Compacted doctrines: Empson and the meanings of words.

This chapter describes the account of word meaning advanced by William Empson in 'The Structure of Complex Words' (1951). Exposition is supported by detailed historical analysis of the word wit, chosen to illustrate the possibilities, as well as difficulties, of the framework Empson devised to investigate meaning ‘equations’ that his selected words are capable of entering into. Noting the apparent likeness between 'Complex Words' and Raymond Williams’s slightly later 'Keywords' (1976/1983), including use by both authors of the term ‘keyword’, the chapter examines important differences of approach between the two authors (differences revealed especially in a review Empson published of Williams’s 'Keywords', discussed in the chapter). In conclusion, it is suggested that despite differences between them some similar implications regarding meaning follow from the work of both authors. These include the idea that, rather than merely describing distinct word meanings, or even meanings attributed to words by individual speakers, historical analyses of meaning should focus on social practices that accompany language use, including practices which find their existence and articulation in institutions. In this more social view of meaning, it is suggested, meaning and social identity are kinds of effect, or produced relation, rather than stable elements outside language with which to begin an analysis

Lifetime reproductive output over two generations in patients with psychosis and their unaffected siblings:the Uppsala 1915-1929 Birth Cohort Multigenerational Study

BACKGROUND: Schizophrenic patients have fewer offspring than the general population but it is unclear whether (i) this persists for more than one generation, (ii) the reduced fertility is compensated by increased fertility in unaffected relatives, (iii) sociodemographic factors confound or interact with the association, and (iv) patients with affective psychosis have a similar fertility disadvantage. This study measured biological fitness over two generations in patients with schizophrenia or affective psychosis, and their unaffected siblings. METHOD: We conducted a historical cohort study using a Swedish birth cohort of 12 168 individuals born 1915-1929 and followed up until 2002. We compared biological fitness over two generations in patients with schizophrenia (n=58) or affective psychosis (n=153), and their unaffected siblings, with the population, adjusting for a range of sociodemographic variables from throughout the lifespan. RESULTS: Patients with schizophrenia had fewer children [fertility ratio (FR) 0.42, 95% confidence interval (CI) 0.29-0.61] and grandchildren (FR 0.51, 95% CI 0.33-0.80) than the population. Some of this reduction was related to lower marriage rates in schizophrenic patients. The unaffected siblings of schizophrenic patients showed no evidence of any compensatory increase in fitness, but there was a trend towards enhanced fertility among the offspring of schizophrenia patients. Patients with affective psychosis and their relatives did not differ from the general population on any fertility measure. CONCLUSIONS: Schizophrenia, but not affective psychosis, is associated with reduced biological fertility; this disadvantage is partly explained by marital status and persists into the second generation

Coded apertures for x-ray scatter imaging

We examine coding strategies for coded aperture scatter imagers. Scatter imaging enables tomography of compact regions from snapshot measurements. We present coded aperture designs for pencil and fan beam geometries, and compare their singular value spectra with that of the Radon transform and selected volume tomography.We show that under dose constraints scatter imaging improves conditioning over alternative techniques, and that specially designed coded apertures enable snapshot 1D and 2

Schizophrenia polygenic risk predicts general cognitive deficit but not cognitive decline in healthy older adults

There has been a long argument over whether schizophrenia is a neurodegenerative disorder associated with progressive cognitive impairment. Given high heritability of schizophrenia, ascertaning if genetic susceptibility to schizophrenia is also associated with cognitive decline in healthy people would support the view that schizophrenia leads to an accelerated cognitive decline. Using the population representative sample of 6817 adults aged >50 years from the English Longitudinal Study of Ageing, we investigated associations between the biennial rate of decline in cognitive ability and the schizophrenia polygenic score (SZ-PGS) during the 10-year follow-up period. SZ-PGS was calculated based on summary statistics from the Schizophrenia Working Group of the Psychiatric Genomics Consortium. Cognition was measured sequentially across four time points using verbal memory and semantic fluency tests. The average baseline verbal memory was 10.4 (SD = 3.4) and semantic fluency was 20.7 (SD = 6.3). One standard deviation (1-SD) increase in SZ-PGS was associated with lower baseline semantic fluency (β = −0.25, 95%CI = −0.40 to −0.10, p = 0.002); this association was significant in men (β = −0.36, 95%CI = −0.59 to −0.12, p = 0.003) and in those who were aged 60–69 years old (β = −0.32, 95%CI = −0.58 to −0.05, p = 0.019). Similarly, 1-SD increase in SZ-PGS was associated with lower verbal memory score at baseline in men only (β = −0.12, 95%CI = −0.23 to −0.01, p = 0.040). However, SZ-PGS was not associated with a greater rate of decline in these cognitive domains during the 10-year follow-up. Our findings highlight that while genetic susceptibility to schizophrenia conveys developmental cognitive deficit, it is not associated with an ongoing cognitive decline, at least in later life. These results do not support the neo-Kraepelinian notion of schizophrenia as a genetically determined progressively deteriorating brain disease

Do schizophrenic patients who managed to get to university have a non-neurodevelopmental form of illness?

Background. Many people who develop schizophrenia have impairments in intellectual and social functioning that are detectable from early childhood. However, some patients do not exhibit such deficits, and this suggests that they may have suffered less neurodevelopmental damage. We hypothesized that the aetiology and form of schizophrenia may differ in such patients. We therefore studied a group of schizophrenic patients who were functioning well enough to enter university prior to illness onset. Methods. The casenotes of 46 university-educated patients and 48 non-university-educated patients were rated on several schedules including the OPCRIT checklist, and the two groups were compared using univariate statistical techniques. Principal components analysis was then performed using data from all patients, and the factor scores for each principal component were compared between groups. Results. Univariate analyses showed the university-educated patients had an excess of depressive symptoms, and a paucity of core schizophrenic symptoms. Four principal components emerged in the principal components analysis: mania, biological depression, schizophrenic symptoms, and a reactive depression. University-educated patients scored significantly higher on the reactive depression principal component, and lower on the schizophrenic symptoms principal component, than the non-university-educated patients. Conclusions. University-educated patients may have a non-developmental subtype of schizophrenia.link_to_subscribed_fulltex

Scholastic achievement at age 16 and risk of schizophrenia and other psychoses: a national cohort study

Background: There is abundant evidence that schizophrenia is associated with cognitive deficits in childhood. However, previous studies investigating school performance have been inconclusive. Furthermore, there are several biological and social factors that could confound the association. We investigated whether school performance at age 16 is associated with risk of adult schizophrenia and other psychoses in a large national cohort, while controlling for multiple confounders. Method: Using a national sample of 907 011 individuals born in Sweden between 1973 and 1983, we used Cox regression to assess whether scholastic achievement at age 15-16 predicted hospital admission for psychosis between ages 17 and 31, adjusting for potential confounders. Results: Poor school performance was associated with increased rates of schizophrenia [hazard ratio (HR) 3.9, 95% confidence interval (CI) 2.8-5.3], schizo-affective disorder (HR 4.2, 95% CI 1.9-9.1) and other psychoses (HR 3.0, 95% CI 2.3-4.0). Receiving the lowest (E) grade was significantly associated with risk for schizophrenia and other psychoses in every school subject. There was no evidence of confounding by migrant status, low birthweight, hypoxia, parental education level or socio-economic group. Conclusions: Poor school performance across all domains is strongly associated with risk for schizophrenia and other psychoses. Copyright © 2007 Cambridge University Press.link_to_subscribed_fulltex

Sodium valproate and clozapine induced neutropenia: A case control study using register data

BACKGROUND: The use of clozapine is limited due to the occurrence of neutropenia, and the rare but life threatening adverse event of agranulocytosis. There is little epidemiological research into clinical factors that may impact on this risk. We conducted a case control study examining the clinical risk factors for neutropenia patients treated with clozapine. METHOD: A case-control study was conducted within a database of anonymised electronic clinical records. All patients who discontinued clozapine due to a neutropenic event were included as cases. Matched controls were selected from patients with a documented clozapine exposure at the time of the clozapine neutropenic event of the case patient, matched by duration of clozapine treatment. RESULTS: 136 cases and 136 controls were included. In multivariable analysis, the concurrent use of sodium valproate was associated with neutropenia (Odds Raito (OR) 2.28, 95%CI: 1.27–4.11, p = 0.006). There was a dose-response effect, with greater associations for higher doses. Patients who discontinued clozapine due to neutropenia were more likely to be of black ethnicity (OR 2.99, p < 0.001), were younger (t = 5.86, df = 267, p < 0.001), and received lower doses of clozapine (t = − 2.587, p = 0.01) than those who did not develop neutropenia. CONCLUSION: We identified an association between the concurrent use of sodium valproate and an increased risk of clozapine associated neutropenia. These results, taken in combination with the results from previous case series, suggest that the risk of clozapine associated neutropenia could be reduced by avoiding concurrent valproate treatment

Extracting antipsychotic polypharmacy data from electronic health records: developing and evaluating a novel process

Background Antipsychotic prescription information is commonly derived from structured fields in clinical health records. However, utilising diverse and comprehensive sources of information is especially important when investigating less frequent patterns of medication prescribing such as antipsychotic polypharmacy (APP). This study describes and evaluates a novel method of extracting APP data from both structured and free-text fields in electronic health records (EHRs), and its use for research purposes. Methods Using anonymised EHRs, we identified a cohort of patients with serious mental illness (SMI) who were treated in South London and Maudsley NHS Foundation Trust mental health care services between 1 January and 30 June 2012. Information about antipsychotic co-prescribing was extracted using a combination of natural language processing and a bespoke algorithm. The validity of the data derived through this process was assessed against a manually coded gold standard to establish precision and recall. Lastly, we estimated the prevalence and patterns of antipsychotic polypharmacy. Results Individual instances of antipsychotic prescribing were detected with high precision (0.94 to 0.97) and moderate recall (0.57-0.77). We detected baseline APP (two or more antipsychotics prescribed in any 6-week window) with 0.92 precision and 0.74 recall and long-term APP (antipsychotic co-prescribing for 6 months) with 0.94 precision and 0.60 recall. Of the 7,201 SMI patients receiving active care during the observation period, 338 (4.7 %; 95 % CI 4.2-5.2) were identified as receiving long-term APP. Two second generation antipsychotics (64.8 %); and first -second generation antipsychotics were most commonly co-prescribed (32.5 %). Conclusions These results suggest that this is a potentially practical tool for identifying polypharmacy from mental health EHRs on a large scale. Furthermore, extracted data can be used to allow researchers to characterize patterns of polypharmacy over time including different drug combinations, trends in polypharmacy prescribing, predictors of polypharmacy prescribing and the impact of polypharmacy on patient outcomes