Please note, due to essential maintenance online transactions will not be possible between 02:30 and 04:00 BST, on Tuesday 17th September 2019 (22:30-00:00 EDT, 17 Sep, 2019). We apologise for any inconvenience.
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 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 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.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
To investigate the percentage of patients who commenced smoking after transferring out of a non-smoking forensic psychiatric unit, the corresponding clozapine dose adjustments, the effects on plasma clozapine/norclozapine concentrations and observed changes in mental state. We reviewed the notes and plasma clozapine/norclozapine concentrations of 46 patients transferred to medium secure units between July 2008 and December 2013.
Thirty-five patients commenced smoking. Their median clozapine dose was increased by 50 mg/d. In the non-smokers, the median clozapine dose remained unchanged. Plasma clozapine/norclozapine concentrations were significantly reduced in smokers despite dosage adjustment. Eighteen patients experienced deterioration in mental state after transfer; almost all these patients were smokers.
Approximately three-quarters of patients who were non-smokers by virtue of being in a secure non-smoking environment commenced smoking after transfer. Monitoring of clozapine serum levels and assessment of mental state in the immediate period after a change in smoking status is indicated.
Equitable access to mental healthcare is a priority for many countries. The National Health Service in England uses a weighted capitation formula to ensure that the geographical distribution of resources reflects need.
To produce a revised formula for estimating local need for secondary mental health, learning disability (intellectual disability) and psychological therapies services for adults in England.
We used demographic records for 43 751 535 adults registered with a primary care practitioner in England linked with service use, ethnicity, physical health diagnoses and type of household, from multiple data-sets. Using linear regression, we estimated the individual cost of care in 2015 as a function of individual- and area-level need and supply variables in 2013 and 2014. We sterilised the effects of the supply variables to obtain individual-need estimates. We aggregated these by general practitioner practice, age and gender to derive weights for the national capitation formula.
Higher costs were associated with: being 30–50 years old, compared with 20–24; being Irish, Black African, Black Caribbean or of mixed ethnicity, compared with White British; having been admitted for specific physical health conditions, including drug poisoning; living alone, in a care home or in a communal environment; and living in areas with a higher percentage of out-of-work benefit recipients and higher prevalence of severe mental illness. Longer distance from a provider was associated with lower cost.
The resulting needs weights were higher in more deprived areas and informed the distribution of some 12% (£9 bn in 2019/20) of the health budget allocated to local organisations for 2019/20 to 2023/24.
Public health strategies have focused largely on physical health. However, there is increasing recognition that raising mental health awareness and tackling stigma is crucial to reduce disease burden. National campaigns have had some success but tackling issues locally is particularly important.
To assess the public's awareness and perception of the monthly BBC Cornwall mental health phone-in programmes that have run for 8.5 years in Cornwall, UK (population 530 000).
A consultation, review and feedback process involving a multiagency forum of mental and public health professionals, people with lived experience and local National Health Service trust's media team was used to develop a brief questionnaire. This was offered to all attendees at two local pharmacies covering populations of 27 000 over a 2-week period.
In total, 14% (95% CI 11.9–16.5) were aware of the radio show, 11% (95% CI 9.0–13.1) have listened and the majority (76%) of those who listened did so more than once. The estimated reach is 70 000 people in the local population, of whom approximately 60 000 listen regularly. The show is highly valued among respondents with modal and median scores of 4 out of 5.
Local radio is a successful, cost-effective and impactful way to reach a significant proportion of the population and likely to raise awareness, reduce stigma and be well received. The format has been adopted in other regions thus demonstrating easy transferability. It could form an essential part of a public health strategy to improve a population's mental well-being.
Declaration of interest
W.H. received support from the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula UK. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. L.R. and D.S. were involved in delivering the programmes but had no role in their evaluation.
Although therapeutic treatments are intended to help alleviate symptoms associated with disease, safety must be carefully considered and monitored to confirm continued positive benefit/risk balance. The objective of MOBILITY was to study the long-term safety of onabotulinumtoxinA for treatment of various therapeutic indications.
A prospective, multicenter, observational, Phase IV Canadian study in patients treated with onabotulinumtoxinA for a therapeutic indication. Dosing was determined by the participating physician. Adverse events (AEs) were recorded throughout the study.
