The precariousness of living with, and caring for people with, dementia: Insights from the IDEAL programme.

This paper uses precarity as a framework to understand the vulnerabilities experienced by those living with or caring for someone living with dementia. Drawing on qualitative interview data from the Improving the Experience of Dementia and Enhancing Active Life (IDEAL) programme, we attend to our participants' reflections on how they manage the condition and the wider circumstances in which this occurs. To interrogate the utility of precarity, we focus on our participants' descriptions of needs and challenges and set these alongside both the wider contexts in which they seek or offer care (formal and informal) and the sets of values attributed to different ways of living with dementia. Building on the work of Portacolone, our analysis identified four interconnected themes: uncertainty; experiences of support and services; independence and personhood; and cumulative pressures and concerns. We develop this analysis by reviewing how our themes reflect, extend, or depart from previously identified markers of precarity and consider the specific ways in which these markers shape the lives of those living with dementia.

Implementing Digitalised Lean Manufacturing Training in a UK Engine Manufacturing Centre During the SARS-CoV2 Pandemic of 2020.

This paper examines a novel way of training Lean Manufacturing Systems and Tools utilising an Industry 4.0 methodology during the SARS-COVID2 Pandemic of 2020. Currently, it is challenging for the Integrated Production Systems Team, responsible for carrying out training on the Lean principles, to undertake the training safely and without the risk of possible disease transmission. This is due to the usual close quarters training carried out in the Engine Manufacturing Centre. Schools, Colleges and Universities have adapted and utilised technology and moved to an Industry 4.0 digitalised approach to learning and development. This is therefore an opportunity for manufacturing to follow suit and create digitised solutions to training and development opportunities, to ensure that the employees within the manufacturing facility have adequate knowledge on the Lean principles.

Replication of bipolar disorder susceptibility alleles and identification of two novel genome-wide significant associations in a new bipolar disorder case-control sample.

We have conducted a genotyping study using a custom Illumina Infinium HD genotyping array, the ImmunoChip, in a new UK sample of 1218 bipolar disorder (BD) cases and 2913 controls that have not been used in any studies previously reported independently or in meta-analyses. The ImmunoChip was designed before the publication of the Psychiatric Genome-Wide Association Study Consortium Bipolar Disorder Working Group (PGC-BD) meta-analysis data. As such 3106 single-nucleotide polymorphisms (SNPs) with a P-value <1 × 10(-3) from the BD meta-analysis by Ferreira et al. were genotyped. We report support for two of the three most strongly associated chromosomal regions in the Ferreira study, CACNA1C (rs1006737, P=4.09 × 10(-4)) and 15q14 (rs2172835, P=0.043) but not ANK3 (rs10994336, P=0.912). We have combined our ImmunoChip data (569 quasi-independent SNPs from the 3016 SNPs genotyped) with the recently published PGC-BD meta-analysis data, using either the PGC-BD combined discovery and replication data where available or just the discovery data where the SNP was not typed in a replication sample in PGC-BD. Our data provide support for two regions, at ODZ4 and CACNA1C, with prior evidence for genome-wide significant (GWS) association in PGC-BD meta-analysis. In addition, the combined analysis shows two novel GWS associations. First, rs7296288 (P=8.97 × 10(-9), odds ratio (OR)=0.9), an intergenic polymorphism on chromosome 12 located between RHEBL1 and DHH. Second, rs3818253 (P=3.88 × 10(-8), OR=1.16), an intronic SNP on chromosome 20q11.2 in the gene TRPC4AP, which lies in a high linkage disequilibrium region along with the genes GSS and MYH7B.

Association at SYNE1 in both bipolar disorder and recurrent major depression.

