Alpha Oscillations during Incidental Encoding Predict Subsequent Memory for New "Foil" Information.

People can employ adaptive strategies to increase the likelihood that previously encoded information will be successfully retrieved. One such strategy is to constrain retrieval toward relevant information by reimplementing the neurocognitive processes that were engaged during encoding. Using EEG, we examined the temporal dynamics with which constraining retrieval toward semantic versus nonsemantic information affects the processing of new "foil" information encountered during a memory test. Time-frequency analysis of EEG data acquired during an initial study phase revealed that semantic compared with nonsemantic processing was associated with alpha decreases in a left frontal electrode cluster from around 600 msec after stimulus onset. Successful encoding of semantic versus nonsemantic foils during a subsequent memory test was related to decreases in alpha oscillatory activity in the same left frontal electrode cluster, which emerged relatively late in the trial at around 1000-1600 msec after stimulus onset. Across participants, left frontal alpha power elicited by semantic processing during the study phase correlated significantly with left frontal alpha power associated with semantic foil encoding during the memory test. Furthermore, larger left frontal alpha power decreases elicited by semantic foil encoding during the memory test predicted better subsequent semantic foil recognition in an additional surprise foil memory test, although this effect did not reach significance. These findings indicate that constraining retrieval toward semantic information involves reimplementing semantic encoding operations that are mediated by alpha oscillations and that such reimplementation occurs at a late stage of memory retrieval, perhaps reflecting additional monitoring processes

Policy guidelines for effective inclusion and reintegration of people with chronic diseases in the workplace : national and European perspectives

The increasing prevalence of chronic diseases among the European working age population, as well as the implications for the individual and societal level, underline the need for policy guidelines targeting the effective inclusion of persons with chronic diseases in the workplace. The aim of the present paper was to explore the perspectives of European and National-level stakeholders on existing strategies for work re-integration of persons with chronic diseases, and to provide policy guidelines. A highly-structured interview protocol was distributed to 58 National level stakeholders (policy makers, professionals and employers) from seven European countries. Additionally, 20 European organizations concerned with health-related issues and employment completed an online survey. The findings reveal that employment-related challenges remain largely unaddressed. Both national and European stakeholders considered the existing legislative frameworks inadequate and appraised the co-ordination for the implementation of employment re-integration policies as ineffective. Policies targeting at work re-integration of persons with chronic diseases at European and national level should focus on consistent cooperation among all key stakeholders, awareness raising to staff and management, dissemination of effective strategies, developing research and evaluation standards and establishing monitoring systems on inclusive labour markets

What is Learned from Longitudinal Studies of Advertising and Youth Drinking and Smoking? A Critical Assessment

This paper assesses the methodology employed in longitudinal studies of advertising and youth drinking and smoking behaviors. These studies often are given a causal interpretation in the psychology and public health literatures. Four issues are examined from the perspective of econometrics. First, specification and validation of empirical models. Second, empirical issues associated with measures of advertising receptivity and exposure. Third, potential endogeneity of receptivity and exposure variables. Fourth, sample selection bias in baseline and follow-up surveys. Longitudinal studies reviewed include 20 studies of youth drinking and 26 studies of youth smoking. Substantial shortcomings are found in the studies, which preclude a causal interpretation

A Unified Framework for Trend Uncertainty Assessment in Climate Data Record: Application to the Analysis of the Global Mean Sea Level Measured by Satellite Altimetry

Estimating trends from Climate Data Records (CDRs) of Essential Climate Variables (ECVs) is necessary to detect persistent changes in Earth’s climate and geophysical processes and states. Accurately describing trend uncertainty is also essential to determining the significance of observed changes and attributing drivers. However, despite the importance of uncertainty, no established trend assessment approach properly accounts for all known sources of trend uncertainty. Most approaches either neglect part of known measurement uncertainty, such as measurement system instability, or ignore the influence of natural climate variability on trend estimation. Such neglect can result in over-confidence in trend estimates. With the intent of providing the most realistic uncertainty intervals for climate data record time series data, this study discusses problems and limitations of current approaches. It emphasizes the need to account for the combined influence of measurement uncertainties (i.e., stability of the observational system) and natural climate variability on trend uncertainty. This study proposes a novel trend-uncertainty assessment approach unifying available measurement uncertainty information with empirical modelling of natural climate variability within the same trend-estimation framework. As a proof of concept, the proposed approach is applied to the analysis of trends in a Global Mean Sea Level (GMSL) time-series. This GMSL application demonstrates that combining available measurement uncertainty assessment with variance modelling is expected to lead to more realistic uncertainty evaluations in sea-level trends. This unified approach is potentially applicable to virtually any CDR and could enhance the reliability of climate change analysis through an improved trend uncertainty assessment in climate studies

Proteome Analysis of Borrelia burgdorferi Response to Environmental Change

We examined global changes in protein expression in the B31 strain of Borrelia burgdorferi, in response to two environmental cues (pH and temperature) chosen for their reported similarity to those encountered at different stages of the organism's life cycle. Multidimensional nano-liquid chromatographic separations coupled with tandem mass spectrometry were used to examine the array of proteins (i.e., the proteome) of B. burgdorferi for different pH and temperature culture conditions. Changes in pH and temperature elicited in vitro adaptations of this spirochete known to cause Lyme disease and led to alterations in protein expression that are associated with increased microbial pathogenesis. We identified 1,031 proteins that represent 59% of the annotated genome of B. burgdorferi and elucidated a core proteome of 414 proteins that were present in all environmental conditions investigated. Observed changes in protein abundances indicated varied replicon usage, as well as proteome functional distributions between the in vitro cell culture conditions. Surprisingly, the pH and temperature conditions that mimicked B. burgdorferi residing in the gut of a fed tick showed a marked reduction in protein diversity. Additionally, the results provide us with leading candidates for exploring how B. burgdorferi adapts to and is able to survive in a wide variety of environmental conditions and lay a foundation for planned in situ studies of B. burgdorferi isolated from the tick midgut and infected animals

Variants in autophagy-related genes and clinical characteristics in melanoma: a population-based study

Autophagy has been linked with melanoma risk and survival, but no polymorphisms in autophagy-related (ATG) genes have been investigated in relation to melanoma progression. We examined five single-nucleotide polymorphisms (SNPs) in three ATG genes (ATG5; ATG10; and ATG16L) with known or suspected impact on autophagic flux in an international population-based case-control study of melanoma. DNA from 911 melanoma patients was genotyped. An association was identified between (GG) (rs2241880) and earlier stage at diagnosis (OR 0.47; 95% Confidence Intervals (CI) = 0.27-0.81, P = 0.02) and a decrease in Breslow thickness (P = 0.03). The ATG16L heterozygous genotype (AG) (rs2241880) was associated with younger age at diagnosis (P = 0.02). Two SNPs in ATG5 were found to be associated with increased stage (rs2245214 CG, OR 1.47; 95% CI = 1.11-1.94, P = 0.03; rs510432 CC, OR 1.84; 95% CI = 1.12-3.02, P = 0.05). Finally, we identified inverse associations between ATG5 (GG rs2245214) and melanomas on the scalp or neck (OR 0.20, 95% CI = 0.05-0.86, P = 0.03); ATG10 (CC) (rs1864182) and brisk tumor infiltrating lymphocytes (TILs) (OR 0.42; 95% CI = 0.21-0.88, P = 0.02), and ATG5 (CC) (rs510432) with nonbrisk TILs (OR 0.55; 95% CI = 0.34-0.87, P = 0.01). Our data suggest that ATG SNPs might be differentially associated with specific host and tumor characteristics including age at diagnosis, TILs, and stage. These associations may be critical to understanding the role of autophagy in cancer, and further investigation will help characterize the contribution of these variants to melanoma progression

Rational Addiction with Optimal Inventories: Theory and Evidence from Cigarette Purchases in Japan

