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 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 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.
Valproate is widely used in psychiatry and neurology, including off-label use. Here we consider its potential benefits and risks, particularly for women of childbearing potential, and the evidence that clinical guidelines are adhered to. Finally, we consider the implications for clinical practice and research into its efficacy in off-label indications.
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 supply disruption alert in 2020, now rescinded, notified UK prescribers of the planned discontinuation of Priadel® (lithium carbonate) tablets. This service evaluation explored lithium dose and plasma levels before and after the switching of lithium brands, in order to determine the interchangeability of different brands of lithium from a pharmacokinetic perspective.
Data on the treatment of 37 patients switched from Priadel® tablets were analysed. Switching to Camcolit® controlled-release tablets at the same dose did not result in meaningful differences in plasma lithium levels. Dose adjustment and known or suspected poor medication adherence were associated with greater variability in plasma lithium levels on switching brands.
For comparable pre- and post-switch doses in adherent patients, the most common brands of lithium carbonate appear to produce similar plasma lithium levels. British National Formulary guidance relating to switching lithium brands may be unnecessarily complex.
We conducted a secondary analysis of data from a Prescribing Observatory for Mental Health audit to assess the quality of requests from intellectual disability services to primary care for repeat prescriptions of antipsychotic medication.
Forty-six National Health Service Trusts submitted treatment data on 977 adults with intellectual disability, receiving antipsychotic medication for more than a year, for whom prescribing responsibility had been transferred to primary care. Therapeutic effects had been monitored in the past 6 months in 80% of cases with a documented communication indicating which service was responsible for this and 72% of those with no such communication. The respective proportions were 69% and 42% for side-effect monitoring, and 79% and 30% for considering reducing/stopping antipsychotic medication.
Where continuing antipsychotic medication is prescribed in primary care for people with intellectual disability, lack of guidance from secondary care regarding responsibilities for monitoring its effectiveness may be associated with inadequate review.
Large-scale archaeogenetic studies of people from prehistoric Europe tend to be broad in scope and difficult to resolve with local archaeologies. However, accompanying supplementary information often contains useful finer-scale information that is comprehensible without specific genetics expertise. Here, we show how undiscussed details provided in supplementary information of aDNA papers can provide crucial insight into patterns of ancestry change and genetic relatedness in the past by examining details relating to a >90 per cent shift in the genetic ancestry of populations who inhabited Chalcolithic and Early Bronze Age Britain (c. 2450–1600 bc). While this outcome was certainly influenced by movements of communities carrying novel ancestries into Britain from continental Europe, it was unlikely to have been a simple, rapid process, potentially taking up to 16 generations, during which time there is evidence for the synchronous persistence of groups largely descended from the Neolithic populations. Insofar as genetic relationships can be assumed to have had social meaning, identification of genetic relatives in cemeteries suggests paternal relationships were important, but there is substantial variability in how genetic ties were referenced and little evidence for strict patrilocality or female exogamy.
Individual choice of insurance is used in several health systems as a means to empower citizens. This is based on the assumption that the insurers will act strategically on behalf of their clients to meet their needs and preferences and ensure access to high quality services, or else risk losing them to a competing insurer. Competition among insurance funds is expected to lead to improved health system efficiency, higher satisfaction with insurer services for clients (such as timely provision of information, easy administration, low waiting times, waiting list mediation, etc.). There is also an expectation that insurance competition will lead to improved care quality and could stimulate the development of more person-centred services.
The degree of choice and competition between insurers varies between health systems that have introduced this approach, as do the expectations that policy-makers in individual settings associate with choice and competition.
This chapter discusses a range of issues related to good clinical practice in psychopharmacology. It has been written to address the wide readership of care professionals who are involved in prescribing, monitoring and/or advising patients about psychiatric medication, which includes psychiatrists, pharmacists, psychiatric nurses, primary care physicians and hospital doctors.
Movement disorders associated with exposure to antipsychotic drugs are common and stigmatising but underdiagnosed.
To develop and evaluate a new clinical procedure, the ScanMove instrument, for the screening of antipsychotic-associated movement disorders for use by mental health nurses.
