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The NAS Genetics Panel (1956) recommended a switch from a threshold to a linear dose response for radiation risk assessment. To support this recommendation, geneticists on the panel provided individual estimates of the number of children in subsequent generations (one to ten) that would be adversely affected due to transgenerational reproductive cell mutations. It was hoped that there would be close agreement among the individual risk estimates. However, extremely large ranges of variability and uncertainty characterized the wildly divergent expert estimates. The panel members believed that sharing these estimates with the scientific community and general public would strongly undercut their linearity recommendation, as it would have only highlighted their own substantial uncertainties. Essentially, their technical report in the journal Science omitted and misrepresented key adverse reproductive findings in an effort to ensure support for their linearity recommendation. These omissions and misrepresentations not only belie the notion of an impartial and independent appraisal by the NAS Panel, but also amount to falsification and fabrication of the research record at the highest possible level, leading ultimately to the adoption of LNT by governments worldwide. Based on previously unexamined correspondence among panel members and Genetics Panel meeting transcripts, this paper provides the first documentation of these historical developments.

Recent European Medicines Agency (final) and US Food and Drug Administration (draft) drug interaction guidances proposed that human circulating metabolites should be investigated in vitro for their drug-drug interaction (DDI) potential if present at ≥ 25% of the parent area under the time-concentration curve (AUC) (US Food and Drug Administration) or ≥ 25% of the parent and ≥ 10% of the total drug-related AUC (European Medicines Agency). To examine the application of these regulatory recommendations, a group of scientists, representing 18 pharmaceutical companies of the Drug Metabolism Leadership Group of the Innovation and Quality Consortium, conducted a scholarship to assess the risk of contributions by metabolites to cytochrome P450 (P450) inhibition-based DDIs. The group assessed the risk of having a metabolite as the sole contributor to DDI based on literature data and analysis of the 137 most frequently prescribed drugs, defined structural alerts associated with P450 inhibition/inactivation by metabolites, and analyzed current approaches to trigger in vitro DDI studies for metabolites. The group concluded that the risk of P450 inhibition caused by a metabolite alone is low. Only metabolites from 5 of 137 drugs were likely the sole contributor to the in vivo P450 inhibition-based DDIs. Two recommendations were provided when assessing the need to conduct in vitro P450 inhibition studies for metabolites: 1) consider structural alerts that suggest P450 inhibition potential, and 2) use multiple approaches (e.g., a metabolite cut-off value of 100% of the parent AUC and the R(met) strategy) to predict P450 inhibition-based DDIs caused by metabolites in the clinic., (Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.)

The Genetics Panel of the National Academy of Sciences' Committee on Biological Effects of Atomic Radiation (BEAR) recommended the adoption of the linear dose-response model in 1956, abandoning the threshold dose-response for genetic risk assessments. This recommendation was quickly generalized to include somatic cells for cancer risk assessment and later was instrumental in the adoption of linearity for carcinogen risk assessment by the Environmental Protection Agency. The Genetics Panel failed to provide any scientific assessment to support this recommendation and refused to do so when later challenged by other leading scientists. Thus, the linearity model used in cancer risk assessment was based on ideology rather than science and originated with the recommendation of the NAS BEAR Committee Genetics Panel. Historical documentation in support of these conclusions is provided in the transcripts of the Panel meetings and in previously unexamined correspondence among Panel members.

Medical devices play an important role in both the diagnostic and therapeutic care of patients. The hope is that particularly innovative medical devices can contribute to the improvement of patient care. However, there is no mandatory need to conduct clinical studies with medical devices that allow an assessment of their benefit within the framework of EU market access or on the way to reimbursement by the statutory health insurance (SHI) in Germany. Numerous examples show that the existing legal framework for market access and for reimbursement in the SHI system is insufficient for providing patients with only those examination and treatment methods, i. e., medical devices, that comply with the benefit requirement and the imperative for quality stipulated in the Social Code Book V. However, it is possible to conduct meaningful clinical trials, i. e., randomized controlled trials, with medical devices as well. Hence, regular, indication-related benefit assessment of medical devices with a higher risk class as a prerequisite for reimbursement for a specific medical device is not only necessary, but also feasible. The 2014 report of the Advisory Council on the Assessment of Developments in the Healthcare System contains a promising recommendation for implementing this. A regulatory framework as described in the report would allow patients the fastest possible access to safe and effective medical device innovations, while increasing planning reliability for the development and marketing of new products, which has often been criticized as insufficient by manufacturers.

The term benefit describes the (positive) causal, patient-relevant consequences of medical interventions, whether diagnostic or therapeutic. Benefit assessments form the basis of rational decision-making within a health care system. They are based on clinical trials that are able to provide valid answers to the question regarding the relevant benefit or harm that can be caused by an intervention. In Germany, evidence-based benefit assessments are fixed by law, i.e., the Social Code Book V. The application and the practical impact of these assessments could be improved.

Probability plays a ubiquitous role in decision-making through a process in which we use data from groups of past outcomes to make inferences about new situations. Yet in recent years, many forensic mental health professionals have become persuaded that overly wide confidence intervals render actuarial risk assessment instruments virtually useless in individual assessments. If this were true, the mathematical properties of probabilistic judgments would preclude forensic clinicians from applying group-based findings about risk to individuals. As a consequence, actuarially based risk estimates might be barred from use in legal proceedings. Using a fictional scenario, I seek to show how group data have an obvious application to individual decisions. I also explain how misunderstanding the aims of risk assessment has led to mistakes about how, when, and why group data apply to individual instances. Although actuarially based statements about individuals' risk have many pitfalls, confidence intervals pose no barrier to using actuarial tools derived from group data to improve decision-making about individual instances., (© 2015 American Academy of Psychiatry and the Law.)

Since the introduction of early benefit assessments in Germany, prices for new medicinal products are set in accordance with the "degree of additional benefit." The major aim of the present work is to point out the economic rationale for the definition of a regulatory price for patent-protected drugs. With regard to the economic objectives of efficient allocation of resources, reducing information asymmetries, and promoting high-value innovation, the applied benefit assessments represent major progress in the German health care sector. In addition to the multifaceted criticism of procedural details, there is a general risk that the institutions involved are lagging behind societal preferences. In this case, early benefit assessments may lead to suboptimal results. The pharmaceutical industry's ability to innovate, on the other hand, may be seen to be a result of the interaction between national benefit assessments and the research activities of internationally oriented drug manufacturers. Accordingly, recent trends toward the implementation of national early benefit assessments in combination with international reference pricing may be seen to be critical; however, Germany is merely following the trend of other countries.

In Germany, new drugs are subject to a benefit assessment at the time of their market access. This "early benefit assessment" is the method primarily used for the benefit assessment of pharmaceuticals in Germany. While for the authorization of a drug a positive risk-benefit ratio is sufficient, early benefit assessment examines whether the new drug has an added benefit compared with other therapies, and thus differs significantly from authorization. For the evaluation, the manufacturer is required to submit a dossier, which must contain all the relevant studies. Early benefit assessment is very transparent in international comparisons, because all the relevant data and the evaluation report will be published. The assessment is carried out with regard to the evidence-based standard of care (the "appropriate comparator"). If the new drug is found to have an additional benefit, the extent of this added benefit is assessed. In addition, groups of patients should be identified with the particular extent of the added benefit. Therefore, subgroup analyses have to be carried out frequently. Often, for new drugs, only registration studies are available. General requirements for such studies (e.g., placebo comparison, endpoints) and decisions regarding the approval process (e.g., dosage regimens) can affect the level of confidence of these studies in the benefit assessment. Joint scientific advice by regulatory authorities and HTA (health technology assessment) agencies are provided to solve this problem. However, this is not possible without additional expense for the pharmaceutical companies.

In its recent guidance document on tiered risk assessment for plant protection products for aquatic organisms, the European Food Safety Authority (EFSA) proposed to use Glyceria maxima as monocotyledonous grass species for the testing of special herbicide groups. However, published toxicity data for this species is very limited and there is no test guideline for Glyceria sp. For this reason a microcosm study was conducted in order to gain experience on the degree of sensitivity of G. maxima to the herbicidal substances clodinafop-propargyl (grass herbicide) and fluroxypyr (auxin) in comparison to the already established test organism water milfoil Myriophyllum spicatum and the duckweed species Landoltia punctata. Five concentrations without replicates were tested for each test substance using 10 microcosms and three microcosms served as controls. The experiment was run for 8 weeks. Morphological endpoints were used to determine growth and EC50 values. The results show that M. spicatum was most sensitive to fluroxypyr (37 days EC50 for roots: 62 µg/L) and G. maxima most sensitive to clodinafop-propargyl (22 days EC50 for total shoot length: 48 µg/L) whereas the duckweed species was considerable less sensitive. Hence, G. maxima turns out to be a good candidate for testing grass specific herbicides, supporting its inclusion as an additional macrophyte test for the risk assessment of herbicides as proposed by the EFSA.

The increased use of violence risk assessment tools in professional practice has sparked the development of best-practice guidelines for communicating about violence risk. The present study examined 166 pre-sentence reports, authored by clinicians and probation officers, to determine the extent to which they are consistent with those guidelines. We examined the frequency with which reports contained information about five topics: the presence of risk factors; the relevance of risk factors; scenarios of future violence; recommended management strategies; and summary risk judgments. Analyses revealed that the topics addressed most frequently in reports were the presence of risk factors and recommended management strategies, but none of the five topics was addressed consistently, completely, or clearly in reports. This was especially the case for probation reports. The findings highlight the need to improve practice through better implementation of guidelines for risk communication. Also needed is research on the extent to which information in risk communications is comprehended, accepted, and used by various stakeholder groups., (Copyright © 2015 John Wiley & Sons, Ltd.)

Benefit assessments according to Sect. 35a of the Social Code Book V are frequently divided into subsets of populations. This division of therapeutic indications is evident in almost every other of the completed appraisals by the Federal Joint Committee (G-BA). The subsets can be deduced from the wording of the approved therapeutic indication (subpopulations) or from potential effect modification (subgroups). Methodological challenges are illustrated on the basis of current scientific knowledge of how to tackle subgroups. Practical assessment examples are used to explain the methods implemented by IQWiG and the G-BA and reveal major problem areas concerning subgroup analyses, subpopulations as well as mismatches between the requirements of early benefit assessment and approval. Overall, it appears there is a need for establishing a more comprehensive discussion regarding the validity of subgroup analyses and their associated limitations., (Copyright © 2015. Published by Elsevier GmbH.)

A dietary survey of 3431 residents was conducted by a 24-h dietary recall method in Shanghai, China, quarterly from September 2013 to September 2014. A total of 400 food samples were tested for aluminium concentration, including wheat flour and puffed products from 2011 to 2013. Probabilistic analysis was used to estimate the dietary exposure to aluminium from wheat and puffed products. The means of dietary aluminium exposure for children (2-6 years old), juveniles (7-17 years old), adults (18-65 years old) and seniors (over 65 years old) were 1.88, 0.94, 0.44 and 0.42 mg kg(-1) body weight (bw) week(-1) respectively, with a population average of 0.51 mg kg(-1) bw week(-1). The proportions of those who had aluminium exposure from wheat and puffed products lower than the provisional tolerable weekly intake (PTWI) were 77%, 90%, 97%, and 97% respectively from children to seniors. We estimated that the proportions of people at risk would decrease by 13%, 6%, 2% and 2% respectively under the new China National Standards - GB 2760-2014 National Food Safety for Standards for using food additives. The results indicated that aluminium from wheat flour and puffed products is unlikely to cause adverse health effects in the general population in Shanghai; however, children were at a higher risk of excess aluminium exposure. Significant improvements in reducing the dietary exposure to aluminium are expected in the population, especially for children after the implementation of GB 2760-2014.

Recidivism of released prisoners, especially violent recidivism, is an important policy issue. Equally important is an understanding of how demographic risk factors may act as moderators of recidivism. Knowledge of such relationships is important in developing a deeper theoretical understanding of the risk of recidivism as well as identifying points of intervention that may need to be re-oriented to reduce recidivism. The present study conducts a meta-analytic review of the violent recidivism literature focusing on the role of several demographic risk factors. Findings show that age, sex, and race (Whites) were significantly related to violent recidivism. Implications and directions for future research are identified., (© The Author(s) 2013.)

Methods of uncertainty analysis are being included increasingly in regulatory chemical risk assessment. Although best practices have been established by several safety agencies in Europe and the United States, they exist only in the grey literature - there has been no comprehensive analysis of the scientific, peer-reviewed literature on these methods. We therefore conducted a systematic review of the recent peer-reviewed literature (2007-2013) on uncertainty analysis relevant to chemical risks. The main objective was to determine whether current methods are robust enough for regulatory use, because the methods used to protect public health must meet the most stringent scientific standards. Based on 297 papers, we concluded that the peer-reviewed literature is much more critical about the disadvantages of those methods, compared to the grey literature. Furthermore, uncertainty analyses can be influenced significantly by subjective expert judgment. As a suggested improvement, we developed guidelines for transparent reporting of uncertainty assessment results.

The overall research objective was to empirically develop the ideas around a system of occupational safety and health (OSH) practices in visual display unit (VDU) work, to describe their relationship with the OSH legislation and to explore how these best practices work to achieve positive results. The aim of the present study was to explore qualitative perceptions of the stakeholders (Finnish Employers' Associations, Employees Organizations and OSH Governmental Inspectorates) concerning the way that the OSH legislation on VDU work is being applied at work. Many stakeholders claim that technological advances require that in OSH the VDU legislation should be updated, especially that it should be clarified, e.g., when does the VDU worker have the right to obtain special eyeglasses needed for VDU work. Many stakeholders believe that additional guidelines concerning practical ergonomic arrangements in VDU work environment and eyeglasses of the VDU workers are needed. In VDU ergonomics, the co-operation between workplace and occupational health care professionals needs to be developed.

Clinicians have an obligation to report to state or territory police any concerns about risk of harm from patients with access to firearms. Dementia is an under-recognised medical problem which may increase the risk of firearm injury or violence in those with such access. There are no guidelines for clinicians regarding mandatory screening for access to firearms, and currently the onus is on the firearm licence holder to declare any relevant medical conditions. We propose that clinicians should screen patients for firearm possession and use a combined capacity and risk assessment approach to evaluating fitness for firearm licences.

Regulatory risk assessment is traditionally based primarily on toxicity studies conducted according to standardized and internationally validated test guidelines. However, health risk assessment of endocrine disrupting chemicals (EDCs) is argued to rely on the efficient integration of findings from academic research. The aim of this review was to provide an overview of current developments to facilitate the use of academic research in regulatory risk assessment of chemicals and how certain aspects of study design and reporting are particularly important for the risk assessment process. By bridging the gap between academic research and regulatory health risk assessment of EDCs, scientific uncertainty in risk assessment conclusions can be reduced, allowing for better targeted policy decisions for chemical risk reduction., (Copyright © 2014. Published by Elsevier Ltd.)

Approximately 40% of all newly approved drugs are subject to safety restrictions inclusive of Risk Evaluation and Mitigation Strategies (REMS), which were created with the US Food and Drug Administration Amendments Act of 2007. This law expanded Food and Drug Administration (FDA) authority to require REMS of manufacturers but left implementation to the FDA. As a result, the potential access to medications that are effective but not without safety concerns has improved, yet the converse is also true because access may be restricted due to REMS requirements (eg, physician or patient registration). With the July 2012 reauthorization of the Prescription Drug User Fee Act, the FDA was given additional authorities and mandates for enhancing and modernizing the drug safety system-specifically, measuring the effectiveness of REMS as well as standardizing and better integrating REMS into the overall health care system. So, are REMS, which were conceived as a tool to improve medication safety, working? Specifically, are REMS achieving their intended outcomes (mitigating safety risks of effective drugs) without causing unintended consequences (creating a burden to the health care system and physicians and/or diminishing patient access to drugs)? Sitting squarely in the crosshairs, the approved shared REMS for extended-release/long-acting opioid analgesics provide a lens through which this question can be examined. This article discusses the current status, stakeholders, and key policy issues for clinicians with a focus on the shared REMS for opioids, as well as the anticipated role of clinicians in optimizing patient care in the new world of REMS., (Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Judges and attorneys often request professional assessments from child custody evaluators when allegations of adult domestic violence (DV) have been made, but it is unclear whether and how evaluators' recommendations are impacted by these allegations. Custody evaluators (N = 607) in the United States responded to a multiple-segment factorial vignette designed to examine the effects of 2 key factors in DV allegations: type of alleged violence (conflict-based, control-based) and counterallegations (none, mutual, and female-initiated). Effects of control- versus conflict-based DV allegations by the mother on custody recommendations were small and the majority of evaluators recommended joint custody regardless of violence type. Reported confidence in making a recommendation increased once the father responded to the allegation, but to a smaller degree when a counterallegation of mutual or female-initiated violence was made. Evaluators were no more skeptical about the potential motive of a counterallegation in the context of controlling behavior than in the context of conflict-based behavior. Overall, results indicate that most custody evaluators are not sufficiently sensitized to distinguish between situational couple violence and coercive controlling behavior, and the postseparation safety of mothers and their children may therefore be jeopardized.

Recent EU legislation has introduced endocrine disrupting properties as a hazard-based "cut-off" criterion for the approval of active substances as pesticides and biocides. Currently, no specific science-based approach for the assessment of substances with endocrine disrupting properties has been agreed upon, although this new legislation provides interim criteria based on classification and labelling. Different proposals for decision making on potential endocrine disrupting properties in human health risk assessment have been developed by the German Federal Institute for Risk Assessment (BfR) and other regulatory bodies. All these frameworks, although differing with regard to hazard characterisation, include a toxicological assessment of adversity of the effects, the evaluation of underlying modes/mechanisms of action in animals and considerations concerning the relevance of effects to humans. Three options for regulatory decision making were tested upon 39 pesticides for their applicability and to analyze their potential impact on the regulatory status of active substances that are currently approved for use in Europe: Option 1, based purely on hazard identification (adversity, mode of action, and the plausibility that both are related); Option 2, based on hazard identification and additional elements of hazard characterisation (severity and potency); Option 3, based on the interim criteria laid down in the recent EU pesticides legislation. Additionally, the data analysed in this study were used to address the questions, which parts of the endocrine system were affected, which studies were the most sensitive and whether no observed adverse effect levels were observed for substance with ED properties. The results of this exercise represent preliminary categorisations and must not be used as a basis for definitive regulatory decisions. They demonstrate that a combination of criteria for hazard identification with additional criteria of hazard characterisation allows prioritising and differentiating between substances with regard to their regulatory concern. It is proposed to integrate these elements into a decision matrix to be used within a weight of evidence approach for the toxicological categorisation of relevant endocrine disruptors and to consider all parts of the endocrine system for regulatory decision making on endocrine disruption., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Under the European chemicals' legislation, REACH, substances that are identified to be of "very high concern" will de facto be removed from the market unless the European Commission grants authorisations permitting specific uses. Companies who apply for an authorisation without demonstrating "adequate control" of the risks have to show by means of a socio-economic analysis (SEA) that positive impacts of use outweigh negative impacts for human health and ecosystems. This paper identifies core challenges where further in-depth guidance is urgently required in order to ensure that a SEA can deliver meaningful results and that it can effectively support decision-making on authorisation. In particular, we emphasise the need (i) to better guide the selection of tools for impact assessment, (ii) to explicitly account for stock pollution effects in impact assessments for persistent and very persistent chemicals, (iii) to define suitable impact indicators for PBT/vPvB chemicals given the lack of reliable information about safe concentration levels, (iv) to guide how impacts can be transformed into values for decision-making, and (v) to provide a well-balanced discussion of discounting of long-term impacts of chemicals., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Concerns about the potential for significant environmental impact from residues of human pharmaceuticals emerged at the beginning of the 21st century. Since then there has been an exponential rise in the number of publications and conferences on this "problem". However, this intense focus on human pharmaceuticals is misplaced. Pharmaceuticals do not consist of a coherent group of substances with similar chemical, structural, biological or toxicological properties. Pharmaceuticals are only identifiable from their use: in other words substances can be divided into two classes, those that are used as pharmaceuticals and those for which a possible pharmaceutical use has not yet been discovered. For example, nitro-glycerine, Warfarin and dimethyl fumarate, initially sold respectively as an explosive, a rodenticide and a mould inhibitor have subsequently all been used as pharmaceuticals. As analytical science advances, an increasing range of environmental contaminants, including pharmaceuticals, is being identified at sub μgL(-1) concentrations. Although, human and environmental exposure to these contaminants will be low, all of them need to be subjected to risk assessment on a case by case basis. Many of these substances, including human pharmaceuticals, may have little, if any, impact on human health or the environment, however for some substances there may be a significant risk and in these cases appropriate action should be taken. However considering all human pharmaceuticals as a special case, isolated from the wider range of emerging contaminants, is scientifically unjustifiable and diverts resources away from the consideration of other substances that may be of considerably more significance., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Every year in France, 201,000 women are victims of physical and/or sexual violence perpetrated by their partner or ex-partner. At the same time, 83,000 are victims of rape or attempted rape, by a known or unknown aggressor. The impact of this violence on the health and overall quality of life of female victims is considerable. Faced with the extent of these violences, initiatives are being set up, instigated by the government and numerous players in the field.

The grouping of substances serves to streamline testing for regulatory purposes. General grouping approaches for chemicals have been implemented in, e.g., the EU chemicals regulation. While specific regulatory frameworks for the grouping of nanomaterials are unavailable, this topic is addressed in different publications, and preliminary guidance is provided in the context of substance-related legislation or the occupational setting. The European Centre for Ecotoxicology and Toxicology of Chemicals Task Force on the Grouping of Nanomaterials reviewed available concepts for the grouping of nanomaterials for human health risk assessment. In their broad conceptual design, the evaluated approaches are consistent or complement each other. All go beyond the determination of mere structure-activity relationships and are founded on different aspects of the nanomaterial life cycle. These include the NM's material properties and biophysical interactions, specific types of use and exposure, uptake and kinetics, and possible early and apical biological effects. None of the evaluated grouping concepts fully take into account all of these aspects. Subsequent work of the Task Force will aim at combining the available concepts into a comprehensive 'multiple perspective' framework for the grouping of nanomaterials that will address all of the mentioned aspects of their life cycles., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Many studies have validated the psychometric properties of the Static-99, the most widely used measure of sexual offender recidivism risk. However much of this research relied on instrument coding completed by well-trained researchers. This study is the first to examine the interrater reliability (IRR) of the Static-99 between practitioners in the field and researchers. Using archival data from a sample of 1,973 formerly incarcerated sex offenders, field raters' scores on the Static-99 were compared with those of researchers. Overall, clinicians and researchers had excellent IRR on Static-99 total scores, with IRR coefficients ranging from "substantial" to "outstanding" for the individual 10 items of the scale. The most common causes of discrepancies were coding manual errors, followed by item subjectivity, inaccurate item scoring, and calculation errors. These results offer important data with regard to the frequency and perceived nature of scoring errors., (© The Author(s) 2013.)

The planning of specific health surveillance programs for police officers is extremely complex due to difficulty in predictability and variety of occupational hazards. Even in the case of conventional occupational risk factors clearly identified by current regulations, particular working conditions may require specific assessment to effectively identify and quantify the risk of occupational exposure. An extensive program of health surveillance, aimed at promoting overall health and effectiveness of the operators, would be really desirable, in order to help better address a number of risks that cannot be easily predicted. The progressive increase in the average age of the working population and the increasing prevalence of chronic degenerative diseases, may also suggest the need for health surveillance procedures designed to verify continued unqualified suitability to police service, providing for the identification of diversified suitability profiles in relation to age and state of health: accordingly, in regard to our field of interest, there is a close link between medico-legal eligibility and occupational medicine.

The verification of the occupational origin of a disease is a forensic medical activity requiring: the confirmation of the existence and of the exact nosographic identification of the disease, as well as the type of work really performed, and the actual exposure to an effective occupational hazard during an adequate time, and finally a reconstruction of the causal relationship based on objective data. Checking the disease is essentially documentary, corroborated by direct survey by medical examination. The assessment of exposure to the occupational hazard must be scrupulous also, not being acceptable the medical history alone: that is, it does require documentary evidence. Finally, the logical process of recognition of causation requires the application of rigorous forensic medical methodology, with references to current scientific knowledge, and the application of legal criteriology from the legal field of law in which you are moving. Indeed, forensic medical methodology is not the same of epidemiological one: probability of occurrence of an event is not a proof, but only a circumstantial element. A forensic medical doctor organizes every evidence and circumstantial evidence in a unique decision-making process, as a result of a logical process, and probabilistic data can be among circumstantial evidence, but they must suit the case in details, in order to reach the so called "logic probability". But this doesn't mean that you have "proven" the occupational origin of a disease. In the "demonstration" of a fact you use the same forensic medical methodology (thus referring to classic criteria: temporality, biological gradient and plausibility, topographical, exclusion, and phenomenal continuity if suitable, too), and also the same general scientific references, nevertheless the law can be different in causality principles admitted (the principles governing the causal link are the same in Criminal Code and Civil law both, but they differ in private insurance), and besides there is a different rule of evidence, that is the "quantum of evidence" required (the amount of evidence needed) and, secondarily, also a different quality of proof required (how reliable such evidence should be considered, and which types of evidence admitted). Therefore in Civil law you can reach a "procedural truth" different from the one in Criminal law, and various from the one needed to prevail in litigation with social security insurance or with private insurance.

In Italy, the Law n. 395/1990 defines the tasks and attributions of prison officers. According to the article 25 of the Legislative Decree n. 81/2008, the occupational physician should participate to risk assessment, and carry out the sanitary surveillance. This report analyzes the various tasks of prison staff, identifies the risk factors, and discusses the preventive strategies, including workers formation and education. Biological agents and work-related stress are the main risk factors, as a consequence of prison overcrowding, personnel shortage and work organization complexity. In his preventive action, and particularly in formulating the judgment on work fitness, the occupational physician often clashes with inadequate ministerial funding.

REACH (registration, evaluation, authorisation and restriction of chemicals) regulation requires that all the chemicals produced or imported in Europe above 1 tonne/year are registered. To register a chemical, physicochemical, toxicological and ecotoxicological information needs to be reported in a dossier. REACH promotes the use of alternative methods to replace, refine and reduce the use of animal (eco)toxicity testing. Within the EU OSIRIS project, integrated testing strategies (ITSs) have been developed for the rational use of non-animal testing approaches in chemical hazard assessment. Here we present an ITS for evaluating the bioaccumulation potential of organic chemicals. The scheme includes the use of all available data (also the non-optimal ones), waiving schemes, analysis of physicochemical properties related to the end point and alternative methods (both in silico and in vitro). In vivo methods are used only as last resort. Using the ITS, in vivo testing could be waived for about 67% of the examined compounds, but bioaccumulation potential could be estimated on the basis of non-animal methods. The presented ITS is freely available through a web tool., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Semipolar polycyclic aromatic compounds (sPACs) are frequently found in association with homocyclic polycyclic aromatic hydrocarbons (PAHs) in substances of unknown or variable composition, complex reaction products, or biological materials (UVCBs) from coal or crude oil and products derived thereof. However, major information deficiencies exist with regard to their prevalence and their toxicological and ecotoxicological potential, persistency, and bioaccumulation characteristics. Therefore, in this work, the environmental concern and relevance of sPACs was addressed in a general, stepwise approach. First, a large list of sPACs was collected and subsequently refined by assessing their persistence, bioaccumulation, and toxicity (PBT) properties by quantitative structure-activity relationship (QSAR) methods and their relevance by determining their respective frequency of occurrence. In this way, 15 priority sPACs were identified. These 15 priority sPACs were further characterized in detail with respect to their ecotoxicological properties, environmental behavior, carcinogenicity, and genotoxicity attributes. All of these 15 substances were quantified in distillate or product samples. In the next step, some principles for nomination of indicator substances, indicative for the overall content of sPACs, are derived. Data gaps on ecotoxicological endpoints preclude final conclusions, but the respective necessary supplemental tests were identified. Five of the 15 sPACs were tentatively characterized as potential substances of very high concern (SVHC) for the environment. The overall results of this study also clearly show that regulatory risk management of homocyclic PAHs within the European Regulation on Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) does not address the environmental concern created by sPACs within UVCBs from coal or crude oil. The study proves the need for additional regulatory steps under REACH and suggests indicator substances for their enforcement., (© 2014 SETAC.)

PETRORISK is a modeling framework used to evaluate environmental risk of petroleum substances and human exposure through these routes due to emissions under typical use conditions as required by the European regulation for the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH). Petroleum substances are often complex substances comprised of hundreds to thousands of individual hydrocarbons. The physicochemical, fate, and effects properties of the individual constituents within a petroleum substance can vary over several orders of magnitude, complicating risk assessment. PETRORISK combines the risk assessment strategies used on single chemicals with the hydrocarbon block approach to model complex substances. Blocks are usually defined by available analytical characterization data on substances that are expressed in terms of mass fractions for different structural chemical classes that are specified as a function of C number or boiling point range. The physicochemical and degradation properties of the blocks are determined by the properties of representative constituents in that block. Emissions and predicted exposure concentrations (PEC) are then modeled using mass-weighted individual representative constituents. Overall risk for various environmental compartments at the regional and local level is evaluated by comparing the PECs for individual representative constituents to corresponding predicted no-effect concentrations (PNEC) derived using the Target Lipid Model. Risks to human health are evaluated using the overall predicted human dose resulting from multimedia environmental exposure to a substance-specific derived no-effect level (DNEL). A case study is provided to illustrate how this modeling approach has been applied to assess the risks of kerosene manufacture and use as a fuel., (© 2014 SETAC.)

Background: The identification of common genetic variants associated with common cancers including breast, prostate and ovarian cancers would allow population stratification by genotype to effectively target screening and treatment. As scientific, clinical and economic evidence mounts there will be increasing pressure for risk-stratified screening programmes to be implemented., Methods: This paper reviews some of the main ethical, legal and social issues (ELSI) raised by the introduction of genotyping into risk-stratified screening programmes, in terms of Beauchamp and Childress's four principles of biomedical ethics--respect for autonomy, non-maleficence, beneficence and justice. Two alternative approaches to data collection, storage, communication and consent are used to exemplify the ELSI issues that are likely to be raised., Results: Ultimately, the provision of risk-stratified screening using genotyping raises fundamental questions about respective roles of individuals, healthcare providers and the state in organizing or mandating such programmes, and the principles, which underpin their provision, particularly the requirement for distributive justice., Conclusions: The scope and breadth of these issues suggest that ELSI relating to risk-stratified screening will become increasingly important for policy-makers, healthcare professionals and a wide diversity of stakeholders., (© The Author 2013. Published by Oxford University Press on behalf of Faculty of Public Health.)

Many sexually violent predator (SVP) laws are ambiguous regarding the degree of reoffense risk that would indicate that an offender is sufficiently "likely to reoffend" to justify civil commitment. We review how SVP statutes operationalize likelihood of reoffending. We then examine what likelihood of recidivism actual SVP jurors considered to indicate that an offender was likely to reoffend. Real jurors (N = 153) from 14 actual SVP hearings completed a questionnaire after deliberating to a verdict. Most jurors (81.7%) considered a 15% estimated chance of recidivism to mean that the respondent was "likely" to reoffend, and many (53.6%) even considered a 1% chance to indicate likely reoffense. Jurors who heard lower risk estimates in trials were more likely to report that a low chance of recidivism (as low as 1%) indicated an offender was likely to reoffend. Results suggest that jurors view risk more in terms of the severity of potential harm than in terms of strict statistical probability. Results also suggest that when laws give jurors discretion to define tolerable risk, jurors consider even a statistically low degree of risk intolerable.

The legal framework and the essentials in traffic and transport psychology and statistics were described in part 1. Safe driving depends on different sensory and mental processes interacting in a complicated manner. Physiological changes and--even more importantly--a variety of diseases result in impaired performance in these functional areas. Moderate to severe dementia certainly means that the person is no longer fit to drive, whereas driving ability may be maintained in mild dementia for some time. There are different approaches and assessment tools, but a single test that could, on its own, answer the question whether a patient with mild dementia is fit to drive does not exist. Driving ability is not only determined by cognitive function. Further assessment of possible risk factors and overall functioning is necessary. If dementia is diagnosed, then the question of fitness to drive must be promptly discussed with the patient because during the course of dementia driving ability will inevitably be lost. The conclusion of the assessment of driving ability must not be pronounced like a verdict, the physician should rather counsel and support the patient and his family on the difficult road towards driving cessation.

In recent years, the official regulation of chemicals and chemical products has been intensified. Explicitly for spray products enhanced requirements to assess the consumers'/professionals' exposure to such product type have been introduced. In this regard the Aerosol-Dispensers-Directive (75/324/EEC) with obligation for marketing aerosol dispensers, and the Cosmetic-Products-Regulation (1223/2009/EC) which obliges the insurance of a safety assessment, have to be mentioned. Both enactments, similar to the REACH regulation (1907/2006/EC), require a robust chemical safety assessment. From such assessment, appropriate risk management measures may be identified to adequately control the risk of these chemicals/products to human health and the environment when used. Currently, the above-mentioned regulations lack the guidance on which data are needed for preparing a proper hazard analysis and safety assessment of spray products. Mandatory in the process of inhalation risk and safety assessment is the determination and quantification of the actual exposure to the spray product and more specifically, its ingredients. In this respect the current article, prepared by the European Aerosol Federation (FEA, Brussels) task force "Inhalation Toxicology", intends to introduce toxicological principles and the state of the art in currently available exposure models adapted for typical application scenarios. This review on current methodologies is intended to guide safety assessors to better estimate inhalation exposure by using the most relevant data., (Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

The assessment of risk for serious, life-threatening drug-induced liver injury (DILI) associated with a suspect drug, biological agent, or herbal product depends on an iterative analysis of pre- and postmarket datastreams. Because serious cases of idiosyncratic DILI are typically rare, regulatory scientists seek strategies that accurately predict from clinical trial data which study drugs will be likely to cause these events in a large postmarket treatment population, e.g., through the identification of cases that are consistent with Hy's law. This objective is only achievable if rigorous standards in study subject monitoring, data collection and analysis of liver injury cases for causality are followed. In the future, the development of more effective predictive and analytic tools in preclinical and clinical testing will provide a framework to reliably identify new agents that have hepatotoxic profiles as well as those individuals who are susceptible to develop serious DILI., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

One of the essential questions placed before a road authority is where to act first, i.e. which road sections should be treated in order to achieve the desired level of reliability of a particular road, while this is at the same time the subject of this research. The paper shows how the reliability reallocation theory can be applied in safety analysis of a road consisting of sections. The model has been successfully tested using two apportionment techniques - ARINC and the minimum effort algorithm. The given methods were applied in the traffic safety analysis as a basic step, for the purpose of achieving a higher level of reliability. The previous methods used for selecting hazardous locations do not provide precise values for the required frequency of accidents, i.e. the time period between the occurrences of two accidents. In other words, they do not allow for the establishment of a connection between a precise demand for increased reliability (expressed as a percentage) and the selection of particular road sections for further analysis. The paper shows that reallocation models can also be applied in road safety analysis, or more precisely, as part of the measures for increasing their level of safety. A tool has been developed for selecting road sections for treatment on the basis of a precisely defined increase in the level of reliability of a particular road, i.e. the mean time between the occurrences of two accidents., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

A large body of research has examined relationships between distal experiences of victimization and the likelihood of engaging in violence later in life. Less is known about the influence of recent violent victimization on risk for violence perpetration. To our knowledge, this is the first study to examine prospectively whether recent victimization in adulthood increases the risk of future violence. Specifically, the present study assessed the incremental validity of recent violent victimization in the prediction of future violence in a sample of justice-involved adults with serious mental illness. The study examined (a) whether recent experiences of violent victimization (i.e., within 6 months of the baseline assessment) predicted a greater likelihood of perpetrating violence in the next year, and (b) whether inclusion of recent victimization enhanced the predictive validity of a model of violence risk in a sample of justice-involved adults with severe mental illness (N = 167). Hierarchical logistic regression analyses indicated that exposure to recent violent victimization at the baseline assessment predicted a greater likelihood of engaging in violent behavior during the year follow-up period. Additionally, recent exposure to violence at the baseline assessment continued to explain a significant amount of variance in a model of future violence perpetration above the variance accounted for by well-established violence risk factors. Taken together, the findings suggest that recent victimization is important to consider in understanding and evaluating risk of violence by persons with mental disorders who are involved in the criminal justice system., (PsycINFO Database Record (c) 2014 APA, all rights reserved.)

Under the current European legislation for the Registration, Evaluation, Authorisation and restriction of Chemicals (REACHs) a Derived No Effect Level (DNEL) has to be delineated for acute and chronic inhalation effects. The majority of available experimental studies are performed by the oral route of exposure. Route to route extrapolation poses particular problems for irritating or corrosive substances but the necessity for additional animal studies with inhalation exposure needs to be balanced with the regulatory information requirements. Existing occupational exposure limits (OEL) as surrogate for cut-off limits representing safe exposure under working conditions were grouped under certain criteria for substances that are legally classified in Europe as irritating or corrosive. As a result, it was shown that the OEL for irritating substances in this dataset is not lower than 10mg/m(3) and for corrosives not lower than 1mg/m(3). Under certain conditions these generic limits could be applied as a pragmatic, but still sufficiently reliable and protective upper cut-off limit approach to avoid additional animal tests with irritating or corrosive chemicals. The respective systemic toxicity profiles and physical-chemical properties need to be considered. Specific exclusion criteria for the discussed concept apply., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Characterisation of the relative sensitizing potency of protein and chemical allergens remains challenging, particularly for materials causing allergic sensitization of the respiratory tract. There nevertheless remains an appetite, for priority setting and risk management, to develop paradigms that distinguish between individual respiratory allergens according to perceptions of the hazards and risks posed to human health. One manifestation thereof is recent listing of certain respiratory allergens as Substances of Very High Concern (SVHC) under the provisions of REACH (Registration, Evaluation, Authorisation and restriction of Chemicals). Although priority setting is a laudable ambition, it is important the process is predicated on evidence-based criteria that are transparent, understood and owned. The danger is that in the absence of rigorous criteria unwanted precedents can be created, and confidence in the process is compromised. A default categorisation of sensitisers as SVHC requiring assessment under the authorisation process is not desirable. We therefore consider here the value and limitations of selective assignment of certain respiratory allergens as being SVHC. The difficulties of sustaining such designations in a sound and equitable way is discussed in the context of the challenges that exist with respect to assessment of potency, and information available regarding the effectiveness of exposure-based risk management., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Emissions of organic substances with potential toxicity to humans and the environment are a major concern surrounding the rapid industrial development in the Athabasca oil sands region (AOSR). Although concentrations of polycyclic aromatic hydrocarbons (PAHs) in some environmental samples have been reported, a comprehensive picture of organic contaminant sources, pathways, and sinks within the AOSR has yet to be elucidated. We sought to use a dynamic multimedia environmental fate model to reconcile the emissions and residue levels reported for three representative PAHs in the AOSR. Data describing emissions to air compiled from two official sources result in simulated concentrations in air, soil, water, and foliage that tend to fall close to or below the minimum measured concentrations of phenanthrene, pyrene, and benzo(a)pyrene in the environment. Accounting for evaporative emissions (e.g., from tailings pond disposal) provides a more realistic representation of PAH distribution in the AOSR. Such indirect emissions to air were found to be a greater contributor of PAHs to the AOSR atmosphere relative to reported direct emissions to air. The indirect pathway transporting uncontrolled releases of PAHs to aquatic systems via the atmosphere may be as significant a contributor of PAHs to aquatic systems as other supply pathways. Emission density estimates for the three PAHs that account for tailings pond disposal are much closer to estimated global averages than estimates based on the available emissions datasets, which fall close to the global minima. Our results highlight the need for improved accounting of PAH emissions from oil sands operations, especially in light of continued expansion of these operations.