RICHARD Project: Regional ICT based Clusters for Healthcare Applications and R&D Integration.

The use of Information Communication Technologies (ICT), in particular telehealth, can be clinically effective for the treatment and management of individuals with a number of long-term conditions (McClean et al, 2011). However, the integration of scalable telehealth technologies and interventions into clinical practice has been slow to develop; due in part to a lack of regional organisational models that facilitate the reorganisation of health provisions. In order to meet the challenges of switching from an application based model of care to a comprehensive and sustainable chronic care model the RICHARD Project has been developed. The Regional ICT based Clusters for Healthcare Applications and R&D Integration (RICHARD) is a € 2, 750. 000 European Commission Seventh Framework Programme, Regions of Knowledge Health, funded partnership between 15 partners involving industry, academia, the health service and local government across 4 European clusters; Italy, United Kingdom (UK), Sweden and Poland. Aims and objectives: The consortium aims are to enhance and promote the study of new or promising European territorial clinical models of ICT-based in the field of home care applied to the management of chronic conditions. To this end a number of work packages were proposed including (WP1) Project management, (WP2) SWOT analysis of regional ICT models for the delivery of care in chronic pathologies, (WP3) the development of a Joint Action Plan (JAP), (WP4) Measures towards the implementation of the JAP, (WP5) Mentoring activities and (WP6) Dissemination and communication. Results: A strong coordination of research resources and innovation stakeholders has been clearly identified. A JAP has been developed inspired by medium-long term vision that looks at e-health services into perspective of economic growth for the European regions along the principles of open competition for better and pan-European healthcare services. United Kingdom partners have taken the lead on (WP4) 'Measures towards the implementation of the JAP'. The work package comprises the organisation of a number of regional healthcare manager study tours on ICT applications and multiple research brokerage workshops; the latter has been developed with the purpose of creating networks and stimulating collaboration, resulting in developed research applications for regional, national and international bids. Finally, to further develop and raise the profile of less advanced regions involved in the project a series of mentoring activities are underway. A significant output from the project is the Ready, Steady, Go toolkit for telehealth deployment at scale http://www.richardproject.eu/richard/publications.html Conclusions: On a national level the RICHARD project builds on the 3millionlives initiative (2012) and provides an excellent example of how industry, health and social care can work with the academic community to the benefit of both the health and wealth of a region

Smart clothing for falls protection and detection: User-centred co-design and feasibility study

The prevalence and impact of hip fractures on the health and wealth of nations is a global problem and source of health inequalities. This paper reports on the co-design and feasibility testing of a new range of protective, smart clothing. The feasibility of research in a population of older adults in supported living is explored, as are the conceptualisation and measurement of adherence

Qualitative exploration of the potential for adverse events when using an online peer support network for mental health: Cross-sectional survey

Background: Online peer support networks are a growing area of mental health support for offering social connection, identity, and support. However, it has been reported that not all individuals have a positive experience on such networks. The potential for adverse events within a moderated online peer support network is a new area of research exploration. Objective: The objective of the study was to determine if use of an online moderated peer networks leads to adverse events for users. Methods: Four biannual online surveys (October 2014 to March 2016) were conducted by a large national UK mental health charity, with users of their online peer support network exploring personal safety, moderation, experiences on the site, and how the site could be improved. Data were analyzed using thematic analysis by 2 independent researchers using a priori themes: negative experiences of moderation, social exclusion, contagion, negative interactions with other users, online relationships, co-rumination and collusion, and other. Results: In total, 2353 survey responses were logged with 197 (8.37%) documenting an adverse event of negative experience. A dominant theme of negative experiences of moderation emerged (73/197, 37.1%) with evidence of social exclusion (50/197, 25.4%). Reading user posts was shown to be a cause of worry and distress for a few users, and analysis highlighted several instances of depressogenic and emotional contagion as well as some limited evidence of behavioral contagion (46/197, 23.4%). Very limited evidence of co-rumination (1/197, 0.5%) and no evidence of collusion were identified. Conclusions: Evidence of adverse events was identified at low levels in the sample of respondents, although we have no comparison data to indicate if levels are low compared with comparable platforms. Not all users of online peer support networks find them wholly beneficial. Research must explore what works for whom. The next stage of service development should consider which users may be likely to receive no benefit, or even deteriorate, as a result of using the service

A cohort study of post-weaning multisystemic wasting syndrome and PCV2 in 178 pigs from birth to 14 weeks on a single farm in England

Our hypothesis was that pigs that develop post-weaning multisystemic wasting syndrome (PMWS) are detectable from an early age with signs of weight loss and other clinical and serological abnormalities. Therefore, the objective of this study was to investigate the temporally varying and fixed events linked with the clinical incidence of PMWS by comparing affected and unaffected pigs in a cohort of 178 male piglets. Piglets were enrolled at birth and examined each week. Samples of blood were collected at regular intervals. The exposures measured were porcine circovirus type 2 (PCV2) antibody titres in all 178 and PCV2 antigen in a subset of 75 piglets. We also observed piglet health and measured their weight, and a post-mortem examination was performed by an external laboratory on all pigs between 6 and 14 weeks of age that died. From the cohort, 14 (8%) pigs died from PMWS and 4% from other causes. A further 37 pigs between 6 and 14 weeks of age died from PMWS (30) and ileitis and other causes (7). PMWS was only apparent in pigs from 1 to 2 weeks before death when they wasted rapidly. There were no other characteristic clinical signs and no obvious gross clinical lesions post-mortem. There was no strong link with PCV2 antibody throughout life but PCV2 antigen level was higher from 4 to 6 weeks of age in pigs that died from PMWS compared with pigs that died from other causes

