To send 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 sending content to .
To send content items to your Kindle, first ensure email@example.com
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 sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent 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.
Individuals with schizophrenia are at higher risk of physical illnesses, which are a major contributor to their 20-year reduced life expectancy. It is currently unknown what causes the increased risk of physical illness in schizophrenia.
To link genetic data from a clinically ascertained sample of individuals with schizophrenia to anonymised National Health Service (NHS) records. To assess (a) rates of physical illness in those with schizophrenia, and (b) whether physical illness in schizophrenia is associated with genetic liability.
We linked genetic data from a clinically ascertained sample of individuals with schizophrenia (Cardiff Cognition in Schizophrenia participants, n = 896) to anonymised NHS records held in the Secure Anonymised Information Linkage (SAIL) databank. Physical illnesses were defined from the General Practice Database and Patient Episode Database for Wales. Genetic liability for schizophrenia was indexed by (a) rare copy number variants (CNVs), and (b) polygenic risk scores.
Individuals with schizophrenia in SAIL had increased rates of epilepsy (standardised rate ratio (SRR) = 5.34), intellectual disability (SRR = 3.11), type 2 diabetes (SRR = 2.45), congenital disorders (SRR = 1.77), ischaemic heart disease (SRR = 1.57) and smoking (SRR = 1.44) in comparison with the general SAIL population. In those with schizophrenia, carrier status for schizophrenia-associated CNVs and neurodevelopmental disorder-associated CNVs was associated with height (P = 0.015–0.017), with carriers being 7.5–7.7 cm shorter than non-carriers. We did not find evidence that the increased rates of poor physical health outcomes in schizophrenia were associated with genetic liability for the disorder.
This study demonstrates the value of and potential for linking genetic data from clinically ascertained research studies to anonymised health records. The increased risk for physical illness in schizophrenia is not caused by genetic liability for the disorder.
Media coverage of non-suicidal self-injury (NSSI) ranges from providing helpful education to displaying graphic images. We offer the first research-informed, consensus-based guidelines for the responsible reporting and depicting of NSSI in the media, while also advising on ideas for dissemination and collaboration between media professionals and healthcare experts.
Recently published diagnostic criteria for mild cognitive impairment with Lewy bodies (MCI-LB) include five neuropsychiatric supportive features (non-visual hallucinations, systematised delusions, apathy, anxiety and depression). We have previously demonstrated that the presence of two or more of these symptoms differentiates MCI-LB from MCI due to Alzheimer's disease (MCI-AD) with a likelihood ratio >4. The aim of this study was to replicate the findings in an independent cohort.
Participants ⩾60 years old with MCI were recruited. Each participant had a detailed clinical, cognitive and imaging assessment including FP-CIT SPECT and cardiac MIBG. The presence of neuropsychiatric supportive symptoms was determined using the Neuropsychiatric Inventory (NPI). Participants were classified as MCI-AD, possible MCI-LB and probable MCI-LB based on current diagnostic criteria. Participants with possible MCI-LB were excluded from further analysis.
Probable MCI-LB (n = 28) had higher NPI total and distress scores than MCI-AD (n = 30). In total, 59% of MCI-LB had two or more neuropsychiatric supportive symptoms compared with 9% of MCI-AD (likelihood ratio 6.5, p < 0.001). MCI-LB participants also had a significantly greater delayed recall and a lower Trails A:Trails B ratio than MCI-AD.
MCI-LB is associated with significantly greater neuropsychiatric symptoms than MCI-AD. The presence of two or more neuropsychiatric supportive symptoms as defined by MCI-LB diagnostic criteria is highly specific and moderately sensitive for a diagnosis of MCI-LB. The cognitive profile of MCI-LB differs from MCI-AD, with greater executive and lesser memory impairment, but these differences are not sufficient to differentiate MCI-LB from MCI-AD.
Mood instability is an important problem but has received relatively little research attention. Natural language processing (NLP) is a novel method, which can used to automatically extract clinical data from electronic health records (EHRs).
To extract mood instability data from EHRs and investigate its impact on people with mental health disorders.
Data on mood instability were extracted using NLP from 27,704 adults receiving care from the South London and Maudsley NHS Foundation Trust (SLaM) for affective, personality or psychotic disorders. These data were used to investigate the association of mood instability with different mental disorders and with hospitalisation and treatment outcomes.
Mood instability was documented in 12.1% of people included in the study. It was most frequently documented in people with bipolar disorder (22.6%), but was also common in personality disorder (17.8%) and schizophrenia (15.5%). It was associated with a greater number of days spent in hospital (B coefficient 18.5, 95% CI 12.1–24.8), greater frequency of hospitalisation (incidence rate ratio 1.95, 1.75–2.17), and an increased likelihood of prescription of antipsychotics (2.03, 1.75–2.35).
Using NLP, it was possible to identify mood instability in a large number of people, which would otherwise not have been possible by manually reading clinical records. Mood instability occurs in a wide range of mental disorders. It is generally associated with poor clinical outcomes. These findings suggest that clinicians should screen for mood instability across all common mental health disorders. The data also highlight the utility of NLP for clinical research.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
To examine the factors that are associated with changes in depression in people with type 2 diabetes living in 12 different countries.
People with type 2 diabetes treated in out-patient settings aged 18–65 years underwent a psychiatric assessment to diagnose major depressive disorder (MDD) at baseline and follow-up. At both time points, participants completed the Patient Health Questionnaire (PHQ-9), the WHO five-item Well-being scale (WHO-5) and the Problem Areas in Diabetes (PAID) scale which measures diabetes-related distress. A composite stress score (CSS) (the occurrence of stressful life events and their reported degree of ‘upset’) between baseline and follow-up was calculated. Demographic data and medical record information were collected. Separate regression analyses were conducted with MDD and PHQ-9 scores as the dependent variables.
In total, there were 7.4% (120) incident cases of MDD with 81.5% (1317) continuing to remain free of a diagnosis of MDD. Univariate analyses demonstrated that those with MDD were more likely to be female, less likely to be physically active, more likely to have diabetes complications at baseline and have higher CSS. Mean scores for the WHO-5, PAID and PHQ-9 were poorer in those with incident MDD compared with those who had never had a diagnosis of MDD. Regression analyses demonstrated that higher PHQ-9, lower WHO-5 scores and greater CSS were significant predictors of incident MDD. Significant predictors of PHQ-9 were baseline PHQ-9 score, WHO-5, PAID and CSS.
This study demonstrates the importance of psychosocial factors in addition to physiological variables in the development of depressive symptoms and incident MDD in people with type 2 diabetes. Stressful life events, depressive symptoms and diabetes-related distress all play a significant role which has implications for practice. A more holistic approach to care, which recognises the interplay of these psychosocial factors, may help to mitigate their impact on diabetes self-management as well as MDD, thus early screening and treatment for symptoms is recommended.
Dislocation-mediated plasticity in stable nanocrystalline metals, where grain boundary motion is suppressed, is revisited in the context of dislocation elastodynamics. The effect of transient waves that emanate from the generation and motion of dislocations is quantified for an idealized Cu–10 at.% Ta system with grain sizes on the order of 50 nanometers. Simulations indicate that for this material, as dislocation velocities approach 0.6–0.8 times the shear wave speed, grains several grain diameters away from the initial glide event experience a large transient shear stress for a finite duration. These transient shear stresses increase with increasing glide velocity and can activate nucleation sites far from the original nucleation event. These considerations are used to explain recent experimental observations of a lack of increase in flow stress with increasing loading rate, as well as localization resistance, in this class of stable nanocrystalline metals.
Dopaminergic imaging has high diagnostic accuracy for dementia with Lewy bodies (DLB) at the dementia stage. We report the first investigation of dopaminergic imaging at the prodromal stage.
We recruited 75 patients over 60 with mild cognitive impairment (MCI), 33 with probable MCI with Lewy body disease (MCI-LB), 15 with possible MCI-LB and 27 with MCI with Alzheimer's disease. All underwent detailed clinical, neurological and neuropsychological assessments and FP-CIT [123I-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)] dopaminergic imaging. FP-CIT scans were blindly rated by a consensus panel and classified as normal or abnormal.
The sensitivity of visually rated FP-CIT imaging to detect combined possible or probable MCI-LB was 54.2% [95% confidence interval (CI) 39.2–68.6], with a specificity of 89.0% (95% CI 70.8–97.6) and a likelihood ratio for MCI-LB of 4.9, indicating that FP-CIT may be a clinically important test in MCI where any characteristic symptoms of Lewy body (LB) disease are present. The sensitivity in probable MCI-LB was 61.0% (95% CI 42.5–77.4) and in possible MCI-LB was 40.0% (95% CI 16.4–67.7).
