Fatigue Behavior of Beam Diaphragm Connections With Intermittent Fillet Welds, Part I, Volume 1, Field Evaluation

This report is the first of a two-part, three volume final report presenting the findings of the research work that was undertaken to evaluate the behavior of Indiana highway bridges with diaphragm members welded directly to the web of the primary beams and girders. Fatigue cracks have been observed at several bridges that utilize the welded diaphragm connection. The seriousness of the cracking and the corresponding potential risk on the integrity of the bridge superstructure were assessed. Inspection and repair guidelines for bridges with the welded diaphragm connections were also developed as part of the research effort. This volume presents the results of load tests on two bridge structures with different diaphragm connections. The importance of diaphragm configuration on the stress levels developed at the connection detail is presented. The titles of the three volumes (Report Number in parentheses) are listed below: Part I, Volume 1: Field Evaluation (FHWA/IN/JTRP– 2001/10 – I-1) Part I, Volume 2: Laboratory Fatigue Evaluation (FHWA/IN/JTRP-2001/10-I-2) Part II: Evaluation of Blue River Bridge Fracture (FHWA/IN/JTRP-2001/10-II

Force‐sensing catheters during pediatric radiofrequency ablation: The FEDERATION Study

Background Based on data from studies of atrial fibrillation ablations, optimal parameters for the TactiCath (TC; St. Jude Medical, Inc) force‐sensing ablation catheter are a contact force of 20 g and a force‐time integral of 400 g·s for the creation of transmural lesions. We aimed to evaluate TC in pediatric and congenital heart disease patients undergoing ablation. Methods and Results Comprehensive chart and case reviews were performed from June 2015 to March 2016. Of the 102 patients undergoing electrophysiology study plus ablation, 58 (57%) underwent ablation initially with a force‐sensing catheter. Patients had an average age of 14 (2.4–23) years and weight of 58 (18–195) kg with 15 patients having abnormal cardiac anatomy. Electrophysiology diagnoses for the + TC group included 30 accessory pathway–mediated tachycardia, 24 atrioventricular nodal reentrant tachycardia, and 7 other. Baseline generator settings included a power of 20 W, temperature of 40°, and 6 cc/min flow during lesion creation with 11 patients (19%) having alterations to parameters. Seventeen patients (30%) converted to an alternate ablation source. A total of 516 lesions were performed using the TC with a median contact force of 6 g, force‐time integral of 149 g·s, and lesion size index of 3.3. Median‐term follow‐up demonstrated 5 (10%) recurrences with no acute or median‐term complications. Conclusions TactiCath can be effectively employed in the treatment of pediatric patients with congenital heart disease with lower forces than previously described in the atrial fibrillation literature. Patients with atrioventricular nodal reentrant tachycardia or atrioventricular reciprocating tachycardia may not require transmural lesions and the TC may provide surrogate markers for success during slow pathway ablation. </jats:sec

Support for infants and young people with sight loss: a qualitative study of sight impairment certification and referral to education and social care services.

OBJECTIVES: To examine the experience of infants, children and their parents, the role of ophthalmologists and other health, social care and education professionals in the certification and registration processes and examine the relationship between certification and referrals and pathways to support. DESIGN: Qualitative study. SETTING: Telephone interviews with health and, social care professionals, qualified teachers of children and young people with vision impairment (QTVIs) and parents of infants/children in England. PARTICIPANTS: 52 health, social care and education professionals who are part of the certification or registration process. 26 parents of infants and children with vision impairment. RESULTS: Referrals to education do not require a Certificate of Vision Impairment (CVI); however, the majority of parents received support from education and social services only after an offer of the CVI, which was often dependent on having a formal diagnosis. Parents stated they wanted support sooner, particularly parents of children with additional complex needs who experienced longer delays. Areas with multidisciplinary teams and support roles such as eye clinic liaison officers (ECLOs) appeared to have more reliable referral pathways. CONCLUSIONS: For infants and children with vision impairment, there should be a consistent mechanism for triggering education and social care support even with uncertainty about diagnosis and/or prognosis. All professionals involved in the certification and registration processes (ophthalmologists, optometrists, ECLOs, orthoptists, social workers, QTVIs) can better communicate the value and benefits of certification and registration

Implantable loop recorder monitoring for refining management of children with inherited arrhythmia syndromes

