Objective: To perform a systematic review and multiple-treatment meta-analysis for the treatment of premature infants with post-hemorrhagic ventricular dilatation (PHVD), to prevent death or long-term neuro-disability. Design/Method: A systematic review was performed using PubMed, EMBASE, and the Cochrane Library. A free-word search was performed to identify likely relevant literature intervention trials of PHVD in preterm infants. Initially, network mapping was performed followed by performing a Bayesian random-effects model using the Markov chain Monte Carlo method. Areas under the cumulative ranking curve (SUCRA) were calculated as a measure of the probability that each intervention was likely to be the 1st, 2nd, 3rd, etc. best therapy. Primary outcome measure was death or moderate or severe neurodevelopmental outcome at or beyond 12 months of corrected age. Results: Ten different trials were identified, enrolling 700 individuals (449 for the primary outcome). Seven intervention categories were identified, and of the 15 possible pair comparisons, 6 have been studied directly. In the multiple-treatment meta-analysis, no comparison reached conventional levels of statistical significance. Drainage Irrigation and Fibrinolytic Therapy (DRIFT) had the highest probability of being the best treatment for the primary outcome (82.1%), followed by CSF removal (10.8%), conservative management (6.7%), and then diuretic therapy (0.4%). Conclusions: PHVD is a significant cause of death and disability in developed countries, yet few therapeutic options have so far been trialed. While new therapies are urgently needed for these infants, at present, NMA shows that DRIFT appears to be the most likely candidate to improve outcomes after sIVH.

Preterm delivery is associated with neurodevelopmental impairment caused by environmental and genetic factors. Dysfunction of the excitatory amino acid transporter 2 (EAAT2) and the resultant impaired glutamate uptake can lead to neurological disorders. In this study, we investigated the role of single nucleotide polymorphisms (SNPs; g.-200C > A and g.-181A > C) in the EAAT2 promoter in susceptibility to brain injury and neurodisability in very preterm infants born at or before 32-week gestation. DNA isolated from newborns' dried blood spots were used for pyrosequencing to detect both SNPs. Association between EAAT2 genotypes and cerebral palsy, cystic periventricular leukomalacia and a low developmental score was then assessed. The two SNPs were concordant in 89.4% of infants resulting in three common genotypes all carrying two C and two A alleles in different combinations. However, in 10.6% of cases, non-concordance was found, generating six additional rare genotypes. The A alleles at both loci appeared to be detrimental and consequently, the risk of developing cerebral palsy increased four- and sixfold for each additional detrimental allele at -200 and -181 bp, respectively. The two SNPs altered the regulation of the EAAT2 promoter activity and glutamate homeostasis. This study highlights the significance of glutamate in the pathogenesis of preterm brain injury and subsequent development of cerebral palsy and neurodevelopmental disabilities. Furthermore, the described EAAT2 SNPs may be an early biomarker of vulnerability to neurodisability and may aid the development of targeted treatment strategies.

Background Very low birth weight infants (VLBW; <1500 g) with late onset sepsis have an increased risk of neurodisability. Care bundles to reduce blood stream infections in NICU have been shown to be effective. Objective To determine if the implementation of a sepsis reduction care bundle was associated with improvement in neurodevelopmental outcomes in VLBW infants. Methods A sepsis improvement care bundle was implemented in a tertiary level NICU between 2006–2007. Mortality and neurological morbidity rates were compared for the pre-intervention (January 2001–December 2007) and post-intervention (July 2008–December 2012) periods. The highest risk VLBW infants (<30 weeks’ gestation) had routine neurodevelopmental assessments at 24 months using the Bayley Scales of Infant development (BSID). Moderate cognitive disability was defined as a cognitive/language score below 2SDs. Results Coagulase Negative Staphylococcus septicaemia rates were 7/1000 care days before implementation of the care bundle and have reduced to an average of 2.8/1000 care days by 2013. In the cohort of VLBW infants there was no significant reduction in mortality rates (66/426(16%) vs. 40/310(13%); p = 0.3). A significant reduction in moderate cognitive disability (16/86(19%) vs. 2/44(5%); p = 0.03) was found after full implementation of the sepsis care bundle. Potentially confounding variables (birth weight and gender) were not different (p > 0.05) in the pre and post intervention cohorts. Conclusions This is the first description of the long term impact of a sepsis improvement care bundle on neurodevelopmental outcomes in VLBW infants. The improvement seen in cognitive function at 2 years is likely to translate into significantly less long term learning disability.