Item selection and content validity assessment for the ScanMove instrument were conducted by a panel of neurologists, psychiatrists and a mental health nurse, who operationalised a 31-item screening procedure. Interrater reliability was measured on ratings for 30 patients with psychosis from ten mental health nurses evaluating video recordings of the procedure. Criterion and concurrent validity were tested comparing the ScanMove instrument-based rating of 13 mental health nurses for 635 community patients from mental health services with diagnostic judgement of a movement disorder neurologist based on the ScanMove instrument and a reference procedure comprising a selection of commonly used rating scales.
Interreliability analysis showed no systematic difference between raters in their prediction of any antipsychotic-associated movement disorders category. On criterion validity testing, the ScanMove instrument showed good sensitivity for parkinsonism (90%) and hyperkinesia (89%), but not for akathisia (38%), whereas specificity was low for parkinsonism and hyperkinesia, and moderate for akathisia.
The ScanMove instrument demonstrated good feasibility and interrater reliability, and acceptable sensitivity as a mental health nurse-administered screening tool for parkinsonism and hyperkinesia.
Over the course of the nineteenth century, Quakerism was transformed. A united body in 1808, Friends had split into three branches by 1860. In 1808, Friends adhered to a lifestyle that served as a “hedge” against “the world,” a distinctive spirituality, and a unique form of worship. By 1920, that unity had disappeared, with little agreement on most matters of Quaker faith and practice.
The United States has been a leader in the creation of disability rights law, providing a policy template for other nations. Yet the social model, the animating philosophy behind the disability rights movement, has had little effect on the wide range of welfare programs that serve people with disabilities. These programs, whose creation preceded the modern disability rights movement, reflect a medical model of disability that is at odds with the social model. Analysing the Americans with Disabilities Act (which embodies the social model) and Social Security Disability Insurance (the largest welfare program for people with disabilities), we explore how and why this layering of contradictory disability rights and welfare programs developed and how it has been maintained. We argue that the tension between these policies engendered a series of patches, or ‘kludges’, that allow the policies to coexist without meaningful synthesis. We contend that the United States is particularly prone to this layering of ‘tense policies’, but that it is likely characteristic of disability policy in many nations. Finally we argue that accurate benchmarking of disability rights regimes across nations requires analysts to dig through all the layers of disability policy.
OBJECTIVES/SPECIFIC AIMS: The goal of this research is to use circulating tumor cells (CTC) enumeration and characterization to monitor anticancer treatment response. Emerging evidence strongly suggests the implications that epithelial-to-mesenchymal transition may have in cancer metastasis. Consequently, we hope to elucidate the significance of mesenchymal and stem-like CTCs in the peripheral blood of metastatic pancreatic cancer patients by analyzing the prevalence and frequency trends of CD133+ CTCs, as they relate to clinical events. We also hope to determine if there is a correlation between EpCAM+ CTCs and CD133+ CTCs numbers with tumor size, disease stage, and patient clinical outcome. METHODS/STUDY POPULATION: Blood samples of patients with metastatic pancreatic cancer (stage IV) were obtained from the University of Florida Health Cancer Center after informed consent through an IRB-approved protocol. CTC capture, characterization, and enumeration was performed on the blood of these cancer patients during their anticancer treatment. Patients had blood drawn for this purpose at time points aligned with clinical phlebotomy (every 2 weeks). CTC capture was performed by introducing treated patient blood samples into antibody-functionalized microdevices. The PDMS devices were functionalized by immobilizing either anti-EpCAM or anti-CD133, through an avidin-biotin complex. After capture, cells were fixated and permeabilized with 4% paraformaldehyde and 0.2% Triton X-100, respectively. Three-color immunocytochemistry (anti-cytokeratin-FITC, anti-CD45-PE, and DAPI) was performed to identify CTCs from nonspecifically captured blood cells. To be counted as a CTC, based on the FDA-approved technical definition, a cell with the appropriate cell size and morphology must be nucleated (DAPI+), express cytokeratin (CK+), and lack the leukocytic CD45 marker (CD45−). RESULTS/ANTICIPATED RESULTS: We tested the clinical utility of the device for monitoring the response of patients with advanced pancreatic cancer to a chemotherapy treatment consisting of anticancer drugs including 5-fluorouracil, leucovorin, oxaliplatin, and dasatinib. We have detected EpCAM+ CTCs in 47/47 (100%) and CD133+ CTCs in 41/47 (87.2%) of blood samples, coming from a cohort of 16 patients. We studied the correlation between the CTC numbers and the clinical result of patients in the study. We found that the size and changes in the size of the primary tumor (confirmed by CT scans) correlated with the frequency and increase/decrease trends in the number of CTCs detected. We expect to find some relationship between the number of detected CD133+ CTCs, or rather stem-like CTCs, and the clinical outcome of patients (eg, disease progression leading to withdrawal from study). DISCUSSION/SIGNIFICANCE OF IMPACT: Enumeration of patient CTCs and stem-like CTCs at different stages of a patient’s treatment may correlate with disease stage and prognosis, and prove useful in monitoring early recurrence, patient-specific treatment response, and newly acquired resistances; all of which would aid in providing guidance for the next step in clinical intervention. This type of liquid biopsy technology has great potential to make an impact in the future of personalized medicine and point-of-care diagnostics, as well as become a sturdy tool for translational research.
