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A higher intake of food rich in flavonoids such as quercetin can reduce the risk of CVD. Enzymatically modified isoquercitrin (EMIQ®) has a bioavailability 17-fold higher than quercetin aglycone and has shown potential CVD moderating effects in animal studies. The present study aimed to determine whether acute ingestion of EMIQ® improves endothelial function, blood pressure (BP) and cognitive function in human volunteers at risk of CVD. Twenty-five participants (twelve males and thirteen females) with at least one CVD risk factor completed this randomised, controlled, crossover study. In a random order, participants were given EMIQ® (2 mg aglycone equivalent)/kg body weight or placebo alongside a standard breakfast meal. Endothelial function, assessed by flow-mediated dilatation (FMD) of the brachial artery was measured before and 1·5 h after intervention. BP, arterial stiffness, cognitive function, BP during cognitive stress and measures of quercetin metabolites, oxidative stress and markers of nitric oxide (NO) production were assessed post-intervention. After adjustment for pre-treatment measurements and treatment order, EMIQ® treatment resulted in a significantly higher FMD response compared with the placebo (1·80 (95 % CI 0·23, 3·37) %; P = 0·025). Plasma concentrations of quercetin metabolites were significantly higher (P < 0·001) after EMIQ® treatment compared with the placebo. No changes in BP, arterial stiffness, cognitive function or biochemical parameters were observed. In this human intervention study, the acute administration of EMIQ® significantly increased circulating quercetin metabolites and improved endothelial function. Further clinical trials are required to assess whether health benefits are associated with long-term EMIQ® consumption.
Outpatient interventions for adult anorexia nervosa typically have a modest impact on weight and eating disorder symptomatology. This study examined whether adding a brief online intervention focused on enhancing motivation to change and the development of a recovery identity (RecoveryMANTRA) would improve outcomes in adults with anorexia nervosa.
Participants with anorexia nervosa (n = 187) were recruited from 22 eating disorder outpatient services throughout the UK. They were randomised to receiving RecoveryMANTRA in addition to treatment as usual (TAU) (n = 99; experimental group) or TAU only (n = 88; control group). Outcomes were measured at end-of-intervention (6 weeks), 6 and 12 months.
Adherence rates to RecoveryMANTRA were 83% for the online guidance sessions and 77% for the use of self-help materials (workbook and/or short video clips). Group differences in body mass index at 6 weeks (primary outcome) were not significant. Group differences in eating disorder symptoms, psychological wellbeing and work and social adjustment (at 6 weeks and at follow-up) were not significant, except for a trend-level greater reduction in anxiety at 6 weeks in the RecoveryMANTRA group (p = 0.06). However, the RecoveryMANTRA group had significantly higher levels of confidence in own ability to change (p = 0.02) and alliance with the therapist at the outpatient service (p = 0.005) compared to the control group at 6 weeks.
Augmenting outpatient treatment for adult anorexia nervosa with a focus on recovery and motivation produced short-term reductions in anxiety and increased confidence to change and therapeutic alliance.
It is becoming clear that post-traumatic stress disorder (PTSD) is not simply a psychiatric disorder, but one that involves pervasive physiological impairments as well. These physiological disturbances deserve attention in any attempt at integrative treatment of PTSD that requires a focus beyond the PTSD symptoms themselves. The physiological disturbances in PTSD range over many systems, but a common thread thought to underlie them is that the chronic effects of PTSD involve problems with allostatic control mechanisms that result in an excess in what has been termed “allostatic load” (AL). A pharmacological approach to reducing AL would be valuable, but, because of the large range of physiological issues involved – including metabolic, inflammatory, and cardiovascular systems – it is unclear whether there exists a simple comprehensive way to address the AL landscape. In this paper, we propose that the cannabinoid system may offer just such an approach, and we outline evidence for the potential utility of cannabinoids in reducing many of the chronic physiological abnormalities seen in PTSD which are thought to be related to excess AL.
Deep neural networks have attracted considerable attention because of their state-of-the-art performance on a variety of image restoration tasks, including image completion, denoising, and segmentation. However, their record of performance is built upon extremely large datasets. In many cases (for example, electron microscopy), it is extremely labor intensive, if not impossible, to acquire tens of thousands of images for a single project. The present work shows the possibility of attaining high-accuracy image segmentation, isolating regions of interest, for small datasets of transmission electron micrographs by employing encoder-decoder neural networks and image augmentation.
