Search

We measured annual prevalence of microbiologically defined nontuberculous mycobacterial lung disease in Ontario, Canada. Mycobacterium avium prevalence was 13 cases/100,000 persons in 2020, a 2.5-fold increase from 2010, indicating a large increase in true M. avium lung disease. During the same period, M. xenopi decreased nearly 50%, to 0.84 cases/100,000 persons.

Abstract The Mycobacterium abscessus complex causes significant morbidity and mortality among patients with Cystic Fibrosis (CF). It has been hypothesized that these organisms are transmitted from patient to patient based on genomics. However, few studies incorporate epidemiologic data to confirm this hypothesis. We longitudinally sampled 27 CF and 7 non-CF patients attending a metropolitan hospital in Ontario, Canada from 2013 to 2018. Whole genome sequencing along with epidemiological data was used to evaluate the likelihood of transmission. Overall, the genetic diversity of M. abscessus was large, with a median pairwise distance (IQR) of 1,279 (143–134) SNVs between all Ontario M. abscessus isolates and 2,908 (21–3,204) single nucleotide variants (SNVs) between M. massiliense isolates. This reflects the global diversity of this pathogen, with Ontario isolates widely dispersed throughout global phylogenetic trees of each subspecies. Using a maximum distance of 25 SNVs as a threshold to identify possible transmission, we identified 23 (of 276 total) pairs of closely-related isolates. However, transmission was probable for only one pair based on both genomic and epidemiological data. This suggests that person-to-person transmission of M. abscessus among CF patients is indeed rare and reinforces the critical importance of epidemiological data for inferences of transmission.

Background Hypertension is a leading risk factor for cardiovascular disease. Despite availability of effective lifestyle and medication treatments, blood pressure (BP) is poorly controlled in the United States. Mindfulness training may offer a novel approach to improve BP control. The objective was to evaluate the effects of Mindfulness‐Based Blood Pressure Reduction (MB‐BP) versus enhanced usual care control on unattended office systolic BP. Methods and Results Methods included a parallel‐group phase 2 randomized clinical trial conducted from June 2017 to November 2020. Follow‐up time was 6 months. Outcome assessors and data analyst were blinded to group allocation. Participants had elevated unattended office BP (≥120/80 mm Hg). We randomized 201 participants to MB‐BP (n=101) or enhanced usual care control (n=100). MB‐BP is a mindfulness‐based program adapted for elevated BP. Loss‐to‐follow‐up was 17.4%. The primary outcome was change in unattended office systolic BP at 6 months. A total of 201 participants (58.7% women; 81.1% non‐Hispanic White race and ethnicity; mean age, 59.5 years) were randomized. Results showed that MB‐BP was associated with a 5.9‐mm Hg reduction (95% CI, −9.1 to −2.8 mm Hg) in systolic BP from baseline and outperformed the control group by 4.5 mm Hg at 6 months (95% CI, −9.0 to −0.1 mm Hg) in prespecified analyses. Plausible mechanisms with evidence to be impacted by MB‐BP versus control were sedentary activity (−350.8 sitting min/wk [95% CI, −636.5 to −65.1] sitting min/wk), Dietary Approaches to Stop Hypertension diet (0.32 score [95% CI, −0.04 to 0.67]), and mindfulness (7.3 score [95% CI, 3.0–11.6]). Conclusions A mindfulness‐based program adapted for individuals with elevated BP showed clinically relevant reductions in systolic BP compared with enhanced usual care. Mindfulness training may be a useful approach to improve BP. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03256890 and NCT03859076.

This is a 'hot new topic' in Indonesia, largely brought about by the cumulative work of heritage conservation educators and activists over the past fifteen years, and by the more recent spurt of mAAN (modern Asian Architecture Network) activities and the recent meetings in Chandigarh, India. Right now a small group of architects and enthusiasts are at work to prepare a Docomomo working party for Indonesia. 2003 has been declared Indonesia Heritage Year by the network of Indonesian heritage societies and ICOMOS Indonesia, who hope to use the initiative to bring attention to the many forms of heritage and conservation efforts throughout the archipelago.

Summary: Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (7·3%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation.

François Labaste,1,2 Jean Porterie,3 Paul Bousquet,1 Bertrand Marcheix,3 Pascale Sanchez-Verlaan,1 Bernard Frances,4 Philippe Valet,2 Cedric Dray,2 Vincent Minville1,2 1Anesthesiology and Intensive Care Department, CHU Toulouse, Toulouse, France; 2Institut des Maladies Métaboliques et Cardiovasculaires, INSERM U1048, Université de Toulouse, Université Paul Sabatier, Toulouse, France; 3Cardiac Surgery Department, CHU Toulouse, Toulouse, France; 4Research Center on Animal Cognition, Center for Integrative Biology, Toulouse University, CNRS, UPS, Toulouse, FranceCorrespondence: Vincent MinvilleDepartment of Anesthesia and Intensive Care Medicine, Toulouse University Hospital, Toulouse, FranceTel +33 5 61 32 27 91Email minville.v@chu-toulouse.frBackground: After cardiac surgery, postoperative delirium (POD) is common and is associated with long-term changes in cognitive function. Impact on health-related quality of life (QOL) and long-term dependence are not well known. This aim of this study is to evaluate the role of POD in poor evolution at three years after surgery including poor QOL and dependence and mortality.Patients and Methods: We enrolled and followed 173 patients 60 years of age or older who were planning to undergo cardiac surgery with cardiopulmonary bypass. The primary composite outcome was death of any causes, or patients with either a loss of QOL (evaluated with of EuroQuol verbal 5D EQ5D less than 50), or a loss of two points on the instrumental activities of daily living occurring three years after surgery. POD was diagnosed with the use of Confusion Assessment Method. Multivariate logistic regression was performed.Results: At three years, 74 patients (42.8%) had a poor evolution. Independent risk factors in poor patient evolution were sex (female gender; OR: 3.6; 95%CI: 1.45– 8.7; p=0.006), metabolic status (diabetic patients; OR: 4; 95%CI: 1.6– 10.2; p=0.002), Euroscore 2 (Euroscore 2 > 1.5; OR: 5.2; 95%CI: 1.7– 15.4; p=0.003) and POD (OR: 3.3; 95%CI 1.4– 7.8; p=0.006). Coronary disease was protective (OR: 0.3; 95%CI: 0.14– 0.71; p=0.006).Conclusion: After cardiac surgery, POD significantly altered patient evolution and increased risk of dependence and loss of QOL.Keywords: cardiac surgery, delirium, dependence, quality of life, mortality

To determine incidence-based healthcare costs attributable to nontuberculous mycobacterial (NTM) pulmonary disease (PD) and NTM pulmonary isolation (PI), from the healthcare payer perspective, we conducted a population-based matched cohort study in Ontario, Canada. We established cohorts of patients with incident NTM-PD and NTM-PI during 2001–2012 by using individually linked laboratory data and health administrative data, matched to unexposed persons from the general population. To estimate attributable costs for acute and long-term illness, we used a phase-of-care approach. Costs were stratified by age, sex, and healthcare resource, and reported in 2018 Canadian dollars (CAD) and US dollars (USD), standardized to 10 days. Costs were highest during the before-death phase (NTM-PD CAD $1,352 [USD $1,044]; NTM-PI CAD $731 [USD $565]). The cumulative mean attributable 1-year costs were CAD $14,953 (USD $11,541) for NTM-PD and CAD $8,729 (USD $6,737) for NTM-PI. Costs for patients with NTM-PD and NTM-PI were higher than those for unexposed persons.

