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Brain imaging studies have shown altered amygdala activity during emotion processing in children and adolescents with oppositional defiant disorder (ODD) and conduct disorder (CD) compared to typically developing children and adolescents (TD). Here we aimed to assess whether aggression-related subtypes (reactive and proactive aggression) and callous-unemotional (CU) traits predicted variation in amygdala activity and skin conductance (SC) response during emotion processing.
We included 177 participants (n = 108 cases with disruptive behaviour and/or ODD/CD and n = 69 TD), aged 8–18 years, across nine sites in Europe, as part of the EU Aggressotype and MATRICS projects. All participants performed an emotional face-matching functional magnetic resonance imaging task.
Differences between cases and TD in affective processing, as well as specificity of activation patterns for aggression subtypes and CU traits, were assessed. Simultaneous SC recordings were acquired in a subsample (n = 63). Cases compared to TDs showed higher amygdala activity in response to negative faces (fearful and angry) v. shapes. Subtyping cases according to aggression-related subtypes did not significantly influence on amygdala activity; while stratification based on CU traits was more sensitive and revealed decreased amygdala activity in the high CU group. SC responses were significantly lower in cases and negatively correlated with CU traits, reactive and proactive aggression.
Our results showed differences in amygdala activity and SC responses to emotional faces between cases with ODD/CD and TD, while CU traits moderate both central (amygdala) and peripheral (SC) responses. Our insights regarding subtypes and trait-specific aggression could be used for improved diagnostics and personalized treatment.
Lewy body dementia, consisting of both dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is considerably under-recognised clinically compared with its frequency in autopsy series.
This study investigated the clinical diagnostic pathways of patients with Lewy body dementia to assess if difficulties in diagnosis may be contributing to these differences.
We reviewed the medical notes of 74 people with DLB and 72 with non-DLB dementia matched for age, gender and cognitive performance, together with 38 people with PDD and 35 with Parkinson's disease, matched for age and gender, from two geographically distinct UK regions.
The cases of individuals with DLB took longer to reach a final diagnosis (1.2 v. 0.6 years, P = 0.017), underwent more scans (1.7 v. 1.2, P = 0.002) and had more alternative prior diagnoses (0.8 v. 0.4, P = 0.002), than the cases of those with non-DLB dementia. Individuals diagnosed in one region of the UK had significantly more core features (2.1 v. 1.5, P = 0.007) than those in the other region, and were less likely to have dopamine transporter imaging (P < 0.001). For patients with PDD, more than 1.4 years prior to receiving a dementia diagnosis: 46% (12 of 26) had documented impaired activities of daily living because of cognitive impairment, 57% (16 of 28) had cognitive impairment in multiple domains, with 38% (6 of 16) having both, and 39% (9 of 23) already receiving anti-dementia drugs.
Our results show the pathway to diagnosis of DLB is longer and more complex than for non-DLB dementia. There were also marked differences between regions in the thresholds clinicians adopt for diagnosing DLB and also in the use of dopamine transporter imaging. For PDD, a diagnosis of dementia was delayed well beyond symptom onset and even treatment.
We describe a widespread laboratory surveillance program for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) at an integrated medical campus that includes a tertiary-care center, a skilled nursing facility, a rehabilitation treatment center, and temporary shelter units. We identified 22 asymptomatic cases of SARS-CoV-2 and implemented infection control measures to prevent SARS-CoV-2 transmission in congregate settings.
In 2019, a 42-year-old African man who works as an Ebola virus disease (EVD) researcher traveled from the Democratic Republic of Congo (DRC), near an ongoing EVD epidemic, to Philadelphia and presented to the Hospital of the University of Pennsylvania Emergency Department with altered mental status, vomiting, diarrhea, and fever. He was classified as a “wet” person under investigation for EVD, and his arrival activated our hospital emergency management command center and bioresponse teams. He was found to be in septic shock with multisystem organ dysfunction, including circulatory dysfunction, encephalopathy, metabolic lactic acidosis, acute kidney injury, acute liver injury, and diffuse intravascular coagulation. Critical care was delivered within high-risk pathogen isolation in the ED and in our Special Treatment Unit until a diagnosis of severe cerebral malaria was confirmed and EVD was definitively excluded.
