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Original article On the relevance of three genetic models for the description of genetic variance in small populations undergoing selection Florence Fournet-Hanocq Jean-Michel Elsen Station d’amélioration génétique des animaux, Institut national de la recherche agronomique, 31326 Castanet-Tolosan cedex, France (Received 15 October 1996; accepted 15 December 1997) Abstract - The conservation of genetic variability is recognized as a necessary objective for the optimization of selection schemes, particularly when populations are small. Numerous models, differing by the genetic model they rely on, are available to better understand and predict the evolution of genetic variance in a small population undergoing selection. This paper compares three genetic models, treated either analytically or with Monte-Carlo simulations, first in order to validate the predictions provided by a ’full-finite model’ for well-known phenomena (e.g. the effect of population management on genetic variability), and second, to evaluate when and how the assumptions made in the two analytical models induce the departure from the third model. The FFM is shown, first, to be in close agreement with the Gaussian theory when used with a large number of loci, the stochastic approach making it much more flexible than the two algebraic models. In the second part of the study, the infinitesimal model appears to be more robust than the semi- infinitesimal one. Major sources of discrepancy between the deterministic models and the FFM are identified, notably the hypothesis of independence between loci, and then the infinite number of loci or alleles per locus. &copy; Inra/Elsevier, Paris modelling / genetic variance / selection / small population * Correspondence and reprints Résumé - De l’intérêt de trois modèles génétiques pour la description de la variance génétique dans les petites populations sélectionnées. La conservation de la variabilité génétique est reconnue comme un objectif nécessaire pour l’optimisation des schémas de sélection, notamment pour les petites populations. De nombreux modèles, différant par les hypothèses de déterminisme génétique sur lesquels ils reposent, sont disponibles pour une meilleure compréhension et une meilleure prédiction de l’évolution de la variabilité génétique dans une petite population soumise à sélection. Cet article compare trois modèles génétiques différents, traités soit par la voie analytique soit par des simulations Monte- Carlo, d’une part pour valider les prédictions fournies par un « modèle fini complet » pour des phénomènes connus (comme l’influence de la gestion de la population sur la variabilité génétique), d’autre part pour évaluer quand et comment les hypothèses faites dans les deux modèles analytiques induisent un écart avec le dernier modèle. Le modèle fini complet apparaît, dans un premier temps, en bon accord avec la théorie gaussienne quand il est utilisé avec un grand nombre de locus, l’approche stochastique le rendant de plus beaucoup plus souple que les deux modèles algébriques. Dans la seconde partie de l’étude, le modèle infinitésimal apparaît plus robuste que le modèle semi-infinitésimal. Des sources majeures d’écart entre les modèles déterministes et le modèle fini complet sont identifiées, notamment l’hypothèse de l’indépendance entre les locus, puis le nombre infini de locus et d’allèles par locus. &copy; Inra/Elsevier, Paris modélisation / variance génétique / sélection / petite population 1. INTRODUCTION Genetic variability is Sucrose for analgesia in newborn infants undergoing painful procedures Vu Thi Hieu Neonatal department Children Hospital No2 Overview      Pain in newborns- pain assessment Painful procedures Pain relief- “analgesia” Sucrose in painful procedures Analgesia practice in NICU and Neonatal department Pain in newborns We think the newborns DON’T feel pain…  Neonatal pain vs adult pain … or less than adults Pain assessment in newborns Pain assessment in newborns Pain assessment in newborns Painful procedure   ‘can cause skin damage or mucosal damage by inserting or removing foreign bodies, and disturbing the body integrity of a neonate through therapeutic or diagnostic methods’ Ex: oral suctioning, tracheal suctioning, venipuncture, IV catheter insertion, heel lancing, wound treatment, ROP exam… The frequency of painful procedures    145 preterm baby, mean GA 35.4 ws, mean BW 2326g An average 105.6 painful procedures were performed in each neonate during weeks, and 7.5 daily The number of painful procedures increases in lower GA babies PAIN Acute effects  Physiology and behavioral responses Changes in stress hormones Long- term effects  Changing levels of neural activity can alter the normal development of the central nervous system  Poorer cognitive and