Genome-wide association studies (GWAS) have identified a number of loci that have strong support for their association with bipolar disorder (BD). The Psychiatric Genome-Wide Association Study (GWAS) Consortium Bipolar Disorder Working Group (PGC-BD) meta-analysis of BD GWAS data sets and replication samples identified evidence (P=6.7 × 10⁻7, odds ratio (OR)=1.147) of association with the risk of BD at the polymorphism rs9371601 within SYNE1, a gene which encodes nesprin-1. Here we have tested this polymorphism in an independent BD case (n=1527) and control (n=1579) samples, and find evidence for association (P=0.0095) with similar effect sizes to those previously observed in BD (allelic OR=1.148). In a combined (meta) analysis of PGC-BD data (both primary and replication data) and our independent BD samples, we found genome-wide significant evidence for association (P=2.9 × 10⁻8, OR=1.104). We have also examined the polymorphism in our recurrent unipolar depression cases (n=1159) and control (n=2592) sample, and found that the risk allele was associated with risk for recurrent major depression (P=0.032, OR=1.118). Our findings add to the evidence that association at this locus influences susceptibility to bipolar and unipolar mood disorders.

Polygenic dissection of the bipolar phenotype.

BACKGROUND: Recent data provide strong support for a substantial common polygenic contribution (i.e. many alleles each of small effect) to genetic susceptibility for schizophrenia and overlapping susceptibility for bipolar disorder. AIMS: To test hypotheses about the relationship between schizophrenia and psychotic types of bipolar disorder. METHOD: Using a polygenic score analysis to test whether schizophrenia polygenic risk alleles, en masse, significantly discriminate between individuals with bipolar disorder with and without psychotic features. The primary sample included 1829 participants with bipolar disorder and the replication sample comprised 506 people with bipolar disorder. RESULTS: The subset of participants with Research Diagnostic Criteria schizoaffective bipolar disorder (n = 277) were significantly discriminated from the remaining participants with bipolar disorder (n = 1552) in both the primary (P = 0.00059) and the replication data-sets (P = 0.0070). In contrast, those with psychotic bipolar disorder as a whole were not significantly different from those with non-psychotic bipolar disorder in either data-set. CONCLUSIONS: Genetic susceptibility influences at least two major domains of psychopathological variation in the schizophrenia-bipolar disorder clinical spectrum: one that relates to expression of a 'bipolar disorder-like' phenotype and one that is associated with expression of 'schizophrenia-like' psychotic symptoms.

Strong genetic evidence for a selective influence of GABAA receptors on a component of the bipolar disorder phenotype.

Despite compelling evidence for a major genetic contribution to risk of bipolar mood disorder, conclusive evidence implicating specific genes or pathophysiological systems has proved elusive. In part this is likely to be related to the unknown validity of current phenotype definitions and consequent aetiological heterogeneity of samples. In the recent Wellcome Trust Case Control Consortium genome-wide association analysis of bipolar disorder (1868 cases, 2938 controls) one of the most strongly associated polymorphisms lay within the gene encoding the GABA(A) receptor beta1 subunit, GABRB1. Aiming to increase biological homogeneity, we sought the diagnostic subset that showed the strongest signal at this polymorphism and used this to test for independent evidence of association with other members of the GABA(A) receptor gene family. The index signal was significantly enriched in the 279 cases meeting Research Diagnostic Criteria for schizoaffective disorder, bipolar type (P=3.8 x 10(-6)). Independently, these cases showed strong evidence that variation in GABA(A) receptor genes influences risk for this phenotype (independent system-wide P=6.6 x 10(-5)) with association signals also at GABRA4, GABRB3, GABRA5 and GABRR3. [corrected] Our findings have the potential to inform understanding of presentation, pathogenesis and nosology of bipolar disorders. Our method of phenotype refinement may be useful in studies of other complex psychiatric and non-psychiatric disorders.

Genetic utility of broadly defined bipolar schizoaffective disorder as a diagnostic concept.

BACKGROUND: Psychiatric phenotypes are currently defined according to sets of descriptive criteria. Although many of these phenotypes are heritable, it would be useful to know whether any of the various diagnostic categories in current use identify cases that are particularly helpful for biological-genetic research. AIMS: To use genome-wide genetic association data to explore the relative genetic utility of seven different descriptive operational diagnostic categories relevant to bipolar illness within a large UK case-control bipolar disorder sample. METHOD: We analysed our previously published Wellcome Trust Case Control Consortium (WTCCC) bipolar disorder genome-wide association data-set, comprising 1868 individuals with bipolar disorder and 2938 controls genotyped for 276 122 single nucleotide polymorphisms (SNPs) that met stringent criteria for genotype quality. For each SNP we performed a test of association (bipolar disorder group v. control group) and used the number of associated independent SNPs statistically significant at P<0.00001 as a metric for the overall genetic signal in the sample. We next compared this metric with that obtained using each of seven diagnostic subsets of the group with bipolar disorder: Research Diagnostic Criteria (RDC): bipolar I disorder; manic disorder; bipolar II disorder; schizoaffective disorder, bipolar type; DSM-IV: bipolar I disorder; bipolar II disorder; schizoaffective disorder, bipolar type. RESULTS: The RDC schizoaffective disorder, bipolar type (v. controls) stood out from the other diagnostic subsets as having a significant excess of independent association signals (P<0.003) compared with that expected in samples of the same size selected randomly from the total bipolar disorder group data-set. The strongest association in this subset of participants with bipolar disorder was at rs4818065 (P = 2.42 x 10(-7)). Biological systems implicated included gamma amniobutyric acid (GABA)(A) receptors. Genes having at least one associated polymorphism at P<10(-4) included B3GALTS, A2BP1, GABRB1, AUTS2, BSN, PTPRG, GIRK2 and CDH12. CONCLUSIONS: Our findings show that individuals with broadly defined bipolar schizoaffective features have either a particularly strong genetic contribution or that, as a group, are genetically more homogeneous than the other phenotypes tested. The results point to the importance of using diagnostic approaches that recognise this group of individuals. Our approach can be applied to similar data-sets for other psychiatric and non-psychiatric phenotypes.

Developing a user-generated measure of continuity of care: brief report.

OBJECTIVE: This paper describes a measure of continuity of care, establishes its reliability and tests it in a field trial sample for evidence of its validity. In contrast to others, this measure has been generated from the perspectives of service users. As continuity of care is a concern particularly for those with severe mental illness, we have confined our work to this population group. METHOD: Service users in focus groups and expert panels generated the measure. The researchers were themselves service users. Test-retest reliability was assessed with an independent sample. The measure was administered to a final independent field trial sample to determine their experiences of continuity of care and for further psychometric testing. RESULTS: The measure generated by service users has satisfactory psychometric properties. Service users in the field trial sample were more satisfied when continuity, as assessed by this measure, was in place. CONCLUSION: It is possible and valid to construct outcome measures in mental health entirely from the user perspective. This has not been done before.

Continuity of care in mental health: understanding and measuring a complex phenomenon.

BACKGROUND: Continuity of care is considered by patients and clinicians an essential feature of good quality care in long-term disorders, yet there is general agreement that it is a complex concept. Most policies emphasize it and encourage systems to promote it. Despite this, there is no accepted definition or measure against which to test policies or interventions designed to improve continuity. We aimed to operationalize a multi-axial model of continuity of care and to use factor analysis to determine its validity for severe mental illness. METHOD: A multi-axial model of continuity of care comprising eight facets was operationalized for quantitative data collection from mental health service users using 32 variables. Of these variables, 22 were subsequently entered into a factor analysis as independent components, using data from a clinical population considered to require long-term consistent care. RESULTS: Factor analysis produced seven independent continuity factors accounting for 62.5% of the total variance. These factors, Experience and Relationship, Regularity, Meeting Needs, Consolidation, Managed Transitions, Care Coordination and Supported Living, were close but not identical to the original theoretical model. CONCLUSIONS: We confirmed that continuity of care is multi-factorial. Our seven factors are intuitively meaningful and appear to work in mental health. These factors should be used as a starting-point in research into the determinants and outcomes of continuity of care in long-term disorders.

Influence of diabetes on the maintenance of sinus rhythm after a successful direct current cardioversion in patients with atrial fibrillation.

