•AcciMap is arguably the most popular accident analysis method.•We reviewed and synthesised 23 published AcciMap studies.•We identified 5587 contributory factors spanning 79 contributory factor ...types.•We found a set of contributory factors that often play a role in major accidents.•Further applications of our contributory factor classification scheme are encouraged.
As AcciMap is now arguably the most popular accident analysis method in the peer-reviewed literature, there are key learnings to be taken from reviewing and synthesising published AcciMap analyses. In particular, the extent to which the network of contributory factors underpinning accidents is consistent across safety critical domains. This study reviewed and synthesised 23 AcciMap analyses published in the peer-reviewed literature. Contributory factors and relationships were extracted and thematically coded to form a single multi-domain, multi-incident AcciMap. The resulting AcciMap contains 5587 contributory factors spanning seventy-nine distinct contributory factor types. The findings reveal a set of generic contributory factors that consistently play a role in major accidents regardless of domain. Additionally, contributory factors previously only associated with sharp-end human operators are, in fact, prevalent across multiple levels of accident systems. The implications of these findings for accident theory and accident analysis and prevention activities are discussed. For future AcciMap analyses it is recommended that the contributory factor classification scheme developed in the present study is used to support the identification and classification of contributory factors. In addition, further education for analysts on the systems thinking perspective on accident causation is recommended.
Marked heterogeneity exists among patients with sepsis, both in terms of distribution of organ dysfunction and its severity. Such heterogeneity could be explained by the presence of multiple subtypes ...of sepsis that may have important implications for treatment.
Narrative review of published literature involving endotoxin from 1970 to 2022.
In humans, endotoxemia is most consistently associated with a specific pattern of organ failure including shock, endothelial dysfunction, acute kidney injury, and hepatic dysfunction. This pattern is consistent with complement activation and uncontrolled inflammation, two features of endotoxemia. Unbiased discovery using artificial intelligence also identifies a subtype of sepsis which features these same organ failures.
Endotoxin appears to represent an important molecular phenotype of sepsis with unique clinical features and high mortality.
Despite the high prevalence and major negative impact of uterine fibroids (UFs) on women's health, their pathogenesis remains largely unknown. While tumor-initiating cells have been previously ...isolated from UFs, the cell of origin for these tumors in normal myometrium has not been identified. We isolated cells with Stro1/CD44 surface markers from normal myometrium expressing stem cell markers Oct-4/c-kit/nanog that exhibited the properties of myometrial stem/progenitor-like cells (MSCs). Using a murine model for UFs, we showed that the cervix was a hypoxic "niche" and primary site (96%) for fibroid development in these animals. The pool size of these MSCs also responded to environmental cues, contracting with age and expanding in response to developmental environmental exposures that promote fibroid development. Translating these findings to women, the number of MSCs in unaffected human myometrium correlated with risk for developing UFs. Caucasian (CC) women with fibroids had increased numbers of MSCs relative to CC women without fibroids, and African-American (AA) women at highest risk for these tumors had the highest number of MSCs: AA-with fibroids > CC-with fibroids > AA-without fibroids > CC-without fibroids. These data identify Stro1
/CD44
MSCs as MSC/progenitor cell for UFs, and a target for ethnic and environmental factors that increase UF risk. Stem Cells 2017;35:666-678.
People who inject drugs (PWID) experience a high prevalence of incarceration and might be at high risk of HIV and hepatitis C virus (HCV) infection during or after incarceration. We aimed to assess ...whether incarceration history elevates HIV or HCV acquisition risk among PWID.
In this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO databases for studies in any language published from Jan 1, 2000 until June 13, 2017 assessing HIV or HCV incidence among PWID. We included studies that measured HIV or HCV incidence among community-recruited PWID. We included only studies reporting original results and excluded studies that evaluated incident infections by self-report. We contacted authors of cohort studies that met the inclusion or exclusion criteria, but that did not report on the outcomes of interest, to request data. We extracted and pooled data from the included studies using random-effects meta-analyses to quantify the associations between recent (past 3, 6, or 12 months or since last follow-up) or past incarceration and HIV or HCV acquisition (primary infection or reinfection) risk among PWID. We assessed the risk of bias of included studies using the Newcastle-Ottawa Scale. Between-study heterogeneity was evaluated using the I2 statistic and the P-value for heterogeneity.
We included published results from 20 studies and unpublished results from 21 studies. These studies originated from Australasia, western and eastern Europe, North and Latin America, and east and southeast Asia. Recent incarceration was associated with an 81% (relative risk RR 1·81, 95% CI 1·40–2·34) increase in HIV acquisition risk, with moderate heterogeneity between studies (I2=63·5%; p=0·001), and a 62% (RR 1·62, 95% CI 1·28–2·05) increase in HCV acquisition risk, also with moderate heterogeneity between studies (I2=57·3%; p=0·002). Past incarceration was associated with a 25% increase in HIV (RR 1·25, 95% CI 0·94–1·65) and a 21% increase in HCV (1·21, 1·02–1·43) acquisition risk.
Incarceration is associated with substantial short-term increases in HIV and HCV acquisition risk among PWID and could be a significant driver of HCV and HIV transmission among PWID. These findings support the need for developing novel interventions to minimise the risk of HCV and HIV acquisition, including addressing structural risks associated with drug laws and excessive incarceration of PWID.
Engineering and Physical Sciences Research Council, National Institute for Health Research, National Institutes of Health.
Reaction databases provide a great deal of useful information to assist planning of experiments but do not provide any interpretation or chemical concepts to accompany this information. In this work, ...reactions are labeled with experimental conditions, and network analysis shows that consistencies within clusters of data points can be leveraged to organize this information. In particular, this analysis shows how particular experimental conditions (specifically solvent) are effective in enabling specific organic reactions (Friedel–Crafts, Aldol addition, Claisen condensation, Diels–Alder, and Wittig), including variations within each reaction class. Network analysis shows data points for reactions tend to break into clusters that depend on the catalyst and chemical structure. This type of clustering, which mimics how a chemist reasons, is derived directly from the network. Therefore, the findings of this work could augment synthesis planning by providing predictions in a fashion that mimics human chemists. To numerically evaluate solvent prediction ability, three methods are compared: network analysis (through the k-nearest neighbor algorithm), a support vector machine, and a deep neural network. The most accurate method in 4 of the 5 test cases is the network analysis, with deep neural networks also showing good prediction scores. The network analysis tool was evaluated by an expert panel of chemists, who generally agreed that the algorithm produced accurate solvent choices while simultaneously being transparent in the underlying reasons for its predictions.
The parasitic protist Trypanosoma brucei is the causative agent of Human African Trypanosomiasis, also known as sleeping sickness. The parasite enters the blood via the bite of the tsetse fly where ...it is wholly reliant on glycolysis for the production of ATP. Glycolytic enzymes have been regarded as challenging drug targets because of their highly conserved active sites and phosphorylated substrates. We describe the development of novel small molecule allosteric inhibitors of trypanosome phosphofructokinase (PFK) that block the glycolytic pathway resulting in very fast parasite kill times with no inhibition of human PFKs. The compounds cross the blood brain barrier and single day oral dosing cures parasitaemia in a stage 1 animal model of human African trypanosomiasis. This study demonstrates that it is possible to target glycolysis and additionally shows how differences in allosteric mechanisms may allow the development of species-specific inhibitors to tackle a range of proliferative or infectious diseases.
There is growing interest in the use of systems-based risk assessment methods in Human Factors and Ergonomics (HFE). The purpose of this study was to test the intra-rater reliability and ...criterion-referenced concurrent validity of three systems-based risk assessment approaches: (i) the Systems-Theoretic Process Analysis (STPA) method; (ii) the Event Analysis of Systemic Teamwork Broken Links (EAST-BL) method; and, (iii) the Network Hazard Analysis and Risk Management System (Net-HARMS) method. Reliability and validity measures were obtained using the Signal Detection Theory (SDT) paradigm. Whilst STPA identified the highest number of risks, the findings indicate a weak to moderate level of reliability and validity for STPA, EAST-BL and Net-HARMS. There were no statistically significant differences between the methods across analyses. The results suggest that there is merit to the continued use of systems-based risk assessment methods following a series of methodological extensions that aim to enhance the reliability and validity of future applications.
Practitioner summary The three risk assessment methods produced weak to moderate levels of stability and accuracy regarding their capability to predict risks. There is a pressing need to further test the reliability and validity of safety methods in Human Factors and Ergonomics.
In the fields of sepsis and systemic inflammation, endotoxin might be the most studied molecule since the term was coined by Richard Pfeiffer in 1892. Paradoxically measuring endotoxin in humans and ...finding an effective treatment for endotoxemia have remained challenging. While advances have been made in understanding the mechanisms of how this simple molecule can trigger an intense immune cascade, there is an ever growing need to develop better treatments. Studies measuring endotoxin levels in patients with septic shock have consistently demonstrated that there is a dose-response relationship between endotoxin levels and adverse outcomes. A rapid assay to measure endotoxin activity has been available for more than a decade, but few studies have synergized the assay with a therapeutic. Polymyxin B hemoperfusion (PMX-HP) leverages a molecule with high affinity for endotoxin with a technique to eliminate exposure. Polymyxin is bound and immobilized to fibers within a cartridge and administered as an extracorporeal therapy via veno-venous hemoperfusion. Clinical evidence of its use is plentiful yet inconsistent in studies based on an outcome for mortality at 28 days. Herein, we describe targeted patient selection using the endotoxin activity assay and clinical phenotyping followed by adsorption of endotoxin using the PMX-HP for endotoxemic sepsis.
The issues being tackled within ergonomics problem spaces are shifting. Although existing paradigms appear relevant for modern day systems, it is worth questioning whether our methods are. This paper ...asks whether the complexities of systems thinking, a currently ubiquitous ergonomics paradigm, are outpacing the capabilities of our methodological toolkit. This is achieved through examining the contemporary ergonomics problem space and the extent to which ergonomics methods can meet the challenges posed. Specifically, five key areas within the ergonomics paradigm of systems thinking are focused on: normal performance as a cause of accidents, accident prediction, system migration, systems concepts and ergonomics in design. The methods available for pursuing each line of inquiry are discussed, along with their ability to respond to key requirements. In doing so, a series of new methodological requirements and capabilities are identified. It is argued that further methodological development is required to provide researchers and practitioners with appropriate tools to explore both contemporary and future problems.
Practitioner Summary: Ergonomics methods are the cornerstone of our discipline. This paper examines whether our current methodological toolkit is fit for purpose given the changing nature of ergonomics problems. The findings provide key research and practice requirements for methodological development.
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