motor scores, impairments of growth, reduced white matter and subcortical gray matter maturation, altered corticospinal tract structure  reduce acute behavioral responses to neonatal pain, but also to protect from persistent sensitization of pain pathways and potential damaging effects of excess activity on brain development Neonatal procedural pain analgesia Procedures Side effects Opioid Tracheal intubation Venipuncture, arterial puncture, IM or SC injection, LP in some cases Post operative in NICU -Respiratory depression -Risk was increased by preterm birth and intercurrent comorbid conditions Paracetamol Ineffective: heel lancing Overdose and hepatotoxicity Regional analgesia Venipuncture, arterial Local reactions EMLA puncture, IM or SC injection, CVC insertion, LP Ineffective: heel lancing Non pharmacological analgesia Venipuncture, arterial puncture,, CVC insertion, LP Non pharmacological pain relief: sucrose   Sucrose has been widely recommended for routine use in procedural pain in newborns Mechanism of action: not precisely understood, maybe the sweet taste increase endorphines release    Advantages: no side effects, easy to use Disadvantages: less effective in prolonged/ more intensive pain procedures Reduce acute effects of pain (behavior responses); long- term effects: not precisely understood Neonatal department and NICU- Children Hospital No2 Conclusion   Sucrose: effective analgesia in some neonatal painful procedures Increase using pharmacological (regional analgesia: EMLA) and nonpharmacological (sucrose) during some painful procedures in newborns, esp preterms References     P Lago, E Garetti, & Merazzi., D (2009) Guidelines for procedural pain in the newborns Acta pediatrica, 932-939 S Goksan (2015) fMRI reveals neural activity overlap between adult and infant pain Elife, 4, 113 SM Walker (2013) Neonatal pain Pediatric Anesthesia, 1-10 S Brummelte (2012) Procedural pain and brain development in premature newborns Ann Neurol, 71(3), 385-396    Stevens, J Yamada, A Ohlsson, S Haliburton, A Shorkey (2016) Sucrose for analgesia in newborn infants undergoing painful procedures (Review) The Cochrane Library, I Sook Jeong, SM Park, & JM Lee (2014) The frequency of painful procedures in neonatal intensive care units in South Korea International Journal of Nursing Practice, 20, 398–407 Lương Thị Ánh Thùy, Đặng Thị Mỹ Tánh, Lê Nguyễn Nhật Trung Kiến thức thực hành điều trị giảm đau thực thủ thuật trẻ sơ sinh điều dưỡng khoa Sơ sinh Hồi sức sơ sinh bệnh viên Nhi Đồng Open Access Available online http://ccforum.com/content/9/5/R549 R549 Vol 9 No 5 Research Does cardiac surgery in newborn infants compromise blood cell reactivity to endotoxin? Kathrin Schumacher 1 , Stefanie Korr 2 , Jaime F Vazquez-Jimenez 3 , Götz von Bernuth 4 , Jean Duchateau 5 and Marie-Christine Seghaye 6 1 Fellow in pediatrics, Department of Pediatric Cardiology, Aachen University, Aachen, Germany 2 Fellow in internal medicine, Department of Pediatric Cardiology, Aachen University, Aachen, Germany 3 Head of department, Department of Pediatric Cardiac Surgery, Aachen University, Aachen, Germany 4 Former head of department, Department of Pediatric Cardiology, Aachen University, Aachen, Germany 5 Director, Department of Immunology, University Hospital Brugmann and Saint-Pierre, Free University of Brussels, Brussels, Belgium 6 Head of department, Department of Pediatric Cardiology, Aachen University, Aachen, Germany Corresponding author: Kathrin Schumacher, kathrin_schumacher@web.de Received: 20 Apr 2005 Revisions requested: 31 May 2005 Revisions received: 13 Jul 2005 Accepted: 15 Jul 2005 Published: 9 Aug 2005 Critical Care 2005, 9:R549-R555 (DOI 10.1186/cc3794) This article is online at: http://ccforum.com/content/9/5/R549 © 2005 Schumacher et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/ 2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Introduction Neonatal cardiac surgery is associated with a systemic inflammatory reaction that might compromise the reactivity of blood cells against an inflammatory stimulus. Our prospective study was aimed at testing this hypothesis. Methods We investigated 17 newborn infants with transposition of the great arteries undergoing arterial switch operation. Ex vivo production of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), of the regulator of the acute- phase response IL-6, and of the natural anti-inflammatory cytokine IL-10 were measured by enzyme-linked immunosorbent assay in the cell culture supernatant after whole blood stimulation by the endotoxin lipopolysaccharide before, 5 and 10 days after the operation. Results were analyzed with respect to postoperative morbidity. Results The ex vivo production of TNF-α and IL-6 was significantly decreased (P < 0.001 and P < 0.002, respectively), whereas ex vivo production of IL-10 