Background: Single-strand conformational polymorphism (SSCP) is still a frequently used genotyping method across different fields for the detection of single nucleotide polymorphisms (SNPs) due to its simplicity, requirement for basic equipment accessible in most laboratories and low cost. This technique was previously used to detect rs4354668: A > C (g.-181A > C) SNP in the promoter of astroglial glutamate transporter (EAAT2) and the same approach was initially used here to investigate this promoter region in a cohort of newborns.Results: Unexpectedly, four distinct DNA migration patterns were identified by SSCP. Sanger sequencing revealed two additional SNPs: g.-200C > A and g.-168C > T giving a rise to a total of ten EAAT2 promoter variants. SSCP failed to distinguish these variants reliably and thus pyrosequencing assays were developed. g.-168C > T was found in heterozygous form in one infant only with minor allele frequency (MAF) of 0.0023. In contrast, g.-200C > A and -181A > C were more common (with MAF of 0.46 and 0.49, respectively) and showed string evidence of linkage disequilibrium (LD). In a systematic comparison, 16% of samples were miss-classified by SSCP with 25-31% errors in the identification of the wild-type and homozygote mutant genotypes compared to pyrosequencing or Sanger sequencing. In contrast, SSCP and pyrosequencing of an unrelated single SNP (rs1835740: C > T), showed 94% concordance.Conclusion: Our data suggest that SSCP cannot always detect reliably several closely located SNPs. Furthermore, caution is needed in the interpretation of the association studies linking only one of the co-inherited SNPs in the EAAT2 promoter to human diseases.

Background Very low birth weight (VLBW) infants with late onset sepsis have increased risk of neurodisability. Care bundles to reduce these infections in NICU are effective. The impact of care bundles on long-term neurodevelopmental outcome has not been described. We aimed to determine if implementation of a sepsis-reduction care bundle was associated with improvement in neurodevelopmental outcomes in VLBW infants. Methods A multimodal sepsis improvement bundle was implemented in a regional NICU from July 2006. This bundle focused on hand hygiene and line care improvements. Mortality and neurological morbidity rates were compared pre- and post intervention (Jan ‘01 - Dec ‘07 vs. Jul ‘08 – Dec ‘12). Infants had neurodevelopmental assessment at 24 months corrected gestation with Bayley Scales of Infant development. Moderate cognitive disability was defined as a cognitive/language score below 2SDs, moderate motor disability as a motor score below 2SDs. Results Birth weight, gestation and gender were similar in both cohorts. Coagulase Negative Staphylococcus septicaemia rates reduced from 7/1000 care days before implementation to 2.8/1000 in 2012. Mortality rates were similar between the groups (66/426 vs. 40/310; p = 0.3). There was no difference in moderate motor disability (17/85 vs. 3/42; p = 0.07). There was a significant reduction in moderate cognitive disability (16/86 vs. 2/44; p = 0.03) after implementation of the sepsis care bundle. Conclusions Sepsis-reduction care bundles improve the 2-year neurodevelopmental outcome of VLBW infants. The improvement seen in cognitive function is likely to translate into significantly less long-term learning disability.

