Reading Sami Moisio’s Geopolitics of the Knowledge-Based Economy

Peer reviewe

A comparison of mantle versus involved-field radiotherapy for Hodgkin's lymphoma: reduction in normal tissue dose and second cancer risk

BACKGROUND: Hodgkin's lymphoma (HL) survivors who undergo radiotherapy experience increased risks of second cancers (SC) and cardiac sequelae. To reduce such risks, extended-field radiotherapy (RT) for HL has largely been replaced by involved field radiotherapy (IFRT). While it has generally been assumed that IFRT will reduce SC risks, there are few data that quantify the reduction in dose to normal tissues associated with modern RT practice for patients with mediastinal HL, and no estimates of the expected reduction in SC risk. METHODS: Organ-specific dose-volume histograms (DVH) were generated for 41 patients receiving 35 Gy mantle RT, 35 Gy IFRT, or 20 Gy IFRT, and integrated organ mean doses were compared for the three protocols. Organ-specific SC risk estimates were estimated using a dosimetric risk-modeling approach, analyzing DVH data with quantitative, mechanistic models of radiation-induced cancer. RESULTS: Dose reductions resulted in corresponding reductions in predicted excess relative risks (ERR) for SC induction. Moving from 35 Gy mantle RT to 35 Gy IFRT reduces predicted ERR for female breast and lung cancer by approximately 65%, and for male lung cancer by approximately 35%; moving from 35 Gy IFRT to 20 Gy IFRT reduces predicted ERRs approximately 40% more. The median reduction in integral dose to the whole heart with the transition to 35 Gy IFRT was 35%, with a smaller (2%) reduction in dose to proximal coronary arteries. There was no significant reduction in thyroid dose. CONCLUSION: The significant decreases estimated for radiation-induced SC risks associated with modern IFRT provide strong support for the use of IFRT to reduce the late effects of treatment. The approach employed here can provide new insight into the risks associated with contemporary IFRT for HL, and may facilitate the counseling of patients regarding the risks associated with this treatment

A pilot randomised controlled trial of personalised care for depressed patients with symptomatic coronary heart disease in South London general practices: the UPBEAT-UK RCT protocol and recruitment.

ABSTRACT: Background: Community studies reveal people with coronary heart disease (CHD) are twice as likely to be depressed as the general population and that this co-morbidity negatively affects the course and outcome of both conditions. There is evidence for the efficacy of collaborative care and case management for depression treatment, and whilst NICE guidelines recommend these approaches only where depression has not responded to psychological, pharmacological, or combined treatments, these care approaches may be particularly relevant to the needs of people with CHD and depression in the earlier stages of stepped care in primary care settings. Methods: This pilot randomised controlled trial will evaluate whether a simple intervention involving a personalised care plan, elements of case management and regular telephone review is a feasible and acceptable intervention that leads to better mental and physical health outcomes for these patients. The comparator group will be usual general practitioner (GP) care. 81 participants have been recruited from CHD registers of 15 South London general practices. Eligible participants have probable major depression identified by a score of ≥8 on the Hospital Anxiety and Depression Scale depression subscale (HADS-D) together with symptomatic CHD identified using the Modified Rose Angina Questionnaire. Consenting participants are randomly allocated to usual care or the personalised care intervention which involves a comprehensive assessment of each participant’s physical and mental health needs which are documented in a care plan, followed by regular telephone reviews by the case manager over a 6-month period. At each review, the intervention participant’s mood, function and identified problems are reviewed and the case manager uses evidence based behaviour change techniques to facilitate achievement of goals specified by the patient with the aim of increasing the patient’s self efficacy to solve their problems. Depressive symptoms measured by HADS score will be collected at baseline and 1, 6- and 12 months post randomisation. Other outcomes include CHD symptoms, quality of life, wellbeing and health service utilisation. Discussion: This practical and patient-focused intervention is potentially an effective and accessible approach to the health and social care needs of people with depression and CHD in primary care. Trial registration: ISRCTN21615909

Alcohol Intake and Risk of Coronary Heart Disease in Younger, Middle-Aged, and Older Adults

BACKGROUND: Light-to-moderate alcohol consumption is associated with a reduced risk of coronary heart disease (CHD). This protective effect of alcohol, however, may be confined to middle-aged or older individuals. CHD Incidence is low in men younger than 40 and in women younger than 50 years and for this reason, study cohorts rarely have the power to investigate effects of alcohol on CHD risk in younger adults. This study examined whether the beneficial effect of alcohol on CHD depends on age. METHODS AND RESULTS: A pooled analysis of eight prospective studies from North America and Europe including 192,067 women and 74,919 men free of cardiovascular diseases, diabetes, and cancers at baseline. Average daily alcohol intake was assessed at baseline using a food frequency or diet history questionnaire. An inverse association between alcohol and risk of coronary heart disease was observed in all age groups: hazard ratios among moderately drinking men (5.0–29.9 g/day) aged 39–50, 50–59, and 60+ years were 0.58 (95% C.I. 0.36 to 0.93), 0.72 (95% C.I. 0.60–0.86), and 0.85 (95% C.I. 0.75 to 0.97) compared with abstainers. However, the analyses indicated a smaller incidence rate difference (IRD) between abstainers and moderate consumers in younger adults (IRD=45 per 100,000; 90% C.I. 8 to 84), than in middle-aged (IRD=64 per 100,000; 90% C.I. 24 to 102) and older adults (IRD=89 per 100,000; 90% C.I. 44 to 140). Similar results were observed in women. CONCLUSIONS: Alcohol is also associated with a decreased risk of CHD in younger adults; however, the absolute risk was small compared with middle-aged and older adults

