Hill Criteria Research Articles

Investigation of the variable elastic unloading modulus coupled with nonlinear kinematic hardening in springback measuring of advanced high-strength steel in U-shaped process

Advanced high strength steels are widely used in the automotive industry due to their appropriate strength to weight ratio. This alloy has unique hardening behavior and variable unloading elastic modulus. In this paper, an analytical model is introduced to predict springback in U-shaped bending process of normal and pre-strained DP780 dual phase steel stripes. It is based on the Hill48 yield criterion and plane strain condition. In this model, the effect of forming history, sheet thinning and the motion of the neutral surface on the springback is taken into account. The anisotropic nonlinear kinematic hardening model (ANK) is used to consider the impact of complex deformation including stretching, bending and reverse bending. This model is able to investigate the Bauschinger effect, transient behavior and permanent softening. Also, a nonlinear function of plastic strain is implemented to capture the variable unloading elastic modulus. This model is used for the Numisheet2011 benchmark U-shaped bending problem. The effect of the sheet holder force, the coefficient of friction, thickness, material anisotropy, hardening parameters, pre-strain and variable elastic modulus on the sheet springback is studied. It can be seen that analytical model with constant young's modulus has better accuracy in predicting springback angles than FEM solutions. Also in the case of variable young's modulus, FEM solution has better agreement with experiments in comparison with the analytical model.

Consequences of bullying victimization in childhood and adolescence: A systematic review and meta-analysis.

AIMTo identify health and psychosocial problems associated with bullying victimization and conduct a meta-analysis summarizing the causal evidence.METHODSA systematic review was conducted using PubMed, EMBASE, ERIC and PsycINFO electronic databases up to 28 February 2015. The study included published longitudinal and cross-sectional articles that examined health and psychosocial consequences of bullying victimization. All meta-analyses were based on quality-effects models. Evidence for causality was assessed using Bradford Hill criteria and the grading system developed by the World Cancer Research Fund.RESULTSOut of 317 articles assessed for eligibility, 165 satisfied the predetermined inclusion criteria for meta-analysis. Statistically significant associations were observed between bullying victimization and a wide range of adverse health and psychosocial problems. The evidence was strongest for causal associations between bullying victimization and mental health problems such as depression, anxiety, poor general health and suicidal ideation and behaviours. Probable causal associations existed between bullying victimization and tobacco and illicit drug use.CONCLUSIONStrong evidence exists for a causal relationship between bullying victimization, mental health problems and substance use. Evidence also exists for associations between bullying victimization and other adverse health and psychosocial problems, however, there is insufficient evidence to conclude causality. The strong evidence that bullying victimization is causative of mental illness highlights the need for schools to implement effective interventions to address bullying behaviours.

Integration of novel approaches demonstrates simultaneous metabolic inactivation and CAR-mediated hepatocarcinogenesis of a nitrification inhibitor.

Nitrapyrin, a nitrification inhibitor, produces liver tumors in mice at high doses. Several experiments were performed to investigate molecular, cellular, and apical endpoints to define the key events leading to the tumor formation. These data support a mode-of-action (MoA) characterized by constitutive androstane receptor (CAR) nuclear receptor activation, increased hepatocellular proliferation leading to hepatocellular foci and tumor formation. Specifically, nitrapyrin induced a dose-related increase in the Cyp2b10/CAR-associated transcript and protein. Interestingly, the corresponding enzyme activity (7-pentoxyresorufin-O-dealkylase (PROD) was not enhanced due to nitrapyrin-mediated suicide inhibition of PROD activity. Nitrapyrin exposure elicited a clear dose-responsive increase in hepatocellular proliferation in wild-type mice, but not in CAR knock-out mice, informing that CAR activation is an obligatory key event in this test material-induced hepatocarcinogenesis. Furthermore, nitrapyrin exposure induced a clear, concentration-responsive increase in cell proliferation in mouse, but not human, hepatocytes in vitro. Evaluation of the data from repeat dose and MoA studies by the Bradford Hill criteria and a Human Relevance Framework (HRF) suggested that nitrapyrin-induced mouse liver tumors are not relevant to human health risk assessment because of qualitative differences between these two species.

