Mapping and phasing of structural variation in patient genomes using nanopore sequencing

Despite improvements in genomics technology, the detection of structural variants (SVs) from short-read sequencing still poses challenges, particularly for complex variation. Here we analyse the genomes of two patients with congenital abnormalities using the MinION nanopore sequencer and a novel computational pipeline—NanoSV. We demonstrate that nanopore long reads are superior to short reads with regard to detection of de novo chromothripsis rearrangements. The long reads also enable efficient phasing of genetic variations, which we leveraged to determine the parental origin of all de novo chromothripsis breakpoints and to resolve the structure of these complex rearrangements. Additionally, genome-wide surveillance of inherited SVs reveals novel variants, missed in short-read data sets, a large proportion of which are retrotransposon insertions. We provide a first exploration of patient genome sequencing with a nanopore sequencer and demonstrate the value of long-read sequencing in mapping and phasing of SVs for both clinical and research applications

Recognition of depression in people of different cultures: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Many minority group patients who attend primary health care are depressed. To identify a depressive state when GPs see patients from other cultures than their own can be difficult because of cultural and gender differences in expressions and problems of communication. The aim of this study was to explore and analyse how GPs think and deliberate when seeing and treating patients from foreign countries who display potential depressive features.</p> <p>Methods</p> <p>The data were collected in focus groups and through individual interviews with GPs in northern Sweden and analysed by qualitative content analysis.</p> <p>Results</p> <p>In the analysis three themes, based on various categories, emerged; "Realizing the background", "Struggling for clarity" and "Optimizing management". Patients' early life events of importance were often unknown which blurred the accuracy. Reactions to trauma, cultural frictions and conflicts between the new and old gender norms made the diagnostic process difficult. The patient-doctor encounter comprised misconceptions, and social roles in the meetings were sometimes confused. GPs based their judgement mainly on clinical intuition and the established classification of depressive disorders was discussed. Tools for management and adequate action were diffuse.</p> <p>Conclusion</p> <p>Dialogue about patients' illness narratives and social context are crucial. There is a need for tools for multicultural, general practice care in the depressive spectrum. It is also essential to be aware of GPs' own conceptions in order to avoid stereotypes and not to under- or overestimate the occurrence of depressive symptoms</p

Patients' preferences for involvement in treatment decision making in Japan

BACKGROUND: A number of previous studies have suggested that the Japanese have few opportunities to participate in medical decision-making, as a result both of entrenched physician paternalism and national characteristics of dependency and passivity. The hypothesis that Japanese patients would wish to participate in treatment decision-making if adequate information were provided, and the decision to be made was clearly identified, was tested by interview survey. METHODS: The subjects were diabetic patients at a single outpatient clinic in Kyoto. One of three case study vignettes (pneumonia, gangrene or cancer) was randomly assigned to each subject and, employing face-to-face interviews, the subjects were asked what their wishes would be as patients, for treatment information, participation in decision-making and family involvement. RESULTS: 134 patients participated in the study, representing a response rate of 90%. The overall proportions of respondents who preferred active, collaborative, and passive roles were 12%, 71%, and 17%, respectively. Respondents to the cancer vignette were less likely to prefer an active role and were more likely to prefer family involvement in decision-making compared to non-cancer vignette respondents. If a physician's recommendation conflicted with their own wishes, 60% of the respondents for each vignette answered that they would choose to respect the physician's opinion, while few respondents would give the family's preference primary importance. CONCLUSIONS: Our study suggested that a majority of Japanese patients have positive attitudes towards participation in medical decision making if they are fully informed. Physicians will give greater patient satisfaction if they respond to the desire of patients for participation in decision-making

Measuring the impact and distress of osteoarthritis from the patients' perspective

<p>Abstract</p> <p>Background</p> <p>To assess the internal construct validity of the Perceived Impact of Problem Profile (PIPP), a patient based outcome measure based on the International Classification of Functioning, Disability and Health (ICF), which assesses impact and distress, in an osteoarthritis (OA) cohort.</p> <p>Methods</p> <p>A questionnaire comprising the 23-item PIPP, which assesses five domains (mobility, participation, self care, psychological well being and relationships), the Western Ontario McMasters University Osteoarthritis Index (WOMAC), the General Well-Being Index (GWBI), and the Hospital Anxiety and Depression Scale (HADS) was posted to people with clinician diagnosed OA. Assessment of the internal construct validity of the PIPP was undertaken using Rasch analysis performed with RUMM2020 software and concurrent validity through comparator measures.</p> <p>Results</p> <p>Two hundred and fifty-nine participants with OA responded. Analysis of the five individual domains of the PIPP indicated that there was good fit to the Rasch model, with high person separation reliability. One item required removal from the Mobility subscale and the Participation subscale. There were strong correlations between the PIPP Mobility scores and the WOMAC disability and pain subscales (rho = .73 and rho = .68), and between the PIPP Psychological well-being and HADS Depression (rho = .71) and GWBI (rho = -.69). High inter-correlations between the impact and distress subscales for each domain (range rho = .85 to .96), suggested redundancy of the latter.</p> <p>Conclusion</p> <p>This study demonstrates that the PIPP has good psychometric properties in an OA population. The PIPP, using just the impact subscales, provides a brief, reliable and valid means of assessing the impact of OA from the individual's perspective and operationalizing the bio-psychosocial model by the application of a single multi-domain questionnaire.</p

Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Correction Volume: 10, Article Number: 2068 DOI: 10.1038/s41467-019-10160-w WOS:000466339700001General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P <5 x 10(-8)) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.Peer reviewe