Interview with David Body-owner of the Alcove

David Body discusses the Alcove and from where their food comes.https://digital.kenyon.edu/elfs_interviews/1031/thumbnail.jp

Interview with David Body

David Body talks about the Alcove restaurant and his role as its owner.https://digital.kenyon.edu/elfs_interviews/1005/thumbnail.jp

Edito

Pour faire suite à la quatrième édition du Colloque doctoral international de l’éducation et de la formation (CIDEF-2018), ce numéro de la revue Recherches en éducation rassemble dix articles issus des communications présentées à Rennes les 23 et 24 octobre 2018. Cette manifestation scientifique co-organisée par les doctorants du Centre de recherche sur l’éducation, les apprentissages et la didactique (CREAD) et ceux du Centre de recherche en éducation de Nantes (CREN) a réuni plus de 150 par..

Advanced cardiovascular risk prediction in the emergency department: updating a clinical prediction model - a large database study protocol.

From Europe PMC via Jisc Publications RouterHistory: ppub 2021-10-01, epub 2021-10-07Publication status: PublishedFunder: Department of Health; Grant(s): NIHR300246Funder: national institute for health research; Grant(s): NIHR300246BackgroundPatients presenting with chest pain represent a large proportion of attendances to emergency departments. In these patients clinicians often consider the diagnosis of acute myocardial infarction (AMI), the timely recognition and treatment of which is clinically important. Clinical prediction models (CPMs) have been used to enhance early diagnosis of AMI. The Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision aid is currently in clinical use across Greater Manchester. CPMs have been shown to deteriorate over time through calibration drift. We aim to assess potential calibration drift with T-MACS and compare methods for updating the model.MethodsWe will use routinely collected electronic data from patients who were treated using TMACS at two large NHS hospitals. This is estimated to include approximately 14,000 patient episodes spanning June 2016 to October 2020. The primary outcome of acute myocardial infarction will be sourced from NHS Digital's admitted patient care dataset. We will assess the calibration drift of the existing model and the benefit of updating the CPM by model recalibration, model extension and dynamic updating. These models will be validated by bootstrapping and one step ahead prequential testing. We will evaluate predictive performance using calibrations plots and c-statistics. We will also examine the reclassification of predicted probability with the updated TMACS model.DiscussionCPMs are widely used in modern medicine, but are vulnerable to deteriorating calibration over time. Ongoing refinement using routinely collected electronic data will inevitably be more efficient than deriving and validating new models. In this analysis we will seek to exemplify methods for updating CPMs to protect the initial investment of time and effort. If successful, the updating methods could be used to continually refine the algorithm used within TMACS, maintaining or even improving predictive performance over time.Trial registrationISRCTN number: ISRCTN41008456

Advanced cardiovascular risk prediction in the emergency department: updating a clinical prediction model – a large database study protocol

From Springer Nature via Jisc Publications RouterHistory: received 2021-07-27, accepted 2021-09-27, registration 2021-09-28, online 2021-10-07, pub-electronic 2021-10-07, collection 2021-12Publication status: PublishedFunder: national institute for health research; doi: http://dx.doi.org/10.13039/501100000272; Grant(s): NIHR300246Abstract: Background: Patients presenting with chest pain represent a large proportion of attendances to emergency departments. In these patients clinicians often consider the diagnosis of acute myocardial infarction (AMI), the timely recognition and treatment of which is clinically important. Clinical prediction models (CPMs) have been used to enhance early diagnosis of AMI. The Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision aid is currently in clinical use across Greater Manchester. CPMs have been shown to deteriorate over time through calibration drift. We aim to assess potential calibration drift with T-MACS and compare methods for updating the model. Methods: We will use routinely collected electronic data from patients who were treated using TMACS at two large NHS hospitals. This is estimated to include approximately 14,000 patient episodes spanning June 2016 to October 2020. The primary outcome of acute myocardial infarction will be sourced from NHS Digital’s admitted patient care dataset. We will assess the calibration drift of the existing model and the benefit of updating the CPM by model recalibration, model extension and dynamic updating. These models will be validated by bootstrapping and one step ahead prequential testing. We will evaluate predictive performance using calibrations plots and c-statistics. We will also examine the reclassification of predicted probability with the updated TMACS model. Discussion: CPMs are widely used in modern medicine, but are vulnerable to deteriorating calibration over time. Ongoing refinement using routinely collected electronic data will inevitably be more efficient than deriving and validating new models. In this analysis we will seek to exemplify methods for updating CPMs to protect the initial investment of time and effort. If successful, the updating methods could be used to continually refine the algorithm used within TMACS, maintaining or even improving predictive performance over time. Trial registration: ISRCTN number: ISRCTN4100845