AIM: To determine independent risk factors for recurrence of atrial fibrillation (AF) after a successful direct current (DC) cardioversion in patients with and without diabetes. DESIGN: We retrospectively analysed the outcome in patients recently diagnosed with persistent AF. METHODS: Of 364 patients included, 289 had a successful direct current (DC) cardioversion. We compared 42 (14.5%) patients known to have diabetes to 247 (85.5%) without. Patients were reviewed in outpatient clinic with assessment of heart rhythm clinically and by electrocardiogram. Median follow-up after DC cardioversion was 74 days [interquartile range (IQR) 69-78 days]. RESULTS: When reviewed in outpatient clinic, only 63.7% (185 of 289) were still in sinus rhythm (SR). Of the group without diabetes, 66.8% (165 of 247) remained in SR vs. 45.2% (19 of 42) of the group with diabetes (P = 0.005). Binary logistic regression analysis showed duration of AF (P < 0.0001) and the presence of diabetes (P = 0.019) have been independent risk factors for recurrence of AF. DISCUSSION: Presence of diabetes and the longer duration of AF were independent risk factors for the recurrence of AF after a successful DC cardioversion.

Systematic screening for mutations in the glycine receptor alpha2 subunit gene (GLRA2) in patients with schizophrenia and other psychiatric diseases.

The glycine receptor, which is a member of the ligand-gated ion channel superfamily, mediates synaptic inhibition in the spinal cord and other brain regions. This superfamily has been implicated in the pathogenesis of schizophrenia and other psychiatric diseases. The complete coding sequence and splice junctions of the GLRA2 gene were scanned by DOVAM-S, a form of SSCP analysis with sufficient redundancy to detect virtually all mutations. Those analyses were performed in 113 patients with schizophrenia, and in pilot studies of patients with bipolar illness, alcoholism, puerperal psychosis, autism, and attention-deficit hyperactivity disorder (533 kb total scanned sequences). We detected three sequence changes in the coding region, all resulting in silent mutations: C894T in exon 5, C1134T in exon 7, and C1476T in exon 9. These do not alter the structure or the expression of the protein. It is unlikely that mutations in the coding region and splice junction of GLRA2 gene are associated with schizophrenia and other psychiatric diseases.

Scanning of estrogen receptor alpha (ERalpha) and thyroid hormone receptor alpha (TRalpha) genes in patients with psychiatric diseases: four missense mutations identified in ERalpha gene.

Estrogen and thyroid hormones exert effects on growth, development, and differentiation of the nervous system. Hormone administration can lead to changes in behavior, suggesting that genetic variants of the estrogen receptor alpha (ERalpha) and the thyroid hormone receptor alpha (TRalpha) genes may predispose to psychiatric diseases. To investigate this possibility, regions of likely functional significance (all coding exons and flanking splice junctions) of the ERalpha and TRalpha genes were scanned in patients with schizophrenia (113), along with pilot studies in patients with bipolar illness (BPI), puerperal psychosis, autism, attention-deficit hyperactivity disorder (ADHD), and alcoholism. A total of 1.18 megabases of the ERalpha gene and 1.16 megabases of the TRalpha gene were scanned with Detection of Virtually All Mutations-SSCP (DOVAM-S), a method that detects virtually all mutations. Four missense mutations, seven silent mutations and one deletion were identified in the ERalpha gene, while only four silent mutations were present in the TRalpha gene. Two of the missense mutations in ERalpha are conserved in the six available mammalian and bird species (H6Y, K299R) and a third sequence variant (P146Q) is conserved in mammals, birds, and Xenopus laevis, hinting that these sequence changes will be of functional significance. These changes were found in one patient each with BPI, puerperal psychosis, and alcoholism, respectively. Analysis of the ERalpha and TRalpha genes in 240 subjects reveals that missense changes and splice site variants are uncommon (1.7% and 0%, respectively). Further analyses are necessary to determine if the missense mutations identified in this study are associated with predisposition or outcome for either psychiatric or nonpsychiatric diseases.

