scholarly journals Rate-of-change analysis in palaeoecology revisited: a new approach

2020 ◽  
Author(s):  
Ondřej Mottl ◽  
John-Arvid Grytnes ◽  
Alistair W.R. Seddon ◽  
Manuel J. Steinbauer ◽  
Kuber P. Bhatta ◽  
...  
Keyword(s):  
Level Density ◽  
Rate Of Change ◽  
High Rate ◽  
Type I ◽  
List Type ◽  
Compositional Change ◽  
Generalised Additive Model ◽  
Peak Point ◽  
Peak Points ◽  
Point Detection

AbstractDynamics in the rate of compositional change beyond the time of human observation are uniquely preserved in palaeoecological sequences from peat or lake sediments. Changes in sedimentation rates and sampling strategies result in an uneven distribution of time intervals within stratigraphical data, which makes assessing rates of compositional change and the detection of periods with a high rate-of-change (RoC) or ‘peak-points’ challenging. Despite these known issues and their importance, and the frequent use of RoC in palaeoecology, there has been relatively little exploration of differing approaches to quantifying RoC.Here, we introduce R-Ratepol (an easy to use R package) that provides a robust numerical technique for detecting and summarising RoC patterns in complex multivariate time-ordered stratigraphical sequences. We compare the performance of common methods of estimating RoC using simulated pollen-stratigraphical data with known patterns of compositional change and temporal resolution. In addition, we apply our new methodology to four representative European pollen sequences.Simulated data show large differences in the successful detection of known patterns in RoC peak-point detection depending on the smoothing methods and dissimilarity coefficients used, and the level density and their taxonomic richness. Building on these results, we propose a new method of binning with a moving window in combination with a generalised additive model for peak-point detection. The method shows a 22% increase in the correct detection of peak-points and 4% lower occurrence of false positives compared to the more traditional way of peak selection by individual levels, as well as achieving a reasonable compromise between type I and type II errors. The four representative pollen sequences from Europe show that our methodological combination also performs well in detecting periods of significant compositional change including the onset of human activity, early land-use transformation, and changes in fire frequency.Expanding the approach using R-Ratepol to the increasingly available stratigraphical data on pollen, chironomids, or diatoms will allow future palaeoecological and macroecological studies to quantify, and then attribute, major changes in biotic composition across broad spatial areas through time.

scholarly journals Insulation Life Span of Low-Voltage Electric Motors—A Survey

Energies ◽  
2021 ◽  
Vol 14 (6) ◽  
pp. 1738
Author(s):  
Vanessa Neves Höpner ◽  
Volmir Eugênio Wilhelm
Keyword(s):  
Life Span ◽  
Electric Motor ◽  
Low Voltage ◽  
Frequency Converter ◽  
Rate Of Change ◽  
High Rate ◽  
Switching Frequency ◽  
Electric Motors ◽  
Frequency Converters ◽  
High Switching Frequency

The use of static frequency converters, which have a high switching frequency, generates voltage pulses with a high rate of change over time. In combination with cable and motor impedance, this generates repetitive overvoltage at the motor terminals, influencing the occurrence of partial discharges between conductors, causing degradation of the insulation of electric motors. Understanding the effects resulting from the frequency converter–electric motor interaction is essential for developing and implementing insulation systems with characteristics that support the most diverse applications, have an operating life under economically viable conditions, and promote energy efficiency. With this objective, a search was carried out in three recognized databases. Duplicate articles were eliminated, resulting in 1069 articles, which were systematically categorized and reviewed, resulting in 481 articles discussing the causes of degradation in the insulation of electric motors powered by frequency converters. A bibliographic portfolio was built and evaluated, with 230 articles that present results on the factors that can be used in estimating the life span of electric motor insulation. In this structure, the historical evolution of the collected information, the authors who conducted the most research on the theme, and the relevance of the knowledge presented in the works were considered.