BackgroundSeptic shock is a low-frequency but high-stakes condition in children requiring prompt resuscitation, which makes it an important target for simulation-based education. ObjectiveIn this study, we aimed to design and implement an augmented reality app (PediSepsisAR) for septic shock simulation, test the feasibility of measuring the timing and volume of fluid administration during septic shock simulation with and without PediSepsisAR, and describe PediSepsisAR as an educational tool. We hypothesized that we could feasibly measure our desired data during the simulation in 90% of the participants in each group. With regard to using PediSepsisAR as an educational tool, we hypothesized that the PediSepsisAR group would report that it enhanced their awareness of simulated patient blood flow and would more rapidly verbalize recognition of abnormal patient status and desired management steps. MethodsWe performed a randomized controlled feasibility trial with a convenience sample of pediatric care providers at a large tertiary care pediatric center. Participants completed a prestudy questionnaire and were randomized to either the PediSepsisAR or control (traditional simulation) arms. We measured the participants’ time to administer 20, 40, and 60 cc/kg of intravenous fluids during a septic shock simulation using each modality. In addition, facilitators timed how long participants took to verbalize they had recognized tachycardia, hypotension, or septic shock and desired to initiate the sepsis pathway and administer antibiotics. Participants in the PediSepsisAR arm completed a poststudy questionnaire. We analyzed data using descriptive statistics and a Wilcoxon rank-sum test to compare the median time with event variables between groups. ResultsWe enrolled 50 participants (n=25 in each arm). The timing and volume of fluid administration were captured in all the participants in each group. There was no statistically significant difference regarding time to administration of intravenous fluids between the two groups. Similarly, there was no statistically significant difference between the groups regarding time to verbalized recognition of patient status or desired management steps. Most participants in the PediSepsisAR group reported that PediSepsisAR enhanced their awareness of the patient’s perfusion. ConclusionsWe developed an augmented reality app for use in pediatric septic shock simulations and demonstrated the feasibility of measuring the volume and timing of fluid administration during simulation using this modality. In addition, our findings suggest that PediSepsisAR may enhance participants’ awareness of abnormal perfusion.

Background: South Africa faces a number of significant challenges apropos mental health service delivery, including a large treatment gap, a high rate of readmission, over-burdened specialist tertiary facilities, and slow integration of mental health into general health services. The South African National Mental Health Education Programme implemented between February 2019 and December 2019, aimed to upskill health workers to diagnose and manage mental disorders at primary and secondary levels of care. Aim: This study aimed to assess the evolution of training participants’ self-reported competency in mental health care and the number of referrals made to higher levels of care as well as to reflect on the possible broader effects of the training. Setting: The programme and study were conducted in South Africa with Medical Officers and Professional Nurses working at public sector primary and secondary level health care facilities. Methods: A descriptive observational study collected data from training participants through a pre- and post-course, and 3-month follow-up survey. Results: The average confidence ratings for performing mental health care activities and managing mental health conditions increased from pre- to post-course, and was either maintained or increased further at 3-month follow-up. A decrease in the self-reported percentage of patients being referred to a higher level of care was observed 3-months after the training. Conclusion: The evaluation suggests that a brief training intervention such this can go a long way in increasing the confidence of primary and secondary level health care workers in managing common mental health conditions and adhering to the provisions of legislation.

Surveys suggest that clinicians diverge from guidelines when treating Mycobacterium avium complex (MAC) pulmonary disease (PD). To determine prescribing patterns, we conducted a cohort study of adults >66 years of age in Ontario, Canada, with MAC or Mycobacterium xenopi PD during 2001–2013. Using linked laboratory and health administrative databases, we studied the first treatment episode (>60 continuous days of >1 of a macrolide, ethambutol, rifamycin, fluoroquinolone, linezolid, inhaled amikacin, or, for M. xenopi, isoniazid). Treatment was prescribed for 24% MAC and 15% of M. xenopi PD patients. Most commonly prescribed was the recommended combination of macrolide, ethambutol, and rifamycin, for 47% of MAC and 36% of M. xenopi PD patients. Among MAC PD patients, 20% received macrolide monotherapy and 33% received regimens associated with emergent macrolide resistance. Although the most commonly prescribed regimen was guidelines-recommended, many regimens prescribed for MAC PD were associated with emergent macrolide resistance.

BackgroundMindfulness-based programs hold promise for improving cardiovascular health (e.g. physical activity, diet, blood pressure). However, despite theoretical frameworks proposed, no studies have reported qualitative findings on how study participants themselves believe mindfulness-based programs improved their cardiovascular health. With an emphasis on in-depth, open-ended investigation, qualitative methods are well suited to explore the mechanisms underlying health outcomes. The objective of this qualitative study was to explore the mechanisms through which the mindfulness-based program, Mindfulness-Based Blood Pressure Reduction (MB-BP), may influence cardiovascular health.MethodsThis qualitative study was conducted as part of a Stage 1 single arm trial with one-year follow-up. The MB-BP curriculum was adapted from Mindfulness-Based Stress Reduction to direct participants' mindfulness skills towards modifiable determinants of blood pressure. Four focus group discussions were conducted (N = 19 participants), and seven additional participants were selected for in-depth interviews. Data analysis was conducted using the standard approach of thematic analysis. Following double-coding of audio-recorded transcripts, four members of the study team engaged in an iterative process of data analysis and interpretation.ResultsParticipants identified self-awareness, attention control, and emotion regulation as key mechanisms that led to improvements in cardiovascular health. Within these broader themes, many participants detailed a process beginning with increased self-awareness to sustain attention and regulate emotions. Many also explained that the specific relationship between self-awareness and emotion regulation enabled them to respond more skillfully to stressors. In a secondary sub-theme, participants suggested that higher self-awareness helped them engage in positive health behaviors (e.g. healthier dietary choices).ConclusionQualitative analyses suggest that MB-BP mindfulness practices allowed participants to engage more effectively in self-regulation skills and behaviors lowering cardiovascular disease risk, which supports recent theory. Results are consistent with quantitative mechanistic findings showing emotion regulation, perceived stress, interoceptive awareness, and attention control are influenced by MB-BP.

