Key Questions For Future Research Research Articles

Malignant pleural effusion: tumor-host interactions unleashed.

Malignant pleural effusion (MPE) poses a significant clinical problem. Current nonetiologic management is suboptimal in terms of efficacy and safety. In light of recent research progress, we propose herein a new view of MPE development, which may rapidly translate into meaningful changes in therapeutics. In addition to tumor-induced impairment of pleural fluid drainage, pertinent findings point toward another pathway to MPE formation: a vicious loop of interactions between pleural-based tumor cells and the host vasculature and immune system that results in increased net fluid production via enhanced plasma extravasation into the pleural space. The ability of tumor cells to trigger this cascade likely rests on a specific and distinct transcriptional repertoire, which results in important vasoactive events in the pleural space. Although the characterization of tumor-derived factors responsible for MPE development is in the making, an additional, indirect path to MPE was recently demonstrated: tumor cells recruit and co-opt host cells and mediators, which, in turn, amplify tumor cell-primed fluid leakage and impact tumor cell functions. Importantly, recent evidence suggests that the biologic events that culminate in clinical MPE are likely amenable to therapeutic inhibition and even prevention. In this perspective, the scientific basis for an update of current concepts of MPE formation is highlighted. Key questions for future research are posed. Finally, a vision for novel, effective, safe, and convenient treatment modalities that can be offered to outpatients with MPE is set forth.

Toward deconstructing the phenotype of late‐onset Pompe disease

Pompe disease (glycogen storage disease type 2 or acid maltase deficiency) is a rare autosomal recessive lysosomal storage disorder. Since the advent of ERT a lot has been learned about the phenotypic spectrum especially in the late onset patients. We describe in detail 44 patients diagnosed with late-onset Pompe disease (LOPD) at our neuromuscular department from 1985 to 2011 and compare them to patients with LOPD in the literature of the past 40 years. Study of the Munich LOPD group revealed varying musculoskeletal and cardio-cerebrovascular manifestation patterns. Several of these symptom patterns commonly appeared in conjunction with one another, highlighting the multisystem involvement of this condition. Common symptom patterns include: (i) Classic limb girdle and diaphragmatic weakness, (ii) rigid spine syndrome (RSS), scoliosis, and low body mass, and (iii) several cardio-cerebrovascular manifestation patterns. The most common presentation, limb girdle and diaphragmatic weakness, appeared in 78% (34/44) of our patients and over 80% of those in the literature. Sixteen percent (7/44) of our patients presented with rigid spine, scoliosis, and low body mass. Although scoliosis had a reported frequency of 33% in the general LOPD patient population, the literature only occasionally reported low body mass and RSS. Importantly, a multisystem extramuscular finding accompanied by cardio-cerebrovascular manifestations was found in 29% (13/44) of our LOPD patients; the literature showed an increasing prevalence of this latter finding. By examining the phenotype of patients with confirmed LOPD, we found a more subtle clinical multisystem involvement in LOPD. Whether patients presenting with the different symptom patterns respond differently to enzyme replacement therapy remains a key question for future research. © 2012 Wiley Periodicals, Inc.

Stimulus generalization and return of fear in C57BL/6J mice

Return of fear following successful exposure therapy is a common problem. More insight into the characteristics of extinction learning is crucial in enhancing the efficiency of therapeutic interventions. In particular, understanding the mechanisms that underlie the generalization of extinction learning to other discrete stimuli is indispensable. Presently, little is known about the molecular and genetic mechanisms underlying this phenomenon. In this study, we attempt to develop a new conditioning protocol to study return of fear, caused by a stimulus change after extinction, in the most commonly used mouse strain of behavioral genetics, C57BL/6J. Perceptual changes to an auditory fear conditioned stimulus led to return of fear after initially successful fear-reduction, relative to appropriate control treatment. We argue that this protocol will be a useful tool to unravel the neurobiological underpinnings that regulate generalization of extinction and return of fear. Key questions for future research include the identification of crucial brain structures, neurotransmitters and signaling pathways that underly this behavioral phenomenon. Arguably, such research will open up new perspectives for neurobiological therapy augmentation.