303 Phase II trial of neoadjuvant nivolumab (Nivo) and intra-tumoral (IT) CMP-001 in high-risk resectable melanoma (Neo-C-Nivo): final results

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A330-A330
Author(s):  
Diwakar Davar ◽  
Arivarasan Karunamurthy ◽  
Douglas Hartman ◽  
Richelle DeBlasio ◽  
Joe-Marc Chauvin ◽  
...  
Keyword(s):  
T Cells ◽  
High Risk ◽  
Cd8 T Cells ◽  
Advanced Melanoma ◽  
Pathologic Response ◽  
Type I ◽  
List Type ◽  
Cell Lung Carcinoma ◽  
Radiographic Response ◽  
Pathologic Features

BackgroundNeoadjuvant PD-1 blockade produces major pathological responses (MPR) in ~30% of patients (pts) with high-risk resectable melanoma (MEL) with durable relapse-free benefit, and increased circulating activated CD8+ T cells.1 2 CMP-001 is a type A CpG packaged within a virus-like particle that activates tumor-associated plasmacytoid dendritic cells (pDC) via TLR9 inducing type I interferons and anti-tumor CD8+ T cells. CMP-001/pembrolizumab produces durable anti-tumor responses in PD-1 refractory melanoma.3 We previously reported preliminary evidence of efficacy of neoadjuvant IT CMP/Nivo in high-risk resectable MEL; and herein present final results on 30 evaluable patients.Methods30 pts with stage III B/C/D MEL were enrolled. Pre-operatively, CMP-001 was dosed at 5 mg subcutaneous (SC, 1st), then 10 mg IT (2nd-7th) weekly; Nivo was dosed 240 mg q2 weeks for 3 doses – both agents given for 7 weeks. Post-operatively, Nivo was dosed 480 mg q4 weeks with CMP-001 5 mg q4 weeks SC for 48 weeks. Primary endpoints included major pathologic response rate (MPR), and incidence of dose-limiting toxicities (DLT). Secondary endpoints were radiographic response, relapse-free survival (RFS) and overall survival (OS). Pathological response was scored blinded by pathologists based on residual volume of tumor (RVT) using prior specified cutoffs:4 60% (complete response, pCR); 0%<rvt<rvt50% (non-response, pNR). Radiographic response was assessed using RECIST v1.1. Sequential blood draws and tumor biopsies were collected and analyzed for CD8+ T cell infiltrate (TIL), multiparameter flow cytometry (MFC) and multiplex immunofluorescence (mIF).Results30 pts with regionally advanced MEL were enrolled, of stages IIIB (57%), IIIC (37%), IIID (7%). 29/30 (97%) of pts completed 7 weeks of neoadjuvant Nivo/CMP; while 1 pt had a delay in surgery related to a pre-operative infection unrelated to therapy. No DLTs were reported; grade 3/4 irAE were reported in 3 pts (11%) leading to CMP-001 discontinuation in 2 pts (7%). Radiographic responses were seen in 13 pts (43%), while 9 pts (30%) had stable disease and 8 pts (27%) had progressive disease. Pathological responses (RVT <50%) were seen in 70% of pts: pCR 15 (50%), pMR 3 (10%), 3 pPR (10%); only 9 (30%) had pNR. Pathological responders (pCR/pMR) had increased CD8+ TIL and CD303+ pDC intra-tumorally by mIF; and peripherally activated PD1+/Ki67+ CD8+ T cells by MFC.ConclusionsNeoadjuvant CMP/Nivo has acceptable toxicity and promising efficacy. MPR is 60% in 30 pts. 1-year RFS was 82% (all pts) and 89% (among those with pCR/pMR); median RFS is 9 months (among pNR/pPR) and not reached (among pCR/pMR). Response is associated with evidence of immune activation intra-tumorally and peripherally. IT CMP001 increases clinical efficacy of PD-1 blockade with minimal additional toxicity in pts with regionally advanced MEL. Further study of this combination in high-risk resectable MEL is planned.AcknowledgementsWe thank Dr. Jagjit Singh and the pathology grossing room staff for their assistance and Checkmate Pharmaceuticals for funding and CMP-001.Trial RegistrationClinical trial information: NCT03618641Ethics ApprovalThe study was approved by University of Pittsburgh’s Institutional Review Board, approval number MOD19040237-002.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.ReferencesAmaria RN, Reddy SM, Tawbi HA, et al. Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma. Nat Med 2018. Nov;24(11):1649–1654.Huang AC, Orlowski RJ, Xu X, et al. A single dose of neoadjuvant PD-1 blockade predicts clinical outcomes in resectable melanoma. Nat Med 2019. Mar;25(3):454–461. doi: 10.1038/s41591-019-0357-y.Milhem M, Gonzales R, Medina T, et al. Abstract CT144: Intratumoral toll-like receptor 9 (TLR9) agonist, CMP-001, in combination with pembrolizumab can reverse resistance to PD-1 inhibition in a phase Ib trial in subjects with advanced melanoma. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14–18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract CT144.Tetzlaff MT, Messina JL, Stein JE, et al. Pathological assessment of resection specimens after neoadjuvant therapy for metastatic melanoma. Ann Oncol 2018. Aug 1;29(8):1861–1868.Cottrell TR, Thompson ED, Forde PM, et al. Pathologic features of response to neoadjuvant anti-PD-1 in resected non-small-cell lung carcinoma: a proposal for quantitative immune-related pathologic response criteria (irPRC). Ann Oncol 2018 Aug 1;29(8):1853–1860. doi: 10.1093/annonc/mdy218.Stein JE, Soni A, Danilova L, et al. Major pathologic response on biopsy (MPRbx) in patients with advanced melanoma treated with anti-PD-1: evidence for an early, on-therapy biomarker of response. Ann Oncol 2019 Apr 1;30(4):589–596. doi: 10.1093/annonc/mdz019.