Objectives: This study was performed to analyze the Canadian invasive serogroup W Neisseria meningitidis (MenW) sequence type 11 (ST-11) clonal complex (CC) isolates by whole genome typing and to compare Canadian isolates with similar isolates from elsewhere. Methods: Whole genome typing of 30 MenW ST-11 CC, 20 meningococcal group C (MenC) ST-11 CC, and 31 MenW ST-22 CC isolates was performed on the Bacterial Isolate Genome Sequence database platform. Canadian MenW ST-11 CC isolates were compared with the 2000 MenW Hajj outbreak strain, as well as with MenW ST-11 CC from other countries. Results: Whole genome typing showed that the Canadian MenW ST-11 CC isolates were distinct from the traditional MenW ST-22 CC; they were not capsule-switched contemporary MenC strains that incorporated MenW capsules. While some recent MenW disease cases in Canada were caused by MenW ST-11 CC isolates showing relatedness to the 2000 MenW Hajj strain, many were non-Hajj isolates similar to current MenW ST-11 isolates found globally. Geographical and temporal variations in genotypes and surface protein antigen genes were found among the MenW ST-11 CC isolates. Conclusions: The current MenW ST-11 isolates did not arise by capsule switching from contemporary MenC ST-11 isolates. Both the Hajj-related and non-Hajj MenW ST-11 CC strains were associated with invasive meningococcal disease in Canada. Keywords: Neisseria meningitidis, Invasive meningococcal disease, Whole genome typing

In Ontario, Canada, during 1998–2010, nontuberculous mycobacteria (NTM) from pulmonary sites comprised 96% of species/patient combinations isolated; annual rates of isolation and cases increased steadily. NTM isolates from nonpulmonary sites comprised 4% of species/patient combinations; annual rates and cases were temporally stable. NTM increases were driven exclusively by pulmonary isolates and disease.

Abstract Background Guidelines recommend an initial intravenous (IV) fluid bolus of 30 ml/kg isotonic crystalloid for patients with sepsis and hypotension. However, there is a lack of evidence from clinical trials to support this. Accumulating observational data suggest harm associated with the injudicious use of fluids in sepsis. There is currently equipoise regarding liberal or restricted fluid-volume resuscitation as first-line treatment for sepsis-related hypotension. A randomised trial comparing these two approaches is, therefore, justified. Methods/design The REstricted Fluid REsuscitation in Sepsis-associated Hypotension trial (REFRESH) is a multicentre, open-label, randomised, phase II clinical feasibility trial. Participants will be patients presenting to the emergency departments of Australian metropolitan hospitals with suspected sepsis and a systolic blood pressure of 65 mmHg, if required (restricted fluid). All will receive further protocolised fluid boluses (500 ml or 250 ml, respectively), if required during the 6-h study period. The primary outcome measure is total volume administered in the first 6 h. Secondary outcomes include fluid volume at 24 h, organ support ‘free days’ to day 28, 90-day mortality, and a range of feasibility and process-of-care measures. Participants will also undergo serial measurement, over the first 24 h, of biomarkers of inflammation, endothelial cell activation and glycocalyx degradation for comparison between the groups. Discussion This is the first randomised trial examining fluid volume for initial resuscitation in septic shock in an industrialised country. A pragmatic, open-label design will establish the feasibility of undertaking a large, international, multicentre trial with sufficient power to assess clinical outcomes. The embedded biomarker study aims to provide mechanistic plausibility for a larger trial by defining the effects of fluid volume on markers of systemic inflammation and the vascular endothelium. Trial registration Australia and New Zealand Clinical Trials Registry, ID: ACTRN12616000006448. Registered on 12 January 2016.