Depression is considered to have the highest disability burden of all conditions. Although treatment-resistant depression (TRD) is a key contributor to that burden, there is little understanding of the best treatment approaches for it and specifically the effectiveness of available augmentation approaches.
We conducted a systematic review and meta-analysis to search and quantify the evidence of psychological and pharmacological augmentation interventions for TRD.
Participants with TRD (defined as insufficient response to at least two antidepressants) were randomised to at least one augmentation treatment in the trial. Pre-post analysis assessed treatment effectiveness, providing an effect size (ES) independent of comparator interventions.
Of 28 trials, 3 investigated psychological treatments and 25 examined pharmacological interventions. Pre-post analyses demonstrated N-methyl-d-aspartate-targeting drugs to have the highest ES (ES = 1.48, 95% CI 1.25–1.71). Other than aripiprazole (four studies, ES = 1.33, 95% CI 1.23–1.44) and lithium (three studies, ES = 1.00, 95% CI 0.81–1.20), treatments were each investigated in less than three studies. Overall, pharmacological (ES = 1.19, 95% CI 1.08–1.30) and psychological (ES = 1.43, 95% CI 0.50–2.36) therapies yielded higher ESs than pill placebo (ES = 0.78, 95% CI 0.66–0.91) and psychological control (ES = 0.94, 95% CI 0.36–1.52).
Despite being used widely in clinical practice, the evidence for augmentation treatments in TRD is sparse. Although pre-post meta-analyses are limited by the absence of direct comparison, this work finds promising evidence across treatment modalities.
Declaration of interest
In the past 3 years, A.H.Y. received honoraria for speaking from AstraZeneca, Lundbeck, Eli Lilly and Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion and Janssen; and research grant support from Janssen. In the past 3 years, A.J.C. received honoraria for speaking from AstraZeneca and Lundbeck; honoraria for consulting with Allergan, Janssen, Livanova, Lundbeck and Sandoz; support for conference attendance from Janssen; and research grant support from Lundbeck. B.B. has recently been (soon to be) on the speakers/advisory board for Hexal, Lilly, Lundbeck, Mundipharma, Pfizer, and Servier. No other conflicts of interest.
Supplementation with n-3 fatty acids can influence inflammation and markers of arterial stiffness that are increased in patients with rheumatoid arthritis (RA). However, it is unknown whether specific patterns of dietary fatty acid intake are similarly associated. In a longitudinal study, eighty-six RA patients reported their dietary intake and had arterial stiffness measured using the augmentation index (AIx) at baseline and 8 months. Latent profile analysis (LPA) was performed to characterise patterns of fatty acid intake using sixteen major fatty acids. Models for two to six profiles were compared using the Akaike and Bayesian information criteria. Associations between AIx and the profiles were adjusted for age, sex, disease activity, fish oil supplementation, medications, physical activity and socio-economic status. LPA identified five distinct profiles. Profile 1 subjects (n 7) reported significantly higher intake of palmitoleic acid (16 : 1), arachidonic acid (20 : 4n-6), EPA (20 : 5n-3), DHA (22 : 6n-3) and docosapentaenoic acid (22 : 5n-3) (P<0·001 for each) than profiles 2 (n 14), 3 (n 19), 4 (n 23) and 5 (n 23) and significantly higher grilled and tinned fish consumption. The AIx varied significantly across the five profiles (P=0·023); subjects in profile 1 had a significantly lower AIx than those in profile 3 (β=–7·2 %; 95 % CI –11·5, –2·9; P=0·001) who had the lowest reported intake of n-3 fatty acids. Fish oil supplementation was also independently associated with lower AIx (β=–4·15 %; 95 % CI –6·73, –1·56; P=0·002). A diet characterised by a higher reported intake of n-3 fatty acids, palmitoleic acid (16 : 1) and arachidonic acid (20 : 4n-6) is associated with a lower AIx in RA patients.
This paper creates a multinomial framework for ideal point estimation (mIRT) using recent developments in Bayesian statistics. The core model relies on a flexible multinomial specification that includes most common models in political science as “special cases.” I show that popular extensions (e.g., dynamic smoothing, inclusion of covariates, and network models) can be easily incorporated whilst maintaining the ability to estimate a model using a Gibbs Sampler or exact EM algorithm. By showing that these models can be written and estimated using a shared framework, the paper aims to reduce the proliferation of bespoke ideal point models as well as extend the ability of applied researchers to estimate models quickly using the EM algorithm. I apply this framework to a thorny question in scaling survey responses—the treatment of nonresponse. Focusing on the American National Election Study (ANES), I suggest that a simple but principled solution is to treat questions as multinomial where nonresponse is a distinct (modeled) category. The exploratory results suggest that certain questions tend to attract many more invalid answers and that many of these questions (particularly when signaling out particular social groups for evaluation) are masking noncentrist (typically conservative) beliefs.