Broadcast network model of pulsars as beacons of extraterrestrial civilizations

2018 ◽  
Vol 18 (05) ◽  
pp. 455-462 ◽  
Author(s):  
Emir Haliki
Keyword(s):  
Network Model ◽  
Type I ◽  
List Type ◽  
Radio Pulsars ◽  
Broadcast Network ◽  
Natural Energy ◽  
Radio Signals ◽  
Celestial Sphere ◽  
The Universe ◽  
Physical Principles

AbstractAccording to the Kardashev scale, likely extraterrestrial civilizations above Type-I might use natural energy sources of the Universe, which is also true for transmitting their signals out to distances. A variety of studies have shown that radio pulsars are most likely candidates for this. First, the current study examined how the radio beams of pulsars scan across their environment. Later when the radio beams of pulsars have been modulated, a network model has been proposed on how many habitable planets possible to be home for other assumed advanced civilizations could be reached. It has been found that size of each pulsar's broadcast network depends on the inclination angle. If a civilization controls multiple pulsars, it could comb a considerable fraction of their own celestial sphere and pulsars share their signals in a decentralized fashion as in the mail servers. Moreover, it is briefly cited how beam-modulating mechanisms can be built and searched around pulsars.Highlights •  It has been shown how pulsars would behave like beacons only when they have been used by modulating their radio signals.•  It has also been indicated how each pulsar could constitute an increasingly growing broadcast network by sweeping geometries and in what way it would emerge as number of controlled pulsars increases.•  It has been interpreted how a modulation mechanism could be established and searched under basic physical principles.

scholarly journals P01.02 TLR-mediated suppression of the CCL22-CCR4 axis as a new target for tumor immunotherapy

2021 ◽  
Vol 9 (Suppl 1) ◽  
pp. A3.2-A4
Author(s):  
J Grün ◽  
I Piseddu ◽  
C Perleberg ◽  
N Röhrle ◽  
S Endres ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
B Cells ◽  
Regulatory T Cells ◽  
Type I ◽  
List Type ◽  
Gm Csf

