Prognostic value of arginase-II expression and regulatory T-cell infiltration in head and neck squamous cell carcinoma.

Tumor-infiltrating lymphocytes are present in a variety of tumors and play a central role in antitumor immune responses. Nevertheless, most cancers progress probably because tumors are only weakly immunogenic and develop multiple immunosuppressive mechanisms. In the present study, on head and neck squamous cell carcinoma, we found high intraepithelial infiltration of regulatory FOXP3(+) T cells, and relatively high levels of BDCA2(+) and FOXP3(+) cells in stromal (peripheral) regions of the tumors. Tumor-infiltrating (intraepithelial) FOXP3(+) T cells were significantly more frequent in patients with oropharynx and oral cavity squamous cell carcinoma and in patients without lymph node metastasis. Furthermore, arginase-II (ARG2) was expressed by 60%, inducible nitric oxide synthetase by 9%, cyclooxygenase-2 by 43%, and B-cell lymphoma 2 (BCL2) by 26% of tumors. Interestingly, the absence of ARG2 expression, enhanced stromal infiltration of CD11c(+) myeloid dendritic cells, and high numbers of FOXP3(+) T cells were each significantly associated with prolonged overall survival, and the latter two parameters were also confirmed by multivariate analysis. For disease-free survival, multivariate analysis revealed significant negative correlations with BCL2 and ARG2 expression by tumor cells. These findings shed new light on mechanisms of cancer progression, and provide rationales for therapeutic inhibition of immunosuppressive mechanisms in head and neck squamous cell carcinoma.

Examining the information content of time-lapse crosshole GPR data collected under different infiltration conditions to estimate unsaturated soil hydraulic properties

Time-lapse geophysical data acquired during transient hydrological experiments are being increasingly employed to estimate subsurface hydraulic properties at the field scale. In particular, crosshole ground-penetrating radar (GPR) data, collected while water infiltrates into the subsurface either by natural or artificial means, have been demonstrated in a number of studies to contain valuable information concerning the hydraulic properties of the unsaturated zone. Previous work in this domain has considered a variety of infiltration conditions and different amounts of time-lapse GPR data in the estimation procedure. However, the particular benefits and drawbacks of these different strategies as well as the impact of a variety of key and common assumptions remain unclear. Using a Bayesian Markov-chain-Monte-Carlo stochastic inversion methodology, we examine in this paper the information content of time-lapse zero-offset-profile (ZOP) GPR traveltime data, collected under three different infiltration conditions, for the estimation of van Genuchten-Mualem (VGM) parameters in a layered subsurface medium. Specifically, we systematically analyze synthetic and field GPR data acquired under natural loading and two rates of forced infiltration, and we consider the value of incorporating different amounts of time-lapse measurements into the estimation procedure. Our results confirm that, for all infiltration scenarios considered, the ZOP GPR traveltime data contain important information about subsurface hydraulic properties as a function of depth, with forced infiltration offering the greatest potential for VGM parameter refinement because of the higher stressing of the hydrological system. Considering greater amounts of time-lapse data in the inversion procedure is also found to help refine VGM parameter estimates. Quite importantly, however, inconsistencies observed in the field results point to the strong possibility that posterior uncertainties are being influenced by model structural errors, which in turn underlines the fundamental importance of a systematic analysis of such errors in future related studies.

U-Pb isotopic dating of fluid infiltration and metasomatism during Dalradian regional metamorphism in Connemara, western Ireland

A metasomatic diopside rock occurs at the top of the dolomitic Connemara Marble Formation of western Ireland and contains titanite and K-feldspar in addition to around 90% diopside (X(Mg) = 0.90-0.97). U-Pb isotopic measurements on this mineral assemblage show that the titanite is both unusually uranium-rich and isotopically concordant, with the result that a precise U-Pb age of 478 +/- 2.5 Ma can be determined. The age is identical within error to a less precise Rb-Sr age of diopside-K-feldspar of 483 +/- 6 Ma. Petrological evidence indicates that the assemblage crystallized at c. 620-degrees-C close to or below the closure temperature of titanite. The age thus provides a precise estimate of the time of metamorphism; this age is 11 +/- 3 Ma younger than the 490 Ma age for nearby gabbroic plutons which has previously been used to constrain the peak metamorphic age. This difference accords well with geological evidence that the gabbros were emplaced prior to the metamorphic peak. Analysis of minerals with high closure temperature from assemblages whose crystallization is unambiguously associated with a specific episode of fluid infiltration at the peak of metamorphism provides the basis for a new approach to dating metamorphism. The success of this approach is demonstrated by the results from Connemara.

Patients' and physicians' preferences for type 2 diabetes mellitus treatments in Spain and Portugal: a discrete choice experiment.

OBJECTIVE To assess Spanish and Portuguese patients' and physicians' preferences regarding type 2 diabetes mellitus (T2DM) treatments and the monthly willingness to pay (WTP) to gain benefits or avoid side effects. METHODS An observational, multicenter, exploratory study focused on routine clinical practice in Spain and Portugal. Physicians were recruited from multiple hospitals and outpatient clinics, while patients were recruited from eleven centers operating in the public health care system in different autonomous communities in Spain and Portugal. Preferences were measured via a discrete choice experiment by rating multiple T2DM medication attributes. Data were analyzed using the conditional logit model. RESULTS Three-hundred and thirty (n=330) patients (49.7% female; mean age 62.4 [SD: 10.3] years, mean T2DM duration 13.9 [8.2] years, mean body mass index 32.5 [6.8] kg/m(2), 41.8% received oral + injected medication, 40.3% received oral, and 17.6% injected treatments) and 221 physicians from Spain and Portugal (62% female; mean age 41.9 [SD: 10.5] years, 33.5% endocrinologists, 66.5% primary-care doctors) participated. Patients valued avoiding a gain in bodyweight of 3 kg/6 months (WTP: €68.14 [95% confidence interval: 54.55-85.08]) the most, followed by avoiding one hypoglycemic event/month (WTP: €54.80 [23.29-82.26]). Physicians valued avoiding one hypoglycemia/week (WTP: €287.18 [95% confidence interval: 160.31-1,387.21]) the most, followed by avoiding a 3 kg/6 months gain in bodyweight and decreasing cardiovascular risk (WTP: €166.87 [88.63-843.09] and €154.30 [98.13-434.19], respectively). Physicians and patients were willing to pay €125.92 (73.30-622.75) and €24.28 (18.41-30.31), respectively, to avoid a 1% increase in glycated hemoglobin, and €143.30 (73.39-543.62) and €42.74 (23.89-61.77) to avoid nausea. CONCLUSION Both patients and physicians in Spain and Portugal are willing to pay for the health benefits associated with improved diabetes treatment, the most important being to avoid hypoglycemia and gaining weight. Decreased cardiovascular risk and weight reduction became the third most valued attributes for physicians and patients, respectively.

How effective are policies to reduce gasoline consumption? evaluating a quasi-natural experiment in Spain

Using a panel of 48 provinces for four years we empirically analyze a series of temporary policies aimed at curbing fuel consumption implemented in Spain between March and June 2011. The first policy was a reduction in the speed limit in highways. The second policy was an increase in the biofuel content of fuels used in the transport sector. The third measure was a reduction of 5% in commuting and regional train fares that resulted in two major metropolitan areas reducing their overall fare for public transit. The results indicate that the speed limit reduction in highways reduced gasoline consumption by between 2% and 3%, while an increase in the biofuel content of gasoline increased this consumption. This last result is consistent with experimental evidence that indicates that mileage per liter falls with an increase in the biofuel content in gasolines. As for the reduction in transit fares, we do not find a significant effect for this policy. However, in specifications including the urban transit fare for the major cities in each province the estimated cross-price elasticity of the demand for gasoline -used as a proxy for car use- with respect to the price of transit is within the range reported in the literature. This is important since one of the main eficiency justification for subsidizing public transit rests on the positive value of this parameter and most of the estimates reported in the literature are quite dated.

Detection of millimetric deformation using a terrestrial laser scanner: experiment and application to a rockfall event

Abstract. Terrestrial laser scanning (TLS) is one of the most promising surveying techniques for rockslope characteriza- tion and monitoring. Landslide and rockfall movements can be detected by means of comparison of sequential scans. One of the most pressing challenges of natural hazards is com- bined temporal and spatial prediction of rockfall. An outdoor experiment was performed to ascertain whether the TLS in- strumental error is small enough to enable detection of pre- cursory displacements of millimetric magnitude. This con- sists of a known displacement of three objects relative to a stable surface. Results show that millimetric changes cannot be detected by the analysis of the unprocessed datasets. Dis- placement measurement are improved considerably by ap- plying Nearest Neighbour (NN) averaging, which reduces the error (1σ ) up to a factor of 6. This technique was ap- plied to displacements prior to the April 2007 rockfall event at Castellfollit de la Roca, Spain. The maximum precursory displacement measured was 45 mm, approximately 2.5 times the standard deviation of the model comparison, hampering the distinction between actual displacement and instrumen- tal error using conventional methodologies. Encouragingly, the precursory displacement was clearly detected by apply- ing the NN averaging method. These results show that mil- limetric displacements prior to failure can be detected using TLS.

