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Snakebite envenoming is a neglected tropical disease that may claim over 100,000 human lives annually worldwide. Snakebite occurs as the result of an interaction between a human and a snake that elicits either a defensive response from the snake or, more rarely, a feeding response as the result of mistaken identity. Snakebite envenoming is therefore a biological and, more specifically, an ecological problem. Snake venom itself is often described as a "cocktail", as it is a heterogenous mixture of molecules including the toxins (which are typically proteinaceous) responsible for the pathophysiological consequences of envenoming. The primary function of venom in snake ecology is pre-subjugation, with defensive deployment of the secretion typically considered a secondary function. The particular composition of any given venom cocktail is shaped by evolutionary forces that include phylogenetic constraints associated with the snake's lineage and adaptive responses to the snake's ecological context, including the taxa it preys upon and by which it is predated upon. In the present article, we describe how conceptual frameworks from ecology and evolutionary biology can enter into a mutually enlightening relationship with clinical toxinology by enabling the consideration of snakebite envenoming from an "ecological stance". We detail the insights that may emerge from such a perspective and highlight the ways in which the high-fidelity descriptive knowledge emerging from applications of -omics era technologies - "venomics" and "antivenomics" - can combine with evolutionary explanations to deliver a detailed understanding of this multifactorial health crisis.

BACKGROUND: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. METHODS: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. FINDINGS: Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years [IQR 0·19-2·44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1·35 (95% CI 1·20-1·50) for the composite outcome of intr

BACKGROUND: Snakebite envenoming is a frequently overlooked cause of mortality and morbidity. Data for snake ecology and existing snakebite interventions are scarce, limiting accurate burden estimation initiatives. Low global awareness stunts new interventions, adequate health resources, and available health care. Therefore, we aimed to synthesise currently available data to identify the most vulnerable populations at risk of snakebite, and where additional data to manage this global problem are needed. METHODS: We assembled a list of snake species using WHO guidelines. Where relevant, we obtained expert opinion range (EOR) maps from WHO or the Clinical Toxinology Resources. We also obtained occurrence data for each snake species from a variety of websites, such as VertNet and iNaturalist, using the spocc R package (version 0.7.0). We removed duplicate occurrence data and categorised snakes into three groups: group A (no available EOR map or species occurrence records), group B (EOR map but <5 species occurrence records), and group C (EOR map and ≥5 species occurrence records). For group C species, we did a multivariate environmental similarity analysis using the 2008 WHO EOR maps and newly available evidence. Using these data and the EOR maps, we produced contemporary range maps for medically important venomous snake species at a 5 × 5 km resolution. We subsequently triangulated these data with three health system metrics (antivenom availability, accessibility to urban centres, and the Healthcare Access and Quality [HAQ] Index) to identify the populations most vulnerable to snakebite morbidity and mortality. FINDINGS: We provide a map showing the ranges of 278 snake species globally. Although about 6·85 billion people worldwide live within range of areas inhabited by snakes, about 146·70 million live within remote areas lacking quality health-care provisioning. Comparing opposite ends of the HAQ Index, 272·91 million individuals (65·25%) of the population within th

There is an unmet need for economical snakebite therapies with long shelf lives that are effective even with delays in treatment. The orally bioavailable, heat-stable, secretory phospholipase A₂ (sPLA₂) inhibitor, LY333013, demonstrates antidotal characteristics for severe snakebite envenoming in both field and hospital use. A murine model of lethal envenoming by a Papuan taipan (Oxyuranus scutellatus) demonstrates that LY333013, even with delayed oral administration, improves the chances of survival. Furthermore, LY333013 improves the performance of antivenom even after it no longer reverses neurotoxic signs. Our study is the first demonstration that neurotoxicity from presynaptic venom sPLA2S can be treated successfully, even after the window of therapeutic antivenom has closed. These results suggest that sPLA₂ inhibitors have the potential to reduce death and disability and should be considered for the initial and adjunct treatment of snakebite envenoming. The scope and capacity of the sPLA2 inhibitors ability to achieve these endpoints requires further investigation and development efforts.

The fall cone test is widely used in soil mechanics to determine the liquid limit of fine-grained soils as an aid to soil classification. The test can also be used to obtain the undrained shear strength of a fine-grained soil, based on the "cone factor," K. Reports from different authors show K values ranging from 0.4-1.33. Differences are mostly attributed to the cone surface roughness. This article presents a reinterpretation of several experimental observations available in the literature. It is observed that besides the cone roughness, testing methods have a clear influence when calibrating the fall cone for determining the undrained shear strength of materials with low and very low consistency. The results show that existing K reports should be extrapolated with care. Finally, we propose a series of recommendations and good practices for future calibrations.

Reliability-based design (RBD) has been proved effective in the application of probability theory to research and practice in geotechnical engineering. However, the limited field and laboratory information makes it difficult to build robust predictions. This note shows some statistical relationships that may help with additional information in this area. Descriptive statistics are performed in the note followed by demonstrations of the close relationship between deformabilty parameters. The strong correlation between the slope of the critical state line and the earth pressure coefficient at rest is found. The applicability of the statistical relationships is also examined using RBD. Numerical analysis of oedometer tests demonstrates how RBD can consider the influence of the uncertainty of the critical state parameters.

BACKGROUND: Accidental injury is a major public health problem in developed countries with 20 years elapsed since a national overview of venomous bites undertaken in Australia. AIM: Provide the first contemporary epidemiological insight into venomous injuries based on demographics and geography nationally in Australia in the period 2000-2013. METHODS: An analysis of national hospitalisation and mortality data was undertaken to examine the incidence of injury and death due to envenoming in Australia. Rates were calculated using the intercensal population for all Australian age groups. RESULTS: Over the study period, deaths occurred due to an anaphylactic event (0.16 per 100 000), snake envenoming (0.13 per 100 000) or box jellyfish envenoming (0.01 per 100 000). Only 44% of cases involving anaphylaxis reached medical care prior to death, compared to 74% of those envenomed by snakes. Over half of all deaths (52%) occurred at home, and 64% of these occurred within a major city or inner regional area, with 48% of work-related anaphylaxis deaths. Hospital admission rates of 199 per 100 000 persons over the 11 years were caused by contact with wasps or bees (31%), spiders (30%) and snakes (15%), with a predominant age range of 30-44 years. CONCLUSIONS: The greatest burden of injury due to envenoming was caused by arthropods and snakes. Causes of death were led by anaphylaxis subsequent to an arthropod bite or sting, followed by death from snake envenoming. Over half the incidents resulting in death occurred at home, in areas where healthcare is accessible. Operational data routinely collected are informative, with variations of injury incidence between the States and Territories, indicating a need for a more localised approach to the management of this injury.