BackgroundUnmethylated CpG-DNA is a potent ligand for the endosomal Toll-like-receptor-9, important for the immune activation to pathogen-associated molecules.1 CpG and other TLR-ligands show effective immunotherapeutic capacities in cancer treatment by inducing an antitumorigenic immunity.2 They are able to reduce tumor progression by reduction of intratumoral secretion of the immunoregulating chemokine CCL223 and subsequent recruitment of immunosuppressive regulatory T cells (Treg), which express CCR4 the only so far known receptor for CCL22.4 Our recent work has shown that CCL22 secretion by dendritic cells (DC) in the lymph node, mediates tolerance by inducing DC-Treg contacts.5 Indeed, in the absence of CCL22, immune responses to vaccination were stronger and resulted in tumor rejection.6 Therefore, we are aiming to investigate the effects of TLR-ligands on systemic CCL22 levels, elucidating all involved mechanisms to identify new targets for cancer immunotherapy.Materials and MethodsT, B and CD11c+ DCs of wildtype (wt) and RAG1-/- mice were isolated from splenocytes by magnetic-activated cell sorting for in vitro assays. Different co-cultures were incubated with CpG and GM-CSF, known as an CCL22 inducer.5 For in vivo experiments, wt mice were treated with CpG, R484 or poly(I:C) alone and in combination with GM-CSF. CCL22-levels in a number of organs were analyzed.ResultsAnalyzing the different immune cell compartments in vitro, we found that DCs in whole splenocytes secrete CCL22 during culture while DC cultured alone showed no CCL22 secretion. When treated with CpG, CCL22-levels were reduced in splenocytes, while it was induced in DC culture alone. The same results were seen when RAG splenocytes, that lack functional B and T cells, were cultured with CpG. CpG treated B cells were able to suppress CCL22 secretion by DC unlike T cells alone. Co-cultures of T and B cells treated with CpG, however, induced the strongest CCL22 suppression in DC. In vivo, we could show that all TLR ligands tested reduced CCL22 in a number of organs significantly. Furthermore, CpG showed the strongest suppression of CCL22 even in the presence of the CCL22 inducer GM-CSF.5ConclusionsWe could show that B cells with T cells mediate CCL22 suppression by TLR ligands. The fact that CpG was able to reduce CCL22 levels even in the presence of the inducer GM-CSF demonstrates the potent CCL22 suppressive capacity of TLR ligands.ReferencesO’Neill LA, et al. The history of toll-like receptors – redefining innate immunity. Nat Rev Immunol 2013;13(6):453–60.Rothenfusser S, et al. Recent advances in immunostimulatory CpG oligonucleotides. Curr Opin Mol Ther 2003;5(2):98–106.Wang S, et al. Intratumoral injection of a CpG oligonucleotide reverts resistance to PD-1 blockade by expanding multifunctional CD8+ T cells. Proc Natl Acad Sci U S A 2016;113(46): E7240–E7249.Rapp M, et al. CCL22 controls immunity by promoting regulatory T cell communication with dendritic cells in lymph nodes. J Exp Med 2019;216(5):1170–1181.Piseddu I, et al. Constitutive expression of CCL22 is mediated by T cell-derived GM-CSF. J Immunol 2020;205(8):2056–2065.Anz D, et al. Suppression of intratumoral CCL22 by type i interferon inhibits migration of regulatory T cells and blocks cancer progression. Cancer Res 2015;75(21):4483–93.Disclosure InformationJ. Grün: None. I. Piseddu: None. C. Perleberg: None. N. Röhrle: None. S. Endres: None. D. Anz: None.

scholarly journals Association between anti-interferon-alpha autoantibodies and COVID-19 in systemic lupus erythematosus

2020 ◽  
Author(s):  
Sarthak Gupta ◽  
Shuichiro Nakabo ◽  
Jun Chu ◽  
Sarfaraz Hasni ◽  
Mariana J. Kaplan
Keyword(s):  
Systemic Lupus Erythematosus ◽  
General Population ◽  
Lupus Erythematosus ◽  
Preventive Measures ◽  
Type I Interferon ◽  
Type I ◽  
List Type ◽  
Signal Transducer ◽  
Systemic Lupus

