Facilitators and barriers to co-research by people with dementia and academic researchers: findings from a qualitative study

Background Public and patient involvement (PPI) is now established in dementia research. Barriers and facilitators to engagement from family carers and people in early stages of dementia have been explored. However, specific barriers and facilitators to co‐research with people with dementia have not previously been investigated. Objective To discover the facilitators of, and barriers to, involving people with dementia as co‐researchers, from the perspectives of people with dementia, gatekeepers (family caregivers, ethics committee members, service providers) and researchers. Design Thematic analysis of data from individual interviews about the co‐research experience. Results Four themes emerged from interviews with 19 participants (five people with dementia): “getting one's head round it” (assumptions about research and dementia; different forms of language); practicalities (eg transport; accessibility of communication); “this feeling of safety” (perceptions of danger, protectiveness and opportunities for building trust); and motivations (“making a difference” and “keeping doing”). Conclusions Findings both replicate and extend previous knowledge on PPI in dementia. Cognitive capacity of potential co‐researchers with dementia is only a part of the picture, with attitudes and expectations of researchers, gatekeepers and people with dementia also forming barriers. Researcher education, adequate resourcing, and both creativity and flexibility are needed to support recruitment of co‐researchers with dementia and to enable meaningful co‐research

Association of Rare Coding Mutations With Alzheimer Disease and Other Dementias Among Adults of European Ancestry

IMPORTANCE Some of the unexplained heritability of Alzheimer disease (AD) may be due to rare variants whose effects are not captured in genome-wide association studies because very large samples are needed to observe statistically significant associations. OBJECTIVE To identify genetic variants associated with AD risk using a nonstatistical approach. DESIGN, SETTING, AND PARTICIPANTS Genetic association study in which rare variants were identified by whole-exome sequencing in unrelated individuals of European ancestry from the Alzheimer’s Disease Sequencing Project (ADSP). Data were analyzed between March 2017 and September 2018. MAIN OUTCOMES AND MEASURES Minor alleles genome-wide and in 95 genes previously associated with AD, AD-related traits, or other dementias were tabulated and filtered for predicted functional impact and occurrence in participants with AD but not controls. Support for several findings was sought in a whole-exome sequencing data set comprising 19 affected relative pairs from Utah high-risk pedigrees and whole-genome sequencing data sets from the ADSP and Alzheimer’s Disease Neuroimaging Initiative. RESULTS Among 5617 participants with AD (3202 [57.0%] women; mean [SD] age, 76.4 [9.3] years) and 4594 controls (2719 [59.0%] women; mean [SD] age, 86.5 [4.5] years), a total of 24 variants with moderate or high functional impact from 19 genes were observed in 10 or more participants with AD but not in controls. These variants included a missense mutation (rs149307620 [p.A284T], n = 10) in NOTCH3, a gene in which coding mutations are associated with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), that was also identified in 1 participant with AD and 1 participant with mild cognitive impairment in the whole genome sequencing data sets. Four participants with AD carried the TREM2 rs104894002 (p.Q33X) high-impact mutation that, in homozygous form, causes Nasu-Hakola disease, a rare disorder characterized by early-onset dementia and multifocal bone cysts, suggesting an intermediate inheritance model for the mutation. Compared with controls, participants with AD had a significantly higher burden of deleterious rare coding variants in dementia-associated genes (2314 vs 3354 cumulative variants, respectively; P = .006). CONCLUSIONS AND RELEVANCE Different mutations in the same gene or variable dose of a mutation may be associated with result in distinct dementias. These findings suggest that minor differences in the structure or amount of protein may be associated with in different clinical outcomes. Understanding these genotype-phenotype associations may provide further insight into the pathogenic nature of the mutations, as well as offer clues for developing new therapeutic targets

Combined adenocarcinoid and mucinous cystadenoma of the appendix: a case report

<p>Abstract</p> <p>Introduction</p> <p>Adenocarcinoid of the appendix is a rare malignant tumour with features of both adenocarcinoma and carcinoid, showing both epithelial and endocrine differentiation. Mucinous cystadenoma is the commonest of the benign neoplasms of the appendix, with an incidence of 0.6% in appendicectomy specimens. We report a rare combination of these tumours and discuss the latest treatment options. To the best of our knowledge, only six cases have been reported in the literature to date.</p> <p>Case presentation</p> <p>A 71-year-old Caucasian man presented to our department with a right iliac fossa mass associated with pain. Laparoscopy revealed an adenocarcinoid of the appendix in combination with mucinous cystadenoma. He underwent a radical right hemicolectomy with clear margins and lymph nodes.</p> <p>Conclusion</p> <p>Adenocarcinoids account for 2% of primary appendiceal malignancies. Most tumours are less than 2 cm in diameter and 20% of them metastasize to the ovaries. The mean age for presentation is 59 years and the 5-year survival rate ranges from 60% to 84%. Right hemicolectomy is generally advised if any of the following features are present: tumours greater than 2 cm, involvement of resection margins, greater than 2 mitoses/10 high-power fields on histology, extension of tumour beyond serosa. Chemotherapy mostly with 5-Fluorouracil and Leucovorin is advised for remnant disease after surgery. Cytoreductive surgery with intraperitoneal chemotherapy can offer improved survival for advanced peritoneal dissemination.</p

'I'm sure we made it a better study…': Experiences of adults with intellectual disabilities and parent carers of patient and public involvement in a health research study.

