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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.
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.
Longitudinal studies of patterns of healthcare contacts in those who die by suicide to identify those at risk are scarce.
To examine type and timing of healthcare contacts in those who die by suicide.
A population-based electronic case–control study of all who died by suicide in Wales, 2001–2017, linking individuals’ electronic healthcare records from general practices, emergency departments and hospitals. We used conditional logistic regression to calculate odds ratios, adjusted for deprivation. We performed a retrospective continuous longitudinal analysis comparing cases’ and controls’ contacts with health services.
We matched 5130 cases with 25 650 controls (5 per case). A representative cohort of 1721 cases (8605 controls) were eligible for the fully linked analysis. In the week before their death, 31.4% of cases and 15.6% of controls contacted health services. The last point of contact was most commonly associated with mental health and most often occurred in general practices. In the month before their death, 16.6 and 13.0% of cases had an emergency department contact and a hospital admission respectively, compared with 5.5 and 4.2% of controls. At any week in the year before their death, cases were more likely to contact healthcare services than controls. Self-harm, mental health and substance misuse contacts were strongly linked with suicide risk, more so when they occurred in emergency departments or as emergency admissions.
Help-seeking occurs in those at risk of suicide and escalates in the weeks before their death. There is an opportunity to identify and intervene through these contacts.
Obtaining objective, dietary exposure information from individuals is challenging because of the complexity of food consumption patterns and the limitations of self-reporting tools (e.g., FFQ and diet diaries). This hinders research efforts to associate intakes of specific foods or eating patterns with population health outcomes.
Dietary exposure can be assessed by the measurement of food-derived chemicals in urine samples. We aimed to develop methodologies for urine collection that minimised impact on the day-to-day activities of participants but also yielded samples that were data-rich in terms of targeted biomarker measurements.
Urine collection methodologies were developed within home settings.
Different cohorts of free-living volunteers.
Home collection of urine samples using vacuum transfer technology was deemed highly acceptable by volunteers. Statistical analysis of both metabolome and selected dietary exposure biomarkers in spot urine collected and stored using this method showed that they were compositionally similar to urine collected using a standard method with immediate sample freezing. Even without chemical preservatives, samples can be stored under different temperature regimes without any significant impact on the overall urine composition or concentration of forty-six exemplar dietary exposure biomarkers. Importantly, the samples could be posted directly to analytical facilities, without the need for refrigerated transport and involvement of clinical professionals.
This urine sampling methodology appears to be suitable for routine use and may provide a scalable, cost-effective means to collect urine samples and to assess diet in epidemiological studies.
To describe the characteristics of people in Central and Eastern Sydney (CES), NSW, who had a General Practice Management Plan (GPMP) and claimed for at least one private allied health service item; and to examine if allied health service use results in less hospitalisations over a five-year period.
The number of people living with chronic health conditions is increasing in Australia. The Chronic Disease Management programme was introduced to the Medicare Benefits Schedule (MBS) to provide a more structured approach to managing patients with chronic conditions and complex care needs. The programme supports general practitioners claiming up to one GPMP and one Team Care Arrangement every year, and the patient additionally claiming for up to five private allied health services visits.
A prospective longitudinal study was conducted. The sample consisted of 5771 participants in CES who had a GPMP within a two-year health service utilisation baseline period (2007–2009). The analysis used the 45 and Up Study questionnaire data linked to the MBS, hospitalisation, death and emergency department data for the period 2006–2014.
Of the eligible participants, 43% (2460) had at least one allied health service item claim in the subsequent 12 months. Allied health services were reported as physiotherapy, podiatry and other allied health services. The highest rates of allied health service use were among participants aged 85 years and over (49%). After controlling for confounding factors, a significant difference was found between having claimed for five or more physiotherapy services and emergency admissions (HR: 0.83; 95% CI: 0.72–0.95) and potentially preventable hospitalisations (HR: 0.79; 95% CI: 0.64–0.96) in the subsequent five years. Use of allied health service items was well targeted towards those with chronic and complex care needs, and use of physiotherapy services was associated with less avoidable hospitalisations.
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.
Neuroticism has often been linked to suicidal thoughts and behaviour.
To examine whether neuroticism is associated with suicide deaths after adjusting for known risks.
UK Biobank participants (n = 389 365) were assessed for neuroticism as well as social, demographic and health-related variables at study entry and followed for up to 10 years. Suicide risk was modelled using Cox regression stratified by gender.
Neuroticism increased the risk of suicide in both men (hazard ratio (HR) = 1.15, 95% CI 1.09–1.22) and women (HR = 1.16, 95% CI 1.06–1.27). In a subsample who were assessed for mood disorders, neuroticism remained a significant predictor for women (HR 1.25, 95% CI 1.03–1.51) but not for men.
Screening and therapeutic interventions for neuroticism may be important for early suicide prevention.
In this paper, we make partial progress on a function field version of the dynamical uniform boundedness conjecture for certain one-dimensional families
of polynomial maps, such as the family
. We do this by making use of the dynatomic modular curves
) which parametrize maps
together with a point (respectively orbit) of period
. The key point in our strategy is to study the set of primes
for which the reduction of
fails to be smooth or irreducible. Morton gave an algorithm to construct, for each
, a discriminant
whose list of prime factors contains all the primes of bad reduction for
. In this paper, we refine and strengthen Morton’s results. Specifically, we exhibit two criteria on a prime
: one guarantees that
is in fact a prime of bad reduction for
, yet this same criterion implies that
is geometrically irreducible. The other guarantees that the reduction of
is actually smooth. As an application of the second criterion, we extend results of Morton, Flynn, Poonen, Schaefer, and Stoll by giving new examples of good reduction of
for several primes dividing
. The proofs involve a blend of arithmetic and complex dynamics, reduction theory for curves, ramification theory, and the combinatorics of the Mandelbrot set.
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.