BACKGROUND: Implantable loop recorders (ILRs) are conventionally utilized to elucidate the mechanism of atypical syncope. The objective of this study was to assess the impact of these devices on management of pediatric patients with known or suspected inherited arrhythmia syndromes. METHODS AND RESULTS: A retrospective chart review was undertaken of all pediatric patients with known or suspected inherited arrhythmia syndromes in whom an ILR was implanted from 2008 to 2015. Captured data included categorization of diagnosis, treatment, transmitted tracings, and the impact of ILR tracings on management. Transmissions were categorized as symptomatic, autotriggered, or routine. Actionable transmissions were abnormal tracings that directly resulted in a change of medical or device therapy. A total of 20 patients met the stated inclusion criteria (long QT syndrome, n=8, catecholaminergic polymorphic ventricular tachycardia,n=9, Brugada syndrome, n=1, arrhythmogenic right ventricular cardiomyopathy, n=2), with 60% of patients being genotype positive. Primary indication for implantation of ILR included ongoing monitoring +/− symptoms (n=15, 75%), suspicion of noncompliance (n=1, 5%), and liberalization of recommended activity restrictions (n=4, 25%). A total of 172 transmissions were received in patients with inherited arrhythmia syndromes, with 7% yielding actionable data. The majority (52%) of symptom events were documented in the long QT syndrome population, with only 1 tracing (5%) yielding actionable data. Automatic transmissions were mostly seen in the catecholaminergic polymorphic ventricular tachycardia cohort (81%), with 21% yielding actionable data. There was no actionable data in routine transmissions. CONCLUSIONS: ILRs in patients with suspected or confirmed inherited arrhythmia syndromes may be useful for guiding management. Findings escalated therapies in 30% of subjects. As importantly, in this high‐risk population, the majority of symptom events represented normal or benign rhythms, reassuring patients and physicians that no further intervention was required

Tissue-specific inactivation of p53 tumor suppression in the mouse.

The p53 gene is the most frequent target of structural and functional genetic mutations in human cancer. Thus, considerable effort has been devoted to mapping the functional domains of p53 with regard to their impact on tumorigenesis in vivo. Studies have shown that the carboxy-terminal domain of p53 is sufficient for transformation in vitro. To determine whether a transdominant-negative p53 protein could be used to elicit a tissue-specific p53-null effect in vivo, we tested whether a carboxy-terminal p53 fragment (amino acids 302-390) could abolish p53-dependent apoptosis in an established tumor progression model. We showed previously that loss of p53-dependent apoptosis accelerates brain tumorigenesis in a transgenic mouse model. Here, we show that the same effect can be elicited by expressing a dominant-negative p53 protein tissue specifically in the presence of wild-type p53. Transgenic mice in which pRb function has been disrupted and that coexpress a p53 carboxy-terminal dominant-negative fragment (p53DD) develop aggressive brain tumors mimicking genetic loss of p53 in this model. Inactivation of endogenous p53, which we show to be complexed with p53DD, results in a reduction in apoptosis and acceleration of tumorigenesis. These studies establish a mechanism for tissue-specific knock out of p53 function in vivo

Soluble Rhesus Lymphocryptovirus gp350 Protects against Infection and Reduces Viral Loads in Animals that Become Infected with Virus after Challenge

Epstein-Barr virus (EBV) is a human lymphocryptovirus that is associated with several malignancies. Elevated EBV DNA in the blood is observed in transplant recipients prior to, and at the time of post-transplant lymphoproliferative disease; thus, a vaccine that either prevents EBV infection or lowers the viral load might reduce certain EBV malignancies. Two major approaches have been suggested for an EBV vaccine- immunization with either EBV glycoprotein 350 (gp350) or EBV latency proteins (e.g. EBV nuclear antigens [EBNAs]). No comparative trials, however, have been performed. Rhesus lymphocryptovirus (LCV) encodes a homolog for each gene in EBV and infection of monkeys reproduces the clinical, immunologic, and virologic features of both acute and latent EBV infection. We vaccinated rhesus monkeys at 0, 4 and 12 weeks with (a) soluble rhesus LCV gp350, (b) virus-like replicon particles (VRPs) expressing rhesus LCV gp350, (c) VRPs expressing rhesus LCV gp350, EBNA-3A, and EBNA-3B, or (d) PBS. Animals vaccinated with soluble gp350 produced higher levels of antibody to the glycoprotein than those vaccinated with VRPs expressing gp350. Animals vaccinated with VRPs expressing EBNA-3A and EBNA-3B developed LCV-specific CD4 and CD8 T cell immunity to these proteins, while VRPs expressing gp350 did not induce detectable T cell immunity to gp350. After challenge with rhesus LCV, animals vaccinated with soluble rhesus LCV gp350 had the best level of protection against infection based on seroconversion, viral DNA, and viral RNA in the blood after challenge. Surprisingly, animals vaccinated with gp350 that became infected had the lowest LCV DNA loads in the blood at 23 months after challenge. These studies indicate that gp350 is critical for both protection against infection with rhesus LCV and for reducing the viral load in animals that become infected after challenge. Our results suggest that additional trials with soluble EBV gp350 alone, or in combination with other EBV proteins, should be considered to reduce EBV infection or virus-associated malignancies in humans

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Cellular Automata Approach to Model Sea Urchin Gastrulation

(Statement of Responsibility) by Tammy L. Bowman(Thesis) Thesis (B.A.) -- New College of Florida, 1986(Electronic Access) RESTRICTED TO NCF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE(Bibliography) Includes bibliographical references.(Source of Description) This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.(Local) Faculty Sponsor: Ruppeiner, George; Morrill, Joh