Mate choice for cognitive traits: a review of the evidence in nonhuman vertebrates

To what extent do individuals assess the cognitive abilities of the opposite sex when choosing a mate? With the exception of song learning in birds, the hypothesis that cognitive traits are under sexual selection has received attention only recently. Here, we evaluate the evidence for this hypothesis in nonhuman vertebrates. We first briefly review the literature on brain development, which shows that cognition may be a sensitive indicator of early developmental conditions. We then consider the empirical evidence that females choose mates with better cognitive skills, which may be reflected in males' courtship displays, foraging performance, courtship feeding, or diet-dependent morphological traits. There is very little research that assesses whether females discriminate between males through direct observation of cognitively demanding behavior. Instead, several studies support female choice on the basis of morphological traits correlated with cognitive abilities. We conclude by highlighting key questions for future research: 1) To what extent do cognitive skills determine foraging success, courtship feeding, and the expression of diet-dependent morphological traits? 2) Do behavioral courtship displays depend on motor development and physiological maturation or learning through practice and experience? 3) How do cognitive abilities affect survival and mating success? Studies on a range of vertebrate taxa, with their diverse mating systems and cognitive ecologies, offer great potential to tackle these questions and deepen our understanding of sexual selection on cognition. Copyright 2011, Oxford University Press.

Outcomes of a National Institute of Allergy and Infectious Diseases Workshop on Understanding HIV-Exposed but Seronegative Individuals

The fascinating conundrum that some individuals who are exposed to HIV in ways that would make viral transmission highly likely, yet are able to remain uninfected, has been appreciated for many years. As early as the late 1980s, reports of such individuals began appearing in the HIV/AIDS literature. Despite the critical importance of understanding possible mechanisms of natural HIV resistance for developing effective prevention strategies, numerous obstacles have prevented this essential area of scientific exploration from moving forward. The Workshop held on July 8-9, 2010 and supported by the Office of AIDS Research (OAR), the National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute on Drug Abuse (NIDA) at the NIH hosted 200 participants and utilized the expertise of 42 AIDS researchers as invited speakers, session chairs, and discussion leaders for presentations and breakout sessions in an attempt to remove some of those obstacles. Accomplishments of the participants included developing a consensus for a new general term for the field, HIV-exposed seronegative (HESN), while recognizing the necessity to identify and utilize secondary descriptive criteria such as exposure level, risk group, duration of seronegativity, or natural resistance. Three key questions for future research were also identified by the group: (1) What is different in HESN versus those who get infected? (2) What is the immune response in HESN and is it just a marker of exposure or a correlate of protection? (3) What are the HESN host factors that help HESN resist infection? This report briefly summarizes the presentations, and describes future directions for addressing these questions and challenges.

The Recognition Heuristic: A Review of Theory and Tests

The recognition heuristic is a prime example of how, by exploiting a match between mind and environment, a simple mental strategy can lead to efficient decision making. The proposal of the heuristic initiated a debate about the processes underlying the use of recognition in decision making. We review research addressing four key aspects of the recognition heuristic: (a) that recognition is often an ecologically valid cue; (b) that people often follow recognition when making inferences; (c) that recognition supersedes further cue knowledge; (d) that its use can produce the less-is-more effect – the phenomenon that lesser states of recognition knowledge can lead to more accurate inferences than more complete states. After we contrast the recognition heuristic to other related concepts, including availability and fluency, we carve out, from the existing findings, some boundary conditions of the use of the recognition heuristic as well as key questions for future research. Moreover, we summarize developments concerning the connection of the recognition heuristic with memory models. We suggest that the recognition heuristic is used adaptively and that, compared to other cues, recognition seems to have a special status in decision making. Finally, we discuss how systematic ignorance is exploited in other cognitive mechanisms (e.g., estimation and preference).

