How do patients want to learn of results of clinical trials? A survey of 1431 breast cancer patients

Questionnaires were circulated to UK patients and health care professionals (HCPs) participating in the Taxotere as Adjuvant ChemoTherapy (TACT) trial in autumn 2004 asking if and how trial results, when available, should be conveyed to patients. A total of 1431 (37% of surviving UK TACT patients) returned questionnaires. In all, 30 (2%) patients did not want results. In all, 554 (40%) patients preferred to receive them via their hospital; 664 (47%) preferred results posted directly to their home, 177 (13%) preferred a letter providing a telephone number to request results. Six hundred and twelve patients thought results should come directly from the trials office. One hundred and seventy-six HCPs from 89 UK centres (86%) returned questionnaires. In all, 169 out of 176 patients (96%) thought results should be written in lay terms for patients. Seventy (41%) preferred patients to receive results via their hospital; 64 (38%) preferred a letter providing a telephone number to request results, and 32 (19%) preferred results posted directly to patients. Thirty-one HCPs (18%) thought results to patients should come directly from the trials office. A total of 868 (61%) patients thought next of kin of deceased patients should receive results, 543 (38%) did not; 47 (27%) HCPs thought they should; 118 (68%) did not

Quanta of Space-Time and Axiomatization of Physics

We consider Hilbert's sixth problem on the axiomatization of physics starting with a higher degree Heisenberg commutation relation involving the Dirac operator and the Feynman slash of scalar fields. The two sided version of the commutation relation in dimension 4 implies volume quantization and determines a noncommutative space which is a tensor product of continuous and discrete spaces. This noncommutative space predicts the full structure of a unified model of all particle interactions based on Pati-Salam symmetries or, as a special case, the Standard Model. We study implications of this quantization condition on Particle Physics, General Relativity, the cosmological constant and dark matter. We demonstrate that, with little input, noncommutative geometry gives a compelling and attractive picture about the nature and structure of space-time.Comment: 47 pages. Contribution to the special issue of IJGMMP celebrating the one century anniversary of the program announced in 1916 by Hilbert entitled " Foundations of Mathematics and Physics", editors, Joseph Kouneiher, John Stachel and Salvatore Capozzieol

Knowledge and perceptions of Alzheimer’s disease in three ethnic groups of younger adults in the United Kingdom

Background: Alzheimer’s disease (AD) is a global public health problem with an ageing population. Knowledge is essential to promote early awareness, diagnosis and treatment of AD symptoms. AD knowledge is influenced by many cultural factors including cultural beliefs, attitudes and language barriers. This study aims: (1) to define AD knowledge level and perceptions amongst adults between 18 and 49 years of age in the UK; (2) to compare knowledge and perceptions of AD among three main ethnic groups (Asian, Blacks, and Whites); and (3) to assess potential associations of age, gender, education level, affinity with older people (65 or over), family history and caregiving history with AD knowledge. Methods: Data was collected from 186 participants as a convenience sample of younger adults of three different ethnicities (16.1% Asian, 16.7% Black, 67.2% White), living in the UK, recruited via an online research platform. The majority of the participants were in the 18–34 years age group (87.6%). Demographic characteristics of participants and AD knowledge correlation were assessed by the 30-item Alzheimer’s Disease Knowledge Scale (ADKS), comprising 7 content domains. ANOVA/ANCOVA were used to assess differences in AD knowledge by ethnicity, gender, education level, age and affinity with dementia and Alzheimer’s patients. Results: For AD general knowledge across all respondents only 45.0% answers were correct. No significant differences were found for the total ADKS score between ethnicities in this younger age group, who did not differ in education level. However, there were significant knowledge differences for the ADKS symptom domain score even after controlling for other demographics variables such as gender, education level (p = 0.005). White respondents were more likely to know about AD symptoms than their Black counterparts (p = 0.026). Conclusion: The study’s findings suggest that the AD knowledge level is not adequate for all ethnic groups. Meanwhile, significant differences were observed in symptoms, between ethnic groups, and therefore, differ in their needs regards health communication. The study contributes to an understanding of ethnicity differences in AD knowledge amongst adults from 18 to 49 years of age in the UK and may also provide input into an intervention plan for different ethnicities’ information needs

Sexing Viking Age horses from burial and non-burial sites in Iceland using ancient DNA

