Some observations on perceptions of radiation risks in the context of nuclear power plant accidents.

As highlighted by public reactions to accidents at nuclear plants in the past, such as those that occurred in Chernobyl (1986) and Fukushima (2011), and from numerous opinion surveys, there are considerable differences or gaps between how the public and radiation experts perceive the risks from radiation. Even within the community of experts, radiation risk perception differences can be present. The reasons for differences in radiation risk perceptions between the public and experts are complex and involve sociological, ethical and behavioural aspects of society. This presents significant challenges to authorities in trying to improve radiation risk communications targeted at the public within the context of radiation emergency preparedness planning. Of particular importance is to make the communications more citizen-centred than heretofore by having meaningful two-way communications and dialogue with the public. It is emphasised that such strategies should take into account and address the significant mental health and socio-economic impacts of such accidents on affected populations. In particular, the mental health impacts are inadequately addressed by current international radiation protection recommendations reflecting their long established emphasis only on physical health effects. This approach is no longer acceptable or justified.

Public perceptions of pharmacogenomic services in Ireland - Are people with chronic disease more likely to want service availability than those without? A questionnaire study.

Background: As pharmacogenomic services begin to emerge in primary care, the insight of the public is crucial for its integration into clinical practice. Objectives: To establish perceptions of pharmacogenomics (awareness, understanding, openness to availability, perceived benefits and concerns, willingness to pay, and service setting) and investigate if they differ between those with and without chronic disease(s). Methods: An anonymous, online questionnaire generated using Qualtrics® and circulated via social media and posters placed in eight participating community pharmacies was conducted with Irish adults. The questions were designed to consider existing literature on patient perceptions of pharmacogenomics. Descriptive statistics were used to summarize questionnaire responses. Chi-square test was used to compare categorical variables, while independent sample t-test and one-way ANOVA were used to compare the mean values of two (with and without chronic disease) and three groups (multimorbidity (two or more chronic conditions) and polypharmacy (prescribed four or more regular medicines) (MMPP), a single chronic disease, and those without existing medical conditions) respectively Logistic regression was used to evaluate age and gender adjusted associations of chronic disease(s) with responses. A p-value <0.05 was considered statistically significant. Results: A total of 421 responses were received, 30% (n = 120) of whom reported having a chronic disease. Overall, respondents reported low awareness (44%, n = 166) and poor knowledge (55%, n = 212) of pharmacogenomics. After explaining pharmacogenomics to respondents, patients with chronic disease(s) were 2.17 times more likely (p < 0.001) to want pharmacogenomic services availability than those without existing conditions, adjusted for age and gender (driven by preferences of those with MMPP than those with single chronic disease). Respondents demonstrated a high level of interest and noted both the potential benefits and downsides of pharmacogenomic testing. Willingness-to-pay was not associated with having a chronic disease and respondents were more positive about primary care (community pharmacy or general practice) rather than hospital-based pharmacogenomics implementation. Conclusion: The Irish public in general and those with chronic disease in particular are strongly supportive of pharmacogenomic testing, highlighting an unmet need for its incorporation in medicines optimization. These data underline the need for more research on the implementation of community-based pharmacogenomics services for MMPP patients and ubiquitous pharmacogenomics education programs.

Suggestions for Improvements in National Radon Control Strategies of Member States Which Were Developed as a Requirement of EU Directive 2013/59 EURATOM.

Exposure to the indoor air pollutant radon is considered to be a significant health risk globally, as has been demonstrated by many studies over time. A recent WHO statement on radon estimates that, worldwide, approximately 80,000 people may die every year due to lung cancer associated with radon exposure. The recent years have also seen huge improvements in radon policies in European countries, as a consequence of the issuing, in 2013, of the Council Directive 2013/59/Euratom. Although the protection of workers from radon exposure is well established, the protection of the general public needs more improvements. The main objective of this paper is, first, to acknowledge and recognise the improvements in radon protection policies, but also to show that there are many areas where improvements are desirable and possible. The final goal is to suggest better ways to protect the general population from exposure to radon gas. The suggestions are based on the experiences of the co-authors, who come from different disciplines related to radon management. The following fields or areas where improvements are possible are identified: risk communication, building codes, radon policies, including funding, research and protection of children. We describe the work that has been conducted, and the possible improvements and solutions in these fields.

AAP principles concerning retail-based clinics.

The American Academy of Pediatrics views retail-based clinics (RBCs) as an inappropriate source of primary care for pediatric patients, as they fragment medical care and are detrimental to the medical home concept of longitudinal and coordinated care. This statement updates the original 2006 American Academy of Pediatrics statement on RBCs, which flatly opposed these sites as appropriate for pediatric care, discussing the shift in RBC focus and comparing attributes of RBCs with those of the pediatric medical home.

Alternative CHRNB4 3'-UTRs mediate the allelic effects of SNP rs1948 on gene expression.

Common genetic factors strongly contribute to both nicotine, the main addictive component of tobacco, and alcohol use. Several lines of evidence suggest nicotinic acetylcholine receptors as common sites of action for nicotine and alcohol. Specifically, rs1948, a single-nucleotide polymorphism (SNP) located in the CHRNB4 3'-untranslated region (UTR), has been associated to early age of initiation for both alcohol and tobacco use. To determine the allelic effects of rs1948 on gene expression, two rs1948-containing sequences of different lengths corresponding to the CHRNB4 3'-UTR were cloned into pGL3-promoter luciferase reporter vectors. Data obtained showed that the allelic effects of SNP rs1948 on luciferase expression are mediated by the length and species of transcripts generated. In addition, it was found that miR-3157 increased the overall luciferase expression while miR-138, a microRNA known to play a role in neuroadaptation to drug abuse, decreased luciferase expression when compared to basal conditions. These findings demonstrate the importance of SNP rs1948 on the regulation of CHRNB4 expression and provide the first evidence of CHRNB4 down-regulation by miR-138.

Impact of human D398N single nucleotide polymorphism on intracellular calcium response mediated by α3ß4α5 nicotinic acetylcholine receptors.

The human CHRNA5 D398N polymorphism (rs16969968) causes an aspartic acid to asparagine change in the nicotinic acetylcholine receptor (nAChR) α5 subunit gene. The N398 variant of CHRNA5 is linked to increased risk for nicotine dependence. In this study, we explored the effect of the CHRNA5 D398N polymorphism on the properties of human α3ß4* nicotinic acetylcholine receptors in human embryonic kidney (HEK) cells. Addition of either D398 or N398 variant of α5 subunit in the α3ß4* receptor did not affect total [(125)I]-epibatidine binding or surface expression of the receptor. However, addition of α5(D398) into α3ß4* receptor decreased the maximal response to agonist without significantly affecting EC(50) in aequorin intracellular calcium assay. α3ß4α5(N398) nAChRs showed further decreased maximal response. The differences in agonist efficacy between the receptor subtypes were found to be dependent upon the concentration of external calcium but independent of external sodium. Moreover, activation of α3ß4α5 nAChRs led to significantly greater intracellular calcium release from IP(3) stores relative to α3ß4 nAChRs although no effect of the α5 polymorphism was observed. Finally, inclusion of the α5 variant caused a small shift to the left in IC(50) for some of the antagonists tested, depending upon α5 variant but did not affect sensitivity of α3ß4* receptors to desensitization in response to incubation with nicotine. In conclusion, addition of either variant of α5 into an α3ß4α5 receptor similarly effects receptor pharmacology and function. However, the N398 variant exhibits a reduced response to agonists when extracellular calcium is high and it may lead to distinct downstream cellular signaling.

Nitric oxide-dependent killing of aerobic, anaerobic and persistent Burkholderia pseudomallei.

Burkholderia pseudomallei infections are fastidious to treat with conventional antibiotic therapy, often involving a combination of drugs and long-term regimes. Bacterial genetic determinants contribute to the resistance of B. pseudomallei to many classes of antibiotics. In addition, anaerobiosis and hypoxia in abscesses typical of melioidosis select for persistent populations of B. pseudomallei refractory to a broad spectrum of antibacterials. We tested the susceptibility of B. pseudomallei to the drugs hydroxyurea, spermine NONOate and DETA NONOate that release nitric oxide (NO). Our investigations indicate that B. pseudomallei are killed by NO in a concentration and time-dependent fashion. The cytoxicity of this diatomic radical against B. pseudomallei depends on both the culture medium and growth phase of the bacteria. Rapidly growing, but not stationary phase, B. pseudomallei are readily killed upon exposure to the NO donor spermine NONOate. NO also has excellent antimicrobial activity against anaerobic B. pseudomallei. In addition, persistent bacteria highly resistant to most conventional antibiotics are remarkably susceptible to NO. Sublethal concentrations of NO inhibited the enzymatic activity of [4Fe-4S]-cofactored aconitase of aerobic and anaerobic B. pseudomallei. The strong anti-B. pseudomallei activity of NO described herein merits further studies on the application of NO-based antibiotics for the treatment of melioidosis.

Prevention and management of positional skull deformities in infants.

Positional skull deformities may be present at birth or may develop during the first few months of life. Since the early 1990s, US pediatricians have seen an increase in the number of children with cranial asymmetry, particularly unilateral flattening of the occiput, likely attributable to parents following the American Academy of Pediatrics "Back to Sleep" positioning recommendations aimed at decreasing the risk of sudden infant death syndrome. Positional skull deformities are generally benign, reversible head-shape anomalies that do not require surgical intervention, as opposed to craniosynostosis, which can result in neurologic damage and progressive craniofacial distortion. Although associated with some risk of positional skull deformity, healthy young infants should be placed down for sleep on their backs. The practice of putting infants to sleep on their backs has been associated with a drastic decrease in the incidence of sudden infant death syndrome. Pediatricians need to be able to properly differentiate infants with benign skull deformities from those with craniosynostosis, educate parents on methods of proactively decreasing the likelihood of the development of occipital flattening, initiate appropriate management, and make referrals when necessary. This report provides guidance for the prevention, diagnosis, and management of positional skull deformity in an otherwise normal infant without evidence of associated anomalies, syndromes, or spinal disease.

Increasing immunization coverage.

In 1977, the American Academy of Pediatrics issued a statement calling for universal immunization of all children for whom vaccines are not contraindicated. In 1995, the policy statement "Implementation of the Immunization Policy" was published by the American Academy of Pediatrics, followed in 2003 with publication of the first version of this statement, "Increasing Immunization Coverage." Since 2003, there have continued to be improvements in immunization coverage, with progress toward meeting the goals set forth in Healthy People 2010. Data from the 2007 National Immunization Survey showed that 90% of children 19 to 35 months of age have received recommended doses of each of the following vaccines: inactivated poliovirus (IPV), measles-mumps-rubella (MMR), varicella-zoster virus (VZB), hepatitis B virus (HBV), and Haemophilus influenzae type b (Hib). For diphtheria and tetanus and acellular pertussis (DTaP) vaccine, 84.5% have received the recommended 4 doses by 35 months of age. Nevertheless, the Healthy People 2010 goal of at least 80% coverage for the full series (at least 4 doses of DTaP, 3 doses of IPV, 1 dose of MMR, 3 doses of Hib, 3 doses of HBV, and 1 dose of varicella-zoster virus vaccine) has not yet been met, and immunization coverage of adolescents continues to lag behind the goals set forth in Healthy People 2010. Despite these encouraging data, a vast number of new challenges that threaten continued success toward the goal of universal immunization coverage have emerged. These challenges include an increase in new vaccines and new vaccine combinations as well as a significant number of vaccines currently under development; a dramatic increase in the acquisition cost of vaccines, coupled with a lack of adequate payment to practitioners to buy and administer vaccines; unanticipated manufacturing and delivery problems that have caused significant shortages of various vaccine products; and the rise of a public antivaccination movement that uses the Internet as well as standard media outlets to advance a position, wholly unsupported by any scientific evidence, linking vaccines with various childhood conditions, particularly autism. Much remains to be accomplished by physician organizations; vaccine manufacturers; third-party payers; the media; and local, state, and federal governments to ensure dependable vaccine supply and payments that are sufficient to continue to provide immunizations in public and private settings and to promote effective strategies to combat unjustified misstatements by the antivaccination movement. Pediatricians should work individually and collectively at the local, state, and national levels to ensure that all children without a valid contraindication receive all childhood immunizations on time. Pediatricians and pediatric organizations, in conjunction with government agencies such as the Centers for Disease Control and Prevention, must communicate effectively with parents to maximize their understanding of the overall safety and efficacy of vaccines. Most parents and children have not experienced many of the vaccine-preventable diseases, and the general public is not well informed about the risks and sequelae of these conditions. A number of recommendations are included for pediatricians, individually and collectively, to support further progress toward the goal of universal immunization coverage of all children for whom vaccines are not contraindicated.

MRI algorithm for medical necessity for auto accident injured patients.

RATIONALE: Magnetic resonance imaging (MRI) is often used as a diagnostic test to evaluate personal injury. However, it increases the health care cost. Therefore, it is important to study the necessity for using MRI. OBJECTIVE: To examine the percentages of MRI ordering between orthopaedic surgeon and non-surgeon referring health care providers, and to propose an MRI an algorithm to reduce unnecessary MRI for patients with personal injuries. METHODS: This is a retrospective study. A total of 2000 patients that received a soft tissue injury and did not require surgery between 1 January 2000 and 31 December 2004, were examined. Among them, 1000 patients came directly to one of the authors, an orthopaedic surgeon, and other 1000 were referred to the same surgeon. The percentages of MRI ordered by the author and the referring health care providers are examined. For referred patients, the orthopaedic author re-examined each patient to determine whether he thought the MRI was necessary. The Chi-square test and McNemar's test are used for comparisons for the percentages, and confidence intervals are reported. The study examines the overall MRI ordering, and MRI ordering separately for body regions. CONCLUSIONS: We found that there was a great disparity between the percentages of MRI ordering between the orthopaedic surgeon and the non-surgeon referring doctors, the orthopaedic surgeon ordered significantly less MRI (P-values < 0.001). Adopting the proposed algorithm of medical necessity for ordering MRI or considering early referral to an orthopaedic surgeon prior to ordering MRI can significantly reduce the medical cost for these patients.

Dronedarone: a new treatment for atrial fibrillation.

Dronedarone. Dronedarone is a benzofuran derivative pharmacologically related to amiodarone but without the iodine moiety. It is designed for the treatment of atrial fibrillation and atrial flutter. Historically, amiodarone has proved most effective in maintaining sinus rhythm and has been used safely in patients with advanced heart failure. However, its use has been limited by cumulative and often irreversible organ toxicity, especially in younger patients. Dronedarone was developed in an effort to provide equivalent efficacy and safety with less toxicity. Dronedarone has proved efficacious without toxic or proarrhythmic effects and has minimal side effects, but remaining concerns exist regarding its use in patients with advanced heart failure.

Inactivation of [Fe-S] metalloproteins mediates nitric oxide-dependent killing of Burkholderia mallei.

BACKGROUND: Much remains to be known about the mechanisms by which O(2)-dependent host defenses mediate broad antimicrobial activity. METHODOLOGY/PRINCIPAL FINDINGS: We show herein that reactive nitrogen species (RNS) generated by inducible nitric oxide (NO) synthase (iNOS) account for the anti-Burkholderia mallei activity of IFNgamma-primed macrophages. Inducible NOS-mediated intracellular killing may represent direct bactericidal activity, because B. mallei showed an exquisite sensitivity to NO generated chemically. Exposure of B. mallei to sublethal concentrations of NO upregulated transcription of [Fe-S] cluster repair genes, while damaging the enzymatic activity of the [Fe-S] protein aconitase. To test whether [Fe-S] clusters are critical targets for RNS-dependent killing of B. mallei, a mutation was constructed in the NO-induced, [Fe-S] cluster repair regulator iscR. Not only was the iscR mutant hypersusceptible to iNOS-mediated killing, but its aconitase pool was readily oxidized by NO donors as compared to wild-type controls. Although killed by authentic H(2)O(2), which also oxidizes [Fe-S] clusters, B. mallei appear to be resilient to NADPH oxidase-mediated cytotoxicity. The poor respiratory burst elicited by this bacterium likely explains why the NADPH oxidase is nonessential to the killing of B. mallei while it is still confined within phagosomes. CONCLUSIONS/SIGNIFICANCE: Collectively, these findings have revealed a disparate role for NADPH oxidase and iNOS in the innate macrophage response against the strict aerobe B. mallei. To the best of our knowledge, this is the first instance in which disruption of [Fe-S] clusters is demonstrated as cause of the bactericidal activity of NO congeners.

Nitric oxide evokes an adaptive response to oxidative stress by arresting respiration.

Aerobic metabolism generates biologically challenging reactive oxygen species (ROS) by the endogenous autooxidation of components of the electron transport chain (ETC). Basal levels of oxidative stress can dramatically rise upon activation of the NADPH oxidase-dependent respiratory burst. To minimize ROS toxicity, prokaryotic and eukaryotic organisms express a battery of low-molecular-weight thiol scavengers, a legion of detoxifying catalases, peroxidases, and superoxide dismutases, as well as a variety of repair systems. We present herein blockage of bacterial respiration as a novel strategy that helps the intracellular pathogen Salmonella survive extreme oxidative stress conditions. A Salmonella strain bearing mutations in complex I NADH dehydrogenases is refractory to the early NADPH oxidase-dependent antimicrobial activity of IFNgamma-activated macrophages. The ability of NADH-rich, complex I-deficient Salmonella to survive oxidative stress is associated with resistance to peroxynitrite (ONOO(-)) and hydrogen peroxide (H(2)O(2)). Inhibition of respiration with nitric oxide (NO) also triggered a protective adaptive response against oxidative stress. Expression of the NDH-II dehydrogenase decreases NADH levels, thereby abrogating resistance of NO-adapted Salmonella to H(2)O(2). NADH antagonizes the hydroxyl radical (OH(.)) generated in classical Fenton chemistry or spontaneous decomposition of peroxynitrous acid (ONOOH), while fueling AhpCF alkylhydroperoxidase. Together, these findings identify the accumulation of NADH following the NO-mediated inhibition of Salmonella's ETC as a novel antioxidant strategy. NO-dependent respiratory arrest may help mitochondria and a plethora of organisms cope with oxidative stress engendered in situations as diverse as aerobic respiration, ischemia reperfusion, and inflammation.

The diagnosis of cardiac arrhythmias: a prospective multi-center randomized study comparing mobile cardiac outpatient telemetry versus standard loop event monitoring.

INTRODUCTION: Ambulatory electrocardiographic monitoring systems are frequently used in the outpatient evaluation of symptoms suggestive of a cardiac arrhythmia; however, they have a low yield in the identification of clinically significant but infrequent, brief, and/or intermittently symptomatic arrhythmias. The purpose of this study was to compare the relative value of a mobile cardiac outpatient telemetry system (MCOT) with a patient-activated external looping event monitor (LOOP) for symptoms thought to be due to an arrhythmia. METHODS AND RESULTS: The study was a 17-center prospective clinical trial with patients randomized to either LOOP or MCOT for up to 30 days. Subjects with symptoms of syncope, presyncope, or severe palpitations who had a nondiagnostic 24-hour Holter monitor were randomized. The primary endpoint was the confirmation or exclusion of a probable arrhythmic cause of their symptoms. A total of 266 patients who completed the monitoring period were analyzed. A diagnosis was made in 88% of MCOT subjects compared with 75% of LOOP subjects (P = 0.008). In a subgroup of patients presenting with syncope or presyncope, a diagnosis was made in 89% of MCOT subjects versus 69% of LOOP subjects (P = 0.008). MCOT was superior in confirming the diagnosis of clinical significant arrhythmias, detecting such events in 55 of 134 patients (41%) compared with 19 of 132 patients (15%) in the LOOP group (P < 0.001). CONCLUSIONS: MCOT provided a significantly higher yield than standard cardiac loop recorders in patients with symptoms suggestive of a significant cardiac arrhythmia.

Social contexts, age and juvenile delinquency: a community perspective.

Objective - Social disorganisation of communities, family bonds, school bonds, the peer group and age, have been shown to be related (either positively or negatively) to delinquency. This study addressed gaps in the literature by (1) using a large and randomly drawn sample of adolescents, within a large number of randomly selected communities; (2) investigating the influence of community social disorganisation directly on delinquency, while including in the same model the moderating effect of community social disorganisation on the micro-contexts of family, school, and peer group, as well as the direct effects of these micro-contexts; and (3) including age as a variable likely to have both direct effects on delinquency and moderating effects on the micro- and macro-level social contexts. Method - The public-use data set of Wave I of the (US) National Longitudinal Study of Adolescent Health was used. The model was tested using hierarchical linear modelling and included the social disorganisation of communities; adolescents' bonds to school and family, family controls and involvement with a deviant peer group; and age and its interaction with these social contexts. Results - Community social disorganisation was found to be positively related to delinquency, but effects of micro-level contexts were not found to be moderated by social disorganisation. Family bonds and controls, and school bonds, were negatively related to delinquency. No effect of peer group was found. Age was found to have a direct effect; effects of the interaction of age with family controls and age with school bonds were also significant. Conclusions - Results strengthen those from previous studies (using more limited samples) which show that integrated views of macro- and micro-level social contexts and developmental trends are necessary to understand delinquency.

A model for predicting dating violence: anxious attachment, angry temperament, and need for relationship control.

Structural equation modeling (SEM) was used to test a model incorporating anxious attachment, angry temperament, and attempts to control one's partner as predictors of the severity and frequency of dating violence. To date, these concepts have not been clearly established as having direct or indirect effects on dating violence. It was hypothesized that anxious attachment and angry temperament would influence the need for and attempts to control one's partner which, in turn, would predict a person's actual use of force. College students (213 males; 199 females) completed measures assessing these constructs. Cross-validation was accomplished through using two successive freshmen samples. Statistics indicated the application of the model fit well to both samples. All specified paths were significant except for the direct path from anxious attachment to need for control in the second sample. While exploratory, this model seemed satisfactory for explaining potentially causal relationships of attachment, anger, and attempts to control one's partner leading to dating violence.

Working memory, short-term memory, and general fluid intelligence: a latent-variable approach.

A study was conducted in which 133 participants performed 11 memory tasks (some thought to reflect working memory and some thought to reflect short-term memory), 2 tests of general fluid intelligence, and the Verbal and Quantitative Scholastic Aptitude Tests. Structural equation modeling suggested that short-term and working memories reflect separate but highly related constructs and that many of the tasks used in the literature as working memory tasks reflect a common construct. Working memory shows a strong connection to fluid intelligence, but short-term memory does not. A theory of working memory capacity and general fluid intelligence is proposed: The authors argue that working memory capacity and fluid intelligence reflect the ability to keep a representation active, particularly in the face of interference and distraction. The authors also discuss the relationship of this capability to controlled attention, and the functions of the prefrontal cortex.