AbstractObjectivesAnti-type I interferon (IFN) autoantibodies have been reported in patients with systemic lupus erythematosus (SLE). Recently, an association of these autoantibodies with severe COVID-19 was reported in the general population. We assessed whether having pre-existing anti-IFNα autoantibodies was associated with COVID-19 infection in SLE patients.MethodsPatients with SLE who developed COVID-19 between April 1st to October 1st, 2020 were studied. Biobanked pre-COVID-19 plasma from these SLE subjects and healthy controls were tested for anti-IFNα IgG autoantibodies by ELISA. The ability of plasma anti-IFNα autoantibodies to block signal transducer and activator of transcription 1 (STAT1) phosphorylation by recombinant human IFNα in vitro was assessed by flow cytometry.ResultsTen SLE subjects with COVID-19 were identified. A 40% of these subjects had stable autoantibodies against IFNα for up to three years preceding COVID-19 diagnosis. A 50% of the subjects with these autoantibodies neutralized IFNα induced STAT1 phosphorylation.None of the other SLE samples blocked IFNα signaling.ConclusionsWe noted an increased prevalence of pre-existing anti-IFNα autoantibodies in SLE patients with COVID-19 compared to the reported prevalence in lupus patients and the general population with severe COVID-19. Autoantibodies against IFNα in SLE patients may be pathogenic and patients with them maybe at-risk of developing COVID-19.Key MessagesWhat is already known about this subject?-Anti-type I interferon (IFN) autoantibodies have been reported in patients with systemic lupus erythematosus (SLE) and have recently been associated with severe COVID-19 in the general population.What does this study add?-SLE subjects with COVID-19 had an increased prevalence of pre-existing anti-IFNα autoantibodies compared to the reported prevalence in lupus patients and the general population with severe COVID-19.-Plasma from 50% of subjects with these autoantibodies were able to block in vitro activity of IFNα.-SLE patients with pre-existing anti-IFNα autoantibodies had more severe COVID-19 manifestations.How might this impact on clinical practice or future developments?-Anti-IFNα autoantibodies may be pathogenic and could prove to be a helpful prognostic marker to predict which SLE patient may develop COVID-19 and inform preventive measures and management of this subset of patients.

scholarly journals Vitamin D monitoring and management within men's secure services

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S337-S338
Author(s):  
Jason Niblett ◽  
Shay-Anne Pantall ◽  
Anis Ahmed
Keyword(s):  
At Risk ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Treatment Effectiveness ◽  
Average Length ◽  
Vitamin D Insufficiency ◽  
Vitamin D Supplementation ◽  
High Rate ◽  
List Type ◽  
Electronic Patient Records

AimsTo audit the investigation, identification and treatment of Vitamin D deficiency within Men's Secure Services.BackgroundVitamin D and/or vitamin D deficiency has been suggested to play a role in the pathogenesis of mental illness. There is evidence that Vitamin D inadequacy is pandemic among rehabilitation patients in inpatient settings. Patients within secure hospitals are similarly considered to be at high risk, due to their limited solar exposure during often lengthy admissions. It has been suggested that these patients should be considered an ‘at-risk’ cohort, for whom Vitamin D supplementation should be routine. Men's secure services in Birmingham comprise of two medium secure units and a low secure rehabilitation unit. Here we present an audit of Vitamin D monitoring and treatment completed in 2019.MethodA three year retrospective review of electronic patient records, for all inpatients admitted within men's secure services as of 1 September 2019 (n = 188). Standards were based on the Trust accepted guidelines for management of Vitamin D deficiency.ResultKey findings included:- The majority of inpatients were Caucasian (43%) and African-Caribbean (24%). Ages ranged from 18 to 70, with a mean age of 39.Approximately two-thirds (65%) had been in hospital for over a year, of which 44% had been admitted for more than 3 years. The average length of admission was 885 days.Only 47% of patients had their Vitamin D level checked within the study period.Of those checked, 24% were tested within 1 month of admission. The mean duration between admission and Vitamin D testing was 464 days.Results ranged from 10.3 to 118.5nmol/L. A high rate of Vitamin D deficiency was identified (54%), whilst a further 16% had ‘inadequate’ levels.23% of those identified as requiring treatment did not receive any supplementation, whilst 59% of those with sufficient Vitamin D were prescribed treatment.Only 48% had their levels rechecked following treatment; of these, only 59% now had an adequate Vitamin D status.ConclusionThis audit demonstrates limited Vitamin D monitoring within male forensic inpatients. There was a high prevalence of Vitamin D insufficiency in this population, yet a substantial proportion of patients with identified deficiency were not prescribed any treatment. Ongoing monitoring and review of treatment effectiveness was poor. We argue that more consideration should be given to this population, with robust guidelines introduced for the treatment of this specific ‘at-risk group’.