© 2018 The Authors Horses are the most common grave goods found in Icelandic Viking Age graves. Horse skeletons have previously been sexed based on pelvis shape and the presence of canine teeth in male horses over 4–5 years of age. Morphological data has shown that all horses from Icelandic burials that were amenable to sexing were male. Yet the use of morphological methods to determine sex is problematic since they rely on finding a well-preserved pelvis and/or robust canine teeth. Furthermore, quantitative data underlying the features of the horse pelvis used for sexing is lacking and canine teeth have been reported to occur in mares. In this study we build upon and extend recently developed methodologies to make use of shotgun sequencing of ancient DNA (aDNA) for molecular sexing of Viking Age horse remains. With minimal sequencing effort we identified the sex of the largest collection (n = 22) of Viking Age Icelandic horses studied to date, sourced from both burial (n = 19) and non-burial (n = 3) sites. Our results revealed a male to female sex bias ratio of 18:1 in burial sites, versus 0:3 in non-burial sites. These findings support the significant over-representation of male horses in Viking Age graves in Iceland, yet show that –albeit rare– mares could also be selected for ritual burial in Viking Age Iceland. This cost-effective method provides statistical confidence to allow for sexing of highly fragmented archaeological specimens with low endogenous DNA content

The promoter polymorphism -232C/G of the PCK1 gene is associated with type 2 diabetes in a UK-resident South Asian population

Background: The PCK1 gene, encoding cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C), has previously been implicated as a candidate gene for type 2 diabetes (T2D) susceptibility. Rodent models demonstrate that over-expression of Pck1 can result in T2D development and a single nucleotide polymorphism (SNP) in the promoter region of human PCK1 (-232C/G) has exhibited significant association with the disease in several cohorts. Within the UK-resident South Asian population, T2D is 4 to 6 times more common than in indigenous white Caucasians. Despite this, few studies have reported on the genetic susceptibility to T2D in this ethnic group and none of these has investigated the possible effect of PCK1 variants. We therefore aimed to investigate the association between common variants of the PCK1 gene and T2D in a UK-resident South Asian population of Punjabi ancestry, originating predominantly from the Mirpur area of Azad Kashmir, Pakistan. \ud \ud Methods: We used TaqMan assays to genotype five tagSNPs covering the PCK1 gene, including the -232C/G variant, in 903 subjects with T2D and 471 normoglycaemic controls. \ud \ud Results: Of the variants studied, only the minor allele (G) of the -232C/G SNP demonstrated a significant association with T2D, displaying an OR of 1.21 (95% CI: 1.03 - 1.42, p = 0.019). \ud \ud Conclusion: This study is the first to investigate the association between variants of the PCK1 gene and T2D in South Asians. Our results suggest that the -232C/G promoter polymorphism confers susceptibility to T2D in this ethnic group. \ud \ud Trial registration: UKADS Trial Registration: ISRCTN38297969

Common variants of the TCF7L2 gene are associated with increased risk of type 2 diabetes mellitus in a UK-resident South Asian population

Background Recent studies have implicated variants of the transcription factor 7-like 2 (TCF7L2) gene in genetic susceptibility to type 2 diabetes mellitus in several different populations. The aim of this study was to determine whether variants of this gene are also risk factors for type 2 diabetes development in a UK-resident South Asian cohort of Punjabi ancestry. Methods We genotyped four single nucleotide polymorphisms (SNPs) of TCF7L2 (rs7901695, rs7903146, rs11196205 and rs12255372) in 831 subjects with diabetes and 437 control subjects. Results The minor allele of each variant was significantly associated with type 2 diabetes; the greatest risk of developing the disease was conferred by rs7903146, with an allelic odds ratio (OR) of 1.31 (95% CI: 1.11 – 1.56, p = 1.96 × 10-3). For each variant, disease risk associated with homozygosity for the minor allele was greater than that for heterozygotes, with the exception of rs12255372. To determine the effect on the observed associations of including young control subjects in our data set, we reanalysed the data using subsets of the control group defined by different minimum age thresholds. Increasing the minimum age of our control subjects resulted in a corresponding increase in OR for all variants of the gene (p ≤ 1.04 × 10-7). Conclusion Our results support recent findings that TCF7L2 is an important genetic risk factor for the development of type 2 diabetes in multiple ethnic groups

Achieving sustainable quality in maternity services – using audit of incontinence and dyspareunia to identify shortfalls in meeting standards