Background Published data suggest that very low birth weight infants (VLBW; <1500 g) with late onset sepsis have increased risk of neurodisability. Care bundles to reduce blood stream infections in NICU have been shown to be effective. No studies have demonstrated the impact of these care bundles on long term neurodevelopmental outcome. Objective To determine if the implementation of a sepsis reduction care bundle was associated with improvement in neurodevelopmental outcomes in VLBW infants. Methods A sepsis improvement care bundle, based on the Vermont Oxford Network iNIQ package, was implemented in stages in a tertiary level NICU between 2006 and 2007. Mortality and neurological morbidity rates were compared for the pre-intervention (January 2001 to December 2007) and post-intervention (July 2008 to December 2012) periods. We excluded the 6 month period directly following full implementation of the intervention. The highest risk VLBW infants (<30 weeks’ gestation) had routine neurodevelopmental assessments at 24 months (corrected for gestation) using the Bayley Scales of Infant development (BSID). Moderate cognitive disability was defined as a cognitive/language score below 2SDs and moderate motor disability as a motor score below 2SDs. The outcome of cerebral palsy (CP) was assessed on neurological assessment at 2 years. Results Coagulase Negative Staphylococcus septicaemia rates were 7/1000 care days before implementation of the care bundle and from 2009, have reduced year on year to an average of 2.8/1000 care days by 2013. In the cohort of VLBW infants there was no significant reduction in mortality rates (66/426(16%) vs. 40/310(13%); p = 0.3). No significant difference was found in moderate motor disability (17/85(20%) vs. 3/42(7%); p = 0.07) or CP (10/94(11%) vs. 6/49(12%); p = 0.7), before and after the intervention. A significant reduction in moderate cognitive disability (16/86(19%) vs. 2/44(5%); p = 0.03) was found after full implementation of the sepsis care bundle. Potentially confounding variables (birth weight and gender) were not different (p > 0.05) in the pre and post intervention cohorts. Conclusions This is the first description of the long term impact of a sepsis improvement care bundle on neurodevelopmental outcomes in VLBW infants. The improvement seen in cognitive function at two years of age is likely to translate into significantly less long term learning disability.

To discern what makes some acquirers more successful than others, Bain & Co. performed a 15‐year longitudinal study of 1,600+ companies in the US, the UK, France, Germany, Italy and Japan doing 11,000+ deals plus interviews with senior executives. Bain’s analysis of the companies that succeed at deal making and integration shows that they share some key practices which can be boiled down to this simple playbook: get into the game in good times and bad. If you’re not doing deals, your odds of outperforming go down relative to your competitors that buy steadily. Do not try to time the market. Start small. Cut your teeth on smaller, lower‐risk deals before you try the big ones. Build your team and your expertise in an environment where mistakes will have the least impact. Create a core deal team. Set up a standing team that will keep gaining transactional experience and will not be subject to much turnover. Pull the line in early. Ensure that line managers buy into the deal and that they know what they’re buying. After all, the operators are the ones who will have to integrate the acquisition and make it a success. Chill deal fever. To cool down deal fever, insist on high‐level approvals for deals or set up the compensation system to tie rewards to the long‐term success of the business, rather than deal completion. Most important, set a walk‐away price and be prepared to walk away from a deal that doesn’t meet your high standards.

Objective: Therapeutic hypothermia (HT) is the standard treatment for newborns after perinatal asphyxia. Preclinical studies report that HT is more effective when started early. Methods: Eighty cooled newborns were analyzed and grouped according to when cooling was started after birth: early (≤180 min) or late (>181 min). For survivors we analyzed whether starting cooling early was associated with a better psychomotor or mental developmental index (PDI or MDI, Bayley Scales of Infant Development II) than late cooling. Results: Forty-three newborns started cooling early and 37 started late. There was no significant difference in the severity markers of perinatal asphyxia between the groups; however, nonsurvivors (n = 15) suffered more severe asphyxia and had significantly lower centiles for weight (BWC; p = 0.009). Of the 65 infants that survived, 35 were cooled early and 30 were cooled late. There was no difference in time to start cooling between those who survived and those who did not. For survivors, median PDI (IQR) was significantly higher when cooled early [90 (77-99)] compared to being cooled later [78 (70-90); p = 0.033]. There was no increase in cardiovascular adverse effects in those cooled early. There was no significant difference in MDI between early and late cooling [93 (77-103) vs. 89 (76-106), p = 0.594]. Conclusion: Starting cooling before 3 h of age in surviving asphyxiated newborns is safe and significantly improves motor outcome. Cooling should be initiated as soon as possible after birth in eligible infants.

