Raymond Queneau: a study of technique in fiction

This study examines technique in the novels of Raymond Queneau, The first section, 'In defence of the novel', seeks to demonstrate Queneau's particular technical awareness. At the same time, it places his work in the context of changing attitudes to fiction in France since the early 1920's and also connects it with international developments in the theory of fiction, with particular reference to those of Joycean origin. The second section, 'The relation of theme, to technique', examines significant features of Queneau's fiction as they recur throughout his work and relates these to the theoretical aspects considered in Part One. The concluding section, 'Surface and the underlying truth', relates Queneau's approach to fiction and the themes he discovers to a consideration of the role of the novelist in terms of literature and reality. The transcript of two interviews with Raymond Queneau are included in an appendix, as is a complete bibliography of Queneau's writing and also of those critical books and articles concerned with his work

Progression of extrapyramidal signs in Alzheimer's disease. clinical and neuropathological correlates

Extrapyramidal signs (EPS) are frequent in Alzheimer's disease (AD) and core manifestation of related diseases, i.e., dementia with Lewy bodies and Parkinson's disease; furthermore, Lewy bodies and AD-type pathology occur in all three conditions

SubtilNet2, a functional interaction model for the validation of potential therapeutic targets

Systems Biology- the study of interactions between components of biological systems, and how these can produce new functions and behaviours, is beginning to produce a more comprehensive understanding of biology. Its development is enabling many new opportunities, including the discovery and development of more effective and targeted therapeutics for a range of different conditions. It was in this context that this investigation began, with focus placed upon identifying therapeutic targets in Bacillus subtilis that could be used to limit the development and spread of infection, so called anti-infective targets. Using an in silico data driven Systems Biology approach, our industrial collaborators, e- Therapeutics predicted pairs of genes from B. subtilis that could act as anti-infective targets when targeted together. This investigation was tasked with the development and testing of experimental models and approaches that could be used to validate these potential targets. In a separate collaboration with the Integrative Bioinformatics Group at Newcastle University, a functional interaction network model for B. subtilis- SubtilNet2, was generated and tested. Compiled from a range of experimental, bioinformatical and literature based sources, it represented all known functional interactions known to occur within B. subtilis. This network was applied to investigate the selection of the predicted targets, and determine any biological basis for the experimental results seen. A single predicted target acting by itself was confirmed to be successful. As a second component to this investigation, Systems Biology was used to complement traditional hypothesis driven research, specifically the possibility of directed targeting and channelling of substrates between two biosynthetic pathways. This was explored by studying the synthesis of carbamoyl phosphate (CP), an intermediate in both the arginine and uracil biosynthetic pathways. Typically, prokaryotes encode a single heterodimeric carbamoyl phosphate synthetase (CPS) that is used by both the arginine and pyrimidine biosynthetic pathways. B. subtilis and its close relatives are unique in encoding arginine- and uracil-specific copies of this enzyme. Moreover, the genes encoding the respective arginine (carA and carB) and uracil (pyrAA and pyrAB) specific CPSs are clustered with the other genes in their respective pathways (e.g. argC,J,B,D-carA,B-argF and pyrB,C,AA,AB,K,D,F,E) This degree of clustering is not found in bacteria with single CPSs. Experimental and SubtilNet2 analysis approaches were developed to express and individually test for the presence of any interaction between the subunits of each systems CPS’s, as well as to other components within associated gene clusters. The presence or absence of interaction would be used to determine if CP produced by one system could be shared with the opposite system. If it couldn’t, could the unusual cluster of genes seen to surround each CPS be used to encode a macromolecular complex structure with a single point of entry and exit to channel CP and other substrates within a biosynthetic system? A failure despite repeated attempts and strategies to produce soluble CPS subunits and other biosynthesis proteins, when expressed independently of one another, suggested a need for the presence of other members of each pathway. SubtilNet2 testing of these components and their functional associations didn’t identify any distinct groups or systems being supplied with system specific CP, however this is more likely to result from limitations of the associated approaches, rather than genuine a biological property.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The Policy Implications of Interactions Among Financial Aid Programs