Performance deficits of NK1 receptor knockout mice in the 5 choice serial reaction time task: effects of d Amphetamine, stress and time of day.

Background The neurochemical status and hyperactivity of mice lacking functional substance P-preferring NK1 receptors (NK1R-/-) resemble abnormalities in Attention Deficit Hyperactivity Disorder (ADHD). Here we tested whether NK1R-/- mice express other core features of ADHD (impulsivity and inattentiveness) and, if so, whether they are diminished by d-amphetamine, as in ADHD. Prompted by evidence that circadian rhythms are disrupted in ADHD, we also compared the performance of mice that were trained and tested in the morning or afternoon. Methods and Results The 5-Choice Serial Reaction-Time Task (5-CSRTT) was used to evaluate the cognitive performance of NK1R-/- mice and their wildtypes. After training, animals were tested using a long (LITI) and a variable (VITI) inter-trial interval: these tests were carried out with, and without, d-amphetamine pretreatment (0.3 or 1 mg/kg i.p.). NK1R-/- mice expressed greater omissions (inattentiveness), perseveration and premature responses (impulsivity) in the 5-CSRTT. In NK1R-/- mice, perseveration in the LITI was increased by injection-stress but reduced by d-amphetamine. Omissions by NK1R-/- mice in the VITI were unaffected by d-amphetamine, but premature responses were exacerbated by this psychostimulant. Omissions in the VITI were higher, overall, in the morning than the afternoon but, in the LITI, premature responses of NK1R-/- mice were higher in the afternoon than the morning. Conclusion In addition to locomotor hyperactivity, NK1R-/- mice express inattentiveness, perseveration and impulsivity in the 5-CSRTT, thereby matching core criteria for a model of ADHD. Because d-amphetamine reduced perseveration in NK1R-/- mice, this action does not require functional NK1R. However, the lack of any improvement of omissions and premature responses in NK1R-/- mice given d-amphetamine suggests that beneficial effects of this psychostimulant in other rodent models, and ADHD patients, need functional NK1R. Finally, our results reveal experimental variables (stimulus parameters, stress and time of day) that could influence translational studies

Bone Tumor Environment as a Potential Therapeutic Target in Ewing Sarcoma

Ewing sarcoma is the second most common pediatric bone tumor, with three cases per million worldwide. In clinical terms, Ewing sarcoma is an aggressive, rapidly fatal malignancy that mainly develops not only in osseous sites (85%) but also in extra-skeletal soft tissue. It spreads naturally to the lungs, bones, and bone marrow with poor prognosis in the two latter cases. Bone lesions from primary or secondary (metastases) tumors are characterized by extensive bone remodeling, more often due to osteolysis. Osteoclast activation and subsequent bone resorption are responsible for the clinical features of bone tumors, including pain, vertebral collapse, and spinal cord compression. Based on the "vicious cycle" concept of tumor cells and bone resorbing cells, drugs, which target osteoclasts, may be promising agents as adjuvant setting for treating bone tumors, including Ewing sarcoma. There is also increasing evidence that cellular and molecular protagonists present in the bone microenvironment play a part in establishing a favorable "niche" for tumor initiation and progression. The purpose of this review is to discuss the potential therapeutic value of drugs targeting the bone tumor microenvironment in Ewing sarcoma. The first part of the review will focus on targeting the bone resorbing function of osteoclasts by means of bisphosphonates or drugs blocking the pro-resorbing cytokine receptor activator of NF-kappa B ligand. Second, the role of this peculiar hypoxic microenvironment will be discussed in the context of resistance to chemotherapy, escape from the immune system, or neo-angiogenesis. Therapeutic interventions based on these specificities could be then proposed in the context of Ewing sarcoma

A high-resolution melt curve toolkit to identify lineage-defining SARS-CoV-2 mutations.

