Travelling wave ion mobility-derived collision cross section for mycotoxins: Investigating interlaboratory and interplatform reproducibility

Parent and modified mycotoxin analysis remains a challenge because of their chemical diversity, the presence of isomeric forms, and the lack of analytical standards. The creation and application of a collision cross section (CCS) database for mycotoxins may bring new opportunities to overcome these analytical challenges. However, it is still an open question whether common CCS databases can be used independently from the instrument type and ion mobility mass spectrometry (IM-MS) technologies, which utilize different methodologies for determining the gas-phase mobility. Here, we demonstrated the reproducibility of CCS measurements for mycotoxins in an interlaboratory study (average RSD 0.14% ± 0.079) and across different traveling wave IM-MS (TWIMS) systems commercially available (ΔCCS% < 2). The separation in the drift time dimension of critical pairs of isomers for modified mycotoxins was also achieved. In addition, the comparison of measured and predicted CCS values, including regulated and emerging mycotoxins, was addressed

Haul-Out Behavior of Harbor Seals (Phoca vitulina) in Hood Canal, Washington

The goal of this study was to model haul-out behavior of harbor seals (Phoca vitulina) in the Hood Canal region of Washington State with respect to changes in physiological, environmental, and temporal covariates. Previous research has provided a solid understanding of seal haul-out behavior. Here, we expand on that work using a generalized linear mixed model (GLMM) with temporal autocorrelation and a large dataset. Our dataset included behavioral haul-out records from archival and VHF radio tag deployments on 25 individual seals representing 61,430 seal hours. A novel application for increased computational efficiency allowed us to examine this large dataset with a GLMM that appropriately accounts for temporal autocorellation. We found significant relationships with the covariates hour of day, day of year, minutes from high tide and year. Additionally, there was a significant effect of the interaction term hour of day : day of year. This interaction term demonstrated that seals are more likely to haul out during nighttime hours in August and September, but then switch to predominantly daylight haul-out patterns in October and November. We attribute this change in behavior to an effect of human disturbance levels. This study also examined a unique ecological event to determine the role of increased killer whale (Orcinus orca) predation on haul-out behavior. In 2003 and 2005 these harbor seals were exposed to unprecedented levels of killer whale predation and results show an overall increase in haul-out probability after exposure to killer whales. The outcome of this study will be integral to understanding any changes in population abundance as a result of increased killer whale predation

Methodology for fitting and updating predictive accident models with trend

Reliable predictive accident models (PAMs) (also referred to as Safety Performance Functions (SPFs)) have a variety of important uses in traffic safety research and practice. They are used to help identify sites in need of remedial treatment, in the design of transport schemes to assess safety implications, and to estimate the effectiveness of remedial treatments. The PAMs currently in use in the UK are now quite old; the data used in their development was gathered up to 30 years ago. Many changes have occurred over that period in road and vehicle design, in road safety campaigns and legislation, and the national accident rate has fallen substantially. It seems unlikely that these ageing models can be relied upon to provide accurate and reliable predictions of accident frequencies on the roads today. This paper addresses a number of methodological issues that arise in seeking practical and efficient ways to update PAMs, whether by re-calibration or by re-fitting. Models for accidents on rural single carriageway roads have been chosen to illustrate these issues, including the choice of distributional assumption for overdispersion, the choice of goodness of fit measures, questions of independence between observations in different years, and between links on the same scheme, the estimation of trends in the models, the uncertainty of predictions, as well as considerations about the most efficient and convenient ways to fit the required models

Onchocerciasis transmission in Ghana: biting and parous rates of host-seeking sibling species of the Simulium damnosum complex

Background: Ghana is renowned for its sibling species diversity of the Simulium damnosum complex, vectors of Onchocerca volvulus. Detailed entomological knowledge becomes a priority as onchocerciasis control policy has shifted from morbidity reduction to elimination of infection. To date, understanding of transmission dynamics of O. volvulus has been mainly based on S. damnosum sensu stricto (s.s.) data. We aim to elucidate bionomic features of vector species of importance for onchocerciasis elimination efforts. Methods: We collected S. damnosum sensu lato from seven villages in four Ghanaian regions between 2009 and 2011, using standard vector collection, and human- and cattle-baited tents. Taxa were identified using morphological and molecular techniques. Monthly biting rates (MBR), parous rates and monthly parous biting rates (MPBR) are reported by locality, season, trapping method and hour of collection for each species. Results: S. damnosum s.s./S. sirbanum were collected at Asubende and Agborlekame, both savannah villages. A range of species was caught in the Volta region (forest-savannah mosaic) and Gyankobaa (forest), with S. squamosum or S. sanctipauli being the predominant species, respectively. In Bosomase (southern forest region) only S. sanctipauli was collected in the 2009 wet season, but in the 2010 dry season S. yahense was also caught. MBRs ranged from 714 bites/person/month at Agborlekame (100% S. damnosum s.s./S. sirbanum) to 8,586 bites/person/month at Pillar 83/Djodji (98.5% S. squamosum). MBRs were higher in the wet season. In contrast, parous rates were higher in the dry season (41.8% vs. 18.4%), resulting in higher MPBRs in the dry season. Daily host-seeking activity of S. damnosum s.s./S. sirbanum was bimodal, whilst S. squamosum and S. sanctipauli had unimodal afternoon peaks. Conclusions: The bionomic differences between sibling species of the S. damnosum complex need to be taken into account when designing entomological monitoring protocols for interventions and parameterising mathematical models for onchocerciasis control and elimination

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The effect of charge location in ion mobility mass spectrometry for small molecule analytes

<p>Presented at the British Mass Spectrometry Society meeting in 2014 and awarded the Bordoli Prize</p> <p> </p> <p>In travelling wave IM-MS an electric field is applied across the IMS cell and analyte collisions with the inert gas give rise to a relationship between the drift time and the molecular shape and overall charge.</p> <p>Recent findings show near baseline IMS separation (R>1) where shape and overall charge appear not to explain the IMS separation. Multiple ion mobility peaks are observed for a single m/z including the fluoroquinolone antibiotics norfloxacin and lomefloxacin, the pesticide indoxacarb and a number of steroids.</p> <p> </p> <p>The Bordoli Award was judged by Prof. Graham Cooks (Henry Bohn Hass Distinguished Professor of Chemistry at Purdue University, ISI Highly Cited Chemist with over 950 publications and an H-index of 81) and Prof. Mike Morris (‎Senior Director MS Research at Waters).</p> <p> </p> <p> </p