significant relationship between sudden sensorineural hearing loss and prior chronic rhinosinusitis was not sustained for patients older than 60 years compared to controls.
Gender and age are the top two risk factors considered in pricing life insurance products. Although it is believed that mortality rates are also related to other factors (e.g. smoking, overweight, and especially marriage), data availability and marketing often limit the possibility of including them. Many studies have shown that married people (particularly men) benefit from the marriage, and generally have lower mortality rates than unmarried people. However, most of these studies used data from a population sample; their results might not apply to the whole population. In this study, we explore if mortality rates differ by marital status using mortality data (1975–2011) from the Taiwan Ministry of the Interior. In order to deal with the problem of small sample sizes in some marital status groups, we use graduation methods to reduce fluctuations in mortality rates. We also use a relational approach to model mortality rates by marital status, and then compare the proposed model with some popular stochastic mortality models. Based on computer simulation, we find that the proposed smoothing methods can reduce fluctuations in mortality estimates between ages, and the relational mortality model has smaller errors in predicting mortality rates by marital status. Analyses of the mortality data from Taiwan show that mortality rates differ significantly by marital status. In some age groups, the differences in mortality rates are larger between marital status groups than between smokers and non-smokers. For the issue of practical consideration, we suggest modifications to include marital status in pricing of life insurance products.
The disease- and mortality-related difference between biological age based on DNA methylation and chronological age (Δage) has been found to have approximately 40% heritability by assuming that the familial correlation is only explained by additive genetic factors. We calculated two different Δage measures for 132 middle-aged female twin pairs (66 monozygotic and 66 dizygotic twin pairs) and their 215 sisters using DNA methylation data measured by the Infinium HumanMethylation450 BeadChip arrays. For each Δage measure, and their combined measure, we estimated the familial correlation for MZ, DZ and sibling pairs using the multivariate normal model for pedigree analysis. We also pooled our estimates with those from a former study to estimate weighted average correlations. For both Δage measures, there was familial correlation that varied across different types of relatives. No evidence of a difference was found between the MZ and DZ pair correlations, or between the DZ and sibling pair correlations. The only difference was between the MZ and sibling pair correlations (p < .01), and there was marginal evidence that the MZ pair correlation was greater than twice the sibling pair correlation (p < .08). For weighted average correlation, there was evidence that the MZ pair correlation was greater than the DZ pair correlation (p < .03), and marginally greater than twice the sibling pair correlation (p < .08). The varied familial correlation of Δage is not explained by additive genetic factors alone, implying the existence of shared non-genetic factors explaining variation in Δage for middle-aged women.