Revision of the Genus Styxosaurus and Relationships of the Late Cretaceous Elasmosaurids (Sauropterygia: Plesiosauria) of the Western Interior Seaway

Growing evidence indicates that elasmosaurid plesiosaurs from the Late Cretaceous Western Interior Seaway are members of a single clade, the Styxosaurinae. The styxosaurines are reported to be mostly Campanian in age, and taxa within the clade obtain the longest necks, by number of cervical vertebrae, of any known vertebrate. The styxosaurines are morphologically diverse and include taxa that exhibit a secondary reduction in neck length. Given the evolutionary plasticity of postcranial characters in plesiosaurs in general, and neck length in elasmosaurs, scrutiny of cranial osteology is pertinent to advancing understanding of Western Interior Seaway elasmosaurids. This study finds that an elasmosaurid specimen (UNSM 50132) from the Cenomanian of Nebraska is remarkably similar in cranial morphology to the Campanian Styxosaurus snowii (KUVP 1301). The phylogenetic affinity of UNSM 50132 was tested with a cladistic analysis with 94 Operational Taxonomic Units (OTU) and 270 anatomical characters, utilizing the Serratos et al. (2017) character matrix with changes and additions. The analysis supports five unambiguous synapomorphies for the genus Styxosaurus: (1) dorsomedian ridge of premaxilla located posteriorly (19.1); (2) dorsal portion of squamosal reflected anteriorly in lateral view (61.1); (3) posteromedian ridge on the supraoccipital (77.1); (4) a sharp ridge or keel located adjacent to the mandibular symphysis (114.1); (5) a retroarticular process that is shorter in anteroposterior length than the glenoid (116.0). Five additional ambiguous synapomorphies that support the monophyly of Styxosaurus include: lateral expansion of the maxilla that supports caniniform teeth, anisodont dentition, anterior embayment of the squamosal arch, an elongate posteromedian process of the premaxilla, a rugose boss on the ectopterygoid, parietals that form a sagittal crest that rises above the cranial roof, and elongate anterior to middle cervical centra. 67% of 100 bootstrap replicates support the monophyly of UNSM 50132, Styxosaurus snowii, Styxosaurus browni, and Styxosaurus sp. (SDSM 451). UNSM 50132 was previously referred to the genus Thalassomedon, a taxon considered to be outside of the Styxosaurinae. The recommended referral of UNSM 50132 to the genus Styxosaurus pushes back the earliest occurrence of Styxosaurinae in the Western Interior Seaway by over ten million years. Maximum parsimony analysis suggests that all Western Interior Seaway elasmosaurids belong to a single clade, including the genera Libonectes and Thalassomedon. Libonectes and Thalassomedon have been previously recovered as outgroup taxa to a clade composed of the sister relationship of Western Interior Seaway elasmosaurids and Aristonectinae. This study provides additional context for furthering understanding of the origins of Elasmosauridae in the Early Cretaceous

Recent educational interventions for improvement of asthma medication adherence

Poor adherence to asthma medication treatment is a dilemma as it decreases the chance of achieving and maintaining a proper asthma control. Another dilemma is that there seems to be a small range of functional interventions that enhance adherence to long-term medication treatments. The aim was to review the last five years of published educational interventions for improving adherence to asthma medication. Through systematic database searches 20 articles were identified, which matched the inclusion criteria and described educational interventions to improve asthma self-management including adherence. The current review showed that addressing unintentional non-adherence in terms of incorrect inhaler technique by recurrent education improved the technique among many patients, but not among all. Phoning patients, as a means to remove medication beliefs as adherence barriers, seemed to be an effective educational strategy, shown as increased adherence. Involving patients in treatment decisions and individualising or tailoring educational support also seemed to have favourable effect on adherence. To conclude, addressing specific adherence barriers such as poor inhaler technique or medication beliefs could favour adherence. To change adherence behavior, the current review proposes that educational adherence support should be a collaborative effort between the patient and the health-care professional based on each individual patient's needs and patient factors, including elements such as personality traits