Human umbilical cord perivascular cells improve human pancreatic islet transplant function by increasing vascularization

Islet transplantation is an efficacious therapy for type 1 diabetes; however, islets from multiple donor pancreata are required, and a gradual attrition in transplant function is seen. Here, we manufactured human umbilical cord perivascular mesenchymal stromal cells (HUCPVCs) to Good Manufacturing Practice (GMP) standards. HUCPVCs showed a stable phenotype while undergoing rapid ex vivo expansion at passage 2 (p2) to passage 4 (p4) and produced proregenerative factors, strongly suppressing T cell responses in the resting state and in response to inflammation. Transplanting an islet equivalent (IEQ):HUCPVC ratio of 1:30 under the kidney capsule in diabetic NSG mice demonstrated the fastest return to normoglycemia by 3 days after transplant: Superior glycemic control was seen at both early (2.7 weeks) and later stages (7, 12, and 16 weeks) versus ratios of 1:0, 1:10, and 1:50, respectively. Syngeneic islet transplantation in immunocompetent mice using the clinically relevant hepatic portal route with a marginal islet mass showed that mice transplanted with an IEQ:HUCPVC ratio of 1:150 had superior glycemic control versus ratios of 1:0, 1:90, and 1:210 up to 6 weeks after transplant. Immunodeficient mice transplanted with human islets (IEQ:HUCPVC ratio of 1:150) exhibited better glycemic control for 7 weeks after transplant versus islet transplant alone, and islets transplanted via the hepatic portal vein in an allogeneic mouse model using a curative islet mass demonstrated delayed rejection of islets when cotransplanted with HUCPVCs (IEQ:HUCPVC ratio of 1:150). The immunosuppressive and proregenerative properties of HUCPVCs demonstrated long-term positive effects on graft function in vivo, indicating that they may improve long-term human islet allotransplantation outcomes

Operando XAFS investigation on the effect of ash deposition on three-way catalyst used in Gasoline Particulate Filters and the effect of the manufacturing process on the catalytic activity

Platinum group metals (PGM) such as palladium and rhodium based catalysts are currently being implemented in Gasoline Particulate Filter (GPF) autoexhaust aftertreatment systems. However, little is known about how the trapped particulate matter, such as the incombustible ash, interacts with the catalyst and so may affect its performance. This operando study follows the evolution of the Pd found in two different model GPF systems: one containing ash components extracted from a GPF and another from a catalyst washcoat prior to adhesion onto the GPF. We show that the catalytic activity of the two systems vary when compared with a 0 g ash containing GPF. Compared to the 0 g ash sample the 20 g ash containing sample had a higher CO light off temperature, in addition, an oscillation profile for CO, CO2 and O2 was observed, which is speculated to be a combination of CO oxidation, C deposition via a Boudouard Reaction and further partial oxidation of the deposited species to CO. During the ageing procedure the washcoat sample reduces NO at a lower temperature than the 0 g ash sample. However, post ageing the 0 g ash sample recovers and both samples reduce NO at 310 circleC. In comparison, the 20 g ash GPF sample maintains a higher NO reduction temperature of 410 circleC post ageing, implying that the combination of high temperature ageing and presence of ash has an irreversible negative effect on catalyst performance

HLA genotyping in the international Type 1 Diabetes Genetics Consortium

Background Although human leukocyte antigen (HLA) DQ and DR loci appear to confer the strongest genetic risk for type 1 diabetes, more detailed information is required for other loci within the HLA region to understand causality and stratify additional risk factors. The Type 1 Diabetes Genetics Consortium (T1DGC) study design included high-resolution genotyping of HLA-A, B, C, DRB1, DQ, and DP loci in all affected sibling pair and trio families, and cases and controls, recruited from four networks worldwide, for analysis with clinical phenotypes and immunological markers

Period and Cohort Changes in Americans’ Support for Marijuana Legalization: Convergence and Divergence across Social Groups

We cast fresh light on how and why Americans’ views on marijuana legalization shifted between 1973 and 2014. Results from age-period-cohort models show a strong negative effect of age and relatively high levels of support for legalization among baby boom cohorts. Despite the baby boom effect, the large increase in support for marijuana legalization is predominantly a broad, period-based change in the population. Additional analyses demonstrate that differences in support for legalization by education, region, and religion decline, that differences by political party increase, and that differences between whites and African Americans reverse direction. We conclude by discussing the implications of these findings and by identifying promising directions for future research on this topic