Effects of anatomical changes on pencil beam scanning proton plans in locally advanced NSCLC patients

Daily anatomical variations can cause considerable differences between delivered and planned dose. This study simulates and evaluates these effects in spot-scanning proton therapy for lung cancer patients. Robust intensity modulated treatment plans were designed on the mid-position CT scan for sixteen locally advanced lung cancer patients. To estimate dosimetric uncertainty, deformable registration was performed on their daily CBCTs to generate 4DCT equivalent scans for each fraction and to map recomputed dose to a common frame. Without adaptive planning, eight patients had an undercoverage of the targets of more than 2GyE (maximum of 14.1GyE) on the recalculated treatment dose from the daily anatomy variations including respiration. In organs at risk, a maximum increase of 4.7GyE in the D1 was found in the mediastinal structures. The effect of respiratory motion alone is smaller: 1.4GyE undercoverage for targets and less than 1GyE for organs at risk. Daily anatomical variations over the course of treatment can cause considerable dose differences in the robust planned dose distribution. An advanced planning strategy including knowledge of anatomical uncertainties would be recommended to improve plan robustness against interfractional variations. For large anatomical changes, adaptive therapy is mandator

Influence of Anesthesia and Clinical Variables on the Firing Rate, Coefficient of Variation and Multi-Unit Activity of the Subthalamic Nucleus in Patients with Parkinson's Disease

BACKGROUND: Microelectrode recordings (MER) are used to optimize lead placement during subthalamic nucleus deep brain stimulation (STN-DBS). To obtain reliable MER, surgery is usually performed while patients are awake. Procedural sedation and analgesia (PSA) is often desirable to improve patient comfort, anxiolysis and pain relief. The effect of these agents on MER are largely unknown. The objective of this study was to determine the effects of commonly used PSA agents, dexmedetomidine, clonidine and remifentanil and patient characteristics on MER during DBS surgery. METHODS: Data from 78 patients with Parkinson's disease (PD) who underwent STN-DBS surgery were retrospectively reviewed. The procedures were performed under local anesthesia or under PSA with dexmedetomidine, clonidine or remifentanil. In total, 4082 sites with multi-unit activity (MUA) and 588 with single units were acquired. Single unit firing rates and coefficient of variation (CV), and MUA total power were compared between patient groups. RESULTS: We observed a significant reduction in MUA, an increase of the CV and a trend for reduced firing rate by dexmedetomidine. The effect of dexmedetomidine was dose-dependent for all measures. Remifentanil had no effect on the firing rate but was associated with a significant increase in CV and a decrease in MUA. Clonidine showed no significant effect on firing rate, CV or MUA. In addition to anesthetic effects, MUA and CV were also influenced by patient-dependent variables. CONCLUSION: Our results showed that PSA influenced neuronal properties in the STN and the dexmedetomidine (DEX) effect was dose-dependent. In addition, patient-dependent characteristics also influenced MER

Increased EEG gamma band activity in Alzheimer’s disease and mild cognitive impairment

High frequency (30–70 Hz) gamma band oscillations in the human electro-encephalogram (EEG) are thought to reflect perceptual and cognitive processes. It is therefore interesting to study these measures in cognitive impairment and dementia. To evaluate gamma band oscillations as a diagnostic biomarker in Alzheimer’s disease (AD) and mild cognitive impairment (MCI), 15 psychoactive drug naïve AD patients, 20 MCI patients and 20 healthy controls participated in this study. Gamma band power (GBP) was measured in four conditions viz. resting state, music listening, story listening and visual stimulation. To evaluate test–retest reliability (TRR), subjects underwent a similar assessment one week after the first. The overall TRR was high. Elevated GBP was observed in AD when compared to MCI and control subjects in all conditions. The results suggest that elevated GBP is a reproducible and sensitive measure for cognitive dysfunction in AD in comparison with MCI and controls

Proposed guidelines to evaluate scientific validity and evidence for genotype-based dietary advice

Nutrigenetic research examines the effects of inter-individual differences in genotype on responses to nutrients and other food components, in the context of health and of nutrient requirements. A practical application of nutrigenetics is the use of personal genetic information to guide recommendations for dietary choices that are more efficacious at the individual or genetic subgroup level relative to generic dietary advice. Nutrigenetics is unregulated, with no defined standards, beyond some commercially adopted codes of practice. Only a few official nutrition-related professional bodies have embraced the subject, and, consequently, there is a lack of educational resources or guidance for implementation of the outcomes of nutrigenetic research. To avoid misuse and to protect the public, personalised nutrigenetic advice and information should be based on clear evidence of validity grounded in a careful and defensible interpretation of outcomes from nutrigenetic research studies. Evidence requirements are clearly stated and assessed within the context of state-of-the-art ‘evidence-based nutrition’. We have developed and present here a draft framework that can be used to assess the strength of the evidence for scientific validity of nutrigenetic knowledge and whether ‘actionable’. In addition, we propose that this framework be used as the basis for developing transparent and scientifically sound advice to the public based on nutrigenetic tests. We feel that although this area is still in its infancy, minimal guidelines are required. Though these guidelines are based on semiquantitative data, they should stimulate debate on their utility. This framework will be revised biennially, as knowledge on the subject increases

Endogenous sex steroids and risk of cervical carcinoma : results from the EPIC study

Background: Epidemiologic data and animal models suggest that, despite the predominant role of human papillomavirus infection, sex steroid hormones are also involved in the etiology of invasive cervical carcinoma (ICC). Methods: Ninety-nine ICC cases, 121 cervical intraepithelial neoplasia grade 3 (CIN3) cases and 2 control women matched with each case for center, age, menopausal status and blood collection-related variables, were identified in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Circulating levels of testosterone (T) and estradiol (E(2)); dehydroepiandrosterone sulfate (DHEAS); progesterone (premenopausal women); and sex hormone-binding globulin (SHBG) were measured using immunoassays. Levels of free (f) T and E(2) were calculated from absolute concentrations of T, E(2), and SHBG. Odds ratios (ORs) and 95% confidence intervals (CI) were computed using regularized conditional logistic regression. Results: Among premenopausal women, associations with ICC were observed for fT (OR for highest vs. lowest tertile 5.16, 95% CI, 1.50-20.1). SHBG level was associated with a significant downward trend in ICC risk. T, E(2), fE(2), and DHEAS showed nonsignificant positive association with ICC. Progesterone was uninfluential. Among postmenopausal women, associations with ICC were found for T (OR 3.14; 95% CI, 1.21-9.37), whereas E(2) and fT showed nonsignificant positive association. SHBG level was unrelated to ICC risk in postmenopausal women. No associations between any hormone and CIN3 were detected in either pre- or postmenopausal women. Conclusions: Our findings suggest for the first time that T and possibly E(2) may be involved in the etiology of ICC. Impact: The responsiveness of cervical tumors to hormone modulators is worth exploring. Cancer Epidemiol Biomarkers Prev; 20(12); 2532-40. (C) 2011 AACR

Circulating concentrations of vitamin D in relation to pancreatic cancer risk in European populations

Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre-diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord-Trøndelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n = 626; HUNT2 n = 112; median follow-up = 6.9 years) were matched to 738 controls. Vitamin D [25(OH)D2 and 25(OH)D3 combined] concentrations were determined using isotope-dilution liquid chromatography-tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42–1.20); 0.94 (0.72–1.22); 1.12 (0.82–1.53) and 1.26 (0.79–2.01) for clinically pre-defined categories of ≤25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend = 0.09). Corresponding analyses by quintiles of season-standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend = 0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre-diagnostic concentrations of vitamin D, they are not statistically significant