This report discusses our experience activating a longitudinal preparedness program designed for rare, resource-intensive events at hospitals physically remote from any active epidemic but serving a high-volume international air travel port-of-entry.
Acute cannabis administration can produce transient psychotic-like effects in healthy individuals. However, the mechanisms through which this occurs and which factors predict vulnerability remain unclear. We investigate whether cannabis inhalation leads to psychotic-like symptoms and speech illusion; and whether cannabidiol (CBD) blunts such effects (study 1) and adolescence heightens such effects (study 2).
Two double-blind placebo-controlled studies, assessing speech illusion in a white noise task, and psychotic-like symptoms on the Psychotomimetic States Inventory (PSI). Study 1 compared effects of Cann-CBD (cannabis containing Δ-9-tetrahydrocannabinol (THC) and negligible levels of CBD) with Cann+CBD (cannabis containing THC and CBD) in 17 adults. Study 2 compared effects of Cann-CBD in 20 adolescents and 20 adults. All participants were healthy individuals who currently used cannabis.
In study 1, relative to placebo, both Cann-CBD and Cann+CBD increased PSI scores but not speech illusion. No differences between Cann-CBD and Cann+CBD emerged. In study 2, relative to placebo, Cann-CBD increased PSI scores and incidence of speech illusion, with the odds of experiencing speech illusion 3.1 (95% CIs 1.3–7.2) times higher after Cann-CBD. No age group differences were found for speech illusion, but adults showed heightened effects on the PSI.
Inhalation of cannabis reliably increases psychotic-like symptoms in healthy cannabis users and may increase the incidence of speech illusion. CBD did not influence psychotic-like effects of cannabis. Adolescents may be less vulnerable to acute psychotic-like effects of cannabis than adults.
It is not unusual for the cardiac anaesthetist to encounter adults with palliated, corrected or newly diagnosed congenital heart disease (CHD). It is essential, therefore, that the anaesthetist has an appreciation of the types of CHD, surgical procedures and perioperative management.
Clinical diagnostics in sudden onset disasters have historically been limited. We set out to design, implement, and evaluate a mobile diagnostic laboratory accompanying a type 2 emergency medical team (EMT) field hospital.
Available diagnostic platforms were reviewed and selected against in field need. Platforms included HemoCue301/WBC DIFF, i-STAT, BIOFIRE FILMARRAY multiplex rt-PCR, Olympus BX53 microscopy, ABO/Rh grouping, and specific rapid diagnostic tests. This equipment was trialed in Katherine, Australia, and Dili, Timor-Leste.
During the initial deployment, an evaluation of FilmArray tests was successful using blood culture identification, gastrointestinal, and respiratory panels. HemoCue301 (n = 20) hemoglobin values were compared on Sysmex XN 550 (r = 0.94). HemoCue WBC DIFF had some variation, dependent on the cell, when compared with Sysmex XN 550 (r = 0.88-0.16). i-STAT showed nonsignificant differences against Vitros 250. Further evaluation of FilmArray in Dili, Timor-Leste, diagnosed 117 pathogens on 168 FilmArray pouches, including 25 separate organisms on blood culture and 4 separate cerebrospinal fluid pathogens.
This mobile laboratory represents a major advance in sudden onset disaster. Setup of the service was quick (< 24 hr) and transport to site rapid. Future deployment in fragmented health systems after sudden onset disasters with EMT2 will now allow broader diagnostic capability.
Apathy and depression are the two most frequent neuropsychiatric symptoms in Alzheimer's disease (AD) and related disorders. Whereas neuroimaging studies have shown different neural pathways for these two symptoms, a clinical overlap between apathy and depression is frequently described.
To describe the prevalence of apathy and depression among elderly subjects with or without dementia criteria using specific diagnostic criteria for apathy and depression.
Subjects from an ongoing cross-sectional study were recruited in 4 centers (France, Indonesia, Spain, Argentina). Apathy and depression were assessed using the diagnostic criteria for apathy and for depression. Additionally, the apathy and dysphoria domains of the NPI-C (Neuropsychiatric Inventory-Clinician), as well as the 12 domains of the original NPI (Neuropsychiatric Inventory) were assessed.