BACKGROUND: Some complications of childbirth (for example, faecal incontinence) are a source of social embarrassment for women, and are often under reported. Therefore, it was felt important to determine levels of complications (against established standards) and to consider obstetric measures aimed at reducing them. METHODS: Clinical information was collected on 1036 primiparous women delivering at North and South Staffordshire Acute and Community Trusts over a 5-month period in 1997. A questionnaire was sent to 970 women which included self-assessment of levels of incontinence and dyspareunia prior to pregnancy, at 6 weeks post delivery and 9 to 14 months post delivery. RESULTS: The response rate was 48%(470/970). Relatively high levels of obstetric interventions were found. In addition, the rates of instrumental deliveries differed between the two hospitals. The highest rates of postnatal symptoms had occurred at 6 weeks, but for many women problems were still present at the time of the survey. At 9–14 months high rates of dyspareunia (29%(102/347)) and urinary incontinence (35%(133/382)) were reported. Seventeen women (4%) complained of faecal incontinence at this time. Similar rates of urinary incontinence and dyspareunia were seen regardless of mode of delivery. CONCLUSION: Further work should be undertaken to reduce the obstetric interventions, especially instrumental deliveries. Improvements in a number of areas of care should be undertaken, including improved patient information, improved professional communication and improved professional recognition and management of third degree tears. It is likely that these measures would lead to a reduction in incontinence and dyspareunia after childbirth

Analysis of IL2/IL21 Gene Variants in Cholestatic Liver Diseases Reveals an Association with Primary Sclerosing Cholangitis

Background/Aims: The chromosome 4q27 region harboring IL2 and IL21 is an established risk locus for ulcerative colitis (UC) and various other autoimmune diseases. Considering the strong coincidence of primary sclerosing cholangitis (PSC) with UC and the increased frequency of other autoimmune disorders in patients with primary biliary cirrhosis (PBC), we investigated whether genetic variation in the IL2/IL21 region may also modulate the susceptibility to these two rare cholestatic liver diseases. Methods: Four strongly UC-associated single nucleotide polymorphisms (SNPs) within the KIAA1109/TENR/IL2/IL21 linkage disequilibrium block were genotyped in 124 PBC and 41 PSC patients. Control allele frequencies from 1,487 healthy, unrelated Caucasians were available from a previous UC association study. Results: The minor alleles of all four markers were associated with a decreased susceptibility to PSC (rs13151961: p = 0.013, odds ratio (OR) 0.34; rs13119723: p = 0.023, OR 0.40; rs6822844: p = 0.031, OR 0.41; rs6840978: p = 0.043, OR 0.46). Moreover, a haplotype consisting of the four minor alleles also had a protective effect on PSC susceptibility (p = 0.0084, OR 0.28). A haplotype of the four major alleles was independently associated with PSC when excluding the patients with concomitant inflammatory bowel disease (p = 0.033, OR 4.18). Conclusion: The IL2/IL21 region may be one of the highly suggestive but so far rarely identified shared susceptibility loci for PSC and UC. Copyright (C) 2011 S. Karger AG, Base

Benznidazole biotransformation and multiple targets in <i>Trypanosoma</i> cruzi revealed by metabolomics

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The first line treatment for Chagas disease, a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, involves administration of benznidazole (Bzn). Bzn is a 2-nitroimidazole pro-drug which requires nitroreduction to become active, although its mode of action is not fully understood. In the present work we used a non-targeted MS-based metabolomics approach to study the metabolic response of T. cruzi to Bzn.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methodology/Principal findings&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Parasites treated with Bzn were minimally altered compared to untreated trypanosomes, although the redox active thiols trypanothione, homotrypanothione and cysteine were significantly diminished in abundance post-treatment. In addition, multiple Bzn-derived metabolites were detected after treatment. These metabolites included reduction products, fragments and covalent adducts of reduced Bzn linked to each of the major low molecular weight thiols: trypanothione, glutathione, γ-glutamylcysteine, glutathionylspermidine, cysteine and ovothiol A. Bzn products known to be generated in vitro by the unusual trypanosomal nitroreductase, TcNTRI, were found within the parasites, but low molecular weight adducts of glyoxal, a proposed toxic end-product of NTRI Bzn metabolism, were not detected.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions/significance&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Our data is indicative of a major role of the thiol binding capacity of Bzn reduction products in the mechanism of Bzn toxicity against T. cruzi

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD