Defining the critical hurdles in cancer immunotherapy.

Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer.

New evidence for a thermogenic defect in human obesity.

A reduced thermogenic response to food ingestion may contribute to the dynamic phase of weight gain in obesity. A defect in diet-induced thermogenesis has been reported in about one third of an unselected group of obese women. After inducing weight loss with a hypocaloric diet, the thermogenic defect does not disappear. Since basal metabolic rate decreases with weight loss, the overall postprandial energy expenditure of 'post-obese' individuals can be lower than that of lean controls. As a consequence, post-obese subjects must reset energy intake to a lower level than the previous maintenance food consumption in order to avoid relapse of body weight gain.

Population density and offspring size in the cladoceran Simocephalus vetulus (Müller)

r/K theory classically predicts that offspring size should increase under density-dependent selection. However, this is questionable, being based on implicit rather than explicit assumption (the logistic model does not include offsring size as a parameter). From recent models of optimal offspring size (Sibly & Calow, 1983; Taylor & Williams, 1984) it can be shown that density should select for larger offspring if density-dependence in the per capita rate of increase is mainly due to a reduction of the juvenile growth rate or survivorship. In contrast, density should select for smaller offspring if such density-dependence is mainly due to a reduction of adult fecundity or survivorship. Therfore, the outcome of selection cannot be predicted without precise knowledge of the density-dependence of age-specific reproduction and mortality rates. To test the above models, genetically identical individuals of Simocephalus vetulus (Müller) were reared in a density gradient; density-dependence in the per capita rate of increase was shown to be mainly due to a reduction of the juvenile growth rate, thereby selecting for larger offspring; offspring size at birth appeared to be phenotypically plastic and to increase with density. Models were therefore qualitatively supported. However, a discrepancy occurred in quantitative predictions; offspring were produced larger than predicted. Field and laboratory studies are suggested to address this.

Body Size, Activity, Employment and Wages in Europe: A First Approach

In this article we present the first empirical analysis on the associations between body size, activity, employment and wages for several European countries. The main advantage of the present work with respect to the previous literature is offered by the comparability of the data and its large geographical coverage. According to our results, for Spanish women, being obese is associated with both a 9% lower wage and probability of being employed, while for Swedish and Danish, obesity is associated with a 12% lower probability of being employed, and a 10% lower wage respectively. In Belgium, obesity is associated with a 19% lower probability of being employed for men. These robust estimates are strongly informative and may be used as a simple statistical rule of thumb to decide the countries in which lab and field experiments should be run.

Recognition judgments and the performance of the recognition heuristic depend on the size of the reference class

In a series of three experiments, participants made inferences about which one of a pair of two objects scored higher on a criterion. The first experiment was designed to contrast the prediction of Probabilistic Mental Model theory (Gigerenzer, Hoffrage, & Kleinbölting, 1991) concerning sampling procedure with the hard-easy effect. The experiment failed to support the theory's prediction that a particular pair of randomly sampled item sets would differ in percentage correct; but the observation that German participants performed practically as well on comparisons between U.S. cities (many of which they did not even recognize) than on comparisons between German cities (about which they knew much more) ultimately led to the formulation of the recognition heuristic. Experiment 2 was a second, this time successful, attempt to unconfound item difficulty and sampling procedure. In Experiment 3, participants' knowledge and recognition of each city was elicited, and how often this could be used to make an inference was manipulated. Choices were consistent with the recognition heuristic in about 80% of the cases when it discriminated and people had no additional knowledge about the recognized city (and in about 90% when they had such knowledge). The frequency with which the heuristic could be used affected the percentage correct, mean confidence, and overconfidence as predicted. The size of the reference class, which was also manipulated, modified these effects in meaningful and theoretically important ways.

Stress, coping and presenteeism in nurses assisting critical and potentially critical patients

Objective to verify the associations between stress, Coping and Presenteeism in nurses operating on direct assistance to critical and potentially critical patients. Method this is a descriptive, cross-sectional and quantitative study, conducted between March and April 2010 with 129 hospital nurses. The Inventory of stress in nurses, Occupational and Coping Questionnaire Range of Limitations at Work were used. For the analysis, the Kolmogorov-Smirnov test, correlation coefficient of Pearson and Spearman, Chi-square and T-test were applied. Results it was observed that 66.7% of the nurses showed low stress, 87.6% use control strategies for coping stress and 4.84% had decrease in productivity. Direct and meaningful relationships between stress and lost productivity were found. Conclusion stress interferes with the daily life of nurses and impacts on productivity. Although the inability to test associations, the control strategy can minimize the stress, which consequently contributes to better productivity of nurses in the care of critical patients and potentially critical.


Management of basic health units in municipalities of different size: profile and management instruments

Objective To identify the characteristics of managers and their use of management instruments in primary care and to analyze differences in these features among municipalities of different sizes. Method The present cross-sectional descriptive study was conducted at 108 basic health units from 21 municipalities in northern Paraná, Brazil. The data were collected using a semi-structured questionnaire during the second half of 2010. Results Most managers had graduate degrees and were female and nurses. The managers from the small municipalities were younger, their payment was lower, and they had less work experience. The use of management instruments was expressive for both the organization and work management; however, the instruments were used less in the small municipalities. Conclusion The managers were committed to their role; it is recommended that policies and guidance should be formulated at the federal and state levels to support small municipalities.

Report of Task Force into Critical Incidents within the Iowa Prison System, 2004

Report #02-04 Concerns about the death of two Iowa inmates at the Anamosa State Penitentiary, asked the Ombudsman Office to review the incidents and provide an assessment of each incident. The Governor also asked the Ombudsman Office to propose a set of recommendations for improving inmate and staff safety within Anamosa State Penitentiary.

Probing the T-cell receptor repertoire with deep sequencing.

PURPOSE OF REVIEW: To review major findings on the T-cell receptor (TCR) repertoire diversity in response to several viral infections based on conventional methods of PCR, cloning and sequencing and to discuss their limitations in light of the recent methodological advances in deep sequencing.¦RECENT FINDINGS: Direct sequencing of TCR expressed by Ag-specific T cells isolated ex vivo has revealed that the TCR repertoire is not as restricted as previously estimated. Furthermore, analyses performed independently of the T-cell clonal hierarchy have brought to light an unexpected diversity. The choice of methods is critical to characterize the complexity of the repertoire. Recent advances in deep sequencing have uncovered the diversity of the TCR repertoire and shown that the size of the repertoire in naive and Ag-experienced memory T cells is three-fold to 15-fold larger than formerly estimated. Interestingly, the TCR complementary determining region 3 sequences are not randomly selected and a certain degree of shared TCR repertoire has been observed between different individuals.¦SUMMARY: Deep sequencing is a major methodological advance allowing more accurate molecular characterization of the TCR repertoire. In the near future, such technologies will further contribute to delineate the complexity of pathogen-specific T-cell response and help defining correlates of a protective immunity.