Patient and public involvement is considered integral to health research in the United Kingdom; however, studies documenting the involvement of adults with intellectual disabilities and parent carers in health research studies are scarce. Through group interviews, this study explored the perspectives and experiences of a group of adults with intellectual disabilities and a group of parent carers about their collaborative/participatory involvement in a 3-year study which explored the effectiveness of annual health checks for adults with intellectual disabilities. Thematic analysis identified five key themes consistent across both groups; authenticity of participation, working together, generating new outcome measures, dissemination of findings and involvement in future research. Although reported anecdotally rather than originating from the analysis, increased self-confidence is also discussed. The groups' unique perspectives led to insights not previously considered by the research team which led to important recommendations to inform healthcare practice

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P &lt; 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms

System Size and Energy Dependence of Jet-Induced Hadron Pair Correlation Shapes in Cu+Cu and Au+Au Collisions at sqrt(s_NN) = 200 and 62.4 GeV

We present azimuthal angle correlations of intermediate transverse momentum (1-4 GeV/c) hadrons from {dijets} in Cu+Cu and Au+Au collisions at sqrt(s_NN) = 62.4 and 200 GeV. The away-side dijet induced azimuthal correlation is broadened, non-Gaussian, and peaked away from \Delta\phi=\pi in central and semi-central collisions in all the systems. The broadening and peak location are found to depend upon the number of participants in the collision, but not on the collision energy or beam nuclei. These results are consistent with sound or shock wave models, but pose challenges to Cherenkov gluon radiation models.Comment: 464 authors from 60 institutions, 6 pages, 3 figures, 2 tables. Submitted to Physical Review Letters. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Transverse momentum and centrality dependence of dihadron correlations in Au+Au collisions at sqrt(s_NN)=200 GeV: Jet-quenching and the response of partonic matter

Azimuthal angle \Delta\phi correlations are presented for charged hadrons from dijets for 0.4 < p_T < 10 GeV/c in Au+Au collisions at sqrt(s_NN) = 200 GeV. With increasing p_T, the away-side distribution evolves from a broad to a concave shape, then to a convex shape. Comparisons to p+p data suggest that the away-side can be divided into a partially suppressed "head" region centered at Delta\phi ~ \pi, and an enhanced "shoulder" region centered at Delta\phi ~ \pi +/- 1.1. The p_T spectrum for the "head" region softens toward central collisions, consistent with the onset of jet quenching. The spectral slope for the "shoulder" region is independent of centrality and trigger p_T, which offers constraints on energy transport mechanisms and suggests that the "shoulder" region contains the medium response to energetic jets.Comment: 420 authors from 58 institutions, 6 pages, 4 figures. Submitted to Physical Review Letters. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Azimuthal Angle Correlations for Rapidity Separated Hadron Pairs in d+Au Collisions at sqrt(s_NN) = 200 GeV

We report on two-particle azimuthal angle correlations between charged hadrons at forward/backward (deuteron/gold going direction) rapidity and charged hadrons at mid-rapidity in deuteron-gold (d+Au) and proton-proton (p+p) collisions at sqrt(s_NN) = 200 GeV. Jet structures are observed in the correlations which we quantify in terms of the conditional yield and angular width of away side partners. The kinematic region studied here samples partons in the gold nucleus carrying nucleon momentum fraction x~0.1 to x~0.01. Within this range, we find no x dependence of the jet structure in d+Au collisions.Comment: 330 authors, 6 pages text, 4 figures, no tables. Submitted to Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Cross sections and double-helicity asymmetries of midrapidity inclusive charged hadrons in p+p collisions at sqrt(s)=62.4 GeV

Unpolarized cross sections and double-helicity asymmetries of single-inclusive positive and negative charged hadrons at midrapidity from p+p collisions at sqrt(s)=62.4 GeV are presented. The PHENIX measurements for 1.0 < p_T < 4.5 GeV/c are consistent with perturbative QCD calculations at next-to-leading order in the strong coupling constant, alpha_s. Resummed pQCD calculations including terms with next-to-leading-log accuracy, yielding reduced theoretical uncertainties, also agree with the data. The double-helicity asymmetry, sensitive at leading order to the gluon polarization in a momentum-fraction range of 0.05 ~< x_gluon ~< 0.2, is consistent with recent global parameterizations disfavoring large gluon polarization.Comment: PHENIX Collaboration. 447 authors, 12 pages, 5 figures, 5 tables. Submitted to Physical Review

Dilepton mass spectra in p+p collisions at sqrt(s)= 200 GeV and the contribution from open charm

The PHENIX experiement has measured the electron-positron pair mass spectrum from 0 to 8 GeV/c^2 in p+p collisions at sqrt(s)=200 GeV. The contributions from light meson decays to e^+e^- pairs have been determined based on measurements of hadron production cross sections by PHENIX. They account for nearly all e^+e^- pairs in the mass region below 1 GeV/c^2. The e^+e^- pair yield remaining after subtracting these contributions is dominated by semileptonic decays of charmed hadrons correlated through flavor conservation. Using the spectral shape predicted by PYTHIA, we estimate the charm production cross section to be 544 +/- 39(stat) +/- 142(syst) +/- 200(model) \mu b, which is consistent with QCD calculations and measurements of single leptons by PHENIX.Comment: 375 authors from 57 institutions, 18 pages, 4 figures, 2 tables. Submitted to Physics Letters B. v2 fixes technical errors in matching authors to institutions. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm