To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
With the aim of producing a 3D representation of tumors, imaging and molecular annotation of xenografts and tumors (IMAXT) uses a large variety of modalities in order to acquire tumor samples and produce a map of every cell in the tumor and its host environment. With the large volume and variety of data produced in the project, we developed automatic data workflows and analysis pipelines. We introduce a research methodology where scientists connect to a cloud environment to perform analysis close to where data are located, instead of bringing data to their local computers. Here, we present the data and analysis infrastructure, discuss the unique computational challenges and describe the analysis chains developed and deployed to generate molecularly annotated tumor models. Registration is achieved by use of a novel technique involving spherical fiducial marks that are visible in all imaging modalities used within IMAXT. The automatic pipelines are highly optimized and allow to obtain processed datasets several times quicker than current solutions narrowing the gap between data acquisition and scientific exploitation.
Cognitive impairment is a core feature of schizophrenia, associated with poor functional outcomes. The course of cognitive function in the years following illness onset has remained a subject of debate, with a previous analysis finding no worsening, providing support for the neurodevelopmental model of schizophrenia. Since then, many more studies have reported on longitudinal cognitive performance in early psychosis, with some indicating deterioration, which does not align with this view.
This study aims to quantitatively review the literature on the longitudinal trajectory of cognitive deficits in the years following psychosis onset, in comparison with healthy controls. It is the first to also synthesise longitudinal data on social cognition.
Electronic databases (‘PubMed’, ‘PsycInfo’ and ‘Scopus’) were searched (to end September 2021). Meta-analyses of 25 longitudinal studies of cognition in early psychosis were conducted (1480 patients, 789 health controls). Unlike previous analyses, randomised controlled trials and those with multiple cognitive testing periods within the first year were excluded to minimise bias (PROSPERO, ID: CRD42021241525).
Small improvements were observed for global cognition (g = 0.25, 95% CI 0.17–0.33) and individual cognitive domains, but these were comparable with healthy controls and likely an artefact of practice effects.
There is no evidence of continued cognitive decline or improvement in the early years following psychosis onset, with a need for more studies over longer follow-up periods. Practice effects highlight the importance of including control samples in longitudinal and intervention studies. Further data are needed to evaluate the course of social cognition subdomains.
The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.
Evidence suggests that cognitive subtypes exist in schizophrenia that may reflect different neurobiological trajectories. We aimed to identify whether IQ-derived cognitive subtypes are present in early-phase schizophrenia-spectrum disorder and examine their relationship with brain structure and markers of neuroinflammation.
161 patients with recent-onset schizophrenia spectrum disorder (<5 years) were recruited. Estimated premorbid and current IQ were calculated using the Wechsler Test of Adult Reading and a 4-subtest WAIS-III. Cognitive subtypes were identified with k-means clustering. Freesurfer was used to analyse 3.0 T MRI. Blood samples were analysed for hs-CRP, IL-1RA, IL-6 and TNF-α.
Three subtypes were identified indicating preserved (PIQ), deteriorated (DIQ) and compromised (CIQ) IQ. Absolute total brain volume was significantly smaller in CIQ compared to PIQ and DIQ, and intracranial volume was smaller in CIQ than PIQ (F(2, 124) = 6.407, p = 0.002) indicative of premorbid smaller brain size in the CIQ group. CIQ had higher levels of hs-CRP than PIQ (F(2, 131) = 5.01, p = 0.008). PIQ showed differentially impaired processing speed and verbal learning compared to IQ-matched healthy controls.
The findings add validity of a neurodevelopmental subtype of schizophrenia identified by comparing estimated premorbid and current IQ and characterised by smaller premorbid brain volume and higher measures of low-grade inflammation (CRP).
A disproportionate number of people with mental ill-health experience social exclusion. Appropriate measurement tools are required to progress opportunities to improve social inclusion. We have developed a novel measure, the Filia Social Inclusion Measure (F-SIM). Here we aimed to present a more concise, easy-to-use form, while retaining its measurement integrity by (i) refining the F-SIM using traditional and contemporary item-reduction techniques; and (ii) testing the psychometric properties of the reduced measure.
Five hundred and six participants completed the F-SIM, younger and older groups of people with serious mental illness (including psychosis, mood, anxiety disorders) and same-aged community counterparts. The F-SIM was completed at baseline and 2-week follow-up, alongside other measures (including social inclusion, loneliness). The F-SIM was refined using multidimensional scaling network analysis, confirmatory factor analysis and item response theory. The psychometric evaluation included assessment of dimensionality, internal consistency, test–retest reliability, discriminant ability and construct validity.
