Quality of life of parents with children living at home: when one parent has cancer

Goals of work This study examined the quality of life (QoL) of cancer patients diagnosed 1-5 years previously and their spouses, with children 4-18 years living at home. Relationships between parents' QoL and the children's functioning were explored. Patients and methods 166 cancer patients and their spouses provided information on their QoL (RAND-36) and on their children's functioning (Child Behavior Checklist). Main results Male and female patients scored similarly to a norm population on five domains. Patients' QoL was clinically relevantly and/or statistically lower on social functioning, role limitations because of physical problems, and vitality than the norm. Male spouses' QoL was comparable to the norm. However, female spouses reported better physical functioning but more social problems. QoL varied according to type of cancer, treatment intensity, and recurrence. Using the QoL composite scores, a significant relationship was found between patients' psychosocial and physical functioning and spouses' psychosocial functioning. Patients' psychosocial functioning correlated moderately strongly to weakly with their reports of their younger children's and adolescents' functioning; physical functioning correlated only weakly with adolescents' functioning. The patients' functioning related weakly to moderately strongly to adolescents' self-reports of functioning. Spouses' psychosocial functioning weakly related to their and adolescents' reports of adolescents' functioning. Conclusion Cancer patients' QoL 1-5 years after diagnosis was decreased in three of eight domains; their spouses seem to be doing well. Parents' physical and psychosocial functioning related weakly to moderately strongly to their children's functioning, depending on the child's age and information source. The patients' functioning related more strongly to the children's functioning than the spouses' did

Construction of an ~700-kb transcript map around the Familial Mediterranean Fever locus on human chromosome 16p13.3

We used a combination of cDNA selection, exon amplification, and computational prediction from genomic sequence to isolate transcribed sequences from genomic DNA surrounding the familial Mediterranean fever (FMF) locus. Eighty-seven kb of genomic DNA around D16S3370, a marker showing a high degree of linkage disequilibrium with FMF, was sequenced to completion, and the sequence annotated. A transcript map reflecting the minimal number of genes encoded within the ∼700 kb of genomic DNA surrounding the FMF locus was assembled. This map consists of 27 genes with discreet messages detectable on Northerns, in addition to three olfactory-receptor genes, a cluster of 18 tRNA genes, and two putative transcriptional units that have typical intron–exon splice junctions yet do not detect messages on Northerns. Four of the transcripts are identical to genes described previously, seven have been independently identified by the French FMF Consortium, and the others are novel. Six related zinc-finger genes, a cluster of tRNAs, and three olfactory receptors account for the majority of transcribed sequences isolated from a 315-kb FMF central region (betweenD16S468/D16S3070 and cosmid 377A12). Interspersed among them are several genes that may be important in inflammation. This transcript map not only has permitted the identification of the FMF gene (MEFV), but also has provided us an opportunity to probe the structural and functional features of this region of chromosome 16.Michael Centola, Xiaoguang Chen, Raman Sood, Zuoming Deng, Ivona Aksentijevich, Trevor Blake, Darrell O. Ricke, Xiang Chen, Geryl Wood, Nurit Zaks, Neil Richards, David Krizman, Elizabeth Mansfield, Sinoula Apostolou, Jingmei Liu, Neta Shafran, Anil Vedula, Melanie Hamon, Andrea Cercek, Tanaz Kahan, Deborah Gumucio, David F. Callen, Robert I. Richards, Robert K. Moyzis, Norman A. Doggett, Francis S. Collins, P. Paul Liu, Nathan Fischel-Ghodsian and Daniel L. Kastne

Noncoding deletions reveal a gene that is critical for intestinal function.

Large-scale genome sequencing is poised to provide a substantial increase in the rate of discovery of disease-associated mutations, but the functional interpretation of such mutations remains challenging. Here we show that deletions of a sequence on human chromosome 16 that we term the intestine-critical region (ICR) cause intractable congenital diarrhoea in infants1,2. Reporter assays in transgenic mice show that the ICR contains a regulatory sequence that activates transcription during the development of the gastrointestinal system. Targeted deletion of the ICR in mice caused symptoms that recapitulated the human condition. Transcriptome analysis revealed that an unannotated open reading frame (Percc1) flanks the regulatory sequence, and the expression of this gene was lost in the developing gut of mice that lacked the ICR. Percc1-knockout mice displayed phenotypes similar to those observed upon ICR deletion in mice and patients, whereas an ICR-driven Percc1 transgene was sufficient to rescue the phenotypes found in mice that lacked the ICR. Together, our results identify a gene that is critical for intestinal function and underscore the need for targeted in vivo studies to interpret the growing number of clinical genetic findings that do not affect known protein-coding genes

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Synthesis and Applications of Dynamic Multivalent Nanostructures

This thesis focuses on the design, synthesis and development of dynamic multivalent nanostructures such as supramolecular dendrimers, liposomes and gold-functionalized nanostructures. These structures can be used for drug delivery and molecular sensing applications. This thesis is divided into three parts: In part one, a general introduction to self-assembly, dynamic systems, metalligand exchange, nanostructured dendritic scaffolds, liposomes and gold nanostructures is given. In part two, a microwave approach is presented as an efficient method for the regioselective deuteration of bipyridine scaffolds. Dynamic systems based on transition metal-bipyridine coordination complexes were investigated. The compositional self-adaptation and kinetics of these dynamic systems were successfully assessed by ESI-MS. Based on this amphiphilic dendrimers/metallodendrimers were also designed and synthesized via  a convergent strategy. Their ability to self-assemble into supramolecular assemblies and their controlled disassembly was effectively demonstrated. In part three, two types of drug delivery systems based on dynamic multivalent nanostructures of glycodendrimers/metalloglycodendrimers and drugpresenting liposomes were developed. The dynamic self-assembly of these architectures into supramolecular nanostructures with site-specific functionality through interacting carbohydrate or cholesterol moieties was assessed. The host-guest interaction/encapsulation and controlled release with external stimuli were studied using a fluorescent probe, as well as selected drug molecules. The antibacterial property of the drug delivery systems was also evaluated, demonstrating an enhanced bactericidal activity. A new, rapid and simple approach for the functionalization of plasmonic gold nanostructured surfaces was also developed. The optical performance and light-specific sensitivity of the fluorescent probe on the resulting nanostructures were also presented.QC 20151119</p