Électroconvulsivothérapie et niveau de preuve : de la causalité à la relation dose-effet

The first objective of this article is to summarize the history of electroconvulsive therapy (ECT) in psychiatry in order to highlight the transition from clinical level of evidence based on phenomenological descriptions to controlled trial establishing causal relationship. The second objective is to apply the criteria of causation for ECT, to focus on the dose-effect relationship criteria, and thus to analyze the conditions of application of these criteria for ECT. A literature review exploring the use of electricity, ECT and electroencephalography (EEG) in psychiatry was conducted. The publications were identified from the Pubmed and GoogleScholar electronic databases. The scientific literature search of international articles was performed in July 2016. In 1784, a Royal commission established in France by King Louis XVI tested Mesmer's claims concerning animal magnetism. By doing that, the commission, including such prominent scientists as the chemist Anton Lavoisier and the scientist and researcher on electricity and therapeutics Benjamin Franklin, played a central role in establishing the criteria needed to assess the level of evidence of electrical therapeutics in psychiatry. Surprisingly, it is possible to identify the classical Bradford Hill criteria of causation in the report of the commission, except the dose-effect relationship criteria. Since then, it has been conducted blinded randomized controlled trials that confirmed the effectiveness of ECT against ECT placebos for the treatment of psychiatric disorders. At present, the dose-effect relationship criteria can be analyzed through an EEG quality assessment of ECT-induced seizures. EEG quality assessment includes several indices: TSLOW (time to onset of seizure activity ≤5Hz, seconds), peak mid-ictal amplitude (mm), regularity (intensity or morphology of the seizure (0-6)), stereotypy (global seizure patterning, 0-3) and post-ictal suppression (0-3). A manual rating sheet is needed to score theses indices. Such manual rating with example of EEG segments recording is proposed in this article. Additional studies are needed to validate this manual, to better establish the dose-response relationship for the ECT, and thus strengthen the position of the EEG as a central element for clinical good practice for ECT.

An Experimental Investigation of the Size Effects in Forming Processes of High-Purity Thin Metallic Sheets

Miniaturization of small metallic systems can lead to a softening of the mechanical behavior due to the reduction of scale. Size effects have been considerably studied recently for materials with various crystallographic structures. Under tensile conditions, thin specimen exhibit softer mechanical properties when the number of grains across thickness is lower than a critical number and this modification appears above a critical strain level. In this work, stamping tests were performed on five hundred micrometers in thickness sheets of hexagonal closed-packed cobalt. The results are compared with those obtained for face centered cubic copper and nickel. The influence of thickness over grain size ratio was studied for several proportional loadings linked to forming processes. Complex loadings were applied with 20 mm hemispherical punch and strain paths were checked with a 3D video extensometer. Hill criterion was systematically used to take into account the anisotropy of the samples. Our results revealed that the critical strain level for which the size effects appears is strongly sensitive to the stress triaxiality which, in turn, is closely dependent to the loading path.

High strain rate behavior of MC2 single crystal under uniaxial compression load at high temperature: Experiments and modeling

This paper presents experimental and numerical investigations on single crystal nickel base superalloy MC2. The purpose of this study is to efficiently predict the consequences of impacts on turbine blades within gas turbine engines. Dynamic compression tests on Split Hopkinson Pressure Bar (SHPB), performed at high temperature, have allowed the identification of anisotropic and viscoplastic material data. The effects of crystal orientation (〈1 0 0〉, 〈1 1 0〉 and 〈1 1 1〉), temperature (25, 750 and 1000 °C) and strain rate (up to 610 s−1) on the compression yield strength and work hardening of MC2 single crystal have been examined. The LS-Dyna solver has been used to calibrate the parameters of a phenomenological behavior law based on a local Hill yield criterion. The results of simulations have been verified by comparison with a ballistic test on a monocrystalline plate, and on a turbine blade heated at 1000 °C. The measured residual deflections and strain fields are consistent with those obtained by calculation.