Various gift-aid, loan, and work-study programs help college students fill the gap between educational costs and their financial resources. Previous research generally has examined the effects of a given program by itself. What is missing are studies that investigate interactions among programs, such as how state or university grants reinforce or offset the targeting policies that are embedded in the Pell program. This article draws on research conducted on colleges in Indiana to describe how federal, state, private, and college-based financial aid programs and practices interact with each other to determine the total amount of gift-aid a student receives. It discusses how these relationships can dilute or enhance a program\u27s implicit targeting policies. The lessons learned from this experience provide important insights for developing a fuller appreciation of how current and future gift-aid programs may affect each other

Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies

Age Factors; Anal human papillomavirus infection; SexualityFactores de edad; Infección anal por virus del papiloma humano; SexualidadFactors d'edat; Infecció anal pel virus del papil·loma humà; SexualitatBackground Robust age-specific estimates of anal human papillomavirus (HPV) and high-grade squamous intraepithelial lesions (HSIL) in men can inform anal cancer prevention efforts. We aimed to evaluate the age-specific prevalence of anal HPV, HSIL, and their combination, in men, stratified by HIV status and sexuality. Methods We did a systematic review for studies on anal HPV infection in men and a pooled analysis of individual-level data from eligible studies across four groups: HIV-positive men who have sex with men (MSM), HIV-negative MSM, HIV-positive men who have sex with women (MSW), and HIV-negative MSW. Studies were required to inform on type-specific HPV infection (at least HPV16), detected by use of a PCR-based test from anal swabs, HIV status, sexuality (MSM, including those who have sex with men only or also with women, or MSW), and age. Authors of eligible studies with a sample size of 200 participants or more were invited to share deidentified individual-level data on the above four variables. Authors of studies including 40 or more HIV-positive MSW or 40 or more men from Africa (irrespective of HIV status and sexuality) were also invited to share these data. Pooled estimates of anal high-risk HPV (HR-HPV, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68), and HSIL or worse (HSIL+), were compared by use of adjusted prevalence ratios (aPRs) from generalised linear models. Findings The systematic review identified 93 eligible studies, of which 64 contributed data on 29 900 men to the pooled analysis. Among HIV-negative MSW anal HPV16 prevalence was 1·8% (91 of 5190) and HR-HPV prevalence was 6·9% (345 of 5003); among HIV-positive MSW the prevalences were 8·7% (59 of 682) and 26·9% (179 of 666); among HIV-negative MSM they were 13·7% (1455 of 10 617) and 41·2% (3798 of 9215), and among HIV-positive MSM 28·5% (3819 of 13 411) and 74·3% (8765 of 11 803). In HIV-positive MSM, HPV16 prevalence was 5·6% (two of 36) among those age 15–18 years and 28·8% (141 of 490) among those age 23–24 years (ptrend=0·0091); prevalence was 31·7% (1057 of 3337) among those age 25–34 years and 22·8% (451 of 1979) among those age 55 and older (ptrend<0·0001). HPV16 prevalence in HIV-negative MSM was 6·7% (15 of 223) among those age 15–18 and 13·9% (166 of 1192) among those age 23–24 years (ptrend=0·0076); the prevalence plateaued thereafter (ptrend=0·72). Similar age-specific patterns were observed for HR-HPV. No significant differences for HPV16 or HR-HPV were found by age for either HIV-positive or HIV-negative MSW. HSIL+ detection ranged from 7·5% (12 of 160) to 54·5% (61 of 112) in HIV-positive MSM; after adjustment for heterogeneity, HIV was a significant predictor of HSIL+ (aPR 1·54, 95% CI 1·36–1·73), HPV16-positive HSIL+ (1·66, 1·36–2·03), and HSIL+ in HPV16-positive MSM (1·19, 1·04–1·37). Among HPV16-positive MSM, HSIL+ prevalence increased with age. Interpretation High anal HPV prevalence among young HIV-positive and HIV-negative MSM highlights the benefits of gender-neutral HPV vaccination before sexual activity over catch-up vaccination. HIV-positive MSM are a priority for anal cancer screening research and initiatives targeting HPV16-positive HSIL+.International Agency for Research on Cancer

Prior human polyomavirus and papillomavirus infection and incident lung cancer: a nested case–control study