An in-frame deletion in the alpha(2C) adrenergic receptor is common in African--Americans.

alpha(2) adrenergic receptors are activated by adrenaline and noradrenaline, and three subtypes (ie, A, B, C) have differential affinities for antagonists and medications. The alpha(2c) adrenergic receptor (ADRA2C), located on chromosome 4p16.3, is a candidate gene for schizophrenia because it binds clozapine, an atypical neuroleptic useful for treatment-resistant schizophrenia. In addition, ADRA2C binds clonidine which is prescribed for three psychiatric diseases. This report communicates the findings of the genetic scanning of this gene of very tough GC content. The complete coding sequences and splice junctions were scanned with [DOVAM]-S in 104 schizophrenics, and pilot probes of patients with alcoholism (41 patients), cocaine abuse (25 patients), puerperal psychosis (30 patients), attention deficient/hyperactivity disorder (25 patients) and autism (25 patients). Six sequence variants were found, including five silent polymorphisms (allele frequencies 0.6--25%) and an in-frame deletion of a homologous repeat at nucleotides 967--978 (ie, TIDRU(1)). Genotyping of the normal two repeat unit of the Third Intracytoplasmic Domain Repeat Unit (TIDRU(2)) and the deleted variant (TIDRU(1)) revealed that TIDRU(1) had allelic frequencies of 39% (11/28) and 3.5% (6/172) in African-American and Caucasian schizophrenics, respectively, and it occurred with equal frequency in controls (44%, 31/70 and 3.0%, 6/198). TIDRU(1) occurs at a location similar to the third intracytoplasmic 48-nucleotide repeat unit in the DRD4 that is associated with ADHD. Although these data do not suggest an association of TIDRU(1) with schizophrenia, additional studies are needed to see whether TIDRU(1) confers a clinical phenotype.

Effect of an internal rotating current on low-frequency inductively coupled plasmas.

The effect of an internal low-frequency rotating current on inductively coupled plasmas in cylindrical chambers is studied. The electromagnetic field structure, power density distribution, the plasma density, and the operating regimes of the discharge are investigated using electrodynamic, power, and particle balance equations. It is shown that the rotating current sheet can dramatically improve the uniformity of the electromagnetic fields and the power transferred to the plasma electrons from that of conventional low-frequency inductively coupled plasma sources with external flat spiral inductive coils.

Five missense variants in the amino-terminal domain of the glucocorticoid receptor: no association with puerperal psychosis or schizophrenia.

Steroid hormone administration causes behavior changes in many and psychosis in a few. The clinical features suggest that genetic variants of the glucocorticoid receptor or cofactors could produce susceptible subpopulations who react adversely to hormonal cascades. To investigate this possibility, coding and splice site sequences of the glucocorticoid receptor were scanned for single nucleotide polymorphisms in genomic DNA samples from 100 schizophrenics (86 Caucasians and 14 African-Americans) and 40 Caucasians with puerperal psychosis. Five amino acid substitutions were found in the amino-terminal domain at frequencies of 0.6 to 3.8% in Caucasians: R23K, F29L, L112F, D233N, and N363S. In addition, four silent nucleotide changes were found: E22E, K293K, D677D, and N766N; a transversion in intron 4 occurred beyond the splice junction. None of these variants can be linked to these disorders at present. However, the N363S variant contributes a new potential phosphorylation site and has been associated with increased body mass and reduced bone mineral density [Huizenga et al., 1998], so it is possible that the other missense variants confer traits that currently are unrecognized. Comparisons to natural glucocorticoid receptor mutants in the familial glucocorticoid resistance syndrome and steroid resistant leukemias suggest that amino acid substitutions at highly conserved residues may cause severe functional defects and serious illness, while changes at less conserved sites produce lesser alterations and milder disease.

No evidence of association from transmission disequilibrium analysis of the hKCa3 gene in bipolar disorder.

OBJECTIVE: A recent case control study has suggested that modest enlargements of a highly polymorphic CAG repeat in exon 1 of the gene encoding potassium channel hKCa3 may be associated with bipolar disorder (BPD). We have examined this hypothesis by genotyping this locus in a family-based association study. METHOD: One hundred and twenty-eight parent offspring trios of British Caucasian origin were examined where the proband was diagnosed with the American Psychiatric Association's Diagnostic and Statistical Manual (DSM)-IV BPD I (n = 123) or II (n = 5). An improved assay was used, with redesigned polymerase chain reaction (PCR) primers, permitting quicker and higher resolution genotyping. The resultant genotypes were analysed using the extended transmission/ disequilibrium test (ETDT). RESULTS: The experimental data did not provide evidence for the preferential transmission of large alleles to bipolar cases (chi2 = 11.12, df = 10, p = 0.349). CONCLUSIONS: Our data provide no support for the hypothesis that variation at the hKCa3 gene contributes to susceptibility to BPD.

Evolutionary psychology and health: confronting an evolving paradigm.

In much the same way that developments in genetics have opened up new areas of activity in health services, the 'new genetics' has also stimulated a renewal in approaches that try to explain the nature of health behaviours within the context of human biological development. Evolutionary psychology, as an umbrella term for these views, stresses the importance of the brain as an intermediary between genes and individual behaviour. From such a perspective, social context is less important than an understanding of why certain behaviours are 'chosen' by the evolutionary process and how they are predicated on reproductive success. Health policy is a key area where these ideas are likely to become important given evolutionary psychology's focus on the interplay between physiological and psychological factors in determining health behaviours. Health research provides a fertile environment because it is already seeking the hidden biological pathways connecting social status with specific diseases. The challenge represented by evolutionary psychology needs to be taken seriously because of the way in which such ideas mesh with the individualistic basis of much health promotion and health policy. In particular, it poses a challenge when it purports to explain how inequalities in health are not necessarily the result of the unequal distribution of income in society but are natural phenomena. It is also important to engage with such ideas because they increasingly seem likely to occupy the empty ideological space created by the disappearance of politics in policy and as such may have a greater impact than would otherwise be the case.

Salmonellosis in North Thames (East), UK: associated risk factors.

We assessed the rate of salmonella infections and risk factors associated with infection in North East Thames in 1993. Cases of culture confirmed infection were identified through microbiology laboratories and environmental health officers in the North East Thames. A total of 1730 cases were reported and 209 of these individuals (those who could be contacted within a 3-week interval after onset of symptoms) and matched controls were interviewed by telephone. In addition randomly selected controls were interviewed over a 4-month period about recent gastric acid lowering medication and antimicrobial ingestion. Sixty-six serotypes were identified: S. enteritidis was isolated from 1179 (69%) cases, S. typhimurium from 221 (13%), S. virchow from 77 (4%) and S. newport 25 (1%). Infections were more frequent in summer months. Highest rates were documented in children under 2 years of age for S. enteritidis (108/100,000) and under 1 year for S. typhimurium (36/100,000). Using the Townsend score, highest isolation rates of S. enteritidis were in more prosperous areas (36/100,000 vs. 27/100,000; odds ratio (OR) 1.3, 95% confidence intervals (CIs) 1.2-1.6, P < 0.0001), while for S. typhimurium, there was no relation between deprivation index and isolation rates areas (6.4/100,000 vs. 6.1/100,000; OR 1.1, 95% CIs 0.8-1.5, P = 0.77). The case control study showed a significant association between ingestion of products containing raw eggs and S. enteritidis infection (8/111 cases vs. 0/110 controls; OR undefined, lower 95% CIs 3.4). Individuals with salmonella infection were significantly more likely to have travelled abroad in the week before the onset of illness [42/186 (23%) vs. 1/182 (0.5%); OR 40, 95% CIs = 5.5-291, P < 0.001] and to report gastroduodenal disease [11/143 (7%) vs. 3/143 (2%); OR 5.0, 95% CIs = 1.1-23, P = 0.04]. There was an association between illness and gastric acid-lowering medications [unmatched controls OR 22.3 (95% CIs 1.5-3.7, P = 0.0002), matched controls OR 3.7 (95% CIs 1.0-3.8, P = 0.07)], but no association with antimicrobial ingestion.