Identifying the science and technology dimensions of emerging public policy issues through horizon scanning

Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security.Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security

The role of noise and positive feedback in the onset of autosomal dominant diseases

<p>Abstract</p> <p>Background</p> <p>Autosomal dominant (AD) diseases result when a single mutant or non-functioning gene is present on an autosomal chromosome. These diseases often do not emerge at birth. There are presently two prevailing theories explaining the expression of AD diseases. One explanation originates from the Knudson two-hit theory of hereditary cancers, where loss of heterozygosity or occurrence of somatic mutations impairs the function of the wild-type copy. While these somatic second hits may be sufficient for stable disease states, it is often difficult to determine if their occurrence necessarily marks the initiation of disease progression. A more direct consequence of a heterozygous genetic background is haploinsufficiency, referring to a lack of sufficient gene function due to reduced wild-type gene copy number; however, haploinsufficiency can involve a variety of additional mechanisms, such as noise in gene expression or protein levels, injury and second hit mutations in other genes. In this study, we explore the possible contribution to the onset of autosomal dominant diseases from intrinsic factors, such as those determined by the structure of the molecular networks governing normal cellular physiology.</p> <p>Results</p> <p>First, simple models of single gene insufficiency using the positive feedback loops that may be derived from a three-component network were studied by computer simulation using Bionet software. The network structure is shown to affect the dynamics considerably; some networks are relatively stable even when large stochastic variations in are present, while others exhibit switch-like dynamics. In the latter cases, once the network switches over to the disease state it remains in that state permanently. Model pathways for two autosomal dominant diseases, AD polycystic kidney disease and mature onset diabetes of youth (MODY) were simulated and the results are compared to known disease characteristics.</p> <p>Conclusions</p> <p>By identifying the intrinsic mechanisms involved in the onset of AD diseases, it may be possible to better assess risk factors as well as lead to potential new drug targets. To illustrate the applicability of this study of pathway dynamics, we simulated the primary pathways involved in two autosomal dominant diseases, Polycystic Kidney Disease (PKD) and mature onset diabetes of youth (MODY). Simulations demonstrate that some of the primary disease characteristics are consistent with the positive feedback - stochastic variation theory presented here. This has implications for new drug targets to control these diseases by blocking the positive feedback loop in the relevant pathways.</p

Specific phobia predicts psychopathology in young women

Contains fulltext : 90255.pdf (publisher's version ) (Closed access)Although specific phobia is characterized by an early age at onset and by high rates of comorbidity, few studies have examined comorbid relationships prospectively. The present study investigated the association between specific phobia and the risk of a broad range of psychopathology among young women in the community. Data came from the Dresden Predictor Study in which 1,538 German women (18-25 years) completed a diagnostic interview at two time points. Women with specific phobia had a twofold increase in odds of developing any anxiety disorder, generalized anxiety disorder, depression, and any somatoform disorder during 17 months, compared to women without specific phobia. Except for depression, these associations persisted after adjustment for all comorbid mental disorders. Specific phobia thus appears to be a risk factor for a variety of problems. The result further underpins the necessity for early intervention for specific phobia to prevent later mental health problems

Comparison of the influence of cyclosporine and tacrolimus on the pharmacokinetics of prednisolone in adult male kidney transplant recipients

Cyclosporine has been observed to precipitate cushingoid features in kidney transplant recipients already on prednisolone. Some pharmacokinetic studies have demonstrated increased prednisolone exposure in patients on cyclosporine therapy compared with azathioprine, whereas other studies have found no difference. The objective of this study was to determine whether cyclosporine impacts on prednisolone exposure as compared with tacrolimus

Serum free light chain measurement aids the diagnosis of myeloma in patients with severe renal failure

<p>Abstract</p> <p>Background</p> <p>Monoclonal free light chains (FLCs) frequently cause rapidly progressive renal failure in patients with multiple myeloma. Immunoassays which provide quantitative measurement of FLCs in serum, have now been adopted into screening algorithms for multiple myeloma and other lymphoproliferative disorders. The assays indicate monoclonal FLC production by the presence of an abnormal κ to λ FLC ratio (reference range 0.26–1.65). Previous work, however, has demonstrated that in patients with renal failure the FLC ratio can be increased above normal with no other evidence of monoclonal proteins suggesting that in this population the range should be extended (reference range 0.37–3.1). This study evaluated the diagnostic sensitivity and specificity of the immunoassays in patients with severe renal failure.</p> <p>Methods</p> <p>Sera from 142 patients with new dialysis-dependent renal failure were assessed by serum protein electrophoresis (SPE), FLC immunoassays and immunofixation electrophoresis. The sensitivity and specificity of the FLC ratio's published reference range was compared with the modified renal reference range for identifying patients with multiple myeloma; by receiver operating characteristic curve analysis.</p> <p>Results</p> <p>Forty one patients had a clinical diagnosis of multiple myeloma; all of these patients had abnormal serum FLC ratios. The modified FLC ratio range increased the specificity of the assays (from 93% to 99%), with no loss of sensitivity. Monoclonal FLCs were identified in the urine from 23 of 24 patients assessed.</p> <p>Conclusion</p> <p>Measurement of serum FLC concentrations and calculation of the serum κ/λ ratio is a convenient, sensitive and specific method for identifying monoclonal FLC production in patients with multiple myeloma and acute renal failure. Rapid diagnosis in these patients will allow early initiation of disease specific treatment, such as chemotherapy plus or minus therapies for direct removal of FLCs.</p

Associations of familial risk factors with social fears and social phobia: evidence for the continuum hypothesis in social anxiety disorder?

We examined parental psychopathology and family environment in subthreshold and DSM-IV threshold conditions of social anxiety disorder (SAD) in a representative cohort sample of 1,395 adolescents. Offspring and parental psychopathology was assessed using the DIA-X/M-CIDI; recalled parental rearing and family functioning via questionnaire. Diagnostic interviews in parents were supplemented by family history reports from offspring. The cumulative lifetime incidence was 23.07% for symptomatic SAD, and 18.38 and 7.41% for subthreshold and threshold SAD, respectively. The specific parent-to-offspring association for SAD occurred for threshold SAD only. For subthreshold and threshold SAD similar associations were found with other parental anxiety disorders, depression and substance use disorders. Parental rearing behaviour, but not family functioning, was associated with offspring threshold SAD, and although less strong and less consistent, also with subthreshold SAD. Results suggest a continued graded relationship between familial risk factors and offspring SAD. Parental psychopathology and negative parental styles may be used defining high-risk groups to assign individuals with already subthreshold conditions of SAD to early intervention programs

A Phenotypic Profile of the Candida albicans Regulatory Network

Candida albicans is a normal resident of the gastrointestinal tract and also the most prevalent fungal pathogen of humans. It last shared a common ancestor with the model yeast Saccharomyces cerevisiae over 300 million years ago. We describe a collection of 143 genetically matched strains of C. albicans, each of which has been deleted for a specific transcriptional regulator. This collection represents a large fraction of the non-essential transcription circuitry. A phenotypic profile for each mutant was developed using a screen of 55 growth conditions. The results identify the biological roles of many individual transcriptional regulators; for many, this work represents the first description of their functions. For example, a quarter of the strains showed altered colony formation, a phenotype reflecting transitions among yeast, pseudohyphal, and hyphal cell forms. These transitions, which have been closely linked to pathogenesis, have been extensively studied, yet our work nearly doubles the number of transcriptional regulators known to influence them. As a second example, nearly a quarter of the knockout strains affected sensitivity to commonly used antifungal drugs; although a few transcriptional regulators have previously been implicated in susceptibility to these drugs, our work indicates many additional mechanisms of sensitivity and resistance. Finally, our results inform how transcriptional networks evolve. Comparison with the existing S. cerevisiae data (supplemented by additional S. cerevisiae experiments reported here) allows the first systematic analysis of phenotypic conservation by orthologous transcriptional regulators over a large evolutionary distance. We find that, despite the many specific wiring changes documented between these species, the general phenotypes of orthologous transcriptional regulator knockouts are largely conserved. These observations support the idea that many wiring changes affect the detailed architecture of the circuit, but not its overall output

A Functional Magnetic Resonance Imaging Assessment of Small Animals Phobia Using Virtual Reality as a Stimulus

[EN] Background: To date, still images or videos of real animals have been used in functional magnetic resonance imaging protocols to evaluate the brain activations associated with small animals phobia. Objective: The objective of our study was to evaluate the brain activations associated with small animals phobia through the use of virtual environments. This context will have the added benefit of allowing the subject to move and interact with the environment, giving the subject the illusion of being there. Methods: We have analyzed the brain activation in a group of phobic people while they navigated in a virtual environment that included the small animals that were the object of their phobia. Results: We have found brain activation mainly in the left occipital inferior lobe (P<.05 corrected, cluster size=36), related to the enhanced visual attention to the phobic stimuli; and in the superior frontal gyrus (P<.005 uncorrected, cluster size=13), which is an area that has been previously related to the feeling of self-awareness. Conclusions: In our opinion, these results demonstrate that virtual stimulus can enhance brain activations consistent with previous studies with still images, but in an environment closer to the real situation the subject would face in their daily lives.This study was funded by Vicerrectorado de Investigación de la Universitat Politècnica de València, Spain, PAID-06-2011, RN 1984; by the Ministerio de Educación y Ciencia Spain, Project Game Teen (TIN2010-20187); and partially by projects Consolider-C (SEJ2006-14301/PSIC), “CIBER of Physiopathology of Obesity and Nutrition, an initiative of ISCIII”, the Excellence Research Program PROMETEO (Generalitat Valenciana. Conselleria de Educación, 2008-157), and the Consolider INGENIO program (CSD2007-00012). Generalitat Valenciana, under a VALi+d Grant, supported the work of MC.Clemente Bellido, M.; Rey Solaz, B.; Rodríguez Pujadas, A.; Breton Lopez, J.; Barros Loscertales, A.; Baños, RM.; Botella, C.... (2014). A Functional Magnetic Resonance Imaging Assessment of Small Animals Phobia Using Virtual Reality as a Stimulus. JMIR Serious Games. 2(1)(6):1-12. https://doi.org/10.2196/games.2836S1122(1)