Intensive Lifestyle (e)Support to Reverse Diabetes-2

Advanced diabetes-type-2 patients often have high insulin resistance. Over the years their insulin medication rises, which further increases their insulin resistance and glucose management problems. A HINTc (High Intensity Nutrition, Training & coaching) pilot study was conducted with 11 insulin-dependent patients. Hybrid eHealth support was given, with electronic support plus a multi-disciplinary health support team. Based on preliminary 12 week results, attractiveness and feasibility of the intervention were high: recommendation 9,0 out of 10 and satisfaction 9,1 out of 10. TAM (Technology Acceptance Model) surveys showed high usefulness, feasibility and intentions for future use. Acceptance and health behaviours were also reinforced by the rapid results (average 9% weight loss, 20% lower fasting glucose and 71% lower insulin medication, plus a 46% increase on the Quality of Life Physical Health dimension). Our analysis supports three types of conclusions. First, patients’ health literacy and quality of life improved strongly, both supporting healthier behaviours. Second, a virtuous cycle was started, helping patients reverse diabetes-2 progression. Third, a design analysis was conducted regarding service mix efficacy in relation to key requirements for designing ICT-enabled lifestyle interventions

Diabetes Lifestyle (e)Coaching 50 Weeks Follow Up; Technology Acceptance & e-Relationships

We report on the 50 weeks follow up results from a healthy lifestyle pilot (High Intensity Nutrition, Training & coaching), conducted with 11 insulin-dependent Type 2 Diabetes Mellites (DM2) patients. Hybrid eHealth support was given, with electronic support plus a multi-disciplinary health support team. Regarding the pilot goal of long term healthy lifestyle adoption in senior DM2 patients, challenges were: low ICT- and health literacy. This exploratory design analysis formulates design lessons based on 50 weeks follow up. The first 12 weeks contained intensive face-to-face and eSupported coaching. After that, patient self- management and eTools were key. After 50 weeks, attractiveness and feasibility of the intervention were perceived as high: recommendation 9,5 out of 10 and satisfaction 9,6 out of 10. TAM (Technology Acceptance Model) surveys showed high usefulness and feasibility. Acceptance and health behaviours were reinforced by the prolonged health results: Aerobic and strength capacity levels were improved at 50 weeks, plus Health Related Quality of Life (and biometric benefits and medication reductions, reported elsewhere). We draw three types of conclusions. First, patients’ health literacy and quality of life improved strongly, which both supported healthy behaviours, even after 50 weeks. Second, regarding eHealth theory, iterative growth cycles are beneficial for long term adoption and e-relationships. Third, a design analysis was conducted regarding long term service mix efficacy in relation to key requirements for designing ICT-enabled lifestyle interventions. Several suggestions for long term lifestyle eSupport are given

Bottom trawl fishing footprints on the world’s continental shelves

Bottom trawlers land around 19 million tons of fish and invertebrates annually, almost one-quarter of wild marine landings. The extent of bottom trawling footprint (seabed area trawled at least once in a specified region and time period) is often contested but poorly described. We quantify footprints using high-resolution satellite vessel monitoring system (VMS) and logbook data on 24 continental shelves and slopes to 1,000-m depth over at least 2 years. Trawling footprint varied markedly among regions: from 50% in some European seas. Overall, 14% of the 7.8 million-km2 study area was trawled, and 86% was not trawled. Trawling activity was aggregated; the most intensively trawled areas accounting for 90% of activity comprised 77% of footprint on average. Regional swept area ratio (SAR; ratio of total swept area trawled annually to total area of region, a metric of trawling intensity) and footprint area were related, providing an approach to estimate regional trawling footprints when high-resolution spatial data are unavailable. If SAR was ≤0.1, as in 8 of 24 regions, there was >95% probability that >90% of seabed was not trawled. If SAR was 7.9, equal to the highest SAR recorded, there was >95% probability that >70% of seabed was trawled. Footprints were smaller and SAR was ≤0.25 in regions where fishing rates consistently met international sustainability benchmarks for fish stocks, implying collateral environmental benefits from sustainable fishing

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

Elasticity, viscosity, and deformation of orbital fat

PURPOSE. For development of a finite element analysis model of orbital mechanics, it was necessary to determine the material properties of orbital fat and its degree of deformation in eye rotation. METHODS. Elasticity and viscosity of orbital fat of eight orbits of four calves and two orbits of one rhesus monkey were measured with a parallel-plate rheometer. The degree of deformation of orbital fat was studied in two human subjects by magnetic resonance imaging (MRI) through the optic nerve in seven (first subject) or fourteen positions of gaze from left to right. Bifurcations of veins in the fat were used as markers for displacement of the fat. RESULTS. The elastic shear modulus (G′) of calf orbital fat was between 250 Pa and 500 Pa, and of monkey orbital fat it was between 500 Pa and 900 Pa. The viscous shear modulus (G″) of calf orbital fat was between 80 Pa and 150 Pa, and for monkey orbital fat it was between 300 Pa and 500 Pa. In the MRI scans, it was found that markers in the fat, 1 to 5 mm posterior to t

Duobody-CD3xCD20 Shows Unique and Potent Preclinical Anti-Tumor Activity in Vitro and In Vivo, and Is Being Evaluated Clinically in Patients with B-Cell Malignancies

Transplantation and autoimmunit