Autoimmune chronic spontaneous urticaria: What we know and what we do not know

Chronic spontaneous urticaria (CSU) is a mast cell-driven skin disease characterized by the recurrence of transient wheals, angioedema, or both for more than 6weeks. Autoimmunity is thought to be one of the most frequent causes of CSU. Type I and II autoimmunity (ie, IgE to autoallergens and IgG autoantibodies to IgE or its receptor, respectively) have been implicated in the etiology and pathogenesis of CSU. We analyzed the relevant literature and assessed the existing evidence in support of a role for type I and II autoimmunity in CSU with the help of Hill's criteria of causality. For each of these criteria (ie, strength of association, consistency, specificity, temporality, biological gradient, plausibility, coherence, experiment, and analogy), we categorized the strength of evidence as "insufficient," "low," "moderate," or "high" and then assigned levels of causality for type I and II autoimmunity in patients with CSU from level 1 (causal relationship) to level 5 (causality not likely). Based on the evidence in support of Hill's criteria, type I autoimmunity in patients with CSU has level 3 causality (causal relationship suggested), and type II autoimmunity has level 2 causality (causal relationship likely). There are still many aspects of the pathologic mechanisms of CSU that need to be resolved, but it is becoming clear that there are at least 2 distinct pathways, type I and type II autoimmunity, that contribute to the pathogenesis of this complex disease.

Epidemiology of Familial Aggregation of Venous Thromboembolism.

Familial aggregation (clustering) of venous thromboembolism (VTE) is the clustering of VTE within a family. Though several genes, such as antithrombin, protein C, protein S, factor V, and prothrombin are associated with the familial clustering of VTE, these loci only partially explain the familial aggregation of VTE. The epidemiology of the familial aggregation of VTE exhibits typical characteristics of complex traits. The family history of VTE in first-degree relatives is associated with a two to three times increased familial relative risk (FRR). The FRR of VTE is higher in younger individuals, increases with a number of affected relatives, decreases as the familial relationship becomes more distant, increases with severity (unprovoked), and exhibits slightly stronger male transmission (Carter effect). High FRR is observed in individuals with two or more affected siblings (FRR > 50). Because familial aggregation represents the sum of shared family environmental and genetic factors, one should not assume that evidence of familial aggregation implies genetic effects. However, studies in twins, extended families, adoptees, and spouses indicate a weak involvement of shared environmental factors to the familial aggregation of VTE. Moreover, familial aggregation of VTE fulfills the Hill's criteria for causation. In conclusion, familial aggregation of VTE signals a clinically relevant inherent predisposition for VTE.

Microbiota is a primary cause of pathogenesis of chronic wounds.

Diverse microorganisms present on the surface of chronic wounds have been established to constitute wound microbiota. The aims of this study were to quantify the viability of wound microbiota, classify dispersal of viable microbes from the wound, and determine if human wound microbiota can produce a chronic wound in an animal model. Wound microbiotas as units (multiple microbial species acting as one infectious agent) were obtained from well-defined human chronic wounds and seeded onto mouse surgical excision wounds to produce chronically infected wounds that closely resembled the chronic wounds observed in the original hosts. We found the wound microbiota harvested from 35 out of 43 (81%) patients could produce similar chronic wounds (producing slough and exudate) in a murine chronic wound model. The top 30 species present in patient wounds were identified in the mouse wounds by molecular sequencing. Koch's postulates could therefore be applied to establish wound microbiota as the cause of the original human chronic wound infections. Evidence-based medicine criteria such as Hill's criteria for causation can all be satisfied by what is currently known about wound microbiota. This study demonstrates that wound microbiota actively disseminates from the chronic wound by forces and mechanisms intrinsic to the wound. Koch's postulates and Hill's criteria for causation together suggest chronic wound microbiota to be the main cause underlying the pathogenesis of chronic wounds. RW has an equity interest in PathoGenius Labs. No funding was received for this study.

The pertussis hypothesis: Bordetella pertussis colonization in the pathogenesis of Alzheimer’s disease

While a number of endogenous risk factors including age and genetics are established for Alzheimer’s disease (AD), identification of acquired, potentially preventable or treatable causes, remains limited. In this paper, we review three epidemiologic case studies and present extensive biologic, immunologic and anatomic evidence to support a novel hypothesis that Bordetella pertussis (BP), the bacterium better known to cause whooping cough, is an important potential cause of AD. Cross-cultural documentation of nasopharyngeal subclinical BP colonization reflecting BP-specific mucosal immunodeficiency, proximate anatomy of intranasal mucosal surfaces to central nervous system (CNS) olfactory pathways, and mechanisms by which BP and BP toxin account for all hallmark pathology of AD are reviewed, substantiating biologic plausibility. Notably, respiratory BP infection and BP toxin secreted from subclinical BP colonization can account for the initiation and accumulation of amyloid β plaques and tau tangles. Additional mechanisms consistent with the immunobiologic effects of subclinical BP colonization include microglial activation and inflammation, atrophy and neurodegeneration, excitotoxicity, distinctive anatomic distribution and sequential spread of disease, impaired glucose utilization, and other characteristic CNS pathology of AD. We conclude by assessing the evidence for causation against the Bradford Hill criteria, and advocate for further investigation into the potential role of BP in the etiology of AD.

The First 500 Registrations to the Research Registry®: Advancing Registration of Under-Registered Study Types.

The Declaration of Helsinki 2013 encourages the registration of all research studies involving human participants. However, emphasis has been placed on prospective clinical trials, and it is estimated that only 10% of observational studies are registered. In response, Research Registry® was launched in February 2015; a retrospectively curated registry that is free and easy to use. Research Registry® enables prospective or retrospective registration of studies, including those study types that cannot be registered on existing registries. In this study, we describe the first 500 registrations on Research Registry®. Since the launch of Research Registry® in February 2015, data of registrations have been collected, including type of studies registered, country of origin, and data curation activity. Inappropriate registrations, such as duplicates, were identified by the data curation process. These were removed from the database or modified as required. A quality score was assigned for each registration, based on Sir Austin Bradford Hill's criteria on what research studies should convey. Changes in quality scores over time were assessed. A total of 500 studies were registered on Research Registry® from February 2015 to October 2015, with a total of 1.7 million patients enrolled. The most common study types were retrospective cohort studies (37.2%), case series (14.8%), and first-in-man case reports (10.4%). Registrations were received from 57 different countries; the most submissions were received from Turkey, followed by China and the United Kingdom. Retrospective data curation identified 80 studies that were initially registered as the incorrect study type, and were subsequently correct. The Kruskal-Wallis test identified a significant improvement in quality scores for registrations from February 2015 to October 2015 (p < 0.0001). Since its conception in February 2015, Research Registry® has established itself as a new registry that is free, easy to use, and enables the registration of various study types, including observational studies and first-in-man case reports. Going forward, our plan is to continue developing Research Registry® in line with user feedback and usability studies. We plan to further promote Research Registry® to advance the cause of registration of research, to increase compliance with the Declaration of Helsinki 2013.

Theoretical prediction of forming limit diagram of AZ31 magnesium alloy sheet at warm temperatures

A theoretical prediction on forming limit diagram (FLD) of AZ31 magnesium alloy sheet was developed at warm temperatures based on the M–K theory. Two different yield criteria of von Mises and Hill’48 were applied in this model. Mechanical properties of AZ31 magnesium alloy used in the prediction were obtained by uniaxial tensile tests and the Fields–Backofen equation was incorporated in the analysis. In addition, experimental FLDs of AZ31 were acquired by conducting rigid die swell test at different temperatures to verify the prediction. It is demonstrated from a comparison between the predicted and the experimental FLDs at 473 K and 523 K that the predicted results are influenced by the type of yield criterion used in the calculation, especially at lower temperatures. Furthermore, a better agreement between the predicted results and experimental data for AZ31 magnesium alloy sheet at warm temperatures was obtained when Hill’48 yield criterion was applied.

Do Selective Serotonin Reuptake Inhibitors (SSRIs) Cause Fractures?

Recent meta-analyses report a 70% increase in fracture risk in selective serotonin reuptake inhibitor (SSRI) users compared to non-users; however, included studies were observational and limited in their ability to establish causality. Here, we use the Bradford Hill criteria to explore causality between SSRIs and fractures. We found a strong, consistent, and temporal relationship between SSRIs and fractures, which appears to follow a biological gradient. However, specificity and biological plausibility remain concerns. In terms of specificity, the majority of available data have limitations due to either confounding by indication or channeling bias. Self-controlled case series address some of these limitations and provide relatively strong observational evidence for a causal relationship between SSRIs and fracture. In doing so, they suggest that falls contribute to fractures in SSRI users. Whether there are also underlying changes in skeletal properties remains unresolved. Initial studies provide some evidence for skeletal effects of SSRIs; however, the pathways involved need to be established before biological plausibility can be accepted. As the link between SSRIs and fractures is based on observational data and not evidence from prospective trials, there is insufficient evidence to definitively determine a causal relationship and it appears premature to label SSRIs as a secondary cause of osteoporosis. SSRIs appear to contribute to fracture-inducing falls, and addressing any fall risk associated with SSRIs may be an efficient approach to reducing SSRI-related fractures. As fractures stemming from SSRI-induced falls are more likely in individuals with compromised bone health, it is worth considering bone density testing and intervention for those presenting with risk factors for osteoporosis.

Some improvements on Sun–Chen’s one-parameter plasticity model for fibrous composites – Part I: Constitutive modelling for tension–compression asymmetry response

Herein, a one-parameter plasticity model proposed by Sun and Chen [Sun CT and Chen JL. A simple flow rule for characterizing nonlinear behavior of fiber composites. J Compos Mater 1989; 23: 1009–1020] demonstrates features that make it highly attractive for characterizing non-linear responses of fibrous composites. However, a detailed exploitation of the model’s potential has been halted by unresolved problems that include tension–compression asymmetry in stress–strain curves, FEM implementation as well as optimal parameters determination, which are addressed in this investigation as well as proposed solutions are presented. The major focus in Part I of this three-part study was devoted to developing a simple model for predicting the tension–compression asymmetry in stress–strain curves for fibrous composites, which was based on Sun and Chen’s one-parameter plasticity model. A generalized Hill yield criterion was proposed from combinations of the Drucker–Prager yield criterion that considers the effect of hydrostatic pressure for isotropic materials and the Hill yield criterion suitable for anisotropic materials. By incorporating the yield strength-differential effect on the plastic flow rule in composite laminates, the one-parameter plasticity model was extended to a strength-differential effect-incorporated model. The improved model has been calibrated and validated by off-axis tension and compression tests on unidirectional carbon/epoxy (IM600/Q133) composite laminates. Results verified that the proposed model captured the complex tension–compression asymmetry in observed non-linear responses of stress–strain curves.

Too much sitting and all-cause mortality: is there a causal link?

BackgroundSedentary behaviours (time spent sitting, with low energy expenditure) are associated with deleterious health outcomes, including all-cause mortality. Whether this association can be considered causal has yet to be established.Using systematic reviews and primary studies from those reviews, we drew upon Bradford Hill’s criteria to consider the likelihood that sedentary behaviour in epidemiological studies is likely to be causally related to all-cause (premature) mortality.MethodsSearches for systematic reviews on sedentary behaviours and all-cause mortality yielded 386 records which, when judged against eligibility criteria, left eight reviews (addressing 17 primary studies) for analysis. Exposure measures included self-reported total sitting time, TV viewing time, and screen time. Studies included comparisons of a low-sedentary reference group with several higher sedentary categories, or compared the highest versus lowest sedentary behaviour groups. We employed four Bradford Hill criteria: strength of association, consistency, temporality, and dose–response. Evidence supporting causality at the level of each systematic review and primary study was judged using a traffic light system depicting green for causal evidence, amber for mixed or inconclusive evidence, and red for no evidence for causality (either evidence of no effect or no evidence reported).ResultsThe eight systematic reviews showed evidence for consistency (7 green) and temporality (6 green), and some evidence for strength of association (4 green). There was no evidence for a dose–response relationship (5 red). Five reviews were rated green overall. Twelve (67 %) of the primary studies were rated green, with evidence for strength and temporality.ConclusionsThere is reasonable evidence for a likely causal relationship between sedentary behaviour and all-cause mortality based on the epidemiological criteria of strength of association, consistency of effect, and temporality.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-016-3307-3) contains supplementary material, which is available to authorized users.

Zika Virus-Associated Microcephaly and Eye Lesions in the Newborn.

On February 1, 2016, Zika virus (ZIKV) was designated as a Public Health Emergency of International Concern by the director of the World Health Organization. Zika virus has spread to numerous countries throughout the Americas, affecting up to an estimated 1.3 million people since the first reports from Brazil in early 2015. Although ZIKV infections are self-limiting, fetal microcephaly and ophthalmic anomalies have been associated with ZIKV infection as a possible result of perinatal transmission. The causal link between maternal ZIKV infection and newborn microcephaly and eye lesions has not been proven beyond doubt and is currently debated. We discuss the possibility of causality by ZIKV using Koch's postulates and the more appropriate Bradford Hill criteria. In this review, we summarize and consolidate the current literature on newborn microcephaly and eye lesions associated with ZIKV infection and discuss current perspectives and controversies.

Vasectomy and prostate cancer risk: a historical synopsis of undulating false causality

The potential influence of vasectomy being a risk factor for the development of prostate cancer is not a new concept, with more than 30 publications addressing the topic. Given the global frequency of vasectomy and the prevalence of prostate cancer, this subject justifiably deserves scrutiny. Several articles have claimed that vasectomy puts men at risk for future development of prostate cancer. We explore articles that have shown the contrary (no link), explore the studies’ strengths and weaknesses, describe possible prostate cancer pathophysiologic mechanisms, and apply Bradford Hill criteria to help discern correlation with causation. The risk and interest of association of prostate cancer with vasectomy has waxed and waned over the last three decades. Based on our review, vasectomy remains a safe form of sterilization and does not increase prostate cancer risk.

From Correlation to Causation: What Do We Need in the Historical Sciences?

Changes in the methodology of the historical sciences make them more vulnerable to unjustifiable speculations being passed off as scientific results. The integrity of historical science is in peril due the way speculative and often unexamined causal assumptions are being used to generate data and underpin the identification of correlations in such data. A step toward a solution is to distinguish between plausible and speculative assumptions that facilitate the inference from measured and observed data to causal claims. One way to do that is by comparing these assumptions against a well-attested set of aspects of causation, such as the so-called "Bradford Hill Criteria" (BHC). The BHC do not provide a test for causation or necessary and sufficient conditions for causation but do indicate grounds for further investigation. By revising the BHC to reflect the needs and focus of historical sciences, it will be possible to assess the cogency of methods of investigation. These will be the Historical Sciences Bradford Hill Criteria (HSBHC). An application to one area in historical science is used to demonstrate the effectiveness of the HSBHC, namely biogeography. Four methods are assessed in order to show how the HSBHC can be used to examine the assumptions between our data and the causal biogeographical processes we infer.

IHD from copper deficiency: a unified theory.

The theory, in brief outline here, implicating deficiency of Cu in the aetiology and pathophysiology of IHD explains more attributes of the disease than any other theory. This theory satisfies several of Hill's criteria of a half-century ago for deducing association between an environmental feature and presence of an illness. Most important is the temporal association between the rise of IHD and the decrease in dietary Cu since the 1930s along with a parallel increase in the supplementation of pregnant women with Fe, a Cu antagonist. There are more than eighty anatomical, chemical and physiological similarities between animals deficient in Cu and individuals with IHD. Few of these similarities have been produced by other dietary manipulations because feeding cholesterol induces Cu deficiency in animals. The most recent of these to be identified is decreased serum dehydroepiandrosterone. Some concomitant aspects of Cu metabolism and utilisation have been identified in other theories about heart disease: fetal programming, homocysteine, and Fe overload.

Prediction and Experimental Validation of Forming Limit Curve of a Quenched and Partitioned Steel

Forming limit curve (FLC) is an effective tool to evaluate the formability of sheet metals. An accurate FLC prediction for a sheet metal is beneficial to its engineering application. A quenched and partitioned steel, known as QP980, is one of the 3rd generation advanced high strength steels and is composed of martensite, ferrite and a considerable amount of retained austenite (RA). Martensite transformation from RA induced by deformation, namely, transformation induced plasticity (TRIP), promotes the capability of work hardening and consequently formability. Nakazima tests were carried out to obtain the experimental forming limit strains with the aid of digital image correlation techniques. Scanning electron microscopy (SEM) was employed to examine the fracture morphologies of Nakazima specimens of the QP980 steel. The observed dimple pattern indicated that tensile stress was the predominant factor which led to failure of QP980 specimens. Therefore, maximum tensile stress criterion (MTSC) was adopted as the forming limit criterion. To predict the FLC of QP980 steel, Von-Mises yield criterion and power hardening law were adopted according to the tested mechanical properties of QP980 steel. Results were compared with those derived from other three representative instability theories, e. g. Hill criterion, Storen-Rice vertex theory and Bressan-Williams model, which shows that the MTSC based FLC is in better agreement with the experimental results.