431 subjects (mean age=74.6 ± 10.4 ; gender=♂ 29%) were recruited (France=100, Spain=90, Indonesia=182, Argentina=79). Among them, 25% were healthy elderly subjects, 9% had a diagnosis of MCI (Mild Cognitive Impairment), 46% had a diagnosis of dementia (including AD, Lewy body, vascular, mixed and fronto-temporal dementia). In the overall population, the prevalence of apathy and depression were respectively 41% and 25%. More specifically, the prevalence of apathy and depression in the AD sample were 67% and 25%.
Diagnostic criteria for apathy and depression, as well as the NPI-C, are recent assessment methods in the field of dementia, developed to increase the accuracy of the clinical evaluation of BPSD. It is therefore critical to propose multicenter observational studies comparing these new tools with classical assessment methods.
La prise en charge non-pharmacologique de la maladie d’Alzheimer et des maladies apparentées (MA) représente un enjeu de santé majeur chez les personnes âgées . L’environnement Enrichi (EE), combinaison de stimulations cognitive, physique et d’engagement social en contexte émotionnel positif, apparaît comme une méthode efficace pour lutter contre la progression d’une MA . La principale difficulté est de proposer aux patients un EE adapté et motivant. Les serious games peuvent aider dans ce sens . Xtorp est un Serious exerGame (à activité physique, SeG) d’action/aventure développé pour KinectTM. Le joueur pilote un sous-marin (Fig. 1). Il doit devenir Amiral 5 étoiles en collectant de l’expérience au cours de batailles et missions. Dix patients (MA stade léger) et 8 témoins ont suivi un programme d’entrainement avec le jeu durant 1 mois, réparties en 12 séances. Les performances au jeu, les émotions perçues (PANAS) et l’intensité d’effort physique induite par le jeu ont été étudiées. Tous les participants ont terminé au moins une fois Xtorp. Les patients ont une capacité de jeu inférieure aux témoins (temps total de jeu et vitesse de progression patents : 420 minutes et 185 points d’expérience/minute, témoins : 489 minutes et 287 points d’expérience/minute). Les patients et les témoins n’ont quasiment ressenti que des émotions positives, légèrement plus fortes pour les témoins (PANAS positifs patients : 27/50, témoins, 36/50 ; PANAS négatifs patients : 12/50, témoins 11/50). Enfin, le jeu a été stimulant physiquement mais à un moindre degré chez les patients (fréquence cardiaque de réserve moyenne et pic par séance patients : 33 % et 53 %, témoins : 44 % et 62 %). En conclusion Xtorp est un EE utilisable, motivant qui permet de réaliser une activité physique potentiellement modérée chez des patients présentant des troubles cognitifs.
Genetic research into human sexuality was scarce at the end of last century. In 1992 Nick developed a 12-page questionnaire to send to twins to investigate the underpinnings of sexuality. The questionnaire included items about sexual orientation, sociosexuality and sexual behavior, and was completed by almost 5000 twins. The resulting data, unique at the time, has been used to investigate many previously unexaminable research questions. Here we describe how Nick’s questionnaire contributed to our understanding of human sexuality and how we got involved in this endeavor.
Ponds that form on sea ice can cause it to thin or break-up, which can promote calving from an adjacent ice shelf. Studies of sea ice ponds have predominantly focused on Arctic ponds formed by in situ melting/ponding. Our study documents another mechanism for the formation of sea ice ponds. Using Landsat 8 and Sentinel-2 images from the 2015–16 to 2018–19 austral summers, we analyze the evolution of sea ice ponds that form adjacent to the McMurdo Ice Shelf, Antarctica. We find that each summer, meltwater flows from the ice shelf onto the sea ice and forms large (up to 9 km2) ponds. These ponds decrease the sea ice's albedo, thinning it. We suggest the added mass of runoff causes the ice to flex, potentially promoting sea-ice instability by the ice-shelf front. As surface melting on ice shelves increases, we suggest that ice-shelf surface hydrology will have a greater effect on sea-ice stability.