Purpose—To test whether infection with select human polyomaviruses (HPyV) and human papillomaviruses (HPV) is associated with incident lung cancer. Methods—We performed a nested case-control study, testing serum from the Carotene and Retinol Efficacy Trial CARET), conducted 1985–2005, for antibodies to Merkel cell (MCV), KI (KIV), and WU (WUV) HPyVs as well as to six high-risk and two low-risk HPV types. Incident lung cancer cases (n=200) were frequency-matched with controls (n=200) on age, enrollment and blood draw dates, intervention arm assignment, and the number of serum freeze / thaw cycles. Sera were tested using multiplex liquid bead microarray antibody assays. We used logistic regression to assess the association between HPyV and HPV antibodies and lung cancer. Results—There was no evidence of a positive association between levels of MCV, KIV, or WUV antibodies and incident lung cancer (P-corrected>0.10 for all trend tests; odds ratio (OR) range 0.72 to 1.09, P-corrected>0.10 for all). There was also no evidence for a positive association between HPV 16 or 18 infection and incident lung cancer (P-corrected≥0.10 for all trend tests; OR range 0.25 to 2.54, P>0.05 for all OR>1), but the number of persons with serologic evidence of these infections was small. Conclusions—Prior infection with any of several types of HPyV or HPV was not associated with subsequent diagnosis of lung cancer. Infection with these viruses likely does not influence a person’s risk of lung cancer in Western smoking populations

Association Between Chronic Hepatitis C Virus Infection and Myocardial Infarction Among People Living With HIV in the United States.

Hepatitis C virus (HCV) infection is common among people living with human immunodeficiency virus (PLWH). Extrahepatic manifestations of HCV, including myocardial infarction (MI), are a topic of active research. MI is classified into types, predominantly atheroembolic type 1 MI (T1MI) and supply-demand mismatch type 2 MI (T2MI). We examined the association between HCV and MI among patients in the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems, a US multicenter clinical cohort of PLWH. MIs were centrally adjudicated and categorized by type using the Third Universal Definition of Myocardial Infarction. We estimated the association between chronic HCV (RNA+) and time to MI while adjusting for demographic characteristics, cardiovascular risk factors, clinical characteristics, and history of injecting drug use. Among 23,407 PLWH aged ≥18 years, there were 336 T1MIs and 330 T2MIs during a median of 4.7 years of follow-up between 1998 and 2016. HCV was associated with a 46% greater risk of T2MI (adjusted hazard ratio (aHR)&nbsp;=&nbsp;1.46, 95% confidence interval (CI): 1.09, 1.97) but not T1MI (aHR&nbsp;=&nbsp;0.87, 95% CI: 0.58, 1.29). In an exploratory cause-specific analysis of T2MI, HCV was associated with a 2-fold greater risk of T2MI attributed to sepsis (aHR&nbsp;=&nbsp;2.01, 95% CI: 1.25, 3.24). Extrahepatic manifestations of HCV in this high-risk population are an important area for continued research

Hypermethylation of CCND2 May Reflect a Smoking-Induced Precancerous Change in the Lung

It remains unknown whether tobacco smoke induces DNA hypermethylation as an early event in carcinogenesis or as a late event, specific to overt cancer tissue. Using MethyLight assays, we analyzed 316 lung tissue samples from 151 cancer-free subjects (121 ever-smokers and 30 never-smokers) for hypermethylation of 19 genes previously observed to be hypermethylated in nonsmall cell lung cancers. Only APC (39%), CCND2 (21%), CDH1 (7%), and RARB (4%) were hypermethylated in >2% of these cancer-free subjects. CCND2 was hypermethylated more frequently in ever-smokers (26%) than in never-smokers (3%). CCND2 hypermethylation was also associated with increased age and upper lobe sample location. APC was frequently hypermethylated in both ever-smokers (41%) and never-smokers (30%). BVES, CDH13, CDKN2A (p16), CDKN2B, DAPK1, IGFBP3, IGSF4, KCNH5, KCNH8, MGMT, OPCML, PCSK6, RASSF1, RUNX, and TMS1 were rarely hypermethylated (<2%) in all subjects. Hypermethylation of CCND2 may reflect a smoking-induced precancerous change in the lung