A conceptional model integrating geographic information systems (GIS) and social media data for disease exposure assessment.

Although previous studies have acknowledged the potential of geographic information systems (GIS) and social media data (SMD) in assessment of exposure to various environmental risks, none has presented a simple, effective and user-friendly tool. This study introduces a conceptual model that integrates individual mobility patterns extracted from social media, with the geographic footprints of infectious diseases and other environmental agents utilizing GIS. The efficacy of the model was independently evaluated for selected case studies involving lead in the ground; particulate matter in the air; and an infectious, viral disease (COVID- 19). A graphical user interface (GUI) was developed as the final output of this study. Overall, the evaluation of the model demonstrated feasibility in successfully extracting individual mobility patterns, identifying potential exposure sites and quantifying the frequency and magnitude of exposure. Importantly, the novelty of the developed model lies not merely in its efficiency in integrating GIS and SMD for exposure assessment, but also in considering the practical requirements of health practitioners. Although the conceptual model, developed together with its associated GUI, presents a promising and practical approach to assessment of the exposure to environmental risks discussed here, its applicability, versatility and efficacy extends beyond the case studies presented in this study.

Nearshore wave buoy data from southeastern Australia for coastal research and management.

Wind wave observations in shallow coastal waters are essential for calibrating, validating, and improving numerical wave models to predict sediment transport, shoreline change, and coastal hazards such as beach erosion and oceanic inundation. Although ocean buoys and satellites provide near-global coverage of deep-water wave conditions, shallow-water wave observations remain sparse and often inaccessible. Nearshore wave conditions may vary considerably alongshore due to coastline orientation and shape, bathymetry and islands. We present a growing dataset of in-situ wave buoy observations from shallow waters (<35 m) in southeast Australia that comprises over 7,000 days of measurements at 20 locations. The moored buoys measured wave conditions continuously for several months to multiple years, capturing ambient and storm conditions in diverse settings, including coastal hazard risk sites. The dataset includes tabulated time series of spectral and time-domain parameters describing wave height, period and direction at half-hourly temporal resolution. Buoy displacement and wave spectra data are also available for advanced applications. Summary plots and tables describing wave conditions measured at each location are provided.

Progressive Reduction in Preventable Mortality in a State Trauma System Using Continuous Preventable Mortality Review to Drive Provider Education: Results of Analyzing 1,979 Trauma Deaths from 2015 to 2022.

BACKGROUND: The state legislature codified and funded the Arkansas Trauma System (ATS) in 2009. Quarterly preventable mortality reviews (PMRs) by the ATS began in 2015 and were used to guide state-wide targeted education to reduce preventable or potentially preventable (P/PP) deaths. We present the results of this PMR-education initiative from 2015 to 2022. STUDY DESIGN: The ATS uses a statistical sampling model of the Arkansas Trauma Registry to select ~40% of the deaths for quarterly review, reflecting the overall the Arkansas Trauma Registry mortality population. A multispecialty PMR committee reviews the medical records from prehospital care to death, and hospital and regional advisory council reviews for each death. The PMR committee assigns opportunities for improvement (OFIs), cause(s) of death, and the likelihood of preventability for each case. Education to improve trauma care includes annual state-wide trauma meetings, novel classes targeted at level III/IV trauma center hospital providers, trauma evidence-based guidelines, and PMR "pearls." RESULTS: We reviewed 1,979 deaths with 211 (10.6%) deaths judged to be P/PP deaths. There was a progressive decrease in P/PP deaths and OFIs for P/PP deaths. Five OFI types targeted by education accounted for 72% of the 24 possible OFI types in the P/PP cases, and 94% of the "contributory OFIs." Reductions in "delay in treatment" resulted in the most rapid decrease in P/PP deaths. CONCLUSIONS: Using ongoing PMR studies to target provider education led to a reduction in P/PP deaths and OFIs for P/PP deaths. Focusing on education designed to improve preventable mortality can result in a substantial decrease in P/PP deaths by 43% (14% to 8%) for trauma systems.

