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Autonomic nervous system (ANS) dysregulation might be relevant to the pathophysiology of fatigue and cognitive impairment in depression and perhaps should be considered when making prescribing decisions.
To determine the relationship of self-reported ANS symptoms with fatigue, cognition and prescribed medication in people with a diagnosis of depression, in comparators without depression but with other mental health, neurodevelopmental or neurodegenerative disorders (active controls) and in healthy controls.
Cross-sectional analysis of an opportunistic sample from England. Self-reported data were collected on demographics, diagnosis, medication, ANS symptoms (Composite Autonomic Symptom Scale-31, COMPASS-31) and fatigue (Visual Analogue Scale for Fatigue, VAS-F). A subsample completed cognitive tests (THINC-it), including the subjective Perceived Deficits Questionnaire five-item version (PDQ-5). Spearman's correlation and mediation models were used to explore the relationship between COMPASS-31, VAS-F and PDQ-5 scores.
Data were obtained for 3345 participants, 22% with depression. The depression group had significantly (P < 0.01) more severe autonomic dysregulation as measured by COMPASS-31 scores (median 30) than active (median 23) and healthy controls (median 10). The depression group had significantly higher symptom severity (P < 0.01) than both control groups on the VAS-F and PDQ-5. Overall, there was a significantly positive correlation (P < 0.01) between COMPASS-31, VAS-F scores (Spearman's rho rs = 0.44) and PDQ-5 scores (rs = 0.56). COMPASS-31 scores mediated greater symptom severity on the VAS-F and PDQ-5 for those with depression. COMPASS-31 scores remained significantly different between the depression group and both control groups independently of medication.
People with a diagnosis of depression report worse fatigue and cognition than active and healthy comparators; this appears to be mediated by ANS dysregulation.
The relationship between major depressive disorder (MDD) and personality disorders is complex, with implications for diagnosis and treatment. We sought to explore the relationship between these disorders quantitatively in an inpatient setting.
We conducted a structured observational study exploring symptoms of depression and selected neurocognitive functions over the span of an inpatient admission in those with depression and personality disorders. Sixty inpatients presenting with symptoms of depression completed ratings of mood and neurocognitive function. Diagnosis was confirmed by structured clinical interview (SCID-5-RV) at discharge and used to allocate patients to one of the two groups for analysis: those with MDD-only and those with a personality disorder (with or without MDD).
On admission, observer-based ratings of depression were significantly higher in the MDD-only group while subjective ratings were higher in the personality disorder group. Depression rating scores lessened in both groups during the admission, but at discharge, the personality disorder group continued to report higher subjective ratings. The personality disorder group also rated themselves as more cognitively impaired than the MDD-only group and unlike the MDD-only group, they did not report subjective improvements in cognitive function over the course of admission. Objective assessment of cognitive function demonstrated improvements in both groups.
In this study, the presence of a personality disorder was associated with greater subjective severity of depressive symptomatology and selected neurocognitive functioning, despite similar or lower objective severity in comparison with those with MDD. This finding has implications for understanding the patient journey through health care settings.
The present study aimed to clarify the neuropsychological profile of the emergent diagnostic category of Mild Cognitive Impairment with Lewy bodies (MCI-LB) and determine whether domain-specific impairments such as in memory were related to deficits in domain-general cognitive processes (executive function or processing speed).
Patients (n = 83) and healthy age- and sex-matched controls (n = 34) underwent clinical and imaging assessments. Probable MCI-LB (n = 44) and MCI-Alzheimer’s disease (AD) (n = 39) were diagnosed following National Institute on Aging-Alzheimer’s Association (NIA-AA) and dementia with Lewy bodies (DLB) consortium criteria. Neuropsychological measures included cognitive and psychomotor speed, executive function, working memory, and verbal and visuospatial recall.
MCI-LB scored significantly lower than MCI-AD on processing speed [Trail Making Test B: p = .03, g = .45; Digit Symbol Substitution Test (DSST): p = .04, g = .47; DSST Error Check: p < .001, g = .68] and executive function [Trail Making Test Ratio (A/B): p = .04, g = .52] tasks. MCI-AD performed worse than MCI-LB on memory tasks, specifically visuospatial (Modified Taylor Complex Figure: p = .01, g = .46) and verbal (Rey Auditory Verbal Learning Test: p = .04, g = .42) delayed recall measures. Stepwise discriminant analysis correctly classified the subtype in 65.1% of MCI patients (72.7% specificity, 56.4% sensitivity). Processing speed accounted for more group-associated variance in visuospatial and verbal memory in both MCI subtypes than executive function, while no significant relationships between measures were observed in controls (all ps > .05)
MCI-LB was characterized by executive dysfunction and slowed processing speed but did not show the visuospatial dysfunction expected, while MCI-AD displayed an amnestic profile. However, there was considerable neuropsychological profile overlap and processing speed mediated performance in both MCI subtypes.
The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.
The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance.
MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.
Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O3.
MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.
Until the past half-century, all agriculture and land management was framed by local institutions strong in social capital. But neoliberal forms of development came to undermine existing structures, thus reducing sustainability and equity. The past 20 years, though, have seen the deliberate establishment of more than 8 million new social groups across the world. This restructuring and growth of rural social capital within specific territories is leading to increased productivity of agricultural and land management systems, with particular benefits for those previously excluded. Further growth would occur with more national and regional policy support.
Late-life depression (LLD) is associated with poor social functioning. However, previous research uses bias-prone self-report scales to measure social functioning and a more objective measure is lacking. We tested a novel wearable device to measure speech that participants encounter as an indicator of social interaction.
Twenty nine participants with LLD and 29 age-matched controls wore a wrist-worn device continuously for seven days, which recorded their acoustic environment. Acoustic data were automatically analysed using deep learning models that had been developed and validated on an independent speech dataset. Total speech activity and the proportion of speech produced by the device wearer were both detected whilst maintaining participants' privacy. Participants underwent a neuropsychological test battery and clinical and self-report scales to measure severity of depression, general and social functioning.
Compared to controls, participants with LLD showed poorer self-reported social and general functioning. Total speech activity was much lower for participants with LLD than controls, with no overlap between groups. The proportion of speech produced by the participants was smaller for LLD than controls. In LLD, both speech measures correlated with attention and psychomotor speed performance but not with depression severity or self-reported social functioning.
Using this device, LLD was associated with lower levels of speech than controls and speech activity was related to psychomotor retardation. We have demonstrated that speech activity measured by wearable technology differentiated LLD from controls with high precision and, in this study, provided an objective measure of an aspect of real-world social functioning in LLD.
A consensus workshop on low-calorie sweeteners (LCS) was held in November 2018 where seventeen experts (the panel) discussed three themes identified as key to the science and policy of LCS: (1) weight management and glucose control; (2) consumption, safety and perception; (3) nutrition policy. The aims were to identify the reliable facts on LCS, suggest research gaps and propose future actions. The panel agreed that the safety of LCS is demonstrated by a substantial body of evidence reviewed by regulatory experts and current levels of consumption, even for high users, are within agreed safety margins. However, better risk communication is needed. More emphasis is required on the role of LCS in helping individuals reduce their sugar and energy intake, which is a public health priority. Based on reviews of clinical evidence to date, the panel concluded that LCS can be beneficial for weight management when they are used to replace sugar in products consumed in the diet (without energy substitution). The available evidence suggests no grounds for concerns about adverse effects of LCS on sweet preference, appetite or glucose control; indeed, LCS may improve diabetic control and dietary compliance. Regarding effects on the human gut microbiota, data are limited and do not provide adequate evidence that LCS affect gut health at doses relevant to human use. The panel identified research priorities, including collation of the totality of evidence on LCS and body weight control, monitoring and modelling of LCS intakes, impacts on sugar reduction and diet quality and developing effective communication strategies to foster informed choice. There is also a need to reconcile policy discrepancies between organisations and reduce regulatory hurdles that impede low-energy product development and reformulation.
Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) have substantial clinical and biological overlap, with cognitive deficits typically observed in the executive and visuospatial domains. However, the neuropsychological profiles of mild cognitive impairment (MCI) associated with these disorders are not well understood.
This systematic review examined existing literature on cognition in MCI due to LB disease (MCI-LB) and PD (PD-MCI) using an electronic search of seven databases (Medline, Embase, Psychinfo, PubMed, ProQuest, Scopus, and ScienceDirect). MCI-LB results were reviewed narratively given the small number of resulting papers (n = 7). Outcome variables from PD-MCI studies (n = 13) were extracted for meta-analysis of standardised mean differences (SMD).
In MCI-LB, executive dysfunction and slowed processing speed were the most prominent impairments, while visuospatial and working memory (WM) functions were also poor. MCI-LB scored significantly lower on verbal memory tests relative to controls, but significantly higher than patients with MCI due to Alzheimer’s disease. Quantitative analysis of studies in PD-MCI showed a similar profile of impairment, with the largest deficits in visuospatial function (Benton Judgement of Line Orientation, SMD g = −2.09), executive function (Trail Making Test B, SMD g = −1.65), verbal ability (Naming Tests, SMD g = −0.140), and WM (Trail Making Test A, SMD g = −1.20). In both MCI-LB and PD-MCI, verbal and visuospatial memory retrieval was impaired, while encoding and storage appeared relatively intact.
The findings of this systematic review indicate similar neuropsychological profiles in the MCI stages of DLB and PDD. Executive impairment may at least partially explain poor performance in other domains.
We present a method for automatic inference of conditions on the initial states of a program that guarantee that the safety assertions in the program are not violated. Constrained Horn clauses (CHCs) are used to model the program and assertions in a uniform way, and we use standard abstract interpretations to derive an over-approximation of the set of unsafe initial states. The precondition then is the constraint corresponding to the complement of that set, under-approximating the set of safe initial states. This idea of complementation is not new, but previous attempts to exploit it have suffered from the loss of precision. Here we develop an iterative specialisation algorithm to give more precise, and in some cases optimal safety conditions. The algorithm combines existing transformations, namely constraint specialisation, partial evaluation and a trace elimination transformation. The last two of these transformations perform polyvariant specialisation, leading to disjunctive constraints which improve precision. The algorithm is implemented and tested on a benchmark suite of programs from the literature in precondition inference and software verification competitions.
Testosterone influences well-being, mood and cognition and may play a role in the pathophysiology of bipolar disorder.
To examine testosterone levels in patients with bipolar disorder compared with healthy controls.
We examined baseline total testosterone levels and current depression scores in male and female patients with bipolar disorder and mild to moderate depression and healthy controls.
A significant interaction between diagnosis and gender was observed (F(2,97)=9.791, P=0.002). Testosterone levels were significantly lower for male patients with bipolar disorder compared with male controls (P=0.001). Women with bipolar disorder had significantly higher testosterone levels than female controls (P=0.03).
Disturbances in testosterone levels may represent an important neurobiological abnormality in bipolar disorder and may differ by gender. If these findings are confirmed, the use of gender appropriate treatment strategies for the normalisation of testosterone levels in bipolar disorder depression should be further explored.
Previous studies of facial emotion processing in bipolar disorder (BD) have reported conflicting findings. In independently conducted studies, we investigate facial emotion labeling in euthymic and depressed BD patients using tasks with static and dynamically morphed images of different emotions displayed at different intensities. Study 1 included 38 euthymic BD patients and 28 controls. Participants completed two tasks: labeling of static images of basic facial emotions (anger, disgust, fear, happy, sad) shown at different expression intensities; the Eyes Test (Baron-Cohen, Wheelwright, Hill, Raste, & Plumb, 2001), which involves recognition of complex emotions using only the eye region of the face. Study 2 included 53 depressed BD patients and 47 controls. Participants completed two tasks: labeling of “dynamic” facial expressions of the same five basic emotions; the Emotional Hexagon test (Young, Perret, Calder, Sprengelmeyer, & Ekman, 2002). There were no significant group differences on any measures of emotion perception/labeling, compared to controls. A significant group by intensity interaction was observed in both emotion labeling tasks (euthymia and depression), although this effect did not survive the addition of measures of executive function/psychomotor speed as covariates. Only 2.6–15.8% of euthymic patients and 7.8–13.7% of depressed patients scored below the 10th percentile of the controls for total emotion recognition accuracy. There was no evidence of specific deficits in facial emotion labeling in euthymic or depressed BD patients. Methodological variations—including mood state, sample size, and the cognitive demands of the tasks—may contribute significantly to the variability in findings between studies. (JINS, 2015, 21, 709–721)
Adequate Zn and Mg intakes may be beneficial for the prevention and treatment of mental health problems, such as depression, anxiety and attention-deficit hyperactivity disorder. We aimed to investigate the prospective association between dietary intakes of Zn and Mg and internalising and externalising behaviour problems in a population-based cohort of adolescents.
Prospective analysis (general linear mixed models) of dietary intakes of Zn and Mg assessed using a validated FFQ and mental health symptoms assessed using the Youth Self-Report (YSR), adjusting for sex, physical activity, family income, supplement status, dietary misreporting, BMI, family functioning and energy intake.
Western Australian Pregnancy Cohort (Raine) Study.
Adolescents (n 684) at the 14- and 17-year follow-ups.
Higher dietary intake of Mg (per sd increase) was significantly associated with reduced externalising behaviours (β=−1·45; 95 % CI −2·40, −0·50; P=0·003). There was a trend towards reduced externalising behaviours with higher Zn intake (per sd increase; β=−0·73; 95 % CI −1·57, 0·10; P=0·085).
The study shows an association between higher dietary Mg intake and reduced externalising behaviour problems in adolescents. We observed a similar trend, although not statistically significant, for Zn intake. Randomised controlled trials are necessary to determine any benefit of micronutrient supplementation in the prevention and treatment of mental health problems in adolescents.
Studies investigating the cognitive effects of serotonin depletion, using the technique of acute tryptophan depletion (ATD) by dietary means, have generally suggested that ATD impairs delayed verbal recall and recognition. In two previous studies in the elderly, this result has not been replicated and ATD impaired working memory. These results may be susceptible to type II error but a similar testing schedule in the individual studies allows data to be pooled in a larger analysis.
Data from two separate double-blind placebo-controlled studies of the effects of ATD on cognitive function in the elderly were combined. In one study, a low dose and in the other a high dose of amino acids was used. In a repeated measures analysis of variance, the effects of ATD and the interaction of this with the other factors (age, gender and dose) on cognitive measures was examined.
Data from 31 healthy subjects aged between 60 and 81 years were analysed. There were no main effects of ATD or consistent interactions between ATD and age, gender or dose. There were significant interactions between ATD, gender and dose. When tryptophan depleted, females having the higher dose drink had reduced scores on Digit span and immediate recall on the Rey Auditory Verbal Learning Test.
The enlarged data set did not confirm an overall effect of ATD on working memory or on delayed word recall but does suggest an effect of ATD on encoding or registration in the subgroup of females receiving a higher strength drink.
New evidence is emerging regarding abnormalities of hypothalamic-pituitary-adrenal (HPA) axis function in subtypes of affective disorders. Adverse effects of HPA axis dysregulation may include dysfunction of monoaminergic transmitter systems, cognitive impairment and peripheral effects. Newer treatments specifically targeting the HPA axis are being developed.