We present a detailed overview of the cosmological surveys that we aim to carry out with Phase 1 of the Square Kilometre Array (SKA1) and the science that they will enable. We highlight three main surveys: a medium-deep continuum weak lensing and low-redshift spectroscopic HI galaxy survey over 5 000 deg2; a wide and deep continuum galaxy and HI intensity mapping (IM) survey over 20 000 deg2 from
$z = 0.35$
to 3; and a deep, high-redshift HI IM survey over 100 deg2 from
$z = 3$
to 6. Taken together, these surveys will achieve an array of important scientific goals: measuring the equation of state of dark energy out to
$z \sim 3$
with percent-level precision measurements of the cosmic expansion rate; constraining possible deviations from General Relativity on cosmological scales by measuring the growth rate of structure through multiple independent methods; mapping the structure of the Universe on the largest accessible scales, thus constraining fundamental properties such as isotropy, homogeneity, and non-Gaussianity; and measuring the HI density and bias out to
$z = 6$
. These surveys will also provide highly complementary clustering and weak lensing measurements that have independent systematic uncertainties to those of optical and near-infrared (NIR) surveys like Euclid, LSST, and WFIRST leading to a multitude of synergies that can improve constraints significantly beyond what optical or radio surveys can achieve on their own. This document, the 2018 Red Book, provides reference technical specifications, cosmological parameter forecasts, and an overview of relevant systematic effects for the three key surveys and will be regularly updated by the Cosmology Science Working Group in the run up to start of operations and the Key Science Programme of SKA1.
Policies addressing the physical health of people with mental disorders have historically focused on those with severe mental illness (SMI), giving less prominence to the more prevalent common mental disorders (CMDs). Little is known about the comparative physical health outcomes of these patient groups. We aimed to first compare the: (a) number of past-year chronic physical conditions and (b) recent physical health service utilization between CMDs vs. SMI, and secondly compare these outcomes between people with CMDs vs. people without mental disorders.
We analyzed cross-sectional data from the third Adult Psychiatric Morbidity Survey, a representative sample of the English population. We determined the presence of physical conditions and health service utilization by self-report and performed logistic regression models to examine associations of these outcomes between participant groups.
Past-year physical conditions were reported by the majority of participants (CMDs, n = 815, 62.1%; SMI = 27, 63.1%) with no variation in the adjusted odds of at least one physical condition between diagnoses (odds ratio [OR] = 0.96, 95% confidence intervals [CI] 0.42–1.98, p = 0.784). People with CMDs were significantly more likely to be recently hospitalized relative to with those with SMI (OR = 6.33, 95% CI 5.50–9.01, p < 0.05). Having a CMD was associated with significantly higher odds of past-year physical conditions and recent health service utilization (all p < 0.001) compared with the general population.
People with CMDs experience excess physical health morbidities in a similar pattern to those found among people with SMI, while their somatic hospitalization rates are even more elevated. Findings highlight the importance of recalibrating existing public health strategies to bring equity to the physical health needs of this patient group.
Shared patient–clinician decision-making is central to choosing between medical treatments. Decision support tools can have an important role to play in these decisions. We developed a decision support tool for deciding between nonsurgical treatment and surgical total knee replacement for patients with severe knee osteoarthritis. The tool aims to provide likely outcomes of alternative treatments based on predictive models using patient-specific characteristics. To make those models relevant to patients with knee osteoarthritis and their clinicians, we involved patients, family members, patient advocates, clinicians, and researchers as stakeholders in creating the models.
Stakeholders were recruited through local arthritis research, advocacy, and clinical organizations. After being provided with brief methodological education sessions, stakeholder views were solicited through quarterly patient or clinician stakeholder panel meetings and incorporated into all aspects of the project.
Participating in each aspect of the research from determining the outcomes of interest to providing input on the design of the user interface displaying outcome predications, 86% (12/14) of stakeholders remained engaged throughout the project. Stakeholder engagement ensured that the prediction models that form the basis of the Knee Osteoarthritis Mathematical Equipoise Tool and its user interface were relevant for patient–clinician shared decision-making.
Methodological research has the opportunity to benefit from stakeholder engagement by ensuring that the perspectives of those most impacted by the results are involved in study design and conduct. While additional planning and investments in maintaining stakeholder knowledge and trust may be needed, they are offset by the valuable insights gained.
Recent investigations now suggest that cerebrovascular reactivity (CVR) is impaired in Alzheimer’s disease (AD) and may underpin part of the disease’s neurovascular component. However, our understanding of the relationship between the magnitude of CVR, the speed of cerebrovascular response, and the progression of AD is still limited. This is especially true in patients with mild cognitive impairment (MCI), which is recognized as an intermediate stage between normal aging and dementia. The purpose of this study was to investigate AD and MCI patients by mapping repeatable and accurate measures of cerebrovascular function, namely the magnitude and speed of cerebrovascular response (τ) to a vasoactive stimulus in key predilection sites for vascular dysfunction in AD.
