Potential of 18F-FDG PET toward personalized radiotherapy or chemoradiotherapy in lung cancer

Purpose We investigated the metabolic response of lung cancer to radiotherapy or chemoradiotherapy by 18F-FDG PET and its utility in guiding timely supplementary therapy. Methods: Glucose metabolic rate (MRglc) was measured in primary lung cancers during the 3 weeks before, and 10–12 days (S2), 3 months (S3), 6 months (S4), and 12 months (S5) after radiotherapy or chemoradiotherapy. The association between the lowest residual MRglc representing the maximum metabolic response (MRglc-MMR) and tumor control probability (TCP) at 12 months was modeled using logistic regression. Results: We accrued 106 patients, of whom 61 completed the serial 18F-FDG PET scans. The median values of MRglc at S2, S3 and S4 determined using a simplified kinetic method (SKM) were, respectively, 0.05, 0.06 and 0.07 μmol/min/g for tumors with local control and 0.12, 0.16 and 0.19 μmol/min/g for tumors with local failure, and the maximum standard uptake values (SUVmax) were 1.16, 1.33 and 1.45 for tumors with local control and 2.74, 2.74 and 4.07 for tumors with local failure (p < 0.0001). MRglc-MMR was realized at S2 (MRglc-S2) and the values corresponding to TCP 95 %, 90 % and 50 % were 0.036, 0.050 and 0.134 μmol/min/g using the SKM and 0.70, 0.91 and 1.95 using SUVmax, respectively. Probability cut-off values were generated for a given level of MRglc-S2 based on its predicted TCP, sensitivity and specificity, and MRglc ≤0.071 μmol/min/g and SUVmax ≤1.45 were determined as the optimum cut-off values for predicted TCP 80 %, sensitivity 100 % and specificity 63 %. Conclusion: The cut-off values (MRglc ≤0.071 μmol/min/g using the SKM and SUVmax ≤1.45) need to be tested for their utility in identifying patients with a high risk of residual cancer after standard dose radiotherapy or chemoradiotherapy and in guiding a timely supplementary dose of radiation or other means of salvage therapy. Electronic supplementary material The online version of this article (doi:10.1007/s00259-013-2348-4) contains supplementary material, which is available to authorized users

Getting shot of elves: healing, witchcraft and fairies in the Scottish witchcraft trials

This paper re-examines the evidence of the Scottish witchcraft trials for beliefs associated by scholars with "elf-shot." Some supposed evidence for elf-shot is dismissed, but other material illuminates the interplay between illness, healing and fairy-lore in early modern Scotland, and the relationship of these beliefs to witchcraft itself

Fiscal policies and car choices in Italy and Norway: A scenario analysis based on a stated-preference survey

Norwegian and Italian car drivers make very different car choices. This paper investigates the influence of fiscal policies on car buyers’ choices, using data collected from a stated preference survey conducted in 2021. After estimating a joint random parameter logit model, we simulated the market shares of five car powertrains under three scenarios: “Italian car buyers face the same net purchase car prices and fuel\electricity costs as the Norwegian car drivers and vice versa”, “Italy adopts the Norwegian registration tax”, and “Both Italy and Norway adopt a social cost internalizing registration tax”. The results indicate that Italian car users are reluctant to switch to battery electric cars (BEVs). They would choose BEVs more frequently in the three scenarios envisaged but without reaching the corresponding Norwegian levels. If Italy would adopt the Norwegian registration tax system, BEVs’ market share would gain 5.4 percentage points relative to the baseline scenario, while under the social cost internalizing scenario, BEVs’ market share would improve by 3.4 and PHEVs’ one by 0.2 percentage points. On the contrary, Norwegians are BEV-oriented and would comparatively preserve a high BEV share. In the social cost internalization scenario, the BEV share relative to the baseline scenario would decrease by 7.2 percentage points, petrol cars would gain 1.2, HEVs 2.9, PHEVs 3.4, and diesel cars would lose 0.3 percentage points. In general, there seems to be a lock-in or path dependence effect that limits BEV penetration in Italy and prevents the decline of the BEV share in Norway

Role of spinal cord glutamate transporter during normal sensory transmission and pathological pain states

Glutamate is a neurotransmitter critical for spinal excitatory synaptic transmission and for generation and maintenance of spinal states of pain hypersensitivity via activation of glutamate receptors. Understanding the regulation of synaptically and non-synaptically released glutamate associated with pathological pain is important in exploring novel molecular mechanisms and developing therapeutic strategies of pathological pain. The glutamate transporter system is the primary mechanism for the inactivation of synaptically released glutamate and the maintenance of glutamate homeostasis. Recent studies demonstrated that spinal glutamate transporter inhibition relieved pathological pain, suggesting that the spinal glutamate transporter might serve as a therapeutic target for treatment of pathological pain. However, the exact function of glutamate transporter in pathological pain is not completely understood. This report will review the evidence for the role of the spinal glutamate transporter during normal sensory transmission and pathological pain conditions and discuss potential mechanisms by which spinal glutamate transporter is involved in pathological pain

Estimating carbon and water footprints associated with commercial milk formula production and use:development and implications of the Green Feeding Climate Action Tool