Recovered memories, satanic abuse, Dissociative Identity Disorder and false memories in the UK: a survey of Clinical Psychologists and Hypnotherapists

An online survey was conducted to examine psychological therapists’ experiences of, and beliefs about, cases of recovered memory, satanic / ritualistic abuse, Multiple Personality Disorder / Dissociative Identity Disorder, and false memory. Chartered Clinical Psychologists (n=183) and Hypnotherapists (n=119) responded. In terms of their experiences, Chartered Clinical Psychologists reported seeing more cases of satanic / ritualistic abuse compared to Hypnotherapists who, in turn, reported encountering more cases of childhood sexual abuse recovered for the first time in therapy, and more cases of suspected false memory. Chartered Clinical Psychologists were more likely to rate the essential accuracy of reports of satanic / ritualistic abuse as higher than Hypnotherapists. Belief in the accuracy of satanic / ritualistic abuse and Multiple Personality Disorder / Dissociative Identity Disorder reports correlated negatively with the belief that false memories were possible

Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry.

Purpose: Type 2 diabetes (T2D) has been reported to be associated with an elevated risk of breast cancer. It is unclear, however, whether this association is due to shared genetic factors. Methods: We constructed a genetic risk score (GRS) using risk variants from 33 known independent T2D susceptibility loci and evaluated its relation to breast cancer risk using the data from two consortia, including 62,328 breast cancer patients and 83,817 controls of European ancestry. Unconditional logistic regression models were used to derive adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) to measure the association of breast cancer risk with T2D GRS or T2D-associated genetic risk variants. Meta-analyses were conducted to obtain summary ORs across all studies. Results: The T2D GRS was not found to be associated with breast cancer risk, overall, by menopausal status, or for estrogen receptor positive or negative breast cancer. Three T2D associated risk variants were individually associated with breast cancer risk after adjustment for multiple comparisons using the Bonferroni method (at p < 0.001), rs9939609 (FTO) (OR 0.94, 95 % CI = 0.92–0.95, p = 4.13E−13), rs7903146 (TCF7L2) (OR 1.04, 95 % CI = 1.02–1.06, p = 1.26E−05), and rs8042680 (PRC1) (OR 0.97, 95 % CI = 0.95–0.99, p = 8.05E−04). Conclusions: We have shown that several genetic risk variants were associated with the risk of both T2D and breast cancer. However, overall genetic susceptibility to T2D may not be related to breast cancer risk

Fine-Scale Mapping of the 5q11.2 Breast Cancer Locus Reveals at Least Three Independent Risk Variants Regulating MAP3K1

Peer reviewe

No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.

BACKGROUND: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. METHODS: We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. RESULTS: The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). CONCLUSIONS: These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.The COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175). BCAC is funded by Cancer Research UK [C1287/A10118, C1287/A12014] and by the European Community´s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 16 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defense (W81XWH-10-1- 0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Project established by the National Cancer Institute and National Human Genome Research Institute.This is the author accepted manuscript. The final version is available from BMJ Group at http://dx.doi.org/10.1136/jmedgenet-2015-103529

Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival

Background Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers. Aim To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Methods Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. Results There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55–0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09–1.56)]. Conclusion Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk

Breast cancer risk genes: association analysis in more than 113,000 women

BACKGROUNDGenetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking.METHODSWe used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes. We evaluated missense-variant associations according to domain and classification of pathogenicity.RESULTSProtein-truncating variants in 5 genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a risk of breast cancer overall with a P value of less than 0.0001. Protein-truncating variants in 4 other genes (BARD1, RAD51C, RAD51D, and TP53) were associated with a risk of breast cancer overall with a P value of less than 0.05 and a Bayesian false-discovery probability of less than 0.05. For protein-truncating variants in 19 of the remaining 25 genes, the upper limit of the 95% confidence interval of the odds ratio for breast cancer overall was less than 2.0. For protein-truncating variants in ATM and CHEK2, odds ratios were higher for estrogen receptor (ER)-positive disease than for ER-negative disease; for protein-truncating variants in BARD1, BRCA1, BRCA2, PALB2, RAD51C, and RAD51D, odds ratios were higher for ER-negative disease than for ER-positive disease. Rare missense variants (in aggregate) in ATM, CHEK2, and TP53 were associated with a risk of breast cancer overall with a P value of less than 0.001. For BRCA1, BRCA2, and TP53, missense variants (in aggregate) that would be classified as pathogenic according to standard criteria were associated with a risk of breast cancer overall, with the risk being similar to that of protein-truncating variants.CONCLUSIONSThe results of this study define the genes that are most clinically useful for inclusion on panels for the prediction of breast cancer risk, as well as provide estimates of the risks associated with protein-truncating variants, to guide genetic counseling. (Funded by European Union Horizon 2020 programs and others.)Molecular tumour pathology - and tumour geneticsMTG1 - Moleculaire genetica en pathologie van borstkanke