Asthma and landscape fire smoke: A Thoracic Society of Australia and New Zealand position statement.

Landscape fires are increasing in frequency and severity globally. In Australia, extreme bushfires cause a large and increasing health and socioeconomic burden for communities and governments. People with asthma are particularly vulnerable to the effects of landscape fire smoke (LFS) exposure. Here, we present a position statement from the Thoracic Society of Australia and New Zealand. Within this statement we provide a review of the impact of LFS on adults and children with asthma, highlighting the greater impact of LFS on vulnerable groups, particularly older people, pregnant women and Aboriginal and Torres Strait Islander peoples. We also highlight the development of asthma on the background of risk factors (smoking, occupation and atopy). Within this document we present advice for asthma management, smoke mitigation strategies and access to air quality information, that should be implemented during periods of LFS. We promote clinician awareness, and the implementation of public health messaging and preparation, especially for people with asthma.

Fermi Surface and Mass Renormalization in the Iron-Based Superconductor YFe_{2}Ge_{2}.

Interaction-enhanced carrier masses are central to the phenomenology of iron-based superconductors. Quantum oscillation measurements in the new unconventional superconductor YFe_{2}Ge_{2} resolve all four Fermi surface pockets expected from band structure calculations, which predict an electron pocket in the Brillouin zone corner and three hole pockets enveloping the centers of the top and bottom of the Brillouin zone. Carrier masses reach up to 20 times the bare electron mass and are among the highest ever observed in any iron-based material, accounting for the enhanced heat capacity Sommerfeld coefficient ≃100 mJ/mol K^{2}. Mass renormalization is uniform across reciprocal space, suggesting predominantly local correlations, as in the Hund's metal scenario.

Anisotropy-driven quantum criticality in an intermediate valence system.

Intermetallic compounds containing f-electron elements have been prototypical materials for investigating strong electron correlations and quantum criticality (QC). Their heavy fermion ground state evoked by the magnetic f-electrons is susceptible to the onset of quantum phases, such as magnetism or superconductivity, due to the enhanced effective mass (m*) and a corresponding decrease of the Fermi temperature. However, the presence of f-electron valence fluctuations to a non-magnetic state is regarded an anathema to QC, as it usually generates a paramagnetic Fermi-liquid state with quasiparticles of moderate m*. Such systems are typically isotropic, with a characteristic energy scale T0 of the order of hundreds of kelvins that require large magnetic fields or pressures to promote a valence or magnetic instability. Here we show the discovery of a quantum critical behaviour and a Lifshitz transition under low magnetic field in an intermediate valence compound α-YbAlB4. The QC origin is attributed to the anisotropic hybridization between the conduction and localized f-electrons. These findings suggest a new route to bypass the large valence energy scale in developing the QC.

5-grass-pollen SLIT effectiveness in seasonal allergic rhinitis: Impact of sensitization to subtropical grass pollen.

Background: Temperate grass (eg, ryegrass) pollen is a major driver of seasonal allergic rhinitis (SAR) and asthma risks, including thunderstorm asthma. Data for the effectiveness of temperate grass pollen allergen immunotherapy (AIT) in SAR patients from the southern hemisphere, who are frequently polysensitized to subtropical grass pollens, are limited. The 300 IR 5-grass pollen sublingual immunotherapy tablet (300 IR 5-grass SLIT) is known to be effective in polysensitized SAR patients with primary allergy to temperate grasses, however, the influence of polysensitization to subtropical grass pollen on treatment responses has yet to be specifically addressed. Key aims of this study were to measure patient treatment satisfaction during 300 IR 5-grass SLIT treatment and evaluate how polysensitization to subtropical grass pollens affects treatment responses. Methods: A prospective observational study was conducted in 63 patients (aged ≥5 years) in several temperate regions of Australia prescribed 300 IR 5-grass SLIT for SAR over 3 consecutive grass pollen seasons. Ambient levels of pollen were measured at representative sites. Patient treatment satisfaction was assessed using a QUARTIS questionnaire. Rhinoconjunctivitis Total Symptom Score (RTSS) and a Hodges-Lehmann Estimator analysis was performed to evaluate if polysensitization to subtropical grass pollen affected SAR symptom intensity changes during SLIT. Results: A diagnosis of ryegrass pollen allergy was nearly universal. There were 74.6% (47/63) polysensitized to subtropical and temperate grass pollens. There were 23.8% (15/63) monosensitized to temperate grass pollens. From the first pollen season, statistically significant improvements occurred in SAR symptoms compared with baseline in both monosensitized and polysensitized patients, particularly in those polysensitized (P = 0.0297). Improvements in SAR symptoms were sustained and similar in both groups in the second and third pollen seasons, reaching 70-85% improvement (P < 0.01). Polysensitized patients from both northerly and southerly temperate regions in Australia showed similar improvements. Grass pollen counts in both regions were consistently highest during springtime. Conclusions: 300 IR 5-grass SLIT is effective in a real-life setting in SAR patients in the southern hemisphere with primary allergy to temperate grass pollen and predominantly springtime grass pollen exposures. Importantly, SLIT treatment effectiveness was irrespective of the patient's polysensitization status to subtropical grass pollens.

Respect, interaction, immediacy and the role community plays in registering an organ donation decision.

BACKGROUND: Registering a donation decision is fundamental to increasing the number of people who donate the organs and tissues essential for transplantation, but the number of registered organ donors is insufficient to meet this demand. Most people in Australia support organ donation, but only a third have registered their decision on the Australian Organ Donor Register (AODR). We addressed this paradox by investigating how feelings of community, engendered through an ethic of hospitality and care and a non-proselytizing dialogue about organ donation, facilitated the decision to register. METHODS: An Immediate Registration Opportunity was set up in a large public hospital in NSW, Australia. The public was approached and invited to engage in an open, respectful dialogic interaction that met people where their beliefs were and allowed their concerns and fears about donation to be discussed. This included a survey that measured positive and negative beliefs about organ donation, mood, atmosphere, and feelings of community coupled with an on-the-spot opportunity to register their donation decision. RESULTS: Over four days, we interacted with 357 participants; 75.5% (210) of eligible-to-register participants registered on the AODR. Generalized Structural Equation Modelling highlighted that as connection to community increased, so did the salience of positive beliefs about organ donation. Positive beliefs, in turn, were negatively correlated with negative beliefs about donation and, as the strength of negative beliefs decreased, the probability of registration on the AODR increased. Participants who registered on the AODR reported stronger connection to the broader community than participants who did not register. CONCLUSION: A respectful non-judgmental interaction that allows beliefs and concerns about organ donation to be discussed, coupled with an immediate opportunity to register, encouraged registration. Within this framework, feelings of belonging to a community were a key determinant that enabled many to make the decision to register.

Thunderstorm asthma in seasonal allergic rhinitis: The TAISAR study.

BACKGROUND: Asthma epidemics associated with thunderstorms have had catastrophic effects on individuals and emergency services. Seasonal allergic rhinitis (SAR) is present in the vast majority of people who develop thunderstorm asthma (TA), but there is little evidence regarding risk factors for TA among the SAR population. OBJECTIVE: We sought to identify risk factors for a history of TA and hospital presentation in a cohort of individuals with SAR. METHODS: This multicenter study recruited adults from Melbourne, Australia, with a past diagnosis of TA and/or self-reported SAR. Clinical information, spirometry results, white blood cell count, ryegrass pollen-specific (RGP-sp) IgE concentration, and fractional exhaled nitric oxide were measured to identify risk factors for a history of TA in individuals with SAR. RESULTS: From a total of 228 individuals with SAR, 35% (80 of 228) reported SAR only (the I-SAR group), 37% (84 of 228) reported TA symptoms but had not attended hospital for treatment (the O-TA group), and 28% (64 of 228) had presented to the hospital for TA (the H-TA group). All patients in the H-TA group reported a previous asthma diagnosis. Logistic regression analysis of factors associated with O-TA and H-TA indicated that lower FEV1 value and an Asthma Control Questionnaire score higher than 1.5 were associated with H-TA. Higher blood RGP-sp IgE concentration, eosinophil counts, and fractional exhaled nitric oxide level were significantly associated with both O-TA and H-TA. Receiver operating curve analysis showed an RGP-sp IgE concentration higher than 10.1 kU/L and a prebronchodilator FEV1 value of 90% or lower to be biomarkers of increased H-TA risk. CONCLUSION: Clinical tests can identify risk of a history of TA in individuals with SAR and thereby inform patient-specific treatment recommendations.