tended to be lower 5 days after the operation in comparison with preoperative values (P < 0.1). Ex vivo production of all cytokines reached preoperative values 10 days after cardiac surgery. Preoperative ex vivo production of IL-6 was inversely correlated with the postoperative oxygenation index 4 hours and 24 hours after the operation (P < 0.02). In contrast, postoperative ex vivo production of cytokines did not correlate with postoperative morbidity. Conclusion Our results show that cardiac surgery in newborn infants is associated with a transient but significant decrease in the ex vivo production of the pro-inflammatory cytokines TNF-α and IL-6 together with a less pronounced decrease in IL-10 production. This might indicate a transient postoperative anti- inflammatory shift of the cytokine balance in this age group. Our results suggest that higher preoperative ex vivo production of IL- 6 is associated with a higher risk for postoperative pulmonary dysfunction. Introduction Cardiac surgery is associated with a systemic inflammatory reaction comprising activation of the complement system, stimulation of leukocytes, synthesis of cytokines, and increased interactions between leukocytes and endothelium [1,2]. In children, contact activation, ischemia/reperfusion injury and endotoxin released from the gut [3,4] are thought to be the major inductors of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) RES E AR C H A R T I C L E Open Access Vacuum assisted birth and risk for cerebral complications in term newborn infants: a population-based cohort study Cecilia Ekéus 1* , Ulf Högberg 2 and Mikael Norman 3 Abstract Background: Few studies have focused on cerebral complications among newborn infants delivered by vacuum extraction (VE). The aim of this study was to determine the risk for intracranial haemorrhage and/or cerebral dysfunction in newborn infants delivered by VE and to compare this risk with that after cesarean section in labour (CS) and spontaneous vaginal delivery, respectively. Methods: Data was obtained from Swedish national registers. In a population-based cohort from 1999 to 2010 including all singleton newborn infants delivered at term after onset of labour by VE (n = 87,150), CS (75,216) or spontaneous vaginal delivery (n = 851,347), we compared the odds for neonatal intracranial haemorrhage, traumatic or non-traumatic, convulsions or encephalopathy. Logistic regressions were used to calculate adjusted (for major risk factors and indication) odds ratios (AOR), using spontaneous vaginal delivery as reference group. Results: The rates of traumatic and non-traumatic intracranial hemorrhages were 0.8/10,000 and 3.8/1,000. VE deliveries provided 58% and 31.5% of the traumatic and non-traumatic cases, giving a ten-fold risk [AOR 10.05 (4.67-21.65)] and double risk [AOR 2.23 (1.57-3.16)], respectively. High birth weight and short mother were associated with the highest risks. Infants delivered by CS had no increased risk for intracranial hemorrhages. The risks for convulsions or encephalopathy were similar among infants delivered by VE and CS, exceeding the OR after non-assisted spontaneous vaginal delivery by two-to-three times. Conclusion: Vacuum assisted delivery is associated with increased risk for neonatal intracranial hemorrhages. Although causality could not be established in this observational study, it is important to be aware of the increased risk of intracranial hemorrhages in VE deliveries, particularly in short women and large infants. The results warrant further studies in decision making and conduct of assisted vaginal delivery. Background Delivery by vacuum extraction (VE) is a common obstet- rical procedure in the western world, and in many coun- tries, it has replaced the use of forceps. The use of VE has increased from 6% in 1980 to 8.8% in all deliveries in Sweden 2011, while the use of forceps currently is 0.2% [1] In the US, vacuum-assisted births have declined to 2.8% of the births in 2011 [2]. While extra-cranial haematomas and skull fractures have been associated with VE assisted deliveries [3-7], a causal link to neonatal intracranial haemorrhage (intracranial hemorrhages;subarachnoid, subdural, and intracerebral) is less e vident [8]. VE is reported to be associated with rare but severe cerebral complications [9], although study limitations have been small sample size and retrospective design [9,10], composite outcomes [11], mixed term and preterm deliveries [12,13], no comparisons of rates of intracranial complications in vacuum extraction and caesarean section (CS) deliveries [9,13]. In addition, few studies have investigated the a ssociation between VE and neonatal encephalopathy and the results are contradictive [13,14]. Intracranial hemorrhage in newborn infants can be obser ved also without a difficult delivery, and its com- plexity in etiology was already described a century ago [15]. Modern neuroimaging techniques—such as ultra- * Correspondence: cecilia.ekeus@ki.se 1 Department of Women’s and Children’s Health, Division of Reproductive Health, Karolinska Institutet, Stockholm, Sweden Full list of author information is available at the end of the article © 2014 Ekéus et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted BS Nguyễn Phạm Minh Trí Khoa Hồi Sức Sơ Sinh Description of the condition  newborn inhales mixture of meconium and amniotic fluid into lungs in delivery Meconium Aspiration: The Statistics  Infants with MEC aspiration syndrome 35% need mechanical ventilation (range 25-60%) 12% die (range 5-37%) Management: at present         Assisted ventilation Sedation Surfactant Nitric oxide ECMO Circulatory support Antibiotics ……  Largely SUPPORTIVE Remove MEC from the lung: Why NOT ??? Lung lavage for meconium aspiration syndrome in newborn infants (Review) Hahn S, Choi HJ, Soll R, Dargaville PA Cochrane Database of Systematic Reviews 2013 Issue Art No.: CD003486 Objectives  Evaluate Effects of LUNG LAVAGE on Morbidity and Mortality in newborn infants with MAS Search methods  Search database:     Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, and EMBASE up to December 2012 previous reviews including cross-references, abstracts, conference proceedings; and expert informants Search words:  meconium aspiration, pulmonary surfactants, bronchoalveolar lavage, lung lavage, pulmonary lavage Selection criteria   Randomised controlled trials that evaluated the effects of lung lavage in infants with MAS Lung lavage: intervention in which fluid is instilled into the lung and then removed by suctioning and/or postural drainage   Fluids that have been used for this purpose include saline, full-strength and dilute surfactant, and perfluorocarbon Standard care: no lavage therapy, but include routine suction of the endotracheal tube to maintain its patency Outcome 1: Death Outcome 2: Use of ECMO Outcome 3: Death or use of ECMO Outcome 4: Pneumothorax Outcome 5: Oxygenation index Outcome 6: AaDO2 Outcome 7: PaO2/FiO2 Result Analysis  Lung lavage has effect in all outcomes, but only these are significant in statistics:   Outcome 3: Death or Use of ECMO Outcome 5: Oxygenation index at 48 hours Comparison LUNG LAVAGE FOLLOWED BY SURFACTANT BOLUS VERSUS SURFACTANT BOLUS Lung lavage followed by surfactant bolus vs surfactant bolus   One study: Gadzinowski 2008 Outcomes:   Death Pneumothorax Outcome 1: Death Outcome 2: Pneumothorax Authour’s conclusion  In infants with MAS, lung lavage with diluted surfactant may be beneficial (Grade 2B)   A Grade recommendation is a weak recommendation It means "this is our suggestion, but you may want to think about it” For Grade recommendations, benefits and risks may be finely balanced, or uncertain Grade B evidence is evidence from randomized trials with important limitations, or very strong evidence of some other form Authour’s conclusion  Additional controlled clinical trials of lavage therapy should be conducted to     confirm the treatment effect refine the method of lavage treatment compare lavage treatment with other approaches, including surfactant bolus therapy Long-term outcomes should be evaluated in further clinical trials [...]... the non lavaged control group were not reported and are not now obtainable Three studies are included in this review  Wiswell 2002; Gadzinowski 2008; Dargaville 2011 Study analysis  Type of lavage fluid •  Lavage aliquot volume • •  All included studies used diluted surfactant for lavage  5 mL/kg in all studies comparing surfactant lavage with standard care  5 mL/kg in the study comparing surfactant... comparing surfactant lavage followed by bolus surfactant with surfactant bolus therapy Timing of lavage • mean age  than six hours in all included studies Comparison 1 LUNG LAVAGE VERSUS STANDARD CARE Lung lavage vs Standard care   Two studies: Dargaville 2011; Wiswell 2002 Outcomes:      Death Use of ECMO Death or Use of ECMO Pneumothorax Indices of pulmonary function: Oxygenation Index, AaDO2 and... 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Pain in newborns- pain assessment Painful procedures Pain relief- analgesia Sucrose in painful procedures Analgesia practice in NICU and Neonatal department Pain in newborns We think the newborns... feel pain…  Neonatal pain vs adult pain … or less than adults Pain assessment in newborns Pain assessment in newborns Pain assessment in newborns Painful procedure   ‘can cause skin damage... (2016) Sucrose for analgesia in newborn infants undergoing painful procedures (Review) The Cochrane Library, I Sook Jeong, SM Park, & JM Lee (2014) The frequency of painful procedures in neonatal intensive

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