The Lantern, 2022-2023

The Genie and the Scotsman • Taxi Driver Savior Complex • Midnight Waltz • Eulogy of Caution • Don\u27t cry over spilled milk!! • I am the spider • The Lamb • The Witch and the Shepherd • Nostalgia • In the Summer I Want Light • I Am (Not) • Thanatophobia • We\u27re not children anymore • Hamlet\u27s Fool • Lemon • the last two people in the world • Amongst Chaos (what captivated me) • How About Now, Billy Joel • Bug Trap • Spring, Musser Hall, Room 219 • Time\u27s Denial • A Song of History • A Haiku for You • Hello! My Name Is: • Toilet Humor • Waterfalls • Communion • Shift • Mama Told Me Not To Waste My Life • Writer\u27s Block • Sharp-Tongued Women • Off Trail • Paper Bag Town • Serenity • Landscape of Ursinus Courtyard • Image #07, Affinist designer • Love Birds • Discount Narnia • False Security • Stripes and Illusions • The Burning of Ophelia • Molly\u27s Folly • The Son of Bethany • Meta • Little Blue Sailboats • Grease Trap • Hitchhiking With My Eyes Closed • The Donna of Our Time • The Magic of Cooking • The Closing Shift • A Baptism of Teeth • Dear Beloved • How Kansas Got to Chicago • Anywhere, if you look hard enoughhttps://digitalcommons.ursinus.edu/lantern/1191/thumbnail.jp

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Post-acute COVID-19 neuropsychiatric symptoms are not associated with ongoing nervous system injury

A proportion of patients infected with severe acute respiratory syndrome coronavirus 2 experience a range of neuropsychiatric symptoms months after infection, including cognitive deficits, depression and anxiety. The mechanisms underpinning such symptoms remain elusive. Recent research has demonstrated that nervous system injury can occur during COVID-19. Whether ongoing neural injury in the months after COVID-19 accounts for the ongoing or emergent neuropsychiatric symptoms is unclear. Within a large prospective cohort study of adult survivors who were hospitalized for severe acute respiratory syndrome coronavirus 2 infection, we analysed plasma markers of nervous system injury and astrocytic activation, measured 6 months post-infection: neurofilament light, glial fibrillary acidic protein and total tau protein. We assessed whether these markers were associated with the severity of the acute COVID-19 illness and with post-acute neuropsychiatric symptoms (as measured by the Patient Health Questionnaire for depression, the General Anxiety Disorder assessment for anxiety, the Montreal Cognitive Assessment for objective cognitive deficit and the cognitive items of the Patient Symptom Questionnaire for subjective cognitive deficit) at 6 months and 1 year post-hospital discharge from COVID-19. No robust associations were found between markers of nervous system injury and severity of acute COVID-19 (except for an association of small effect size between duration of admission and neurofilament light) nor with post-acute neuropsychiatric symptoms. These results suggest that ongoing neuropsychiatric symptoms are not due to ongoing neural injury

Long COVID and cardiovascular disease: a prospective cohort study

Background Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known. Objectives To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors. Methods In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months. Patients were stratified by the presence of either CVD or cardiovascular risk factors prior to hospitalisation with COVID-19 and compared with controls with neither. Full recovery was determined by the response to a patient-perceived evaluation of full recovery from COVID-19 in the context of physical, physiological and cognitive determinants of health. Results From a total population of 2545 patients (38.8% women), 472 (18.5%) and 1355 (53.2%) had CVD or cardiovascular risk factors, respectively. Compared with controls (n=718), patients with CVD and cardiovascular risk factors were older and more likely to have had severe COVID-19. Full recovery was significantly lower at 12 months in patients with CVD (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.89) and cardiovascular risk factors (aOR 0.66, 95% CI 0.50 to 0.86). Conclusion Patients with CVD or cardiovascular risk factors had a delayed recovery at 12 months following hospitalisation with COVID-19. Targeted interventions to reduce the impact of COVID-19 in patients with cardiovascular disease remain an unmet need