Thirty-three subjects (age range: 52–83 years, 20 males) were prospectively recruited. CVR and τ were assessed using blood oxygen level-dependent MRI during a standardized carbon dioxide stimulus. Temporal and parietal cortical regions of interest (ROIs) were generated from anatomical images using the FreeSurfer image analysis suite.
Of 33 subjects recruited, 3 individuals were excluded, leaving 30 subjects for analysis, consisting of 6 individuals with early AD, 11 individuals with MCI, and 13 older healthy controls (HCs). τ was found to be significantly higher in the AD group compared to the HC group in both the temporal (p = 0.03) and parietal cortex (p = 0.01) following a one-way ANCOVA correcting for age and microangiopathy scoring and a Bonferroni post-hoc correction.
The study findings suggest that AD is associated with a slowing of the cerebrovascular response in the temporal and parietal cortices.
The transmission rate of methicillin-resistant Staphylococcus aureus (MRSA) to gloves or gowns of healthcare personnel (HCP) caring for MRSA patients in a non–intensive care unit setting was 5.4%. Contamination rates were higher among HCP performing direct patient care and when patients had detectable MRSA on their body. These findings may inform risk-based contact precautions.
Recent work suggests that antihypertensive medications may be useful as repurposed treatments for mood disorders. Using large-scale linked healthcare data we investigated whether certain classes of antihypertensive, such as angiotensin antagonists (AAs) and calcium channel blockers, were associated with reduced risk of new-onset major depressive disorder (MDD) or bipolar disorder (BD).
Two cohorts of patients treated with antihypertensives were identified from Scottish prescribing (2009–2016) and hospital admission (1981–2016) records. Eligibility for cohort membership was determined by a receipt of a minimum of four prescriptions for antihypertensives within a 12-month window. One treatment cohort (n = 538 730) included patients with no previous history of mood disorder, whereas the other (n = 262 278) included those who did. Both cohorts were matched by age, sex and area deprivation to untreated comparators. Associations between antihypertensive treatment and new-onset MDD or bipolar episodes were investigated using Cox regression.
For patients without a history of mood disorder, antihypertensives were associated with increased risk of new-onset MDD. For AA monotherapy, the hazard ratio (HR) for new-onset MDD was 1.17 (95% CI 1.04–1.31). Beta blockers' association was stronger (HR 2.68; 95% CI 2.45–2.92), possibly indicating pre-existing anxiety. Some classes of antihypertensive were associated with protection against BD, particularly AAs (HR 0.46; 95% CI 0.30–0.70). For patients with a past history of mood disorders, all classes of antihypertensives were associated with increased risk of future episodes of MDD.
There was no evidence that antihypertensive medications prevented new episodes of MDD but AAs may represent a novel treatment avenue for BD.
Rehabilitation of memory after stroke remains an unmet need. Telehealth delivery may overcome barriers to accessing rehabilitation services.
We conducted a non-randomized intervention trial to investigate feasibility and effectiveness of individual telehealth (internet videoconferencing) and face-to-face delivery methods for a six-week compensatory memory rehabilitation program. Supplementary analyses investigated non-inferiority to an existing group-based intervention, and the role of booster sessions in maintaining functional gains. The primary outcome measure was functional attainment of participants’ goals. Secondary measures included subjective reports of lapses in everyday memory and prospective memory, reported use of internal and external memory strategies, and objective measures of memory functioning.
Forty-six stroke survivors were allocated to telehealth and face-to-face intervention delivery conditions. Feasibility of delivery methods was supported, and participants in both conditions demonstrated treatment-related improvements in goal attainment, and key subjective outcomes of everyday memory, and prospective memory. Gains on these measures were maintained at six-week follow-up. Short-term gains in use of internal strategies were also seen. Non-inferiority to group-based delivery was established only on the primary measure for the telehealth delivery condition. Booster sessions were associated with greater maintenance of gains on subjective measures of everyday memory and prospective memory.
This exploratory study supports the feasibility and potential effectiveness of telehealth options for remote delivery of compensatory memory skills training after a stroke. These results are also encouraging of a role for booster sessions in prolonging functional gains over time.