Pollination ecology in the 21st Century: Key questions for future research

To inspire new ideas in research on pollination ecology, we list the most important unanswered questions in the field. This list was drawn up by contacting 170 scientists from different areas of pollination ecology and asking them to contribute their opinion on the greatest knowledge gaps that need to be addressed. Almost 40% of them took part in our email poll and we received more than 650 questions and comments, which we classified into different categories representing various aspects of pollination research. The original questions were merged and synthesised, and a final vote and ranking led to the resultant list. The categories cover plant sexual reproduction, pollen and stigma biology, abiotic pollination, evolution of animal-mediated pollination, interactions of pollinators and floral antagonists, pollinator behaviour, taxonomy, plant-pollinator assemblages, geographical trends in diversity, drivers of pollinator loss, ecosystem services, management of pollination, and conservation issues such as the implementation of pollinator conservation. We focused on questions that were of a broad scope rather than case-specific; thus, addressing some questions may not be feasible within single research projects but constitute a general guide for future directions. With this compilation we hope to raise awareness of pollination-related topics not only among researchers but also among non-specialists including policy makers, funding agencies and the public at large. download Appendix

Assessment and management of methotrexate hepatotoxicity in psoriasis patients: report from a consensus conference to evaluate current practice and identify key questions toward optimizing methotrexate use in the clinic

Experts in psoriasis, hepatology, pharmacokinetics and pharmacogenetics convened to discuss the safety and monitoring of methotrexate with respect to hepatotoxicity when used in the treatment of psoriasis. Methotrexate is an efficacious and cost-effective treatment for psoriasis, but is associated with significant safety issues, particularly relating to hepatotoxicity. Current British, Dutch, German, EU and US guidelines for baseline evaluations, monitoring and prevention of hepatotoxicity in patients with psoriasis receiving methotrexate were evaluated. Liver safety monitoring is currently reliant upon multiple methods, including biopsy, serological tests for biomarkers such as type III procollagen amino terminal propeptide (PIIINP), and liver function tests based on liver enzymes. Monitoring of patients receiving long-term therapy is expected to be improved by the utilization of serum biomarkers currently in development such as the Enhanced Liver Fibrosis (ELF) panel and other non-invasive tests of hepatic architecture, such as fibroelastography, microbubbles and magnetic resonance imaging. Appropriate studies to determine optimal dosing to maximize efficacy and minimize toxicity, potentially utilizing pharmacogenetic principles, are clearly needed. Key questions for future research are identified including needs for optimal screening and monitoring, identification of appropriate biomarkers, assessment of relationships between dosing and safety, utility of liver biopsy, optimal dosing regimens (including route of administration), methods to measure methotrexate levels in blood, and use of methotrexate as a standardized active comparator in trials of experimental drugs used to treat psoriasis.

Emotional Prosperity and the Stiglitz Commission

AbstractThis article argues — in line with the proposals of the recent Stiglitz Commission on the Measurement of Economic Performance and Social Progress — that we should now be measuring a nation's emotional prosperity rather than its economic prosperity (i.e. we ought to focus on the level of mental well‐being, not on the number of pounds in people's bank accounts). The article reviews recent ideas in this field. It also describes seven recent studies that, worryingly, suggest that emotional prosperity may be declining through time. For labour‐market specialists, a key question for future research is how much this downward trend can be traced back to increased pressures in working life. That question currently remains open.

Personalities of Self-Identified “Dog People” and “Cat People”

ABSTRACTAlleged personality differences between individuals who self-identify as “dog people” and “cat people” have long been the topic of wide-spread speculation and sporadic research. Yet existing studies offer a rather conflicting picture of what personality differences, if any, exist between the two types of person. Here we build on previous research to examine differences in the Big Five personality dimensions between dog people and cat people. Using a publicly accessible website, 4,565 participants completed the Big Five Inventory and self-identified as a dog person, cat person, both, or neither. Results suggest that dog people are higher on Extraversion, Agreeableness, and Conscientiousness, but lower on Neuroticism and Openness than are cat people. These differences remain significant even when controlling for sex differences in pet-ownership rates. Discussion focuses on the possible sources of personality differences between dog people and cat people and identifies key questions for future research.

The Impact of Self‐Affirmation on Health‐Related Cognition and Health Behaviour: Issues and Prospects

AbstractIn a recent paper (Harris & Epton, Social and Personality Psychology Compass, 2009; 3, 962–978), we reviewed the evidence showing that self‐affirming – the act of reflecting upon cherished values or attributes – can reduce resistance to health‐risk information. In this companion paper, we extend the discussion of issues arising from that review and describe key questions for future research. Overall, we regard the picture emerging from this nascent literature as encouraging. Nevertheless, more needs to be discovered about how self‐affirming achieves its effects and their limits. Despite lowering an important barrier to health behaviour change by reducing message resistance, there is currently only limited evidence that self‐affirming changes subsequent health behaviour. We consider why. We also discuss issues to address in interventions involving self‐affirmation and examine evidence that self‐affirming alters relationships between variables. There is also scope for extending the range of samples, health information and health behaviours examined and for assessing more spontaneous self‐affirmation.

Overview of aircraft en‐route noise prediction.

Community noise near airports is a major aviation noise concern, prompting the development of various modeling tools to predict the noise changes due to airport expansion and fleet changes. Once aircraft leave the terminal area and reach high altitudes, the aircraft noise received on the ground is assumed to be insignificant relative to urban ambient noise and is often neglected. However, this might not be the case, under either of the following conditions: (1) when aircraft fly over areas with very low ambient noise levels, such as in wildness areas, or (2) when an aircraft is powered by advanced propulsion systems that produces high noise levels. There is an increasing need to address both of these issues. Over the past 2 decades, some limited noise modeling capabilities and related research have begun to quantify the high‐altitude aircraft noise or “en‐route” noise. The purpose of this paper is to review and summarize related noise prediction research conducted through direct technical exchange with researchers, some simple data analysis as well as through a literature review. The authors will draw on experience in developing current aircraft community noise tools and formulate key future research questions and options.

Emotional Prosperity and the Stiglitz Commission

This paper argues – in line with the proposals of the recent Stiglitz Commission on the Measurement of Economic Performance and Social Progress – that we should now be measuring a nation's emotional prosperity rather than its economic prosperity (that is, we ought to focus on the level of mental well-being not the number of pounds in people's bank accounts). The paper reviews recent ideas in this field. It also describes seven recent studies that, worryingly, suggest that emotional prosperity may be declining through time. For labour-market specialists, a key question for future research is how much this downward trend can be traced back to increased pressures in working life. That question currently remains open.

Improving the self-report of HIV antiretroviral medication adherence: Is the glass half full or half empty?

Self-reports are the most widely used method for measuring antiretroviral adherence. The association between self-reports and viral loads has been repeatedly demonstrated, but this association does not address how well self-reports measure actual medication-taking behaviors. Understanding adherence self-reports requires studying the science of memory and the reporting of behaviors. In the first section of this review, we discuss research in cognitive psychology that pertains to adherence self-reports, focusing primarily on studies that examine cognitive processes respondents use to answer survey questions. In the second section, we review recent articles examining the relationship between self-reports and objective measures of adherence, highlighting the strength of associations and key methodologic issues. We conclude with key questions for future research and methodologic recommendations.

Symbolic, numeric, and magnitude representations in the parietal cortex

AbstractWe concur with Cohen Kadosh & Walsh (CK&W) that representation of numbers in the parietal cortex is format dependent. In addition, we suggest that all formats do not automatically, and equally, access analog magnitude representation in the intraparietal sulcus (IPS). Understanding how development, learning, and context lead to differential access of analog magnitude representation is a key question for future research.

Domestic Diversity and Foreign Policy Making in Canada

The World in Canada: Diaspora, Demography, and Domestic Politics. Edited by David Carment, David Bercuson. Montreal: McGill-Queen's University Press, 2008. 256 pp., $29.95 paperback (ISBN-13: 978-0-7735-3297-7). This is a very interesting and useful collection of essays that summarizes research on the influence of changing demography and domestic interests on the foreign policy making processes in Canada. At the same time, it identifies the key questions for future research in this important area. The editors identify three potentially critical independent variables that influence Canadian foreign policy and provide the raison d’etre for the volume: (1) changes in the ethnic mosaic in Canada; (2) government responsiveness to demographic changes; (3) influences derived from domestic politics. Each of the 10 chapters (plus the introduction and conclusion) responds to one or more of the three basic questions posed in the book about the influence of these variables on foreign policy making. If we had …

Trade and Development: Lessons from Vietnam’s Past Trade Agreements

History, not predictions of CGE models or cross-country growth studies, shows a strong relationship between trade and development. Vietnam’s experience with bilateral trade agreements, comparing actual outcomes with predictions from existing models, demonstrates this and the limitations of research methodologies. Forecasts for Vietnam greatly underestimated the impact of past agreements because tariff reform was not the main factor driving adjustments. Addressing market imperfections through institutional reform was central to bringing output and trade expansion. Key questions for future research are whether policy reform will result in new institutional changes, and how resulting incentives determine the evolution of investment by sector.

Key future research questions on mediators and moderators of behaviour change processes for substance abuse

In summarizing the key themes and results of the second meeting of the German Addiction Research Network 'Understanding Addiction: Mediators and Moderators of Behaviour Change Process', the following concrete steps forward were laid out to improve knowledge. The steps included pleas to (1) redefine substance abuse disorders, especially redefine the concept of abuse and harmful use; (2) increase the use of longitudinal and life-course studies with more adequate statistical methods such as latent growth modelling; (3) empirically test more specific and theoretically derived common factors and mechanisms of behavioural change processes; (4) better exploit cross-regional and cross-cultural differences.Funding agencies are urged to support these developments by specifically supporting interdisciplinary research along the lines specified above. This may include improved forms of international funding of groups of researchers from different countries, where each national group conducts a specific part of an integrated proposal.

Avirulence proteins from haustoria-forming pathogens

A major insight that has emerged in the study of haustoria-forming plant pathogens over the last few years is that these eukaryotic biotrophs deliver suites of secreted proteins into host cells during infection. This insight has largely derived from successful efforts to identify avirulence (Avr) genes and their products from these pathogens. These Avr genes, identified from a rust and a powdery mildew fungus and three oomycete species, encode small proteins that are recognized by resistance proteins in the host plant cytoplasm, suggesting that they are transported inside plant cells during infection. These Avr proteins probably represent examples of fungal and oomycete effector proteins with important roles in subverting host cell biology during infection. In this respect, they represent a new opportunity to understand the basis of disease caused by these biotrophic pathogens. Elucidating how these pathogen proteins gain entry into plant cells and their biological function will be key questions for future research.

Suspicious minds: The psychology of persecutory delusions

At least 10–15% of the general population regularly experience paranoid thoughts and persecutory delusions are a frequent symptom of psychosis. Persecutory ideation is a key topic for study. In this article the empirical literature on psychological processes associated with persecutory thinking in clinical and non-clinical populations is comprehensively reviewed. There is a large direct affective contribution to the experience. In particular, anxiety affects the content, distress and persistence of paranoia. In the majority of cases paranoia does not serve a defensive function, but instead builds on interpersonal concerns conscious to the person. However, affect alone is not sufficient to produce paranoid experiences. There is also evidence that anomalous internal experiences may be important in leading to odd thought content and that a jumping to conclusions reasoning bias is present in individuals with persecutory delusions. Theory of mind functioning has received particular research attention recently but the findings do not support a specific association with paranoia. The threat anticipation cognitive model of persecutory delusions is presented, in which persecutory delusions are hypothesised to arise from an interaction of emotional processes, anomalous experiences and reasoning biases. Ten key future research questions are identified, including the need for researchers to consider factors important to the different dimensions of delusional experience.