The emergence of severe acute respiratory syndrome 2 (SARS-CoV-2) variants of concern (VOCs), with mutations linked to increased transmissibility, vaccine escape and virulence, has necessitated the widespread genomic surveillance of SARS-CoV-2. This has placed a strain on global sequencing capacity, especially in areas lacking the resources for large scale sequencing activities. Here we have developed three separate multiplex high-resolution melting assays to enable the identification of Alpha, Beta, Delta and Omicron VOCs. The assays were evaluated against whole genome sequencing on upper-respiratory swab samples collected during the Alpha, Delta and Omicron [BA.1] waves of the UK pandemic. The sensitivities of the eight individual primer sets were all 100%, and specificity ranged from 94.6 to 100%. The multiplex HRM assays have potential as a tool for high throughput surveillance of SARS-CoV-2 VOCs, particularly in areas with limited genomics facilities

The RAPID-CTCA trial (Rapid Assessment of Potential Ischaemic Heart Disease with CTCA) - a multicentre parallel-group randomised trial to compare early computerised tomography coronary angiography versus standard care in patients presenting with suspected or confirmed acute coronary syndrome: study protocol for a randomised controlled trial.

BACKGROUND: Emergency department attendances with chest pain requiring assessment for acute coronary syndrome (ACS) are a major global health issue. Standard assessment includes history, examination, electrocardiogram (ECG) and serial troponin testing. Computerised tomography coronary angiography (CTCA) enables additional anatomical assessment of patients for coronary artery disease (CAD) but has only been studied in very low-risk patients. This trial aims to investigate the effect of early CTCA upon interventions, event rates and health care costs in patients with suspected/confirmed ACS who are at intermediate risk. METHODS/DESIGN: Participants will be recruited in about 35 tertiary and district general hospitals in the UK. Patients ≥18 years old with symptoms with suspected/confirmed ACS with at least one of the following will be included: (1) ECG abnormalities, e.g. ST-segment depression >0.5 mm; (2) history of ischaemic heart disease; (3) troponin elevation above the 99(th) centile of the normal reference range or increase in high-sensitivity troponin meeting European Society of Cardiology criteria for 'rule-in' of myocardial infarction (MI). The early use of ≥64-slice CTCA as part of routine assessment will be compared to standard care. The primary endpoint will be 1-year all-cause death or recurrent type 1 or type 4b MI at 1 year, measured as the time to such event. A number of secondary clinical, process and safety endpoints will be collected and analysed. Cost effectiveness will be estimated in terms of the lifetime incremental cost per quality-adjusted life year gained. We plan to recruit 2424 (2500 with ~3% drop-out) evaluable patients (1212 per arm) to have 90% power to detect a 20% versus 15% difference in 1-year death or recurrent type 1 MI or type 4b MI, two-sided p < 0.05. Analysis will be on an intention-to-treat basis. The relationship between intervention and the primary outcome will be analysed using Cox proportional hazard regression adjusted for study site (used to stratify the randomisation), age, baseline Global Registry of Acute Coronary Events score, previous CAD and baseline troponin level. The results will be expressed as a hazard ratio with the corresponding 95% confidence intervals and p value. DISCUSSION: The Rapid Assessment of Potential Ischaemic Heart Disease with CTCA (RAPID-CTCA) trial will recruit 2500 participants across about 35 hospital sites. It will be the first study to investigate the role of CTCA in the early assessment of patients with suspected or confirmed ACS who are at intermediate risk and including patients who have raised troponin measurements during initial assessment. TRIAL REGISTRATION: ISRCTN19102565 . Registered on 3 October 2014. ClinicalTrials.gov: NCT02284191

Physiological models of body composition and human obesity

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens