Hill Criteria Research Articles

Asbestos in Talc and Mesothelioma: Review of the Causality Using Epidemiology

Talcum powder has long been contaminated with asbestos fibers depending on the source of the talc.  Pleural and peritoneal mesothelioma are scientifically established as caused by asbestos exposures.  However, when investigating causality of mesothelioma from asbestos fibers in talcum powder, epidemiology is complicated by various methodological issues and inadequacies in existing studies.  The occupational and case studies are explored in an effort to bring clarity to the issue of talcum powder usage and mesothelioma.   Talc is randomly and sporadically contaminated with asbestos fibers including chrysotile, tremolite and anthophyllite.  Case studies of mesothelioma victims whose only asbestos exposure was to talc, found anthophyllite, tremolite and chrysotile asbestos fibers in their tissues.  Exposure to all three types of asbestos fibers increases the risk of mesothelioma.   The Hill criteria of causality, which considers all aspects of toxicology, biology and epidemiology, are applied to the issue.  This analysis results in compelling evidence that asbestos in talcum powder is causative for mesothelioma.  Thus, precaution would dictate the avoidance of the use of talcum powders. 

Review of Recent Advances in Understanding the Role of Vitamin D in Reducing Cancer Risk: Breast, Colorectal, Prostate, and Overall Cancer.

This article is a narrative review of recent epidemiological findings regarding ultraviolet-B (UVB) dose or exposure, serum 25-hydroxyvitamin D [25(OH)D] concentrations, vitamin D supplementation, and genetic variations in 25(OH)D concentration for incidence, survival, and mortality rates of overall and breast, colorectal, and prostate cancer. According to ecological studies, solar UVB doses are inversely correlated with incidence/mortality rates for about 20 cancer types. Observational studies support a role of higher 25(OH)D concentrations in reducing risk of breast and colorectal cancer incidence and mortality rates but, for prostate cancer, in increasing incidence rates while reducing mortality rates. Mendelian randomization studies offer little support for vitamin D in reducing cancer risk. Their primary limitation is that they only investigate small variations in genetically predicted 25(OH)D concentration near the population mean value. The secondary analyses from the VITAL clinical trial indicated significant reductions from 2000 IU/d of vitamin D3 supplementation in all-cancer incidence and mortality rates for selected subgroups. Thus, Hill's criteria for causality in a biological system are now largely satisfied for supporting the claim that vitamin D reduces the risk of cancer incidence and death.

An enhanced François distortional yield model: Theoretical framework and experimental validation

A distorted yield surface with a higher curvature in the preloading direction and a rather flat curve in the reverse direction has been observed in numerous materials that experience a preloading process. To describe such distorted yield surfaces, a novel distortional yield model was proposed. The model involves the distorted stress extended from the original version defined by François, and can be theoretically applied to any quadratic or nonquadratic yield functions. The original Hill48 and Barlat91 yield criteria were adopted as representatives in this work, for describing the behavior of different steel and aluminum sheets in a two-stage loading experiment. The experimental outcomes obtained from previous publications were employed for the validation of the model. A case of application in a deliberately designed two-stage loading experiment with annealed 6061 aluminum sheet was presented as well. Distinct yield surface distortion has been observed in the second loading stage at small deformation levels with the prestrained sheet metals, and the surface distortion gradually recovers and stabilizes within a small range of strain thereafter. Additionally, initial distortion is positively correlated with the prestrain level. Associated with a novel evolution rule of back stress, the distorted yield surface, as well as the transient phenomena including the Bauschinger effect, orthogonal softening and permanent softening effects in the second loading stage, was successfully described by the proposed model.

Modeling material behavior of AA5083 aluminum alloy sheet using biaxial tensile tests and its application in numerical simulation of deep drawing

Improvement in accuracy of the predicted results from numerical simulation results into a reduction of cost and time involved in tool design and experimental trials. However, the predicted results from finite element simulations are significantly affected by the chosen yield criterion and work hardening law. The selection of yield criterion and work hardening law depends on the characterization methods used for defining the material behavior. In this work, the mechanical behavior of AA5083-O aluminum alloy sheet is modeled by performing biaxial tensile tests using cruciform specimen and hydraulic bulging experiments in addition to uniaxial tensile tests. Biaxial to uniaxial yield stress ratios are determined using the equal plastic work principle from the flow curves obtained from these tests. The obtained ratios are used to find the coefficients of Yld2000-2d and Hill48 yield criteria which is then used in the numerical simulations of cylindrical cup deep drawing. Numerical simulations are also carried out using uniaxial and biaxial flow curves fitted with different isotropic hardening laws. Thickness distributions and the load-displacement curves are predicted and validated by performing cylindrical cup deep drawing experiments.

Acute kidney injury and adverse outcomes of critical illness: correlation or causation?

Critically ill patients who develop acute kidney injury (AKI) are more than twice as likely to die in hospital. However, it is not clear to what extent AKI is the cause of excess mortality, or merely a correlate of illness severity. The Bradford Hill criteria for causality (plausibility, temporality, magnitude, specificity, analogy, experiment & coherence, biological gradient and consistency) were applied to assess the extent to which AKI may be causative in adverse short-term outcomes of critical illness.Plausible mechanisms exist to explain increased risk of death after AKI, both from direct pathophysiological effects of renal dysfunction and mechanisms of organ cross-talk in multiple-organ failure. The temporal relationship between increased mortality following AKI is consistent with its pathophysiology. AKI is associated with substantially increased mortality, an association that persists after accounting for known confounders. A biological gradient exists between increasing severity of AKI and increasing short-term mortality. This graded association shares similar features to the increased mortality observed in ARDS; an analogous condition with a multifactorial aetiology. Evidence for the outcomes of AKI from retrospective cohort studies and experimental animal models is coherent however both of these forms of evidence have intrinsic biases and shortcomings. The relationship between AKI and risk of death is maintained across a range of patient ages, comorbidities and underlying diagnoses.In conclusion many features of the relationship between AKI and short-term mortality suggest causality. Prevention and mitigation of AKI and its complications are valid targets for studies seeking to improve short-term survival in critical care.

Characterization of yield criteria for zinc coated steel sheets using nano-indentation with knoop indenter

An indentation based method to characterize the yield locus for steel sheets is developed and implemented. Knoop hardness based indentation experiments have been performed on the surface as well as on the cross sections of an uncoated steel sheet to obtain the corresponding yield locus in the deviatoric and plane-stress situation. Stress ratios following the indenter's geometry are used to plot the yield locus from indentation data. The stress ratios have been corrected for the anisotropy of the material by an optimization algorithm. Points are then plotted in the plane-stress plane using the corrected stress ratios, the strain increment vectors and indentation hardness data. The parameters for the Hill's quadratic yield criteria are obtained from the indentation data based on a curve fitted yield locus. The results obtained using nano-indentation have been compared with those obtained from the standard characterization tests for steel sheet and shown to have good agreement. The method is also applied to the yield locus characterization of zinc coatings on steel sheet for multi-scale modelling of friction in deep drawing.

Helicobacter pylori And Duodenal Ulcer: Systematic Review Of Controversies In Causation.

BackgroundThere are controversies on the causal role of H. pylori in duodenal ulceration. Helicobacter pylori are curved gram-negative microaerophilic bacteria found at the layer of gastric mucous or adherent to the epithelial lining of the stomach. It’s a public health significance bacteria starting from discovery, and the prevalence and severity of the infection varies considerably among populations. H. pylori are a risk for various diseases, while the extent of host response like gastric inflammation and the amount of acid secretion by parietal cells affects the outcome of infection.MethodRelevant literature were searched from databases such as Google Scholar, PubMed, Hinari, Web of Science, Scopus, and Science Direct.ResultThe review evidence supports a strong causal relation between H. pylori infection and duodenal ulcer, as patients are more likely to be infected by virulent strains which later cause duodenal ulceration. Thus, eradication of H. pylori infection decreases the incidence of duodenal ulcers, and prevents its recurrence by reducing both basal gastrin release and acid secretion without affecting parietal cell sensitivity. On the other hand, some studies show that H. pylori infection is not associated with the development of duodenal ulcers and such a lack of association revealed that duodenal ulceration has different pathogenesis.ConclusionDespite controversies observed in the causal role of H. pylori to duodenal ulceration by various studies, Hill criteria of causation proved the presence of a causal relation between H. pylori infection and duodenal ulcers. Other factors are also responsible for the development of duodenal ulcers and such factors are responsible for the differences in the prevalence of the diseases.