Mid-Cenozoic climate change, extinction, and faunal turnover in Madagascar, and their bearing on the evolution of lemurs.

BACKGROUND: Was there a mid-Cenozoic vertebrate extinction and recovery event in Madagascar and, if so, what are its implications for the evolution of lemurs? The near lack of an early and mid-Cenozoic fossil record on Madagascar has inhibited direct testing of any such hypotheses. We compare the terrestrial vertebrate fauna of Madagascar in the Holocene to that of early Cenozoic continental Africa to shed light on the probability of a major mid-Cenozoic lemur extinction event, followed by an "adaptive radiation" or recovery. We also use multiple analytic approaches to test competing models of lemur diversification and the null hypothesis that no unusual mid-Cenozoic extinction of lemurs occurred. RESULTS: Comparisons of the terrestrial vertebrate faunas of the early Cenozoic on continental Africa and Holocene on Madagascar support the inference that Madagascar suffered a major mid-Cenozoic extinction event. Evolutionary modeling offers some corroboration, although the level of support varies by phylogeny and model used. Using the lemur phylogeny and divergence dates generated by Kistler and colleagues, RPANDA and TESS offer moderate support for the occurrence of unusual extinction at or near the Eocene-Oligocene (E-O) boundary (34 Ma). TreePar, operating under the condition of obligate mass extinction, found peak diversification at 31 Ma, and low probability of survival of prior lineages. Extinction at the E-O boundary received greater support than other candidate extinctions or the null hypothesis of no major extinction. Using the lemur phylogeny and divergence dates generated by Herrera & Dàvalos, evidence for large-scale extinction diminishes and its most likely timing shifts to before 40 Ma, which fails to conform to global expectations. CONCLUSIONS: While support for large-scale mid-Cenozoic lemur extinction on Madagascar based on phylogenetic modeling is inconclusive, the African fossil record does provide indirect support. Furthermore, a major extinction and recovery of lemuriforms during the Eocene-Oligocene transition (EOT) would coincide with other major vertebrate extinctions in North America, Europe, and Africa. It would suggest that Madagascar's lemurs were impacted by the climate shift from "greenhouse" to "ice-house" conditions that occurred at that time. This could, in turn, help to explain some of the peculiar characteristics of the lemuriform clade.

Respect, Interaction, and Immediacy: Addressing the Challenges Associated With the Different Religious and Cultural Approaches to Organ Donation in Australia.

Australia is a multicultural society of just over 25 million people, with approximately 310 different ancestries, 300 languages, and 150 religions. This diversity suggests that Australia's people might hold a multiplicity of beliefs regarding organ donation. Research shows that most people in Australia have a strong, positive perception of organ donation; they believe that organ donation helps others and benefits society. However, the current rate of 21.6 donors per million population is below expectations and below the demand for organs needed for transplantation. This has led us to ask whether donation consent rates are differentiated by religious and cultural affiliation. We present a case study of New South Wales, Australia, to address this issue. New South Wales is the most populous state in Australia and is also religiously and culturally diverse. Donation consent data (2016-2019) by ethnicity and by religion show that donation consent rates have improved but not across all groups. Initiatives to increase awareness and support for organ and tissue donation among culturally and linguistically diverse and Aboriginal and Torres Strait Islander communities are discussed. Research is also presented that investigates whether registration rates on the Australian Organ Donor Register can be increased and the implications of this for increasing consent for donation. This research underscores the importance of respecting the diversity of beliefs held regarding organ donation, both positive and negative; offering all people a face-to-face interaction opportunity to consider their beliefs about organ donation, ask questions, and raise concerns without judgment; and providing people with an immediate opportunity to register their donation decision on the Australian Organ Donor Register. The challenges associated with adopting these initiatives are considered along with the role of religious and cultural leaders within the context of organ donation and registration; the unspoken concerns of cultural and religious groups are also addressed. In conclusion, we propose that the rich diversity of Australian society is more of a backdrop than a barrier to organ donation.

