The 2020 special report of the MJA–Lancet Countdown on health and climate change: lessons learnt from Australia's "Black Summer"

The MJA-Lancet Countdown on health and climate change was established in 2017, and produced its first Australian national assessment in 2018 and its first annual update in 2019. It examines indicators across five broad domains: climate change impacts, exposures and vulnerability; adaptation, planning and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement. In the wake of the unprecedented and catastrophic 2019-20 Australian bushfire season, in this special report we present the 2020 update, with a focus on the relationship between health, climate change and bushfires, highlighting indicators that explore these linkages. In an environment of continuing increases in summer maximum temperatures and heatwave intensity, substantial increases in both fire risk and population exposure to bushfires are having an impact on Australia's health and economy. As a result of the "Black Summer" bushfires, the monthly airborne particulate matter less than 2.5 μm in diameter (PM2.5 ) concentrations in New South Wales and the Australian Capital Territory in December 2019 were the highest of any month in any state or territory over the period 2000-2019 at 26.0 μg/m3 and 71.6 μg/m3 respectively, and insured economic losses were $2.2 billion. We also found growing awareness of and engagement with the links between health and climate change, with a 50% increase in scientific publications and a doubling of newspaper articles on the topic in Australia in 2019 compared with 2018. However, despite clear and present need, Australia still lacks a nationwide adaptation plan for health. As Australia recovers from the compounded effects of the bushfires and the coronavirus disease 2019 (COVID-19) pandemic, the health profession has a pivotal role to play. It is uniquely suited to integrate the response to these short term threats with the longer term public health implications of climate change, and to argue for the economic recovery from COVID-19 to align with and strengthen Australia's commitments under the Paris Agreement

LGP2 plays a critical role in sensitizing mda-5 to activation by double-stranded RNA.

The DExD/H box RNA helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation associated gene-5 (mda-5) sense viral RNA in the cytoplasm of infected cells and activate signal transduction pathways that trigger the production of type I interferons (IFNs). Laboratory of genetics and physiology 2 (LGP2) is thought to influence IFN production by regulating the activity of RIG-I and mda-5, although its mechanism of action is not known and its function is controversial. Here we show that expression of LGP2 potentiates IFN induction by polyinosinic-polycytidylic acid [poly(I:C)], commonly used as a synthetic mimic of viral dsRNA, and that this is particularly significant at limited levels of the inducer. The observed enhancement is mediated through co-operation with mda-5, which depends upon LGP2 for maximal activation in response to poly(I:C). This co-operation is dependent upon dsRNA binding by LGP2, and the presence of helicase domain IV, both of which are required for LGP2 to interact with mda-5. In contrast, although RIG-I can also be activated by poly(I:C), LGP2 does not have the ability to enhance IFN induction by RIG-I, and instead acts as an inhibitor of RIG-I-dependent poly(I:C) signaling. Thus the level of LGP2 expression is a critical factor in determining the cellular sensitivity to induction by dsRNA, and this may be important for rapid activation of the IFN response at early times post-infection when the levels of inducer are low

The what and where of adding channel noise to the Hodgkin-Huxley equations

One of the most celebrated successes in computational biology is the Hodgkin-Huxley framework for modeling electrically active cells. This framework, expressed through a set of differential equations, synthesizes the impact of ionic currents on a cell's voltage -- and the highly nonlinear impact of that voltage back on the currents themselves -- into the rapid push and pull of the action potential. Latter studies confirmed that these cellular dynamics are orchestrated by individual ion channels, whose conformational changes regulate the conductance of each ionic current. Thus, kinetic equations familiar from physical chemistry are the natural setting for describing conductances; for small-to-moderate numbers of channels, these will predict fluctuations in conductances and stochasticity in the resulting action potentials. At first glance, the kinetic equations provide a far more complex (and higher-dimensional) description than the original Hodgkin-Huxley equations. This has prompted more than a decade of efforts to capture channel fluctuations with noise terms added to the Hodgkin-Huxley equations. Many of these approaches, while intuitively appealing, produce quantitative errors when compared to kinetic equations; others, as only very recently demonstrated, are both accurate and relatively simple. We review what works, what doesn't, and why, seeking to build a bridge to well-established results for the deterministic Hodgkin-Huxley equations. As such, we hope that this review will speed emerging studies of how channel noise modulates electrophysiological dynamics and function. We supply user-friendly Matlab simulation code of these stochastic versions of the Hodgkin-Huxley equations on the ModelDB website (accession number 138950) and http://www.amath.washington.edu/~etsb/tutorials.html.Comment: 14 pages, 3 figures, review articl

Assessing the bioactivity of crystalline silica in heated high-temperature insulation wools

High-Temperature Insulation Wools (HTIW), such as alumino silicate wools (Refractory Ceramic Fibers) and Alkaline Earth Silicate wools, are used in high-temperature industries for thermal insulation. These materials have an amorphous glass-like structure. In some applications, exposure to high temperatures causes devitrification resulting in the formation of crystalline species including crystalline silica. The formation of this potentially carcinogenic material raises safety concerns regarding after-use handling and disposal. This study aims to determine whether cristobalite formed in HTIW is bioactive in vitro. Mouse macrophage (J774A.1) and human alveolar epithelial (A549) cell lines were exposed to pristine HTIW of different compositions, and corresponding heat-treated samples. Cell death, cytokine release, and reactive oxygen species (ROS) formation were assessed in both cell types. Cell responses to aluminum lactate-coated fibers were assessed to determine if responses were caused by crystalline silica. DQ12 α-quartz was used as positive control, and TiO2 as negative control. HTIW did not induce cell death or intracellular ROS, and their ability to induce pro-inflammatory mediator release was low. In contrast, DQ12 induced cytotoxicity, a strong pro-inflammatory response and ROS generation. The modest pro-inflammatory mediator responses of HTIW did not always coincide with the formation of cristobalite in heated fibers; therefore, we cannot confirm that devitrification of HTIW results in bioactive cristobalite in vitro. In conclusion, the biological responses to HTIW observed were not attributable to a single physicochemical characteristic; instead, a combination of physicochemical characteristics (cristobalite content, fiber chemistry, dimensions and material solubility) appear to contribute to induction of cellular responses

Automated manufacturing of chimeric antigen receptor T cells for adoptive immunotherapy using CliniMACS prodigy

Novel cell therapies derived from human T lymphocytes are exhibiting enormous potential in early-phase clinical trials in patients with hematologic malignancies. Ex vivo modification of T cells is currently limited to a small number of centers with the required infrastructure and expertise. The process requires isolation, activation, transduction, expansion and cryopreservation steps. To simplify procedures and widen applicability for clinical therapies, automation of these procedures is being developed. The CliniMACS Prodigy (Miltenyi Biotec) has recently been adapted for lentiviral transduction of T cells and here we analyse the feasibility of a clinically compliant T-cell engineering process for the manufacture of T cells encoding chimeric antigen receptors (CAR) for CD19 (CAR19), a widely targeted antigen in B-cell malignancies. Using a closed, single-use tubing set we processed mononuclear cells from fresh or frozen leukapheresis harvests collected from healthy volunteer donors. Cells were phenotyped and subjected to automated processing and activation using TransAct, a polymeric nanomatrix activation reagent incorporating CD3/CD28-specific antibodies. Cells were then transduced and expanded in the CentriCult-Unit of the tubing set, under stabilized culture conditions with automated feeding and media exchange. The process was continuously monitored to determine kinetics of expansion, transduction efficiency and phenotype of the engineered cells in comparison with small-scale transductions run in parallel. We found that transduction efficiencies, phenotype and function of CAR19 T cells were comparable with existing procedures and overall T-cell yields sufficient for anticipated therapeutic dosing. The automation of closed-system T-cell engineering should improve dissemination of emerging immunotherapies and greatly widen applicability

Grid computing in image analysis

Diagnostic surgical pathology or tissue–based diagnosis still remains the most reliable and specific diagnostic medical procedure. The development of whole slide scanners permits the creation of virtual slides and to work on so-called virtual microscopes. In addition to interactive work on virtual slides approaches have been reported that introduce automated virtual microscopy, which is composed of several tools focusing on quite different tasks. These include evaluation of image quality and image standardization, analysis of potential useful thresholds for object detection and identification (segmentation), dynamic segmentation procedures, adjustable magnification to optimize feature extraction, and texture analysis including image transformation and evaluation of elementary primitives

Health inequities: lower socio-economic conditions and higher incidences of intestinal parasites

<p>Abstract</p> <p>Background</p> <p>Intestinal parasitic infections affect child health and development and slow down growth, while reducing adults' productivity and work capacity. The aim of the present study was to determine and compare the incidences of intestinal parasitic infections and the socio-economic status of two near primary school children in Manisa, a western city of Turkey.</p> <p>Methods</p> <p>A total of 352 children were involved a questionnaire study from a private school (Ülkem Primary School – ÜPS, 116 children) and a community-based school (Şehzadeler Primary School – ŞPS, 236 children). Of these, stool samples could be obtained from a total of 294 students; 97 (83.6%) from ÜPS, and 197 (83.5%) from ŞPS. The wet mount preparations of the stool samples were examined; samples were also fixed in polyvinyl alcohol and examined with modified formalin ethyl acetate sedimentation and trichrome staining techniques. Data were analyzed using SPSS for Windows version 10.0. The chi-squared test was used for the analytic assessment.</p> <p>Results</p> <p>The percentages of the students found to be infected with intestinal parasites, were 78 (39.6%) and 13 (13.4%) in ŞPS and ÜPS, respectively. Totally 91 (31.0%) of the students from both schools were found to be infected with at least one intestinal parasite. <it>Giardia lamblia </it>was found to be the most common pathogenic intestinal parasite and <it>Blastocystis hominis </it>was prevalent independently from the hygienic conditions. The factors which significantly (<it>p </it>< 0.05) increase the incidence of intestinal parasites were uneducated and unemployed mother, lower social status of father, living in crowded houses with insufficient indoor spaces, using the tap water as drinking water, and living at shanty areas.</p> <p>Conclusion</p> <p>Intestinal parasitic infections in school children were found to be a public health problem that increased due to lower socio-economic conditions. We conclude that organization of education seminars including the topics such as prevention of the infectious diseases, improving general hygienic conditions, and application of supportive programs for the parents may be suggested not only to reduce intestinal parasitic infections, but also to elevate the socio-cultural levels.</p