Carbon offset frameworks like the UN Clean Development Mechanism (CDM) have largely overlooked interventions involving food, health, and care systems, including breastfeeding. The innovative Green Feeding Climate Action Tool (GFT) assesses the environmental impact of commercial milk formula (CMF) use, and advocates for breastfeeding support interventions as legitimate carbon offsets. This paper provides an overview of the GFT’s development, key features, and potential uses. The offline and online GFT were developed using the DMADV methodology (Define, Measure, Analyze, Design, Verify). The GFT reveals that the production and use of CMF by infants under 6 months results in annual global greenhouse gas (GHG) emissions of between 5.9 and 7.5 billion kg CO2 eq. and consumes 2,562.5 billion liters of water. As a national example, in India, one of the world’s most populous countries, CMF consumption requires 250.6 billion liters of water and results in GHG emissions ranging from 579 to 737 million kg CO2 eq. annually, despite the country’s high breastfeeding prevalence among infants under 6 months. The GFT mainly draws on data for low- and middle-income countries (LMICs), as many high-income countries (HICs) do not collect suitable data for such calculations. Despite poor official data on breastfeeding practices in HICs, GFT users can input their own data from smaller-scale surveys or their best estimates. The GFT also offers the capability to estimate and compare baseline with counterfactual scenarios, such as for interventions or policy changes that improve breastfeeding practices. In conclusion, the GFT is an important innovation to quantify CMF’s environmental impact and highlight the significance of breastfeeding for planetary as well as human health. Women’s contributions to environmental preservation through breastfeeding should be recognized, and breastfeeding interventions and policies should be funded as legitimate carbon offsets. The GFT quantifies CMF’s carbon and water footprints and facilitates financing breastfeeding support as a carbon offset initiative under CDM funding facilities.</p

Workplace psychosocial resources and risk of cardiovascular disease among employees: a multi-cohort study of 135 669 participants

Objective In terms of prevention, it is important to determine effects on cardiovascular disease (CVD) when some workplace psychosocial resources are high while others are low. The aim of the study was to assess the prospective relationship between clustering of workplace psychosocial resources and risk of CVD among employees. Methods We pooled data from three cohort studies of 135 669 employees (65% women, age 18–65 years and free of CVD) from Denmark, Finland and Sweden. Baseline horizontal resources (culture of collaboration and support from colleagues) and vertical resources (leadership quality and procedural justice) were measured using standard questionnaire items. Incident CVD, including coronary heart and cerebrovascular disease, was ascertained using linked electronic health records. We used latent class analysis to assess clustering (latent classes) of workplace psychosocial resources. Cox proportional hazard models were used to examine the association between these clusters and risk of CVD, adjusting for demographic and employment-related factors and pre-existing physical and mental disorders. Results We identified five clusters of workplace psychosocial resources from low on both vertical and horizontal resources (13%) to generally high resources (28%). High horizontal resources were combined with either inter-mediate [hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.74–0.95] or high (HR 0.88, 95% CI 0.78–1.00) vertical resources were associated with lower risks of CVD compared to those with generally low resources. The association was most prominent for cerebrovascular disease (eg, general high resources: HR 0.80, 95% CI 0.67–0.96). Conclusions Individuals with high levels of workplace psychosocial resources across horizontal and vertical dimensions have a lower risk of CVD, particularly cerebrovascular disease

Three-year results from a preclinical implantation study of a long-term resorbable surgical mesh with time-dependent mechanical characteristics

PURPOSE: The purpose of this study was to evaluate the biocompatibility, local tissue effects and performance of a synthetic long-term resorbable test mesh (TIGR(®) Matrix Surgical Mesh) compared to a non-resorbable polypropylene control mesh following implantation in a sheep model. METHODS: Full-thickness abdominal wall defects were created in 14 sheep and subsequently repaired using test or control meshes. Sacrifices were made at 4, 9, 15, 24 and 36 months and results in terms of macroscopic observations, histology and collagen analysis are described for 4, 9, 15, 24 and 36 months. RESULTS: The overall biocompatibility was good, and equivalent in the test and control meshes while the resorbable mesh was characterized by a collagen deposition more similar to native connective tissue and an increased thickness of the integrating tissue. The control polypropylene mesh provoked a typical chronic inflammation persistent over the 36-month study period. As the resorbable test mesh gradually degraded it was replaced by a newly formed collagen matrix with an increasing ratio of collagen type I/III, indicating a continuous remodeling of the collagen towards a strong connective tissue. After 36 months, the test mesh was fully resorbed and only microscopic implant residues could be found in the tissue. CONCLUSIONS: This study suggests that the concept of a long-term resorbable mesh with time-dependent mechanical characteristics offers new possibilities for soft tissue repair and reinforcement

High-dose alectinib for RET fusion-positive non-small cell lung cancer in the Blood First Assay Screening Trial.

This paper presents results from Cohort B (rearranged during transfection [RET], fusion-positive) of the Blood First Assay Screening Trial in patients with advanced non-small cell lung cancer (NSCLC) screened for genetic alterations using blood-based next-generation sequencing. Adults with advanced RET fusion-positive NSCLC received alectinib 900 mg twice daily (BID) in Phase I. Enrolment closed prematurely with Phase II uninitiated. Among eight treated patients, confirmed best overall responses in evaluable patients were stable disease (4/5) and progressive disease (1/5). One dose-limiting toxicity (death, unknown cause) was considered by the investigator to be related to treatment and underlying disease. Serious adverse events (SAEs) occurred in five patients, and SAEs that may be related to treatment occurred in two patients. Alectinib showed limited activity in advanced RET fusion-positive NSCLC, and further investigation was not conducted due to the development of selective RET inhibitors pralsetinib and selpercatinib. No new safety signals were observed, and the safety profile of alectinib was in line with previous reports at the 600 mg BID dose