Archaeological tunneling is a standard excavation strategy in Mesoamerica. The ancient Maya built new structures atop older ones that were no longer deemed usable, whether for logistical or ideological reasons. This means that as archaeologists excavate horizontal tunnels into ancient Maya structures, they are essentially moving back in time. As earlier constructions are encountered, these tunnels may deviate in many directions in order to document architectural remains. The resultant excavations often become intricate labyrinths, extending dozens of meters. Traditional forms of archaeological documentation, such as photographs, plan views, and profile drawings, are limited in their ability to convey the complexity of tunnel excavations. Terrestrial Lidar (light detection and ranging) instruments are able to generate precise 3D models of tunnel excavations. This article presents the results of a model created with a Faro™ Focus 3D 120 Scanner of tunneling excavations at the site of El Zotz, Guatemala. The lidar data document the excavations inside a large mortuary pyramid, including intricately decorated architecture from an Early Classic (A.D. 300–600) platform buried within the present form of the structure. Increased collaboration between archaeologists and scholars with technical expertise maximizes the effectiveness of 3D models, as does presenting digital results in tandem with traditional forms of documentation.
Knowledge on the ecology of humpback whales in the eastern North Atlantic is lacking by comparison with most other ocean basins. Humpback whales were historically over-exploited in the region and are still found in low relative abundances. This, coupled with their large range makes them difficult to study. With the aim of informing more effective conservation measures in Ireland, the Irish Whale and Dolphin Group began recording sightings and images suitable for photo-identification of humpback whales from Irish waters in 1999. Validated records submitted by members of the public and data from dedicated surveys were analysed to form a longitudinal study of individually recognizable humpback whales. The distribution, relative abundance and seasonality of humpback whale sighting records are presented, revealing discrete important areas for humpback whales in Irish coastal waters. An annual easterly movement of humpback whales along the southern coast of Ireland is documented, mirroring that of their preferred prey: herring and sprat. Photo-identification images were compared with others collected throughout the North Atlantic (N = 8016), resulting in matches of two individuals between Ireland and Iceland, Norway and the Netherlands but no matches to known breeding grounds (Cape Verde and West Indies). This study demonstrates that combining public records with dedicated survey data is an effective approach to studying low-density, threatened migratory species over temporal and spatial scales that are relevant to conservation and management.
Audit is an important tool for quality improvement. The collection of data on clinical performance against evidence-based and clinically relevant standards, which are considered by clinicians to be realistic in routine practice, can usefully prompt reflective practice and the implementation of change. Evidence of participation in clinical audit is required to achieve intended learning outcomes for trainees in psychiatry and revalidation for those who are members of the Royal College of Psychiatrists. This article addresses some of the practical steps involved in conducting an audit project, and, to illustrate key points, draws on lessons learnt from a national, audit-based, quality improvement programme of lithium prescribing and monitoring conducted through the Prescribing Observatory for Mental Health.