Survival implications of nontuberculous mycobacterial pulmonary disease (NTM-PD) and NTM pulmonary isolation without disease (NTM-PI) are unclear. To study deaths associated with NTM-PD and NTM-PI and differences in survival between them, we conducted a population-based cohort study of persons with microbiologically defined NTM-PD or NTM-PI diagnosed during 2001–2013 in Ontario, Canada. We used propensity score matching and Cox proportional hazards models to compare survival. Among 9,681 NTM-PD patients and 10,936 NTM-PI patients, 87% and 91%, respectively, were successfully matched with unexposed controls. Both NTM-PD and NTM-PI were associated with higher rates of death for all species combined and for most individual species. Compared with NTM-PI, NTM-PD was associated with higher death rates for all species combined, Mycobacterium avium complex, and M. xenopi. NTM-PD and NTM-PI were significantly associated with death, NTM-PD more so than NTM-PI.

ObjectivesCompare the molecular epidemiology of tuberculosis (TB) between two large Canadian provinces-Ontario and British Columbia (BC)-to identify genotypic clusters within and across both provinces, allowing for an improved understanding of genotype data and providing context to more accurately identify clusters representing local transmission.DesignWe compared 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) genotyping for 3,314 Ontario and 1,602 BC clinical Mycobacterium tuberculosis isolates collected from 2008 through 2014. Laboratory data for each isolate was linked to case-level records to obtain clinical and demographic data.ResultsThe demographic characteristics of persons with TB varied between provinces, most notably in the proportion of persons born outside Canada, which was reflected in the large number of unique genotypes (n = 3,461). The proportion of clustered isolates was significantly higher in BC. Substantial clustering amongst non-Lineage 4 TB strains was observed within and across the provinces. Only two large clusters (≥10 cases/cluster) representing within province transmission had interprovincial genotype matches.ConclusionWe recommend expanding analysis of shared genotypes to include neighbouring jurisdictions, and implementing whole genome sequencing to improve identification of TB transmission, recognize outbreaks, and monitor changing trends in TB epidemiology.

BackgroundPopulation-based cancer registries have treatment information for all patients making them an excellent resource for population-level monitoring. However, specific treatment details, such as drug names, are contained in a free-text format that is difficult to process and summarize. We assessed the accuracy and efficiency of a text-mining algorithm to identify systemic treatments for lung cancer from free-text fields in the California Cancer Registry.MethodsThe algorithm used Perl regular expressions in SAS 9.4 to search for treatments in 24,845 free-text records associated with 17,310 patients in California diagnosed with stage IV non-small cell lung cancer between 2012 and 2014. Our algorithm categorized treatments into six groups that align with National Comprehensive Cancer Network guidelines. We compared results to a manual review (gold standard) of the same records.ResultsPercent agreement ranged from 91.1% to 99.4%. Ranges for other measures were 0.71-0.92 (Kappa), 74.3%-97.3% (sensitivity), 92.4%-99.8% (specificity), 60.4%-96.4% (positive predictive value), and 92.9%-99.9% (negative predictive value). The text-mining algorithm used one-sixth of the time required for manual review.ConclusionSAS-based text mining of free-text data can accurately detect systemic treatments administered to patients and save considerable time compared to manual review, maximizing the utility of the extant information in population-based cancer registries for comparative effectiveness research.

Background and objectivesImpacts of mindfulness-based programs on blood pressure remain equivocal, possibly because the programs are not adapted to engage with determinants of hypertension, or due to floor effects. Primary objectives were to create a customized Mindfulness-Based Blood Pressure Reduction (MB-BP) program, and to evaluate acceptability, feasibility, and effects on hypothesized proximal self-regulation mechanisms. Secondary outcomes included modifiable determinants of blood pressure (BP), and clinic-assessed systolic blood pressure (SBP).MethodsThis was a Stage 1 single-arm trial with one year follow-up. Focus groups and in-depth interviews were performed to evaluate acceptability and feasibility. Self-regulation outcomes, and determinants of BP, were assessed using validated questionnaires or objective assessments. The MB-BP curriculum was adapted from Mindfulness-Based Stress Reduction to direct participants' mindfulness skills towards modifiable determinants of blood pressure.ResultsAcceptability and feasibility findings showed that of 53 eligible participants, 48 enrolled (91%). Of these, 43 (90%) attended at least 7 of the 10 MB-BP classes; 43 were followed to one year (90%). Focus groups (n = 19) and semi-structured interviews (n = 10) showed all participants viewed the delivery modality favorably, and identified logistic considerations concerning program access as barriers. A priori selected primary self-regulation outcomes showed improvements at one-year follow-up vs. baseline, including attention control (Sustained Attention to Response Task correct no-go score, pConclusionMB-BP has good acceptability and feasibility, and may engage with self-regulation and behavioral determinants of hypertension.

