Herbicide Regulation in Michigan

Lawn care herbicides are a type of pesticide regulated under federal and state pesticide legislation. The Michigan Department of Agriculture implements herbicide regulation to protect the public’s health and welfare. Yet, due to gaps that exist in all levels of government in the regulation of lawn care herbicide application, the public is placed at risk. The federal pesticide legislation (Federal Insecticide, Fungicide, and Rodenticide Act) provides for a lower standard of safety in the classification of herbicides applied in the residential context as opposed to the agricultural context. Michigan legislation (The Pesticide Control Act) exempts persons from the law applying general herbicides on their own premises. The state does not require public notification of risks or safety precautions prior to commercial application of these herbicides. Furthermore, on-site inspections are not performed for residential application of herbicides and the state applicator certification program is not assessed for effectiveness. These results confirm that gaps exist in the regulation of lawn care herbicide use.Master of Public AdministrationPublic AdministrationUniversity of Michigan-Flinthttps://deepblue.lib.umich.edu/bitstream/2027.42/143473/1/BarberK.pd

An Independent and External Validation of the ACC NCDR Bleeding Risk Score among a National Multi-Site Community Hospital Registry of Cardiac Interventions

Background: An accurate tool with good discrimination for bleeding would be useful to clinicians for improved management of all their patients. Bleeding risk models have been published but not externally validated in independent clinical dataset. We chose the NCDR PCI score to validate within a large, multi-site community datasets. The aim of the study was to determine the diagnostic utility of this bleeding risk score tool. Methods: This is a large-scale retrospective analysis utilizing American College of Cardiology data from a 37-hospital health system. The central repository of PCI procedures between 6-1-2009 and 6-30-2012 was utilized to validate the NCDR PCI bleeding risk score (BRS) among 4693 patients. The primary endpoint was major bleeding. Discriminant analysis calculating the receiver operating characteristic curve was performed. Results: There were 143 (3.0%) major bleeds. Mean bleeding risk score was 14.7 (range 3 - 42). Incidence of bleeding by risk category: low (0.5%), intermediate (1.7%), and high risk (7.6%). Patients given heparin had 113 (3.7%) major bleeds and those given bivalirudin had 30 (2.1%) major bleeds. Tool accuracy was poor to fair (AUC 0.78 heparin, 0.65 bivalirudin). Overall accuracy was 0.71 (CI: 0.66-0.76). Accuracy did not improve when confined to just the intermediate risk group (AUC 0.58; CI: 0.55-0.67). Conclusion: Bleeding risk tools have low predictive value. Adjustment for anticoagulation use resulted in poor discrimination because bivalirudin differentially biases outcomes toward no bleeding. The current state of bleeding risk tools provides little support for diagnostic utility in regards to major bleeding and therefore have limited clinical applicability

Phylogeography of the crown-of-thorns starfish in the Indian Ocean

Background: Understanding the limits and population dynamics of closely related sibling species in the marine realm is particularly relevant in organisms that require management. The crown-of-thorns starfish Acanthaster planci, recently shown to be a species complex of at least four closely related species, is a coral predator infamous for its outbreaks that have devastated reefs throughout much of its Indo-Pacific distribution. Methodology/Principal Findings: In this first Indian Ocean-wide genetic study of a marine organism we investigated the genetic structure and inferred the paleohistory of the two Indian Ocean sister-species of Acanthaster planci using mitochondrial DNA sequence analyses. We suggest that the first of two main diversification events led to the formation of a Southern and Northern Indian Ocean sister-species in the late Pliocene-early Pleistocene. The second led to the formation of two internal clades within each species around the onset of the last interglacial. The subsequent demographic history of the two lineages strongly differed, the Southern Indian Ocean sister-species showing a signature of recent population expansion and hardly any regional structure, whereas the Northern Indian Ocean sister-species apparently maintained a constant size with highly differentiated regional groupings that were asymmetrically connected by gene flow. Conclusions/Significance: Past and present surface circulation patterns in conjunction with ocean primary productivity were identified as the processes most likely to have shaped the genetic structure between and within the two Indian Ocean lineages. This knowledge will help to understand the biological or ecological differences of the two sibling species and therefore aid in developing strategies to manage population outbreaks of this coral predator in the Indian Ocean

Treatment Patterns of Tocilizumab Utilization for Progressive Respiratory Distress during the COVID-19 Pandemic

Purpose: This study’s objective was to describe treatment patterns of patients receiving then experimental drug tocilizumab for severe respiratory illness. Methodology: It is a retrospective case series of patients receiving tocilizumab for COVID-19 at a 380-bed hospital between 03/01/202 and 05/31/2020. Treatment patterns for tocilizumab for this series of ICU patients was modeled using a Spearman rho correlation for ranked associations. Results: There was significant variation in frequency and serial testing of inflammatory markers. There was no correlation between tocilizumab initiation and worsening respiratory status (r=0.19, p=.48) or between days since dosing and survival (R= -0.02, p= .95). No clear pattern emerged from tocilizumab administration during the pandemic. Conclusion: Protocols for untested new treatments are needed to overcome the uncertainty physicians face during pandemics

Evolving coral reef conservation with genetic information

Targeted conservation and management programs are crucial for mitigating anthropogenic threats to declining biodiversity. Although evolutionary processes underpin extant patterns of biodiversity, it is uncommon for resource managers to explicitly consider genetic data in conservation prioritization. Genetic information is inherently relevant to management because it describes genetic diversity, population connectedness, and evolutionary history; thereby typifying their behavioral traits, physiological climate tolerance, evolutionary potential, and dispersal ability. Incorporating genetic information into spatial conservation prioritization starts with reconciling the terminology and techniques used in genetics and conservation science. Genetic data vary widely in analyses and their interpretations can be challenging even for experienced geneticists. Therefore, identifying objectives, decision rules, and implementations in decision support tools specifically for management using genetic data is challenging. Here, we outline a framework for eight genetic system characteristics, their measurement, and how they could be incorporated in spatial conservation prioritization for two contrasting objectives: biodiversity preservation vs maintaining ecological function and sustainable use. We illustrate this framework with an example using data from Tridacna crocea (Lamarck, 1819) (boring giant clam) in the Coral Triangle. We find that many reefs highlighted as conservation priorities with genetic data based on genetic subregions, genetic diversity, genetic distinctness, and connectivity are not prioritized using standard practices. Moreover, different characteristics calculated from the same samples resulted in different spatial conservation priorities. Our results highlight that omitting genetic information from conservation decisions may fail to adequately represent processes regulating biodiversity, but that conservation objectives related to the choice of genetic system characteristics require careful consideration

Dual Role for Inflammasome Sensors NLRP1 and NLRP3 in Murine Resistance to Toxoplasma gondii

Induction of immunity that limits Toxoplasma gondii infection in mice is critically dependent on the activation of the innate immune response. In this study, we investigated the role of cytoplasmic nucleotide-binding domain and leucine-rich repeat containing a pyrin domain (NLRP) inflammasome sensors during acute toxoplasmosis in mice. We show that in vitro Toxoplasma infection of murine bone marrow-derived macrophages activates the NLRP3 inflammasome, resulting in the rapid production and cleavage of interleukin-1β (IL-1β), with no measurable cleavage of IL-18 and no pyroptosis. Paradoxically, Toxoplasma-infected mice produced large quantities of IL-18 but had no measurable IL-1β in their serum. Infection of mice deficient in NLRP3, caspase-1/11, IL-1R, or the inflammasome adaptor protein ASC led to decreased levels of circulating IL-18, increased parasite replication, and death. Interestingly, mice deficient in NLRP1 also displayed increased parasite loads and acute mortality. Using mice deficient in IL-18 and IL-18R, we show that this cytokine plays an important role in limiting parasite replication to promote murine survival. Our findings reveal T. gondii as a novel activator of the NLRP1 and NLRP3 inflammasomes in vivo and establish a role for these sensors in host resistance to toxoplasmosis. IMPORTANCE Inflammasomes are multiprotein complexes that are a major component of the innate immune system. They contain “sensor” proteins that are responsible for detecting various microbial and environmental danger signals and function by activating caspase-1, an enzyme that mediates cleavage and release of the proinflammatory cytokines interleukin-1β (IL-1β) and IL-18. Toxoplasma gondii is a highly successful protozoan parasite capable of infecting a wide range of host species that have variable levels of resistance. We report here that T. gondii is a novel activator of the NLRP1 and NLRP3 inflammasomes in vivo and establish a role for these sensors in host resistance to toxoplasmosis. Using mice deficient in IL-18 and IL-18R, we show that the IL-18 cytokine plays a pivotal role by limiting parasite replication to promote murine survival.National Institutes of Health (U.S.) (Intramural Research Program of the NIH and NIAID)Crohn's and Colitis Foundation of America (Research Fellowship)Crohn's and Colitis Foundation of America (CCFA Helmsley Scholar)National Institutes of Health (U.S.) (NIH grant AI104170)National Institutes of Health (U.S.) (R01-AI080621)Pew Charitable Trusts (Pew Scholars Program in the Biomedical Sciences)Canadian Institute for Advanced Research (CIFAR Program for Integrated Microbial Biodiversity

Individual-level factors associated with the risk of acquiring human Plasmodium knowlesi malaria in Malaysia: a case-control study.

BACKGROUND: The emergence of human malaria due to the monkey parasite Plasmodium knowlesi threatens elimination efforts in southeast Asia. Changes in land use are thought to be driving the rise in reported P knowlesi cases, but the role of individual-level factors is unclear. To address this knowledge gap we assessed human and environmental factors associated with zoonotic knowlesi malaria risk. METHODS: We did this population-based case-control study over a 2 year period in the state of Sabah in Malaysia. We enrolled cases with microscopy-positive, PCR-confirmed malaria who presented to two primary referral hospitals serving the adjacent districts of Kudat and Kota Marudu. We randomly selected three malaria-negative community controls per case, who were matched by village within 2 weeks of case detection. We obtained questionnaire data on demographics, behaviour, and residential malaria risk factors, and we also assessed glucose-6-phosphate dehydrogenase (G6PD) enzyme activity. We used conditional logistic regression models to evaluate exposure risk between P knowlesi cases and controls, and between P knowlesi and human-only Plasmodium spp malaria cases. FINDINGS: From Dec 5, 2012, to Jan 30, 2015, we screened 414 patients and subsequently enrolled 229 cases with P knowlesi malaria mono-infection and 91 cases with other Plasmodium spp infection. We enrolled 953 matched controls, including 683 matched to P knowlesi cases and 270 matched to non-P knowlesi cases. Age 15 years or older (adjusted odds ratio [aOR] 4·16, 95% CI 2·09-8·29, p<0·0001), male gender (4·20, 2·54-6·97, p<0·0001), plantation work (3·50, CI, 1·34-9·15, p=0·011), sleeping outside (3·61, 1·48-8·85, p=0·0049), travel (2·48, 1·45-4·23, p=0·0010), being aware of the presence of monkeys in the past 4 weeks (3·35, 1·91-5·88, p<0·0001), and having open eaves or gaps in walls (2·18, 1·33-3·59, p=0·0021) were independently associated with increased risk of symptomatic P knowlesi infection. Farming occupation (aOR 1·89, 95% CI 1·07-3·35, p=0·028), clearing vegetation (1·89, 1·11-3·22, p=0·020), and having long grass around the house (2·08, 1·25-3·46, p=0·0048) increased risk for P knowlesi infection but not other Plasmodium spp infection. G6PD deficiency seemed to be protective against P knowlesi (aOR 0·20, 95% CI 0·04-0·96, p=0·045), as did residual insecticide spraying of household walls (0·52, 0·31-0·87, p=0·014), with the presence of young sparse forest (0·35, 0·20-0·63, p=00040) and rice paddy around the house (0·16, 0·03-0·78, 0·023) also associated with decreased risk. INTERPRETATION: Adult men working in agricultural areas were at highest risk of knowlesi malaria, although peri-domestic transmission also occurrs. Human behavioural factors associated with P knowlesi transmission could be targeted in future public health interventions. FUNDING: United Kingdom Medical Research Council, Natural Environment Research Council, Economic and Social Research Council, and Biotechnology and Biosciences Research Council