The effects of walking while working on productivity and health: a field experiment

Lack of physical activity can cause health problems and diminish organizational productivity. We conducted a 12-months long field experiment in a financial services company to study the effects of slow-moving treadmills outfitted for office work on employee productivity and health. 43 sedentary volunteers were assigned randomly to two groups to receive treadmill workstations 7 months apart. Employees could opt at will for standard chair-desk arrangement. Biometric measurements were taken quarterly and weekly online performance surveys were administered to study participants and to more than 200 non-participants and their supervisors.In this study we explore three questions concerning the effects of the introduction of treadmills in the workplace. (1) Does it improve overall physical activity? (2) Does it improve health measures? (3) Does it improve performance? The answers are as follows. (1) Yes (net effect of almost half an hour a day). (2) Yes (small gains, one minor decline). (3) No and yes (initial decline followed by increase to recover to initial level within one year) – based on weekly employee self reports.

Supporting life-long competence development using the TENCompetence infrastructure: a first experiment

This paper describes an experiment to explore the effects of the TENCompetence infrastructure for supporting lifelong competence development which is now in development. This infrastructure provides structured, multi-leveled access to learning materials, based upon competences. People can follow their own learning path, supported by a listing of competences and their components, by competence development plans attached to competences and by the possibility to mark elements as complete. We expected the PCM to have an effect on (1) control of participants of their own learning, and (2) appreciation of their learning route, (3) of the learning resources, (4) of their competence development, and (5) of the possibilities of collaboration. In the experiment, 44 Bulgarian teachers followed a distance learning course on a specific teaching methodology for six weeks. Part of them used the TENCompetence infrastructure, part used an infrastructure which was similar, except for the characterizing elements mentioned above. The results showed that in the experimental condition, more people passed the final competence assess-ment, and people felt more in control of their own learning. No differences between the two groups were found on the amount and appreciation of collaboration and on further measures of competence development.

Health Information and the Choice of Fish Species: An Experiment Measuring the Impact of Risk and Benefit Information, April 2006

An experiment was conducted in France to evaluate the impact of health information on consumers’ choice between two different types of fish. Successive messages revealing risks (methylmercury) and benefits (omega-3s) of consuming the fish, along with consumption recommendations, were delivered. Results show a significant difference of reaction according to the order and type of information. The information about risks had a larger marginal impact on change in willingness to pay (WTP) than did the information about benefits. While the results show that detailed messages on risks/benefits, including recommendations for nutrition behavior, matter in the modification of WTP, 40% of respondents did not change their initial choices after the revelation of health information.

Optimal Contracts, Adverse Selection, and Social Preferences: An Experiment

It has long been standard in agency theory to search for incentive-compatible mechanisms on the assumption that people care only about their own material wealth. However, this assumption is clearly refuted by numerous experiments, and we feel that it may be useful to consider nonpecuniary utility in mechanism design and contract theory. Accordingly, we devise an experiment to explore optimal contracts in an adverse-selection context. A principal proposes one of three contract menus, each of which offers a choice of two incentive-compatible contracts, to two agents whose types are unknown to the principal. The agents know the set of possible menus, and choose to either accept one of the two contracts offered in the proposed menu or to reject the menu altogether; a rejection by either agent leads to lower (and equal) reservation payoffs for all parties. While all three possible menus favor the principal, they do so to varying degrees. We observe numerous rejections of the more lopsided menus, and approach an equilibrium where one of the more equitable contract menus (which one depends on the reservation payoffs) is proposed and agents accept a contract, selecting actions according to their types. Behavior is largely consistent with all recent models of social preferences, strongly suggesting there is value in considering nonpecuniary utility in agency theory.

Financial Repression in a Natural Experiment: Loan Allocation and the Change in the Usury Laws in 1714

If financial deepening aids economic growth, then financial repression should be harmful. We use a natural experiment – the change in the English usury laws in 1714 – to analyze the effects of interest rate restrictions. We use a sample of individual loan transactions to demonstrate how the reduction of the legal maximum rate of interest affected the supply and demand for credit. Average loan size and minimum loan size increased strongly, and access to credit worsened for those with little ‘social capital.’ While we have no direct evidence that loans were misallocated, the discontinuity in loan receipts makes this highly likely. We conclude that financial repression can undermine the positive effects of financial deepening.

Altruism, Equity, and Reciprocity in a Gift-Exchange Experiment: An Encompassing Approach

Considerable experimental evidence suggests that non-pecuniary motives must be addressed when modeling behavior in economic contexts. Recent models of non-pecuniary motives can be classified as either altruism- based, equity-based, or reciprocity-based. We estimate and compare leading approaches in these categories, using experimental data. We then offer a flexible approach that nests the above three approaches, thereby allowing for nested hypothesis testing and for determining the relative strength of each of the competing theories. In addition, the encompassing approach provides a functional form for utility in different settings without the restrictive nature of the approaches nested within it. Using this flexible form for nested tests, we find that intentional reciprocity, distributive concerns, and altruistic considerations all play a significant role in players' decisions.