Field and greenhouse studies were conducted to investigate the influence of sequence and timing of synthetic auxins and glufosinate on large Palmer amaranth (Amaranthus palmeri) control. Field studies were performed in Henry County, AL where treatments were applied to Palmer amaranth with average heights of 37 and 59 cm in 2018 and 2019, respectively. Sequential applications of 2,4-D/dicamba + glyphosate followed by (fb) glufosinate at labeled rates 3 or 7 days after initial treatment (DAIT) were used in addition to the reverse sequence with a 7-day interval. Time intervals of 3 or 7 days between applications did not influence Palmer amaranth control. Palmer amaranth was controlled 100% by dicamba + glyphosate fb glufosinate and 2,4-D + glufosinate fb glufosinate 7 DAIT in 2018. However, herbicide performance was reduced due to delayed application and taller plants in 2019 with up to 23% less visual injury. To further investigate Palmer amaranth response to dicamba and glufosinate applied sequentially, a greenhouse study was conducted in 2019 where physiological measurements were recorded over a 35-day period. Treatments were applied to Palmer amaranth averaging 38 cm tall and included dicamba + glyphosate fb glufosinate 7 DAIT, the reverse sequence, and a single application of dicamba + glufosinate + glyphosate. Glufosinate severely inhibited mid-day photosynthesis compared to dicamba with up to 90% reductions in CO2 assimilation 1 DAIT. In general, Palmer amaranth respiration and stomatal conductance were not affected by herbicides in this study. Applications of dicamba + glyphosate fb glufosinate 7 DAIT was the only treatment hindered Palmer amaranth regrowth with 52% reduction in leaf biomass compared to nontreated control. These data suggest Palmer amaranth infested fields are more likely to be rescued with sequential applications of synthetic auxins and glufosinate, but consistent control of large Palmer is not probable.

The commercial launch of dicamba-tolerant (DT) crops has resulted in increased dicamba usage and a high number of dicamba off-target movement complaints on sensitive soybeans (Glycine max L.). Dicamba is a synthetic auxin and low dosages as 0.028 g ae ha−1 can induce injury on sensitive soybean. Tank contamination has been identified as one of the sources for unintended sensitive crop exposure. The labels of new dicamba formulations require a triple rinse cleanout procedure following applications. Cleanout efficacy might vary based on the sprayer type and procedure followed. This study was performed to quantify dicamba retention in commercial sprayers and assess the risk for crop injury from remaining contaminants. The results indicate triple rinse with water was comparable to cleanout procedures utilizing ammonium, commercial tank cleaners, and glyphosate in rinses. Dicamba contaminants in final rinsates resulted in −1, with concentrations of less than 1 ug mL−1 detected rinsates from the fourth rinse. A dose response experiment predicted dosages causing 5% visual injury and the yield losses were 0.1185 and 2.8525 g ae ha−1. However, symptomology was observed for all tested dosages, including the rate as low as 0.03 g ae ha−1. The results from this study suggest triple rinsing with sufficient amount of water (≥10% of tank volume) is adequate for the removal of dicamba residues from sprayers to avoid sensitive soybean damage. This study can provide producers with confidence in cleanout procedures following dicamba applications, and aid in minimizing risk for off-target movement through tank contamination.

BACKGROUND: Tuberculosis (TB) remains a leading cause of death worldwide and the emergence of multidrug-resistant TB (MDR TB) poses a threat to its control. There is scanty evidence regarding optimal management of MDR TB. The majority of Canadian cases of MDR TB are diagnosed in Ontario; most are managed by the Tuberculosis Service at West Park Healthcare Centre in Toronto. The authors reviewed 93 cases of MDR TB admitted from January 1, 2000 to December 31, 2011.