Dopaminergic imaging had high specificity at the pre-dementia stage and gave a clinically important increase in diagnostic confidence and so should be considered in all patients with MCI who have any of the diagnostic symptoms of DLB. As expected, the sensitivity was lower in MCI-LB than in established DLB, although over 50% still had an abnormal scan. Accurate diagnosis of LB disease is important to enable early optimal treatment for LB symptoms.
The accurate clinical characterisation of mild cognitive impairment (MCI) is becoming increasingly important. The aim of this study was to compare the neuropsychiatric symptoms and cognitive profile of MCI with Lewy bodies (MCI-LB) with Alzheimer's disease MCI (MCI-AD).
Participants were ⩾60 years old with MCI. Each had a thorough clinical and neuropsychological assessment and 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single photon emission computed tomography FP-CIT SPECT). MCI-LB was diagnosed if two or more diagnostic features of dementia with Lewy bodies were present (visual hallucinations, cognitive fluctuations, motor parkinsonism, rapid eye movement sleep behaviour disorder or positive FP-CIT SPECT). A Lewy body Neuropsychiatric Supportive Symptom Count (LBNSSC) was calculated based on the presence or absence of the supportive neuropsychiatric symptoms defined by the 2017 DLB diagnostic criteria: non-visual hallucinations, delusions, anxiety, depression and apathy.
MCI-LB (n = 41) had a higher LBNSSC than MCI-AD (n = 24; 1.8 ± 1.1 v. 0.7 ± 0.9, p = 0.001). 67% of MCI-LB had two or more of those symptoms, compared with 16% of MCI-AD (Likelihood ratio = 4.2, p < 0.001). MCI-LB subjects scored lower on tests of attention, visuospatial function and verbal fluency. However, cognitive test scores alone did not accurately differentiate MCI-LB from MCI-AD.
MCI-LB is associated with neuropsychiatric symptoms and a cognitive profile similar to established DLB. This supports the concept of identifying MCI-LB based on the presence of core diagnostic features of DLB and abnormal FP-CIT SPECT imaging. The presence of supportive neuropsychiatric clinical features identified in the 2017 DLB diagnostic criteria was helpful in differentiating between MCI-LB and MCI-AD.
Imaging biomarkers for Alzheimer's disease include medial temporal lobe
atrophy (MTLA) depicted on computed tomography (CT) or magnetic resonance
imaging (MRI) and patterns of reduced metabolism on fluorodeoxyglucose
positron emission tomography (FDG-PET).
To investigate whether MTLA on head CT predicts the diagnostic usefulness
of an additional FDG-PET scan.
Participants had a clinical diagnosis of Alzheimer's disease
(n = 37) or dementia with Lewy bodies (DLB;
n = 30) or were similarly aged controls
(n = 30). We visually rated MTLA on coronally
reconstructed CT scans and, separately and blind to CT ratings, abnormal
appearances on FDG-PET scans.
Using a pre-defined cut-off of MTLA ⩾5 on the Scheltens (0–8) scale, 0/30
controls, 6/30 DLB and 23/30 Alzheimer's disease had marked MTLA. FDG-PET
performed well for diagnosing Alzheimer's disease v. DLB
in the low-MTLA group (sensitivity/specificity of 71%/79%), but in the
high-MTLA group diagnostic performance of FDG-PET was not better than
In the presence of a high degree of MTLA, the most likely diagnosis is
Alzheimer's disease, and an FDG-PET scan will probably not provide
significant diagnostic information. However, in cases without MTLA, if
the diagnosis is unclear, an FDG-PET scan may provide additional
clinically useful diagnostic information.
There is a paucity of data on the effect of preterm birth on the immunological composition of breast milk throughout the different stages of lactation. We aimed to characterise the effects of preterm birth on the levels of immune factors in milk during the 1st month postpartum, to determine whether preterm milk is deficient in antimicrobial factors. Colostrum (days 2–5 postpartum), transitional milk (days 8–12) and mature milk (days 26–30) were collected from mothers of extremely preterm (<28 weeks of gestation, n 15), very preterm (28–<32 weeks of gestation, n 15), moderately preterm (32–<37 weeks of gestation, n 15) and term infants (37–41 weeks of gestation, n 15). Total protein, lactoferrin, secretory IgA, soluble CD14 receptor (sCD14), transforming growth factor-β2 (TGF-β2), α defensin 5 (HD5), β defensins 1 (HBD1) and 2, IL-6, IL-10, IL-13, interferon-γ, TNF-α and lysozyme (LZ) were quantified in milk. We examined the effects of lactation stage, gestational age, volume of milk expressed, mode of delivery, parity and maternal infection on milk immune factor concentrations using repeated-measures regression analysis. The concentrations of all factors except LZ and HD5 decreased over the 1st month postpartum. Extremely preterm mothers had significantly higher concentrations of HBD1 and TGF-β2 in colostrum than term mothers did. After controlling for other variables in regression analyses, preterm birth was associated with higher concentrations of HBD1, LZ and sCD14 in milk samples. In conclusion, preterm breast milk contains significantly higher concentrations of some immune proteins than term breast milk.