Given the advanced breakthroughs in the field of supportive robotic technologies, interest in the integration of the human body and a robot into a single system has rapidly increased. The aim of this work is to provide an overview of empowering lower limbs exoskeletons. Along with lower exoskeleton limbs, their unique design concepts, operator–exoskeleton interactions and control strategies are described. Although many problems have been solved in recent development, many challenges remain. Especially in the context of infantry soldiers, fire fighters and rescuers, the challenges of empowering exoskeletons are discussed, and improvements are outlined and described. This study is not only a summary of the current state, but also points to weaknesses of empowering lower limbs exoskeletons and outlines possible improvements.
This article offers an architectural blueprint for the study of economic connections between warfare in the early modern period and the long-term growth of Europe's competing national economies. It surveys and critically investigates the concepts derived mainly from economic theory and the statistical evidence accessible in primary and secondary sources for the investigation of this meta-problem for students of economic theory.
The potential of the mirid predator Dicyphus hesperus Knight (Heteroptera: Miridae) as a biological control agent of the sweetpotato whitefly, Bemisia tabaci Gennadius (Hemiptera: Aleyrodidae) and the potato psyllid, Bactericera cockerelli Sulcer (Hemiptera: Psyllidae) in tomato was investigated in two experiments. The first experiment focused on the study of the life history traits of D. hesperus when fed on nymphs of the potato psyllid compared with the factitious prey Ephestia kuehniella Zeller (Lepidoptera: Pyrallidae) eggs. Although reproductive and development rates were higher on E. kuehniella eggs, the predator exhibited a good intrinsic rate of natural increase (rm) when feeding on B. cockerelli nymphs (rm: B. cockerelli 0.069 ± 0.0001; E. kuehniella 0.078 ± 0.0001), thus reflecting good potential as a biocontrol agent of this pest. The second experiment focused on the efficacy of D. hesperus as a biocontrol agent of the potato psyllid and the sweetpotato whitefly in a tomato greenhouse. Prey species were offered individually or together in a series of five treatments in greenhouse cages. Results showed that the predator was able to establish and suppress populations of both pests inhabiting tomato plants when pests occurred alone or together. Thus, D. hesperus was demonstrated to be a suitable biocontrol agent of these two important pests that could be used in tomato greenhouses.
Atherosclerotic cardiovascular disease is a leading cause of death and disability worldwide, and the atherosclerotic process begins in childhood. Prevention or containment of risk factors that accelerate atherosclerosis can delay the development of atherosclerotic cardiovascular disease. Although current recommendations are to periodically screen for commonly prevailing risk factors for atherosclerosis in children, a single test that could quantify the cumulative effect of all risk factors on the vasculature, thus assessing arterial health, would be helpful in further stratifying risk. Measurement of pulse wave velocity and assessment of augmentation index – measures of arterial stiffness – are easy-to-use, non-invasive methods of examining arterial health. Various studies have assessed pulse wave velocity and augmentation index in children with commonly occurring conditions including obesity, hypertension, insulin resistance, diabetes mellitus, dyslipidaemia, physical inactivity, chronic kidney disease, CHD and acquired heart diseases, and in children who were born premature or small for gestational age. This article summarises pulse wave velocity and augmentation index assessments and the effects of commonly prevailing chronic conditions on arterial health in children. In addition, currently available reference values for pulse wave velocity and augmentation index in healthy children are included. Further research to establish widely applicable normative values and the effect of lifestyle and pharmacological interventions on arterial health in children is needed.
Pulmonary valvular stenosis is a relatively common disorder, accounting for approximately 10% of all CHDs. Pulmonic valvular disease can get clinically detected at different ages of life. The more severe the obstruction, the earlier detected the valvular abnormality. Surgical pulmonary valvotomy has been available as a treatment since 1956. This article is about a case of pulmonary annular and valvular stenosis in a 1-year-old child, and it also explores surgical operation of this condition. Transannular patches are usually used within the 1st year of age in pulmonary annular and valvular stenosis. In recent years, anterior leaflet augmentation has been preferred for annulus enlargements. In our 1-year-old case, we expanded the annulus by the anterior leaflet expansion technique and we also augmented other leaflets by polytetrafluoroethylene patch.
Pragmatic studies indicate that a substantial number of depressed patients do not remit with current first-line antidepressant treatments and after two failed treatment steps the chance of remission with subsequent therapies is around 15%. This paper focuses on current evidence for pharmacological treatments in resistant depression as well as possible future developments. For patients who have failed to respond to two antidepressant trials, augmentation with atypical antipsychotic drugs, specifically quetiapine and aripiprazole, has the best evidence for efficacy, though older treatments such as lithium and triiodothyronine still have utility. The striking antidepressant effect of ketamine in resistant depression has stimulated research into glutamatergic compounds; however, capturing the efficacy of ketamine with drugs suitable for continuous use has proved challenging. Growing knowledge of the pathophysiological role of inflammation in depression offers great opportunities for future treatment in terms of repurposing anti-inflammatory agents from general medicine and pre-treatment stratification of those depressed patients in whom such interventions are likely to be beneficial. Finally an older drug, the dopamine receptor agonist pramipexole, if used carefully may well improve the prospects of depressed patients who are refractory to current approaches.
Emerging CVD risk factors (e.g. HDL function and central haemodynamics) may account for residual CVD risk experienced by individuals who meet LDL-cholesterol and blood pressure (BP) targets. Recent evidence suggests that these emerging risk factors can be modified by polyphenol-rich interventions such as soya, but additional research is needed. This study was designed to investigate the effects of an isoflavone-containing soya protein isolate (delivering 25 and 50 g/d soya protein) on HDL function (i.e. ex vivo cholesterol efflux), macrovascular function and blood markers of CVD risk. Middle-aged adults (n 20; mean age=51·6 (sem 6·6) years) with moderately elevated brachial BP (mean systolic BP=129 (sem 9) mmHg; mean diastolic BP=82·5 (sem 8·4) mmHg) consumed 0 (control), 25 and 50 g/d soya protein in a randomised cross-over design. Soya and control powders were consumed for 6 weeks each with a 2-week compliance break between treatment periods. Blood samples and vascular function measures were obtained at baseline and following each supplementation period. Supplementation with 50 g/d soya protein significantly reduced brachial diastolic BP (−2·3 mmHg) compared with 25 g/d soya protein (Tukey-adjusted P=0·03) but not the control. Soya supplementation did not improve ex vivo cholesterol efflux, macrovascular function or other blood markers of CVD risk compared with the carbohydrate-matched control. Additional research is needed to clarify whether effects on these CVD risk factors depend on the relative health of participants and/or equol producing capacity.
To determine the effectiveness of augmentation surgery using polydimethylsiloxane elastomer injection for the management of patulous eustachian tube.
All patients were treated with eustachian tube injection augmentation performed via a combined transnasal-transoral endoscopic approach. Clinical presentation, volume of injection, complications and initial response were all prospectively recorded. Longer-term follow up was conducted through structured telephone interviews using previously described patient-reported outcome measures.
Overall, 8 of 11 patients (73 per cent) derived complete or significant symptom improvement; 1 patient had significant improvements but was dissatisfied, and in 2 patients the symptoms were unchanged. The eight satisfied patients showed improvement in their quality-of-life scores.
This study describes an effective treatment option for patulous eustachian tube. Unlike many prior published reports, previously described patient-reported outcome measures were utilised in order to allow more direct comparison.
Combined isometric exercise or metaboreflex activation (post-exercise muscle ischaemia (PEMI)) and cold pressor test (CPT) increase cardiac afterload, which may lead to adverse cardiovascular events. l-Citrulline supplementation (l-CIT) reduces systemic arterial stiffness (brachial-ankle pulse wave velocity (baPWV)) at rest and aortic haemodynamic responses to CPT. The aim of this study was to determine the effect of l-CIT on aortic haemodynamic and baPWV responses to PEMI+CPT. In all, sixteen healthy, overweight/obese males (age 24 (sem 6) years; BMI 29·3 (sem 4·0) kg/m2) were randomly assigned to placebo or l-CIT (6 g/d) for 14 d in a cross-over design. Brachial and aortic systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP), aortic augmented pressure (AP), augmentation index (AIx), baPWV, reflection timing (Tr) and heart rate (HR) were evaluated at rest and during isometric handgrip exercise (IHG), PEMI and PEMI+CPT at baseline and after 14 d. No significant effects were evident after l-CIT at rest. l-CIT attenuated the increases in aortic SBP and wave reflection (AP and AIx) during IHG, aortic DBP, MAP and AIx during PEMI, and aortic SBP, DBP, MAP, AP, AIx and baPWV during PEMI+CPT compared with placebo. HR and Tr were unaffected by l-CIT in all conditions. Our findings demonstrate that l-CIT attenuates aortic blood pressure and wave reflection responses to exercise-related metabolites. Moreover, l-CIT attenuates the exaggerated arterial stiffness response to combined metaboreflex activation and cold exposure, suggesting a protective effect against increased cardiac afterload during physical stress.
Augmentative biological control is not commonly used in commercial orchards. We used an exclusion system to evaluate the potential of early-season releases of the European earwig (Forficula auricularia L., Dermaptera: Forficulidae) for control of the rosy apple aphid (Dysaphis plantaginea Passerini, Hemiptera: Aphididae) in the spring of 2009 in two pesticide-free apple orchards. In order to conduct this experiment we successfully reared earwigs with a high survival rate of nymphs (more than 96%) which may have commercial application. There were three treatments in the study: (i) a ‘release treatment’ where we confined the released earwigs in the canopy by using a barrier system; (ii) an ‘exclusion treatment’ where we blocked free access of earwigs into the canopy using the same barrier system; and (iii) a ‘control treatment’ that represented the natural situation. Contrary to expectations, earwig releases did not reduce D. plantaginea populations. In general, the abundance of natural enemies and their groups did not differ significantly among treatments, except for earwigs. We observed that the exclusion systems we used successfully kept both earwigs and ants away from tree canopies; total numbers on trees in the ‘exclusion treatment’ were significantly lower than on the other two treatments. Due to the complexity and difficulty of evaluating augmentative releases of natural enemies in open orchard conditions, we conclude that new technical approaches to control site conditions are needed when conducting such studies.
Outbreaks of soft tissue or skin infection due to non-tuberculous mycobacteria are reported frequently in scientific journals but in general the infection source in these outbreaks remains unknown. In Venezuela, in two distinct outbreaks, one after breast augmentation surgery and another after hydrolipoclasy therapy, 16 patients contracted a soft tissue infection due to Mycobacterium abscessus subsp. abscessus. Searching for the possible environmental infection sources in these outbreaks, initially the tap water (in the hydrolipoclasy therapy outbreak) and a surgical skin marker (in the breast implant surgery outbreak), were identified as the infection sources. Molecular typing of the strains with a variable number tandem repeat typing assay confirmed the tap water as the infection source but the molecular typing technique excluded the skin marker. We discuss the results and make a call for the implementation of stringent hygiene and disinfection guidelines for cosmetic procedures in Venezuela.
Little is known about the clustering patterns of lifestyle behaviours in adult populations. We explored clusters in multiple lifestyle behaviours including physical activity (PA), smoking, alcohol use and eating habits in a sample of adult population. A cross-sectional and multi-centre study was performed with six participating groups distributed throughout Spain. Participants (n 1327) were part of the Lifestyles and Endothelial Dysfunction (EVIDENT) study and were aged between 20 and 80 years. The lifestyle and cardiovascular risk (CVR) factors were analysed using a clustering method based on the HJ-biplot coordinates to understand the variables underlying these groupings. The following three clusters were identified. Cluster 1: unhealthy, 677 subjects (51 %), with a slight majority of men (58·7 %), who were more sedentary and smokers with higher consumption of whole-fat dairy products, bigger waist circumference as well as higher TAG levels, systolic blood pressure (SBP) and CVR. Cluster 2: healthy/PA, 265 subjects (20 %), including 24·0 % of males with high PA. Cluster 3: healthy/diet, including 29 % of the participants, with a higher consumption of olive oil, fish, fruits, nuts, vegetables and lower alcohol consumption. Using the unhealthy cluster as a reference, and after adjusting for age and sex, the multiple regression analysis showed that belonging to the healthy/PA cluster was associated with a lower waist circumference, body fat percentage, SBP and CVR. In summary, the three clusters were identified according to lifestyles. The ‘unhealthy’ cluster had the least favourable clinical parameters, the ‘healthy/PA’ cluster had good HDL-cholesterol levels and low SBP and the ‘healthy/diet’ cluster had lower LDL-cholesterol levels and clinical blood pressure.