Background and objectivesCurative intent therapy is the standard of care for early-stage hepatocellular carcinoma (HCC). However, these therapies are under-utilized, with several treatment and survival disparities. We sought to demonstrate whether the type of facility and distance from treatment center (with transplant capabilities) contributed to disparities in curative-intent treatment and survival for early-stage HCC in California.MethodsWe performed a retrospective analysis of the California Cancer Registry for patients diagnosed with stage I or II primary HCC between 2005 and 2017. Primary and secondary outcomes were receipt of treatment and overall survival, respectively. Multivariable logistic regression and Multivariable Cox proportional hazards regression were used to evaluate associations.ResultsOf 19 059 patients with early-stage HCC, only 36% (6778) received curative-intent treatment. Compared to Non-Hispanic White patients, Hispanic patients were less likely, and Asian/Pacific Islander patients were more likely to receive curative-intent treatment. Our results showed that rural residence, public insurance, lower neighborhood SES, and care at non-National Cancer Institute-designated cancer center were associated with not receiving treatment and decreased survival.ConclusionsAlthough multiple factors influence receipt of treatment for early-HCC, our findings suggest that early intervention programs should target travel barriers and access to specialist care to help improve oncologic outcomes.

PurposeBreast cancer (BC) is the most common secondary cancer and has poorer survival than primary BC (pBC) after any prior malignancy. For BC survivors, developing a contralateral secondary BC (CSBC) is the most frequent second-cancer event and is currently treated similarly to pBC. Identifying survival differences between pBC and CSBC could influence future counseling and treatments for patients with CSBC.MethodsWomen (≥15 years) diagnosed with pBC from 1991 to 2015 in the California Cancer Registry (n = 377,176) were compared with those with CSBC (n = 15,586) by age group (15-39 years, n = 406; 40-64 years, n = 6814; ≥ 65 years, n = 8366). Multivariable logistic regression models assessed factors associated with CSBC. Multivariable Cox proportional hazards regression models assessed BC-specific survival (BCSS), while accounting for the competing risk of death.ResultsAcross all ages, CSBC patients were more likely to have smaller tumors (T2 vs. T1a; 15-39 yeras: OR 0.25, CI 0.16-0.38; 40-64 years: OR 0.41, CI 0.37-0.45; ≥ 65 years: OR 0.46, CI 0.42-0.51) and lymph node-negative disease (positive vs. negative; 15-39 years: OR 0.86, CI 0.69-1.08; 40-64 years: OR 0.88, CI 0.83-0.93; ≥ 65 years: OR 0.89, CI 0.84-0.94). Additionally, CSBC was associated with worse survival compared with pBC across all ages (15-39 years: HR 2.73, CI 2.30-3.25; 40-64 years: HR 2.13, CI 2.01-2.26; ≥ 65 years: HR 1.52, CI 1.43-1.61).ConclusionBCSS is worse among all women diagnosed with CSBC compared with pBC, with the strongest impact seen in adolescent and young adult women. Worse survival after CSBC, despite associations with smaller tumors and lymph node negativity, suggests that CSBC may need eventual treatment reconsideration.

Tuberculosis remains one of the most difficult to control infectious diseases in the world. Many different factors contribute to the complexity of this disease. These include the ability of the host to control the infection which may directly relate to nutritional status, presence of co-morbidities and genetic predisposition. Pathogen factors, in particular the ability of different Mycobacterium tuberculosis strains to respond to the harsh environment of the host granuloma, which includes low oxygen and nutrient availability and the presence of damaging radical oxygen and nitrogen species, also play an important role in the success of different strains to cause disease. In this study we evaluated the impact of a naturally occurring 12 gene 15 Kb genomic deletion on the physiology and virulence of M. tuberculosis. The strains denominated ON-A WT (wild type) and ON-A NM (natural mutant) were isolated from a previously reported TB outbreak in an inner city under-housed population in Toronto, Canada. Here we subjected these isogenic strains to transcriptomic (via RNA-seq) and proteomic analyses and identified several gene clusters with differential expression in the natural mutant, including the DosR regulon and the molybdenum cofactor biosynthesis genes, both of which were found in lower abundance in the natural mutant. We also demonstrated lesser virulence of the natural mutant in the guinea pig animal model. Overall, our findings suggest that the ON-A natural mutant is less fit to cause disease, but nevertheless has the potential to cause extended transmission in at-risk populations.