Influences on uptake of cancer screening in mental health service users: A qualitative study

Background: Cancers are a leading cause of death worldwide. People with mental illness are 30 % more likely to die from cancer than the general population. One reason for this may be low uptake of nationally offered cancer screening tests by people with mental illness. We aimed to identify barriers and facilitators for breast, cervical and bowel cancer screening uptake by people with mental illness in order to inform interventions to promote equal access. Methods: The interview study was conducted in both urban and rural settings. The study was informed by the Theoretical Domains Framework, using framework analysis and triangulation across participant groups. Participants included 45 mental health service users (service users) eligible for cancer screening, 29 mental health professionals and 11 professionals involved in cancer screening. Results: Themes emerging from the data that affected uptake included knowledge of screening programmes by both service users and healthcare providers; knowledge of, and attitudes towards, mental illness; health service-delivery factors; service users' beliefs and concerns about cancer screening, and practical issues. These are relevant to different stages of the screening process. Service users do not receive invitations to screening or cancer testing kits if they are admitted to hospital. They are not routinely invited for screening if they are not registered with a general practitioner (GP). Lack of integrated care means that mental health staff do not know if someone is overdue for a test and cancer screening is often not considered during health promotion. Barriers including information processing problems, the extent to which the screening process aggravates symptoms, poor staff client relationships and travel difficulties vary between individuals. Screening professionals are motivated to help, but may lack time or training to manage mental health needs. Reactive measures are available, but service users must request help which they may find difficult. Conclusions: There are specific barriers to cancer screening uptake for mental health service users that prevent equality of care. Interventions that can be personalised are needed at individual, policy and service-delivery levels. Primary and secondary care staff and policy-makers should work together to develop an integrated approach to cancer screening in this population. © 2016 The Author(s)

Additional file 2: Tables S1 to S3. of Influences on uptake of cancer screening in mental health service users: a qualitative study

Barriers and Facilitators by participant and screening type. Themes, barriers and facilitators identified in the sample of people living with a diagnosis of mental illness, in the sample of screening professionals and in the sample of mental health professionals. (DOCX 19 kb

Verification of cardiac tissue electrophysiology simulators using an N-version benchmark

Ongoing developments in cardiac modelling have resulted, in particular, in the development of advanced and increasingly complex computational frameworks for simulating cardiac tissue electrophysiology. The goal of these simulations is often to represent the detailed physiology and pathologies of the heart using codes that exploit the computational potential of high-performance computing architectures. These developments have rapidly progressed the simulation capacity of cardiac virtual physiological human style models; however, they have also made it increasingly challenging to verify that a given code provides a faithful representation of the purported governing equations and corresponding solution techniques. This study provides the first cardiac tissue electrophysiology simulation benchmark to allow these codes to be verified. The benchmark was successfully evaluated on 11 simulation platforms to generate a consensus gold-standard converged solution. The benchmark definition in combination with the gold-standard solution can now be used to verify new simulation codes and numerical methods in the future

Reducing Uncertainties About the Effects of Chemoradiotherapy for Cervical Cancer: A Systematic Review and Meta-Analysis of Individual Patient Data From 18 Randomized Trials

Background After a 1999 National Cancer Institute (NCI) clinical alert was issued, chemoradiotherapy has become widely used in treating women with cervical cancer. Two subsequent systematic reviews found that interpretation of the benefits was complicated, and some important clinical questions were unanswered. Patients and Methods We initiated a meta-analysis seeking updated individual patient data from all randomized trials to assess the effect of chemoradiotherapy on all outcomes. We prespecified analyses to investigate whether the effect of chemoradiotherapy differed by trial or patient characteristics. Results On the basis of 13 trials that compared chemoradiotherapy versus the same radiotherapy, there was a 6% improvement in 5-year survival with chemoradiotherapy (hazard ratio [HR] = 0.81, P <.001). A larger survival benefit was seen for the two trials in which chemotherapy was administered after chemoradiotherapy. There was a significant survival benefit for both the group of trials that used platinum-based (HR = 0.83, P = .017) and non-platinum-based (HR = 0.77, P <.009) chemoradiotherapy, but no evidence of a difference in the size of the benefit by radiotherapy or chemotherapy dose or scheduling was seen. Chemoradiotherapy also reduced local and distant recurrence and progression and improved disease-free survival. There was a suggestion of a difference in the size of the survival benefit with tumor stage, but not across other patient subgroups. Acute hematologic and GI toxicity was increased with chemoradiotherapy, but data were too sparse for an analysis of late toxicity. Conclusion These results endorse the recommendations of the NCI alert, but also demonstrate their applicability to all women and a benefit of non-platinum-based chemoradiotherapy. Furthermore, although these results suggest an additional benefit from adjuvant chemotherapy, this requires testing in randomized trials