Antiviral anticoagulation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel envelope virus that causes coronavirus disease 2019 (COVID-19). Hallmarks of COVID-19 are a puzzling form of thrombophilia that has elevated D-dimer but only modest effects on other parameters of coagulopathy. This is combined with severe inflammation, often leading to acute respiratory distress and possible lethality. Coagulopathy and inflammation are interconnected by the transmembrane receptor, tissue factor (TF), which initiates blood clotting as a cofactor for factor VIIa (FVIIa)-mediated factor Xa (FXa) generation. TF also functions from within the nascent TF/FVIIa/FXa complex to trigger profound changes via protease-activated receptors (PARs) in many cell types, including SARS-CoV-2-trophic cells. Therefore, aberrant expression of TF may be the underlying basis of COVID-19 symptoms. Evidence suggests a correlation between infection with many virus types and development of clotting-related symptoms, ranging from heart disease to bleeding, depending on the virus. Since numerous cell types express TF and can act as sites for virus replication, a model envelope virus, herpes simplex virus type 1 (HSV1), has been used to investigate the uptake of TF into the envelope. Indeed, HSV1 and other viruses harbor surface TF antigen, which retains clotting and PAR signaling function. Strikingly, envelope TF is essential for HSV1 infection in mice, and the FXa-directed oral anticoagulant apixaban had remarkable antiviral efficacy. SARS-CoV-2 replicates in TF-bearing epithelial and endothelial cells and may stimulate and integrate host cell TF, like HSV1 and other known coagulopathic viruses. Combined with this possibility, the features of COVID-19 suggest that it is a TFopathy, and the TF/FVIIa/FXa complex is a feasible therapeutic target.

Sustained depletion of FXIII-A by inducing acquired FXIII-B deficiency.

The activated form of coagulation factor XIII (FXIII-A2B2), FXIII-A*, is a hemostatic enzyme essential for inhibiting fibrinolysis by irreversibly crosslinking fibrin and antifibrinolytic proteins. Despite its importance, there are no modulatory therapeutics. Guided by the observation that humans deficient in FXIII-B have reduced FXIII-A without severe bleeding, we hypothesized that a suitable small interfering RNA (siRNA) targeting hepatic FXIII-B could safely decrease FXIII-A. Here we show that knockdown of FXIII-B with siRNA in mice and rabbits using lipid nanoparticles resulted in a sustained and controlled decrease in FXIII-A. The concentration of FXIII-A in plasma was reduced by 90% for weeks after a single injection and for more than 5 months with repeated injections, whereas the concentration of FXIII-A in platelets was unchanged. Ex vivo, crosslinking of α2-antiplasmin and fibrin was impaired and fibrinolysis was enhanced. In vivo, reperfusion of carotid artery thrombotic occlusion was also enhanced. Re-bleeding events were increased after challenge, but blood loss was not significantly increased. This approach, which mimics congenital FXIII-B deficiency, provides a potential pharmacologic and experimental tool to modulate FXIII-A2B2 activity.

Coagulation factor VIIa binds to herpes simplex virus 1-encoded glycoprotein C forming a factor X-enhanced tenase complex oriented on membranes.

BACKGROUND: The cell membrane-derived initiators of coagulation, tissue factor (TF) and anionic phospholipid (aPL), are constitutive on the herpes simplex virus type 1 (HSV1) surface, bypassing physiological regulation. TF and aPL accelerate proteolytic activation of factor (F) X to FXa by FVIIa to induce clot formation and cell signaling. Thus, infection in vivo is enhanced by virus surface TF. HSV1-encoded glycoprotein C (gC) is implicated in this tenase activity by providing viral FX binding sites and increasing FVIIa function in solution. OBJECTIVE: To examine the biochemical influences of gC on FVIIa-dependent FX activation. METHODS: Immunogold electron microscopy (IEM), kinetic chromogenic assays and microscale thermophoresis were used to dissect tenase biochemistry. Recombinant TF and gC were solubilized (s) by substituting the transmembrane domain with poly-histidine, which could be orientated on synthetic unilamellar vesicles containing Ni-chelating lipid (Ni-aPL). These constructs were compared to purified HSV1 TF±/gC ± variants. RESULTS: IEM confirmed that gC, TF, and aPL are simultaneously expressed on a single HSV1 particle where the contribution of gC to tenase activity required the availability of viral TF. Unlike viral tenase activity, the cofactor effects of sTF and sgC on FVIIa was additive when bound to Ni-aPL. FVIIa was found to bind to sgC and this was enhanced by FX. Orientation of sgC on a lipid membrane was critical for FVIIa-dependent FX activation. CONCLUSIONS: The assembly of gC with FVIIa/FX parallels that of TF and may involve other constituents on the HSV1 envelope with implications in virus infection and pathology.

Utilizing a Hospital-based Setting to Increase Organ Donor Registrations.

BACKGROUND: Shortages of organs for transplantation are a concern for many countries. In Australia's "opt-in" system, people register their donation decision on the Australian Organ Donor Register (AODR) in their own time, yet <30% of the population have done so. Consent registrations are honored by the next-of-kin in 90% of cases, so increasing registrations will increase donated organs for transplantation. This study investigated the efficacy of offering an immediate registration opportunity in 2 hospitals, and the role that beliefs about organ donation play in registration behavior. METHODS: An immediate registration opportunity was offered at a public and a private hospital in New South Wales, Australia. Participants (N = 168) categorized as medical/healthcare (eg, doctor and nurse) and nonhealthcare (eg, teacher and chef) completed a measure of beliefs about organ donation, were encouraged to discuss their fears and concerns about organ donation, and given an immediate opportunity to register on the AODR. RESULTS: A total of 81.5% of medical/healthcare participants who were eligible registered, and 71.5% of all eligible participants registered on the spot. Beliefs about the negative consequences of donation and concerns over the medical care given to potential donors predicted (non)registration. Medical/healthcare participants reported lower levels of fears and concerns than nonhealthcare participants. Although both groups reported strong positive beliefs about donation, these did not predict registration. CONCLUSIONS: Offering an immediate registration opportunity in 2 hospitals notably increased the number of registrations on the AODR, suggesting this is a strategy that could potentially increase registrations in opt-in donation systems.

A new interpretation of Madagascar's megafaunal decline: The "Subsistence Shift Hypothesis".

Fundamental disagreements remain regarding the relative importance of climate change and human activities as triggers for Madagascar's Holocene megafaunal extinction. We use stable isotope data from stalagmites from northwest Madagascar coupled with radiocarbon and butchery records from subfossil bones across the island to investigate relationships between megafaunal decline, climate change, and habitat modification. Archaeological and genetic evidence support human presence by 2000 years Before Common Era (BCE). Megafaunal decline was at first slow; it hastened at ∼700 Common Era (CE) and peaked between 750 and 850 CE, just before a dramatic vegetation transformation in the northwest that resulted in the replacement of C3 woodland habitat with C4 grasslands, during a period of heightened monsoonal activity. Cut and chop marks on subfossil lemur bones reveal a shift in primary hunting targets from larger, now-extinct species prior to ∼900 CE, to smaller, still-extant species afterwards. By 1050 CE, megafaunal populations had essentially collapsed. Neither the rapid megafaunal decline beginning ∼700 CE, nor the dramatic vegetation transformation in the northwest beginning ∼890 CE, was influenced by aridification. However, both roughly coincide with a major transition in human subsistence on the island from hunting/foraging to herding/farming. We offer a new hypothesis, which we call the "Subsistence Shift Hypothesis," to explain megafaunal decline and extinction in Madagascar. This hypothesis acknowledges the importance of wild-animal hunting by early hunter/foragers, but more critically highlights negative impacts of the shift from hunting/foraging to herding/farming, settlement by new immigrant groups, and the concomitant expansion of the island's human population. The interval between 700 and 900 CE, when the pace of megafaunal decline quickened and peaked, coincided with this economic transition. While early megafaunal decline through hunting may have helped to trigger the transition, there is strong evidence that the economic shift itself hastened the crash of megafaunal populations.

Beta-blocker use is an independent risk factor for thunderstorm asthma.

OBJECTIVE: To identify risk factors for thunderstorm asthma (TA) in subjects ≥15 years of age from information available in routine clinical records. METHODS: Retrospective and hospital-based case-control study of various clinical factors in all TA cases (n = 53) who presented to a single-site ED in November 2016 (TA16) and in a control group of patients (n = 156) who presented to the same ED with asthma during the pollen season over eight non-TA years. Bivariate analysis and multivariable logistic regression modelling was performed to calculate the odds of TA asthma in the presence of potential risk factors. RESULTS: A logistic regression model revealed that the odds of TA were lower for age (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.95-0.99), higher for Asian country of birth (OR 4.09, 95% CI 1.40-11.95) and higher for oral beta-blocker use (OR 6.43, 95% CI 1.58-26.33) compared to controls. No difference was found between TA16 cases and controls for allergies (to medication, grass pollen, animal), hayfever, smoking, oral non-steroidal anti-inflammatory drugs, or aspirin. Newly diagnosed asthma was higher in TA16 cases versus controls (32.1% vs 12.2%, P = 0.001). CONCLUSIONS: Oral beta-blocker medications, younger age and Asian-born heritage are risk factors for TA. Further study is required to explore the potential association between beta-blockers and TA.

Virus envelope tissue factor promotes infection in mice.

Essentials The coagulation initiator, tissue factor (TF), is on the herpes simplex virus 1 (HSV1) surface. HSV1 surface TF was examined in mice as an antiviral target since it enhances infection in vitro. HSV1 surface TF facilitated infection of all organs evaluated and anticoagulants were antiviral. Protease activated receptor 2 inhibited infection in vivo and its pre-activation was antiviral. SUMMARY: Background Tissue factor (TF) is the essential cell surface initiator of coagulation, and mediates cell signaling through protease-activated receptor (PAR) 2. Having a diverse cellular distribution, TF is involved in many biological pathways and pathologies. Our earlier work identified host cell-derived TF on the envelope covering several viruses, and showed its involvement in enhanced cell infection in vitro. Objective In the current study, we evaluated the in vivo effects of virus surface TF on infection and on the related modulator of infection PAR2. Methods With the use of herpes simplex virus type 1 (HSV1) as a model enveloped virus, purified HSV1 was generated with or without envelope TF through propagation in a TF-inducible cell line. Infection was studied after intravenous inoculation of BALB/c, C57BL/6J or C57BL/6J PAR2 knockout mice with 5 × 105 plaque-forming units of HSV1, mimicking viremia. Three days after inoculation, organs were processed, and virus was quantified with plaque-forming assays and quantitative real-time PCR. Results Infection of brain, lung, heart, spinal cord and liver by HSV1 required viral TF. Demonstrating promise as a therapeutic target, virus-specific anti-TF mAbs or small-molecule inhibitors of coagulation inhibited infection. PAR2 modulates HSV1 in vivo as demonstrated with PAR2 knockout mice and PAR2 agonist peptide. Conclusion TF is a constituent of many permissive host cell types. Therefore, the results presented here may explain why many viruses are correlated with hemostatic abnormalities, and indicate that TF is a novel pan-specific envelope antiviral target.