A model of rational addiction (RA) with optimal inventories is developed and empirically tested using data on purchases in Japan. If a consumer has information regarding a future price increase, then she may hoard addictive goods; in this case, the optimal inventory period increases with the price hike but decreases with the inventory cost. Owing to the creation of such inventories by consumers, the absolute value of the price elasticity of demand is smaller in the case of a price increase than in that of a price decrease, and this difference is especially salient in the short-run. The evidence provided by daily cigarette purchases is consistent with this asymmetric price effect. Monthly cigarette purchase data do not support the RA hypothesis when inventory is ignored, as inventory becomes an omitted variable that correlates with price; however, this hypothesis does find support if inventory is identified in the demand equation.The Seventh ISER-Moriguchi Prize (2005) Awarded Paper

Effective Profit Taxation and the Elasticity of the Corporate Income Tax Base: Evidence from German Corporate Tax Return Data

We estimate the elasticity of corporate taxable income with respect to the effective corporate tax rate on the basis of a pseudo-panel constructed from corporate tax return micro data for the period 1998-2001, a period which saw the introduction of a major corporate tax reform in Germany. Endogeneity of the effective tax rate is controlled for by an instrumental variable approach. Our instrument for the observed effective corporate tax rate is the counterfactual effective tax rate a corporation would face in a particular period had there be no endogenous change of corporate profits. This counterfactual is obtained from a detailed microsimulation model of the corporate sector based on tax return micro data. We find a statistically significant and relatively large point estimate of the average tax base elasticity, which implies that a reduction of the statutory corporate tax rate would reduce corporate tax receipts less tha n proportionally due to income shifting activities. We also find some statistically weak evidence for the hypothesis that the tax base elasticity is higher for corporations that may benefit from various forms of tax shields

Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinsons disease study.

Estimates of the spectrum and frequency of pathogenic variants in Parkinsons disease (PD) in different populations are currently limited and biased. Furthermore, although therapeutic modification of several genetic targets has reached the clinical trial stage, a major obstacle in conducting these trials is that PD patients are largely unaware of their genetic status and, therefore, cannot be recruited. Expanding the number of investigated PD-related genes and including genes related to disorders with overlapping clinical features in large, well-phenotyped PD patient groups is a prerequisite for capturing the full variant spectrum underlying PD and for stratifying and prioritizing patients for gene-targeted clinical trials. The Rostock Parkinsons disease (ROPAD) study is an observational clinical study aiming to determine the frequency and spectrum of genetic variants contributing to PD in a large international cohort. We investigated variants in 50 genes with either an established relevance for PD or possible phenotypic overlap in a group of 12 580 PD patients from 16 countries [62.3% male; 92.0% White; 27.0% positive family history (FH+), median age at onset (AAO) 59 years] using a next-generation sequencing panel. Altogether, in 1864 (14.8%) ROPAD participants (58.1% male; 91.0% White, 35.5% FH+, median AAO 55 years), a PD-relevant genetic test (PDGT) was positive based on GBA1 risk variants (10.4%) or pathogenic/likely pathogenic variants in LRRK2 (2.9%), PRKN (0.9%), SNCA (0.2%) or PINK1 (0.1%) or a combination of two genetic findings in two genes (∼0.2%). Of note, the adjusted positive PDGT fraction, i.e. the fraction of positive PDGTs per country weighted by the fraction of the population of the world that they represent, was 14.5%. Positive PDGTs were identified in 19.9% of patients with an AAO ≤ 50 years, in 19.5% of patients with FH+ and in 26.9% with an AAO ≤ 50 years and FH+. In comparison to the idiopathic PD group (6846 patients with benign variants), the positive PDGT group had a significantly lower AAO (4 years, P = 9 × 10-34). The probability of a positive PDGT decreased by 3% with every additional AAO year (P = 1 × 10-35). Female patients were 22% more likely to have a positive PDGT (P = 3 × 10-4), and for individuals with FH+ this likelihood was 55% higher (P = 1 × 10-14). About 0.8% of the ROPAD participants had positive genetic testing findings in parkinsonism-, dystonia/dyskinesia- or dementia-related genes. In the emerging era of gene-targeted PD clinical trials, our finding that ∼15% of patients harbour potentially actionable genetic variants offers an important prospect to affected individuals and their families and underlines the need for genetic testing in PD patients. Thus, the insights from the ROPAD study allow for data-driven, differential genetic counselling across the spectrum of different AAOs and family histories and promote a possible policy change in the application of genetic testing as a routine part of patient evaluation and care in PD