We assessed evidence of exposure to viruses and bacteria in an unmanaged and long-isolated population of Soay sheep (Ovis aries) inhabiting Hirta, in the St Kilda archipelago, 65 km west of Benbecula in the Outer Hebrides of Scotland. The sheep harbour many metazoan and protozoan parasites but their exposure to viral and bacterial pathogens is unknown. We tested for herpes viral DNA in leucocytes and found that 21 of 42 tested sheep were infected with ovine herpesvirus 2 (OHV-2). We also tested 750 plasma samples collected between 1997 and 2010 for evidence of exposure to seven other viral and bacterial agents common in domestic Scottish sheep. We found evidence of exposure to Leptospira spp., with overall seroprevalence of 6·5%. However, serological evidence indicated that the population had not been exposed to border disease, parainfluenza, maedi-visna, or orf viruses, nor to Chlamydia abortus. Some sheep tested positive for antibodies against Mycobacterium avium subsp. paratuberculosis (MAP) but, in the absence of retrospective faecal samples, the presence of this infection could not be confirmed. The roles of importation, the pathogen–host interaction, nematode co-infection and local transmission warrant future investigation, to elucidate the transmission ecology and fitness effects of the few viral and bacterial pathogens on Hirta.
Iodine-129 is a high-yield fission product formed in nuclear reactors and is a risk-driving radionuclide in both contaminated land and radioactive waste disposal due to its high mobility and long half-life. Here, the bioreduction behaviour of iodate was investigated by tracking iodine speciation and concentration in solution during the development of progressive anoxia in sediment microcosm experiments incubated at neutral pH. Experiments with acetate added as an electron donor showed the expected cascade of terminal electron-accepting processes. Analysis of solution chemistry showed reduction of iodate to iodide during the early stages of metal (Mn(IV) and Fe(III)) reduction, but with no significant retention of iodine species on solids. There was, however, a net release of natural iodine associated with the sediments to solution when robust iron reduction / sulfate reduction had developed. In addition, over 210 days, the controls with no electron donor and the sterile controls showed no Mn(IV) or Fe(III) reduction but displayed modest sorption of iodate to the sediments in the absence of bioreduction. Overall these results show that under oxic conditions iodate may be partially sorbed to sediments over extended periods but that development of mildly reducing conditions leads to the reductive release of iodine to solution as iodide.
In Australia, hepatitis B (HBV) vaccination is recommended for injecting drug users (IDUs), Indigenous adults and prisoners. We compared immunity to HBV in prisoners and the general population obtained from national serosurveys in 2007. Individuals with HBV surface antibody (HBsAb) positive sera were considered immune from past infection [HBV core antibody (HBcAb) positive] or from vaccination (HBcAb negative). Male prisoners aged 18–58 years had a higher HBsAb seroprevalence than the general population (46·4% vs. 39·4%, P = 0·061). Comparison of HBcAb results was possible for males aged 18–29 years. In this group, higher HBsAb seroprevalence was due to past infection (12·9% vs. 3·0%, P < 0·001), rather than vaccine-conferred immunity (35·3% vs. 43·4%, P = 0·097). All prisoner groups, but especially IDUs, those of Indigenous heritage or those with a previous episode of imprisonment had higher levels of immunity from past infection than the general population (19·3%, 33·0%, 17·1%, respectively, vs. 3·0%, P < 0·05). Indigenous prisoners, non-IDUs and first-time entrants had significantly lower levels of vaccine-conferred immunity than the general population (26·4%, 26·2% and 20·7% respectively vs. 43·4%, P < 0·05). Improving prison-based HBV vaccination would prevent transmission in the prison setting and protect vulnerable members of the community who are at high risk of both infection and entering the prison system.