First Ply Failure Analysis of Rectangular Fiber Metal Laminated Composite Plates Subjected to Uniformly Distributed Loads

Fiber metal laminates (FMLs) are the hybrid composite materials that needed analysis for using them toward applications as rectangular plates subjected to uniformly distributed loads. Determination of first ply failure (FPF) loads is the focus of the present study. These loads are identified by the procedure developed on the basis classical laminate theory (CLT), and Tsai–Hill criterion is used to identify the failure load. The developed procedure was validated by applying it to the standard cases reported in the literature. The failure loads and deformation of FMLs are presented in the form of dimensionless parameters, and their variation was studied for width-to-length ratios. FMLs of GLARE and Ti-CFRP are studied based on their importance to research.

Numerical simulation of material failure in single point incremental forming process

The sheet metal parts obtained through single point incremental forming process show a thinning and also there is a high possibility of material failure. In order to avoid the failure of the material during the process, it is a good practice to use numerical simulation through finite element method to prevent this phenomenon. The aim of this paper is to investigate the prediction of the failure moment of the aluminium sheet metal using various failure criteria. Commonly used failure criteria are: Tresca or maximum shear stress criterion, von Mises yield criterion, Hill yield criteria and various invariants of the Cauchy stress tensor. For the numerical simulation of the single point incremental forming process, the semi-finished part is discretized using shell elements which allow determination of material thinning and also it is possible to observe the moment of material failure. This paper will treat also the influence of the wall angle over the moment of material failure.

Penetration resistance and the critical cavitation velocity for an ogive-nosed rigid projectile penetrating into a semi-infinite metallic target

This paper studies penetration resistance and projectile-target separation for an ogive-nosed rigid projectile penetrating into a metallic target. A prescribed normal velocity field is introduced to determine the contact stress on the projectile nose, based on which the dynamic equation of a rigid projectile is formulated. Projectile-target separation occurs when the impact velocity of the projectile is greater than the critical cavitation velocity according to Hill's cavitation criterion. Target material is assumed incompressible in both elastic and rigid, perfectly plastic regions in order to simplify the analyses. It shows that the penetration resistance derived from the prescribed velocity field has a different form from that based on the dynamic cavity expansion model. When the impact velocity is greater than the critical cavitation velocity, the projectile-target separation point moves further to the nose tip, leading to the reduction of the contact area between the projectile nose and the target and a large increase of the inertia term (velocity square term) in penetration resistance. The predicted penetration depth and critical cavitation velocity agree reasonably with experimental and numerical results.

Interruptions in Health Care: Assessing Their Connection With Error and Patient Harm.

We address the problem of how researchers investigate the actual or potential causal connection between interruptions and medical errors, and whether interventions might reduce the potential for harm. It is widely assumed that interruptions lead to errors and patient harm. However, many reviewers and authors have commented that there is not strong evidence for a causal connection. We introduce a framework of criteria for assessing how strongly evidence implies causality: the so-called Bradford Hill criteria. We then examine four key "metanarratives" of research into interruptions in health care-applied cognitive psychology, epidemiology, quality improvement, and cognitive systems engineering-and assess how each tradition has addressed the causal connection between interruptions and error. Outcomes of applying the Bradford Hill criteria are that the applied cognitive psychology and epidemiology metanarratives address the causal connection relatively directly, whereas the quality improvement metanarrative merely assumes causality, and the cognitive systems engineering metanarrative either implicitly or explicitly questions the feasibility of finding a direct causal connection with harm. The Bradford Hill criteria are useful for evaluating the existing literature on the relationship between interruptions in health care, clinical errors, and the potential for patient harm. In the future, more attention is needed to the issue of why interruptions usually do not lead to harm, and the implications for how we approach patient safety.

A numerical study on indentation properties of cortical bone tissue: influence of anisotropy.

The purpose of this study is to investigate the effect of anisotropy of cortical bone tissue on measurement of properties such as direction-dependent moduli and hardness. An advanced three-dimensional finite element model of microindentation was developed. Different modelling schemes were considered to account for anisotropy of elastic or/and plastic regimes. The elastic anisotropic behaviour was modelled employing an elasticity tensor, and Hill's criteria were used to represent the direction-dependent post-yield behaviour. The Oliver-Pharr method was used in the data analysis. A decrease in the value of the transverse elasticity modulus resulted in the increased material's indentation modulus measured in the longitudinal direction and a decreased one in the transverse direction, while they were insensitive to the anisotropy in post-elastic regime. On the other hand, an increase in plastic anisotropy led to a decrease in measured hardness for both directions, but by a larger amount in the transverse one. The size effect phenomenon was found to be also sensitive to anisotropy. The undertaken analysis suggests that the Oliver-Pharr method is a useful tool for first-order approximations in the analysis of mechanical properties of anisotropic materials similar to cortical bone, but not necessarily for the materials with low hardening reserves in the plastic regime.

Stress constraint topology optimization using layerwise theory for composite laminates

An improved stress-based topology optimization method for laminated composites is proposed by applying the layerwise theory in this research. The layerwise theory is an analysis technique for laminated composites or fiber-reinforced composites that has been developed to overcome the disadvantages of the classical laminated plate theory (CLPT). Because transverse shear deformation is ignored in the CLPT, it cannot be used for thick plates or multiple-layered composites. Therefore, new methods have been developed for analyzing them, and one of them is the layerwise theory. Using the layerwise theory, it is possible to accurately analyze a thick plate and predict the behavior of multiple layers of composites. In the layerwise theory, because a new displacement field and a modified finite element (FE) model are used, the FE model of the stress-based topology optimization method (STOM) is reconstructed to apply the layerwise theory. To apply the STOM for composite materials, the specific failure criterion developed for anisotropic materials must be selected. Therefore, the Tsai–Hill criterion and Tsai–Wu criterion are adapted to the STOM formula to consider the failure of composite materials. Further, the orientation of each layer in a composite significantly affects the optimization result as well as stiffness. Therefore, in this study, we optimize the density and orientation simultaneously by setting the orientation as a design variable. Finally, several types of p-norm approaches are proposed, and one of them can be chosen depending on the location of the maximum value of the constraint.

Breast cancer and cytomegalovirus.

To determine whether cytomegalovirus is causally associated with breast cancer and whether cytomegalovirus should be categorised as an oncogenic virus. We undertook a review of published epidemiological and laboratory studies, using established causal criteria: Bradford Hill criteria to determine whether cytomegalovirus is associated with breast cancer; and Evans/Mueller criteria to determine whether cytomegalovirus should be categorised as an oncogenic virus. Although there are inconsistencies in the findings of published epidemiological and laboratory studies, these may be explained by factors such as: differences in timing of blood samples, differences in selection of cases and controls, or high cytomegalovirus seroprevalence among participants in the epidemiological studies; and, in the laboratory studies, differences in sample preparations, age of sample, whether or not paired breast cancer and normal breast tissue samples were used, differences in the tests, primers and/or antibodies used, differences in histological types of breast cancer studied, and/or features of the virus. Overall, the results of published studies of cytomegalovirus and breast cancer suggest cytomegalovirus is a causal factor for at least some types of breast cancer. If the evidence for a link between cytomegalovirus and breast cancer continues to strengthen, further research could lead to: targeted screening; therapy using antiviral drugs; and, perhaps, primary prevention of a significant proportion of breast cancer. Vaccination against viruses has already been shown to be effective in preventing cervix and liver cancer; cytomegalovirus vaccines are already under development.

Intestinal dysbiosis and necrotizing enterocolitis: assessment for causality using Bradford Hill criteria.

In recent years, several studies have shown that premature infants who develop NEC frequently display enteric dysbiosis with increased Gram-negative bacteria for several days to weeks prior to NEC onset. The importance of these findings, for the possibility of a causal role of these bacteria in NEC pathogenesis, and for potential value of gut dysbiosis as a biomarker of NEC, is well-recognized. In this review, we present current evidence supporting the association between NEC in premature infants and enteric dysbiosis, and its evaluation using the Bradford Hill criteria for causality. To provide an objective appraisal, we developed a novel scoring system for causal inference. Despite important methodological and statistical limitations, there is support for the association from several large studies and a meta-analysis. The association draws strength from strong biological plausibility of a role of Gram-negative bacteria in NEC and from evidence for temporality, that dysbiosis may antedate NEC onset. The weakness of the association is in the low level of consistency across studies, and the lack of specificity of effect. There is a need for an improved definition of dysbiosis, either based on a critical threshold of relative abundances or at higher levels of taxonomic resolution.

Ciprofloxacin and risk of hypoglycemia in non-diabetic patients

BackgroundFluoroquinolones have been associated with hypoglycemia in patients taking diabetic medications, most commonly due to drug-drug interactions and other associated risk factors. Except for four published case reports, there are no studies that have found positive associations between ciprofloxacin and hypoglycemia. In all but one of the cases, ciprofloxacin was taken with other hypoglycemic drugs. Recently, the Eritrean National Pharmacovigilance Centre received a serious case of hypoglycemia with recurrent episodes in a young and healthy patient without diabetes following use of oral ciprofloxacin. The aim of the present study is therefore to assess the causal relationship between ciprofloxacin and hypoglycemia in patients without diabetes using the World Health Organization-Uppsala Monitoring Centre global adverse drug reaction database (VigiBase®).MethodsA search was made on the World Health Organization global adverse drug reaction database (August 15, 2018) using “ciprofloxacin” as the drug substance and “hypoglycemia” as the reaction term. Cases that used hypoglycemic drugs (patients with diabetes) concurrently with ciprofloxacin and those with a completeness score below 50% were excluded to control for confounders and to improve the strength of the data. Hill criteria were used to assess causation.ResultsA total of 35 cases of hypoglycemia reported since 1989 from 17 countries in patients without diabetes associated with ciprofloxacin use with a median time to onset of 4 days were retrieved. The cases have a median age of 64 years (interquartile range, 50–85) with a similar male–to-female ratio. Ciprofloxacin was the only suspect and the sole drug administered in 48.5% of the cases. In ten cases, hypoglycemia abated following withdrawal of ciprofloxacin, and reaction recurred in one case on the subsequent rechallenge. Hypoglycemia was marked as “serious” in 20 cases, and the outcome was fatal in two cases.ConclusionsThis assessment found a suggestive causal link between use of ciprofloxacin and hypoglycemia in patients without diabetes.

Applying the Bradford Hill criteria to evaluate the association between hypoglycaemia and cardiovascular events/mortality (CVEM) [Data from meta-analysis (MA), Randomized Controlled Trials (RCTs), and observational outcome studies (OBS)

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Structural behaviors of bolted connections using laminated bamboo and steel plates

The objective of this study is to investigate the mechanical properties of laminated bamboo and the behavior of bolted connections using laminated bamboo and steel plates. Seeking more sustainable materials to reducing the carbon impact onto our environment has put bamboo on the map as an alternative building material, especially in the regions such as China, Southern Asia, and South America, where the bamboo is abundant. The application of a composite bolted connection using laminated bamboo and steel plates in a laminated bamboo silo structure necessitates a detailed investigation of its behavior. An experimental program was designed and employed to perform a set of specimen tests on both single-bolted and multiple-bolted connections using laminated bamboo and steel plates. The impacts of the edge distance, bolt size, and thickness of laminated bamboo strips were observed for single-bolted connections. Meanwhile, the test results for multiple-bolted connections revealed that the spacing influenced the capacity in a similar manner as the edge distance on single-bolted connections and the stagger configuration of the bolts improved the capacity of the multiple-bolted connection. The observed failure modes of the connections specimens were the longitudinal splitting, shear out, and combined longitudinal splitting and bamboo crushing. In addition, the material properties of the laminated bamboo used in this study were carefully measured and recorded to provide a first-hand database on the parameters of the constitutive relations and Hill's failure criterion of such material. The measured material parameters were employed in the detailed finite element models of these connections and their numerical solutions were compared with the test results.

An Adverse Outcome Pathway Linking Organohalogen Exposure to Mitochondrial Disease.

Adverse outcome pathways (AOPs) are pragmatic tools in human health hazard characterization and risk assessment. As such, one of the main goals of AOP development is to provide a clear, progressive, and linear mechanistic representation of pertinent toxicological key events (KEs) occurring along the different levels of biological organization. Here, we present an AOP framework that depicts how exposure to organohalogens can lead to mitochondrial disease. Organohalogens are disinfectant by-products (DBPs) found in our drinking water. Chloroform, trichloroacetic acid, and trichlorophenol were selected to represent specific types of organohalogens for the development of this AOP. Although each of these compounds contains chlorine atoms, they differ in aromaticity and solubility, which have a significant impact on their potency. This AOP consists of two main pathways, both of which are triggered by the molecular initiating event (MIE) of excessive reactive oxygen species generation. Pathway 1 details the downstream consequences of oxidative stress, which include mitochondrial DNA damage, protein aggregation, and depolarization of the mitochondrial membrane. Pathway 2 shows the KEs that result from inadequate supply of glutathione, including calcium dysregulation and ATP depletion. Pathways 1 and 2 converge at a common KE: opening of the mitochondrial membrane transition pore (mPTP). This leads to the release of cytochrome c, caspase activation, apoptosis, and mitochondrial disease. This AOP was developed according to the Organisation for Economic Co-operation and Development guidance, including critical consideration of the Bradford Hill criteria for Weight of Evidence assessment and key questions for evaluating confidence. The presented AOP is expected to serve as the basis for designing new toxicological tests as well as the characterization of novel biomarkers for disinfectant by-product exposure and adverse health effects.

Safety and risks of shiatsu: Protocol for a systematic review

IntroductionPeople use shiatsu for health maintenance and help with illness. Shiatsu is often considered safe, but there has been no published systematic review of its possible risks. The review aims to assess the evidence of safety and risk of harm from shiatsu. MethodsAll types of studies, independent of control and with any style of shiatsu will be eligible. Reports in any language will be included. Peer-reviewed studies and non-peer-reviewed literature will be handled in separate parts of the review. Electronic databases (including among others MEDLINE, AMED, Alt HealthWatch, Web of Science, CiNii) will be searched for identification of peer-reviewed publications. Hand-search will be used for non-peer-reviewed literature. Risk of bias will be assessed using RoB 2.0 in conjunction with McHarm (randomised trials), ROBINS:I in conjunction with McHarm (non-randomised studies), a modified PHARMA checklist (adverse reports). When appropriate, reporting bias will be assessed using ORBIT. The relevance of the described intervention to shiatsu will be based on clinical experience, using CARE for massage and bodywork and TIDieR. Root cause analysis of adverse events will consider Bradford Hill's criteria in the light of clinical experience. ResultsMeta-analysis is not planned. Results for each study will be presented in tables. Relationships within and between studies will be explored. A theory about the safety profile of shiatsu will be developed. Identified incidents will be presented in a narrative way and tabular categories. ConclusionThe relevance to various stakeholders will be highlighted and the issues occurring from the review will be explored.