Patients (n = 1372) with adult focal spasticity, blepharospasm, cerebral palsy, cervical dystonia, hemifacial spasm, hyperhidrosis, or “other” diagnoses were enrolled into the safety cohort. Eighty-three patients (6%) reported 209 AEs; 44 AEs in 24 patients (2%) were considered treatment-related AEs. Seventy-two serious AEs were reported by 38 patients (3%); 10 serious AEs in 5 patients (0.4%) were considered treatment related. Most commonly reported treatment-related AEs were muscular weakness (n = 7/44) and dysphagia (n = 6/44).
In patients with follow-up for up to six treatments with onabotulinumtoxinA, treatment-related AEs were reported in <2% of the safety population over the course of nearly 5 years. Our findings from MOBILITY provide further evidence that onabotulinumtoxinA treatment is safe for long-term use across a variety of therapeutic indications.
One of the foundations of product design is the division between production and design. This division manifests as designers aspiring to create fixed iconic archetypes and production replicates endlessly in thousands or millions. Today innovation and technological change are challenging this idea of product design and manufacturing. The evolution of Rapid Prototyping into Additive Manufacturing (AM), is challenging the notion of mass manufacture and consumer value. As AM advances in capability and capacity, the ability to economically manufacture products in low numbers with high degrees of personalisation poses questions of the accepted product development process. Removing the need for dedicated expensive tooling also eliminates the cyclical timescales and commitment to fixed designs that investment in tooling demands. The ability to alter designs arbitrarily, frequently and responsively means that the traditional design process need not be applied and because of this, design processes and practice might be radically different in the future. In this paper, we explore this possible evolution by drawing parallels with principles and development models found in software development.
In late summer, sometime between cal a.d. 340–405, a hoard of tightly packed, stacked copper-alloy vessels was deposited in the Vale of Pewsey, Wiltshire. The corrosion of the vessels allowed for the preservation of delicate plant macrofossils and pollen. Analysis of this material has provided insights into the date, season and context of this act of structured deposition. A second hoard of similar vessels was deposited in the fourth or fifth century only a few miles away at Wilcot. The hoards and their deposition relate to Romano-British lifeways, at a time when the region was on the cusp of a dramatic period of change. The distribution of late Roman coins and belt fittings offers further insights into the social and economic character of Wiltshire at their times of deposition.
We propose the concept of the “Fish Revolution” to demarcate the dramatic increase in North Atlantic fisheries after AD 1500, which led to a 15-fold increase of cod (Gadus morhua) catch volumes and likely a tripling of fish protein to the European market. We consider three key questions: (1) What were the environmental parameters of the Fish Revolution? (2) What were the globalising effects of the Fish Revolution? (3) What were the consequences of the Fish Revolution for fishing communities? While these questions would have been considered unknowable a decade or two ago, methodological developments in marine environmental history and historical ecology have moved information about both supply and demand into the realm of the discernible. Although much research remains to be done, we conclude that this was a major event in the history of resource extraction from the sea, mediated by forces of climate change and globalisation, and is likely to provide a fruitful agenda for future multidisciplinary research.
A procedure for conveniently determining the orientation of noncubic crystals is presented. The methods usually employed for cubic crystals, flat-film backreflection Laue patterns interpreted with the aid of a table of interplanar angles, is not readily adaptable to noncubics. In general, tables of interplanar angles for noncubics do not exist and if the effort is expended to generate them, such a vast array of angles result that they are virtually impossible to use. It is thus necessary to use the symmetry of the pattern to identify the low-index planes. However, on flat-film geometry, due to the small angular range of the data, insufficient low-index points are present to permit orientation.
In order to alleviate this problem we have developed the necessary techniques for the interpretation of back-reflection Laue patterns employing cylindrical-film geometry. The necessary overlays and their use are presented along with some of the results obtained.
Why have accounts of botched executions not played a larger role in the struggle to end capital punishment in the United States? In the twentieth century, when methods of execution became increasingly controlled and sterilized, botched executions would seem to have had real abolitionist potential. This article examines newspaper coverage of botched executions to determine and describe the way they were presented to the public and why they have contributed little to the abolitionist cause. Although botched executions reveal pain, violence, and inhumanity associated with state killing, newspaper coverage of these events neutralizes the impact of that revelation. Throughout the last century, newspapers presented botched executions as misfortunes rather than injustices. We identify three distinct modes by which newspaper coverage neutralized the impact of botched executions and presented them as misfortunes rather than as systemic injustices: (1) the dual narratives of sensationalism and recuperation in the early years of the twentieth century, (2) the decline of sensationalism and the rise of “professionalism” in the middle of the century, and (3) the emphasis on “balanced” reporting toward the end of the century.