scholarly journals Development and evaluation of the focused assessment of sonographic pathologies in the intensive care unit (FASP-ICU) protocol

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Stefan Schmidt ◽  
Jana-Katharina Dieks ◽  
Michael Quintel ◽  
Onnen Moerer
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Conclusive Evidence ◽  
Rate Of Change ◽  
University Hospital ◽  
High Rate ◽  
Whole Body ◽  
Routine Surveillance ◽  
Organ Systems ◽  
Training Schemes

Abstract Background The use of ultrasonography in the intensive care unit (ICU) is steadily increasing but is usually restricted to examinations of single organs or organ systems. In this study, we combine the ultrasound approaches the most relevant to ICU to design a whole-body ultrasound (WBU) protocol. Recommendations and training schemes for WBU are sparse and lack conclusive evidence. Our aim was therefore to define the range and prevalence of abnormalities detectable by WBU to develop a simple and fast bedside examination protocol, and to evaluate the value of routine surveillance WBU in ICU patients. Methods A protocol for focused assessments of sonographic abnormalities of the ocular, vascular, pulmonary, cardiac and abdominal systems was developed to evaluate 99 predefined sonographic entities on the day of admission and on days 3, 6, 10 and 15 of the ICU admission. The study was a clinical prospective single-center trial in 111 consecutive patients admitted to the surgical ICUs of a tertiary university hospital. Results A total of 3003 abnormalities demonstrable by sonography were detected in 1275 individual scans of organ systems and 4395 individual single-organ examinations. The rate of previously undetected abnormalities ranged from 6.4 ± 4.2 on the day of admission to 2.9 ± 1.8 on day 15. Based on the sonographic findings, intensive care therapy was altered following 45.1% of examinations. Mean examination time was 18.7 ± 3.2 min, or 1.6 invested minutes per detected abnormality. Conclusions Performing the WBU protocol led to therapy changes in 45.1% of the time. Detected sonographic abnormalities showed a high rate of change in the course of the serial assessments, underlining the value of routine ultrasound examinations in the ICU. Trial registration The study was registered in the German Clinical Trials Register (DRKS, 7 April 2017; retrospectively registered) under the identifier DRKS00010428.

scholarly journals CryoEM structures of MDA5-dsRNA filaments at different stages of ATP hydrolysis

2018 ◽  
Author(s):  
Qin Yu ◽  
Kun Qu ◽  
Yorgo Modis
Keyword(s):  
Rna Binding ◽  
Atp Hydrolysis ◽  
Type I ◽  
List Type ◽  
Base Pairs ◽  
Nucleotide Analogs ◽  
Double Stranded Rna ◽  
Transition State Analogs ◽  
Helical Twist ◽  
Dsrna Binding

SummaryDouble-stranded RNA (dsRNA) is a potent proinflammatory signature of viral infection. Long cytosolic dsRNA is recognized by MDA5. The cooperative assembly of MDA5 into helical filaments on dsRNA nucleates the assembly of a multiprotein type-I-interferon signaling platform. Here, we determined cryoEM structures of MDA5-dsRNA filaments with different helical twists and bound nucleotide analogs, at resolutions sufficient to build and refine atomic models. The structures identify the filament forming interfaces, which encode the dsRNA binding cooperativity and length specificity of MDA5. The predominantly hydrophobic interface contacts confer flexibility, reflected in the variable helical twist within filaments. Mutation of filament-forming residues can result in loss or gain of signaling activity. Each MDA5 molecule spans 14 or 15 RNA base pairs, depending on the twist. Variations in twist also correlate with variations in the occupancy and type of nucleotide in the active site, providing insights on how ATP hydrolysis contributes to MDA5-dsRNA recognition.eTOCStructures of MDA5 bound to double-stranded RNA reveal a flexible, predominantly hydrophobic filament forming interface. The filaments have variable helical twist. Structures determined with ATP and transition state analogs show how the ATPase cycle is coupled to changes in helical twist, the mode of RNA binding and the length of the RNA footprint of MDA5.HighlightsCryoEM structures of MDA5-dsRNA filaments determined for three catalytic statesFilament forming interfaces are flexible and predominantly hydrophobicMutation of filament-forming residues can cause loss or gain of IFN-β signalingATPase cycle is coupled to changes in filament twist and size of the RNA footprint