The F-SIM was reduced from 135-items to 16; with 4-items in each domain of housing and neighbourhood, finances, employment and education and social participation and relationships. Psychometric properties were sound, including strong internal consistency within domains (all α > 0.85) and excellent overall (α = 0.92). Test–retest reliability was also high (γ = 0.90). Differences between groups were observed; clinical subgroups consistently reported lower levels of social inclusion compared to community counterparts.
The F-SIM16 is a sound, reliable, brief self-report measure of social inclusion suitable for use in clinical and research settings. It has the potential to evaluate the effectiveness of interventions, and aid in fostering targeted and personalised needs-based care.
Childhood anxiety disorders (CAD) are a common childhood mental disorder and understanding early developmental pathways is key to prevention and early intervention. What is not understood is whether early life stress predictors of CAD might be both mediated by infant cortisol reactivity and moderated by infant attachment status. To address this question, this exploratory study draws on 190 women recruited in early pregnancy and followed together with their children until 4 years of age. Early life stress is operationalized as maternal depression measured using the Structured Clinical Interview for the DSM, Childhood Trauma Questionnaire, Parenting Stress Index, and antenatal maternal hair cortisol concentrations. Infant cortisol reactivity was measured at 12 months together with the Strange Situation Procedure and CAD assessed at 4 years of age using the Preschool Age Psychiatric Assessment. There was no direct association between attachment classification and CAD. Furthermore, infant cortisol reactivity neither mediated nor attachment moderated the association of early life stress predictors and CAD. However, only for infants with organized attachment classifications, higher maternal antenatal depression, and hair cortisol were associated with a higher risk of CAD.
The development of childhood anxiety disorders (CADs) is likely to depend on pathways that can be programmed by early-life risk factors. We test the hypothesis that early-life maternal factors can predict this programming effect on CAD.
Data were obtained from 198 women and children from the Mercy Pregnancy and Emotional Wellbeing Study (MPEWS), a cohort study with data collected across pregnancy, postpartum and until 4 years of age. Maternal antenatal depression was measured using the Structured Clinical Interview for DSM-IV (SCID-IV), together with antenatal hair cortisol concentrations, maternal childhood trauma and parenting stress at 6 months postpartum. CAD was assessed with the Preschool Age Psychiatric Assessment and the Child Behaviour Checklist.
Antenatal depression, a history of maternal childhood trauma and lower gestational age at birth were each associated with anxiety disorders at 4 years of age in their children. A multivariate binary logistic model with these early predictors explained approximately 9% of variance in CAD outcome at 4 years of age; however, only maternal trauma and gestational age were significant predictors in the model. The effect of early parenting stress on CAD was found to vary by the concentration of maternal antenatal hair cortisol, whereby postpartum parenting stress was associated with CAD only when there were higher maternal antenatal cortisol levels.
This study suggests the importance of maternal factors pre-conception, pregnancy and in the postnatal period, which predict CADs and this is consistent with a developmental programming hypothesis for CAD.
There is an established relationship between depression and sexual functioning in women. However, there is limited research examining the relationship between perinatal depression and sexual functioning.
This study draws on the Mercy Pregnancy and Emotional Wellbeing Study and reports on 211 women recruited in early pregnancy and followed to 12 months postpartum. Women were assessed for depression using the Structured Clinical Interview for the DSM-IV, repeated measurement of depressive symptoms using the Edinburgh Postnatal Depression Scale and sexual functioning using the Female Sexual Functioning Inventory. Data were also collected on antidepressant use, mode of delivery, history of childhood trauma, breastfeeding and partner support.
Women showed a decline in sexual functioning over pregnancy and the first 6 months postpartum, which recovered by 12 months. For women with depression, sexual functioning was lower throughout pregnancy and continued to be lower at 6 months postpartum than those without depression. Ongoing depressive symptoms at 12 months were also associated with lower sexual functioning. Sexual functioning was not predicted by mode of delivery, antidepressant use or childhood trauma. Breastfeeding predicted lower sexual functioning only at 6 months. Higher partner support predicted higher female sexual functioning.
Pregnancy and the postpartum are a time of reduced sexual functioning for women; however, women with depression are more likely to have lower levels of sexual functioning and this was not predicted by antidepressant use. In women with perinatal depression, consideration of the impact on sexual functioning should be an integral part of care.
The Taipan galaxy survey (hereafter simply ‘Taipan’) is a multi-object spectroscopic survey starting in 2017 that will cover 2π steradians over the southern sky (δ ≲ 10°, |b| ≳ 10°), and obtain optical spectra for about two million galaxies out to z < 0.4. Taipan will use the newly refurbished 1.2-m UK Schmidt Telescope at Siding Spring Observatory with the new TAIPAN instrument, which includes an innovative ‘Starbugs’ positioning system capable of rapidly and simultaneously deploying up to 150 spectroscopic fibres (and up to 300 with a proposed upgrade) over the 6° diameter focal plane, and a purpose-built spectrograph operating in the range from 370 to 870 nm with resolving power R ≳ 2000. The main scientific goals of Taipan are (i) to measure the distance scale of the Universe (primarily governed by the local expansion rate, H0) to 1% precision, and the growth rate of structure to 5%; (ii) to make the most extensive map yet constructed of the total mass distribution and motions in the local Universe, using peculiar velocities based on improved Fundamental Plane distances, which will enable sensitive tests of gravitational physics; and (iii) to deliver a legacy sample of low-redshift galaxies as a unique laboratory for studying galaxy evolution as a function of dark matter halo and stellar mass and environment. The final survey, which will be completed within 5 yrs, will consist of a complete magnitude-limited sample (i ⩽ 17) of about 1.2 × 106 galaxies supplemented by an extension to higher redshifts and fainter magnitudes (i ⩽ 18.1) of a luminous red galaxy sample of about 0.8 × 106 galaxies. Observations and data processing will be carried out remotely and in a fully automated way, using a purpose-built automated ‘virtual observer’ software and an automated data reduction pipeline. The Taipan survey is deliberately designed to maximise its legacy value by complementing and enhancing current and planned surveys of the southern sky at wavelengths from the optical to the radio; it will become the primary redshift and optical spectroscopic reference catalogue for the local extragalactic Universe in the southern sky for the coming decade.
Background: Differentiating Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), two of the commonest forms of dementia in older age, remains a diagnostic challenge. To assist with better understanding of the differences between the conditions during life, we assessed limbic and subcortical brain volumes in AD, DLB, and healthy older individuals using magnetic resonance imaging (MRI), with the hypothesis that when compared with controls, subcortical volumes would be reduced to a greater extent in DLB than in AD.
Methods: One hundred participants (35 healthy controls, 32 AD, and 33 DLB) underwent 3 Tesla T1 weighted MR scanning. Volumes were automatically segmented for each participant using FreeSurfer, then expressed as a percentage of their total intracranial volumes. Group effects were assessed using multivariate analysis of covariance, controlling for age and gender.
Results: Significant group effects were apparent among subcortical brain volumes (F28,162 = 4.8, p < 0.001; Wilk's Λ = 0.30, partial η2 = 0.45), while univariate tests showed differences in all volumetric measures (p < 0.03) except in right caudate (p = 0.08). Post-hoc analyses indicated that while not significantly different from AD, changes compared to healthy subjects in left caudate, bilateral putamen, left thalamus, brainstem and total subcortical grey volume were more pronounced in DLB. Significant differences between AD and DLB were confined to the bilateral hippocampus (DLB > AD, p < 0.008).
Conclusions: For similar levels of dementia severity, DLB appears to have greater involvement of subcortical brain atrophy than AD. Further investigation of the subcortical brain structures in DLB is warranted to fully understand their neurobiological role in this disease.
We describe the internal cerebral vein (ICV) sign, which is a hypo-opacification of the ICV on computed tomogram angiography (CTA) as a new marker of increased cerebral blood transit-time in ipsilateral internal carotid artery occlusions (ICAO).
A retrospective analysis of 153 patients with acute unilateral M1 middle cerebral artery (MCA) occlusions ± ICAOs was performed. The degree of contrast opacification of the ICV on the ipsilesional side was compared to that of the unaffected side.
Of 153 patients in our study, 135 had M1 MCA occlusions ± intra-cranial ICAO (M1±iICAO) and 18 had isolated extracranial ICAO (eICAO). In the patients with proximal M1±iICAO, 57/65 (87.1%) showed the ICV sign. Of the 8 patients without the ICV sign in this group, 6 had prominent lenticulostriate arteries arising from the non-occluded M1 segment, 1 had a recurrent artery of Huebner, and 1 had filling of distal ICA/M1 segment through prominent Circle of Willis collaterals. For the 70 patients with isolated distal M1±iICAO, 7/70 (10%) showed the ICV sign, with all 7 showing occluded lenticulostriate arteries. Of the patients with eICAO, 8/18 showed the ICV sign, all 8 with the ICV sign had poor Circle of Willis collaterals.
The ICV sign correlates well with presence of proximal M1±iICAO in patients with either occluded lenticulostriate arteries or poor Circle of Willis collaterals. In patients with eICAO, the sign correlates with reduced Circle of Willis collaterals and may be a marker of increased ipsilateral cerebral blood transit time.
Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are common forms of dementia, yet diagnosis is often difficult. Diffusion tensor imaging (DTI) is an MR technique used to assess neuronal microstructural integrity that may help develop a better understanding of the differences between the conditions.
We recruited subjects with DLB (n = 35), AD (n = 36), and similar aged healthy controls (n = 35). T1 weighted anatomical and diffusion MR images were acquired at 3 Tesla. Region of interest (ROI) analysis was used to measure fractional anisotropy (FA) and mean diffusivity (MD) in five structures: precuneus, thalamus, pons, midbrain, and amygdala. Where appropriate diffusivity measures (FA, MD) were correlated with selected clinical measures.
Compared to controls, DLB subjects were characterized by reduced FA (p = 0.016) and increased MD (p = 0.007) in the precuneus. Amygdala diffusivity was positively correlated with UPDRS-III score in DLB (p = 0.003). In AD, reduced FA in the precuneus was also observed compared to controls (p = 0.026), and was associated with impaired global cognition (MMSE score) (p = 0.03).
Our findings highlight the potential importance of the precuneus in the pathogenesis of DLB as well as AD. Diffusion tensor MRI may shed new light on the different neurobiological changes underpinning the key clinical features of DLB and AD.
The Next Generation Transit Survey (NGTS) is a new ground-based survey for transiting exoplanets. Our primary goal is to find the first statistically-significant sample of Neptunes and super-Earths that are bright enough for radial velocity confirmation. By measuring precise masses and radii we will constrain the bulk composition and internal structure of planets that span the transition between the gas giants and terrestrial planets. Our brightest exoplanets will also be suitable for atmospheric characterisation with large facilities such as the VLT, JWST and the E-ELT. NGTS construction began in June 2013, and the survey is due to commence in 2014.
Background: Previous studies suggest that posterior cortical atrophy may be a useful marker for early onset Alzheimer's disease (AD). Dementia with Lewy bodies (DLB) is associated with less temporal lobe atrophy than AD, though posterior cortical atrophy may be greater. Therefore, we assessed whether visual rating scales for assessing posterior atrophy (PA), medial temporal lobe atrophy (MTA), and ventricular enlargement (VEn) aid in the discrimination between AD, DLB, and normal aging.
Methods: T1-weighted MRI scans acquired at 3 Tesla were visually rated for PA (range 0–3), MTA (range 0–4), and VEn (range 0–3) in older subjects with AD (n = 36), DLB (n = 35), and healthy controls (n = 35). The diagnostic utility of MTA, PA, and VEn visual ratings in distinguishing AD and DLB from controls as well as AD from DLB was investigated.
Results: Significantly higher MTA ratings were associated with AD and DLB compared to controls (p < 0.001). MTA ratings were greater in AD relative to DLB (U = 384.5, p = 0.004). For PA ratings, scores did not differ between groups (p = 0.20). VEn ratings were significantly higher in AD and DLB compared to controls (p = 0.003), but similar between AD and DLB (U = 384.5, p = 0.4).
Conclusions: Unlike findings reported in younger subjects, visual ratings for PA are not a reliable marker at older ages for distinguishing AD from controls, or for distinguishing DLB from AD. However, visual ratings of MTA and VEn may be useful markers in distinguishing both AD and DLB from older subjects without dementia.
An analysis was undertaken to measure age-specific vaccine effectiveness (VE) of 2010/11 trivalent seasonal influenza vaccine (TIV) and monovalent 2009 pandemic influenza vaccine (PIV) administered in 2009/2010. The test-negative case-control study design was employed based on patients consulting primary care. Overall TIV effectiveness, adjusted for age and month, against confirmed influenza A(H1N1)pdm 2009 infection was 56% (95% CI 42–66); age-specific adjusted VE was 87% (95% CI 45–97) in <5-year-olds and 84% (95% CI 27–97) in 5- to 14-year-olds. Adjusted VE for PIV was only 28% (95% CI −6 to 51) overall and 72% (95% CI 15–91) in <5-year-olds. For confirmed influenza B infection, TIV effectiveness was 57% (95% CI 42–68) and in 5- to 14-year-olds 75% (95% CI 32–91). TIV provided moderate protection against the main circulating strains in 2010/2011, with higher protection in children. PIV administered during the previous season provided residual protection after 1 year, particularly in the <5 years age group.
This chapter reviews the relevant studies with human and animal cells aimed at the development of artificial gametes. During female gametogenesis (oogenesis), oogonia start the first meiotic division in the fetal period of life, but the process becomes arrested at a late prophase until puberty. Unlike oogenesis, male gametogenesis (spermatogenesis) is a continuous process in which spermatogonia enter meiosis and form primary spermatocytes. The chapter outlines the main methodological problems in artificial female and male gamete production, and suggests possible ways of their solution. As compared with mature oocytes, the use of germinal vesicle oocytes for somatic cell nucleus haploidization represents an even greater challenge because two steps of reduction are necessary. Experiments with the embryonic stem (ES) cells can help understand the mechanisms guiding the differentiation of stem cells towards the germline and thus prepare the route for the work with the adult stem (AS) cells.