To review these developments focusing particularly on the glucocorticoid receptor (GR) antagonist mifepristone.
A selective review of the literature.
The function of GRs is increasingly being defined. The role of corticotrophin-releasing hormone (CRH) and dehydroepiandrosterone (DHEA) in the brain is also increasingly understood. HPA axis function is particularly likely to be abnormal in psychotic depression and bipolar disorder, and it is in these conditions that trials of the GR antagonist mifepristone are being focused. CRH antagonists and DHEA are also being investigated as potential treatments.
Initial studies of mifepristone and other HPA-axis-targeting agents in psychotic depression and bipolar disorder are encouraging and confirmatory studies are awaited.
To describe the role, contribution and value of research nurses in New Zealand community-based or primary health care research.
Research nurses are increasingly recognised as having a key role in undertaking successful research in hospitals and clinical trial units however only limited work has been undertaken to examine their role in community-based research. Undertaking health research in the community has unique challenges particularly in relation to research design and recruitment and retention of participants.
We describe four community-based research projects involving research nurses, each with particular recruitment, retention and logistical problems. Vignettes are used to illustrate the role, contribution and value of research nurses in a diverse range of community research projects.
The knowledge and skills used by research nurses in these projects included familiarity with communities, cultural competence, health care systems and practice philosophies and in particular with vulnerable populations. Their research actions and activities include competence with a broad range of research methodologies, organisational efficiency, family-centred approach, along with advocacy and flexibility. These are underpinned by nursing knowledge and clinical expertise contributing to an ability to work autonomously. These four projects demonstrate that research nurses in community-based research possess specific attributes which facilitate successful study development, implementation and outcome.
White matter (WM) change plays an important role in age-related cognitive decline. In this review, we consider methodological advances with particular relevance to the role of WM in age-related changes in processing speed. In this context, intra-individual variability in processing speed performance has emerged as a sensitive proxy of cognitive and neurological decline while neuroimaging techniques used to assess WM change have become increasingly more sensitive. Together with a carefully designed task protocol, we emphasize that the combined implementation of intra-individual variability and neuroimaging techniques hold promise for specifying the WM-processing speed relationship with implications for normative and clinical samples. (JINS, 2014, 20, 1–6)
Alzheimer's disease (AD) is considered to be a disorder predominantly affecting memory. It is increasingly recognized that the cognitive profile may be heterogeneous. We hypothesized that it would be possible to define distinct “cognitive phenotypes” in older people with AD.
Participants from three individual studies were included, consisting of 109 patients with a diagnosis of probable AD, and 91 age- and gender-matched control participants. All had demographic and cognitive assessment data available, including the Cambridge Cognitive Examination of the Elderly (CAMCOG). The CAMCOG scores and sub-scores were further analyzed using hierarchical cluster analysis and factor analysis.
Three clusters were identified. The scores loaded onto three factors representing the domains of attention, praxis, calculation, and perception; memory; and language comprehension and executive function. The main difference between the clusters related to degree of memory impairment. The composite score for memory between the clusters remained significantly different despite adjustment for illness duration and age of onset (p < 0.001).
These data suggest clinical heterogeneity within an older group of people with AD. This may have implications for diagnosis, prognosis, response to currently available treatments, and the development of novel therapies.
Using unique daily fund-manager trade data, we examine the role of institutional trading in influencing firm performance. We show that short-horizon informed trading by multiple institutional investors effectively disciplines corporate management. Our focus is on short-term “swing” trades, sequences with three phases (e.g., buy-sell-buy). We find swing trades increase stock price informativeness, are profitable after costs, and improve market efficiency. This increase in stock price informativeness is associated with subsequent firm outperformance. Trades are most beneficial with optimal stock holdings that reflect the information acquisition incentives of investors as well as liquidity costs.