The biological basis of aptitude: the endurance runner

1981 ◽  
Vol 13 (S7) ◽  
pp. 103-112 ◽  
Author(s):  
Clyde Williams
Keyword(s):  
Oxygen Transport ◽  
High Speed ◽  
Endurance Athlete ◽  
Endurance Athletes ◽  
High Rate ◽  
Type I ◽  
Carbon Dioxide Elimination ◽  
Endurance Runner ◽  
Genetic Endowment ◽  
The Individual

SummaryAptitude for a particular sport is governed by many factors, not least of which are obvious environmental influences. There are, however, individuals who, through genetic endowment, have the necessary biological characteristics which identify them as potentially elite athletes. These characteristics have been described more fully for endurance athletes because prolonged, almost steady-state running, lends itself more readily to investigation by biologists, than do the more complex sports.These studies show that the potentially elite endurance athlete is an individual endowed with an above average cardio-respiratory system, capable of a high rate of oxygen transport and carbon dioxide elimination. Not only does the elite endurance athlete have a greater rate of oxygen transport than the average sportsman or sportswoman, but the muscles receiving the oxygen are composed mainly of type I, i.e. low-twitch oxidative fibres, which are designed for endurance exercise. Furthermore, the elite endurance athlete also appears to be pre-programmed genetically to lay down less fat, in the form of sub-cutaneous adipose tissue, than the average sportsman or sportswoman of the same age and sex.Although genetic endowment dictates the potential ability of an individual for sustained high speed running, only appropriate training will allow the realization of this potential and so enable the individual to join the fraternity of the world's elite endurance athletes.

DOZ047.39: Respiratory morbidity at the age of one year in children with esophageal atresia: data from the French National Esophageal Atresia Register

2019 ◽  
Vol 32 (Supplement_1) ◽  
Author(s):  
S Lejeune ◽  
V Rousseau ◽  
A Bonnard ◽  
L Michaud ◽  
T Gelas ◽  
...  
Keyword(s):  
Respiratory Disease ◽  
Esophageal Atresia ◽  
Maintenance Treatment ◽  
Inhaled Corticosteroids ◽  
Population Based ◽  
Gastrostomy Tube ◽  
High Rate ◽  
Respiratory Morbidity ◽  
Type I ◽  
One Year

Summary Respiratory diseases are common in children with esophageal atresia (EA), leading to an increased morbidity and mortality in the first months of life. Objective Assess the prevalence of hospitalizations linked to a respiratory disease and of maintenance inhaled therapy at the age of 1 year in French children. Methods Population based-study using data from the French national EA register. We included all children born between 2010 and 2015 with data available at birth and at follow-up at one year of age. Results A total of 981 patients born with EA were included in the register, 75 of them (8%) being deceased at the age of 1 year. Data were missing for 60 patients, thus 846 children (86%) were retained for analysis. EAs were type III of Ladd classification in 89% and type I in 7%. Rate of prematurity was 37% while 51% presented associated malformations. At 1 year of age, 1297 hospitalizations were reported for 508 patients (60%), at least one hospitalization for a respiratory disease for 251 children (51%). Factors significantly associated with respiratory hospitalizations were longer median length of oxygen supplementation (P < 10−2) and noninvasive ventilation in the neonatal period (P = 0.02), gastrostomy tube (P < 10−2), esophageal anastomosis dilation (P < 10−2). At 1 year of age, 29% had an inhaled maintenance treatment, and 85% inhaled corticosteroids. Factors significantly associated with inhaled maintenance treatment were male gender (P = 0.04), advanced older median age at gastrostomy tube insertion (P < 10−3), enteral feeding at one year of age (P < 10−3). Conclusion This study shows a high rate of respiratory problems responsive of frequent hospitalizations and inhaled maintenance treatment in children born with EA in the first year of life.

Sign in / Sign up

Export Citation Format

Share Document