Transitions from school to university are major life events impacting previously established routines. This has potential for elevating stress that entails coping. Employing focus groups, this unique study endeavoured to understand the struggles, strengths, challenges and the year experience of the of the first cohort of medical students at a newly developed medical school. Three main themes identified were: (i) unique experience of being the cohort; (ii) year experience and (iii) perceptions of personal growth. Supportive peers, faculty and novel teaching approaches could potentially off-set stressful aspects of transition like altered routines; absence of seniors; past exam resources and weakening friendships. Both content (course structure; curriculum; teaching methodology) and context of teaching (supportive faculty; adequate social support; resourced environment) have policy implications for educators. Appropriate scaffolding (type and extent of support) will promote student wellbeing and minimize attrition. © Common Ground, Renu Narchal, Leanne S. Cowin, Ian Wilson, David Harding.

We present a 26 weeks gestation boy with a complication of central venous catheterisation. He was intubated in delivery suite, and admitted for intensive care. An umbilical venous catheter (UVC) was placed and used; however, there was difficulty obtaining umbilical arterial catheterisation (UAC) access due to thin cord. During subsequent attempts to place …

Seventy-two hours of therapeutic hypothermia (HT) with a core temperature of 33.5–34.5 C commenced within 6 h of life is becoming the standard of care aiming to reduce death ⁄disability after neonatal encephalopathy (NE) (1–3). As a result of concerns about maintaining haemodynamic stability and normal clotting during surgery, and post-operative wound healing (4), infants with NE born with major congenital abnormalities requiring surgery were excluded in the HT trials. In the UK, infants undergoing HT since the end of total body hypothermia (TOBY) trial are registered into the TOBY registry and managed using a standardized protocol (5). There is no previous report of undertaking surgery in an encephalopathic infant during therapeutic HT. We report our first infant with NE and oesophageal atresia and tracheoesophageal fistula (TEF) who underwent surgery while undergoing therapeutic HT. A 29-year old gravida three para one mother with adequately controlled diabetes mellitus and asthma, noted to have polyhydramnios and foetal unilateral severe hydronephrosis and possible TEF in antenatal scans, delivered a male baby at 39 + 3 weeks gestation, weighing 3340 g by emergency caesarean section following foetal distress, poor cardiotocograph (CTG) trace and ante partum haemorrhage. He needed resuscitation and satisfied the NE inclusion criteria for HT [cord pH: 6.92, base deficit: 16 mmol ⁄L, ventilated, hypotonic and encephalopathic and moderately abnormal amplitude integrated electroencephalography (aEEG) (Fig. 1)]. He was then diagnosed with TEF needing imminent surgery, as well as a ventricular septal defect (VSD). As congenital malformation was a relative contraindication for HT, the benefits over risks were weighed with the surgical team, and HT was commenced after discussion with the parents. At 1.5 h, therapeutic HT was initiated using gloves filled with cold water placed around his head and body and external heating was turned off. At 3.5 h, the rectal temperature (Trec) was 34 C and the infant was transferred to surgery (Fig. 1). HT [Trec (33.1–34 C) (Fig. 1)] was then maintained by not actively warming (passive HT) until returning to neonatal intensive care unit (NICU) after 7 h of surgery. Anaesthesia was induced and maintained with isoflurane (0.86–0.97%), atracurium, fentanyl and morphine throughout the 3 h surgery. In our patient, the TEF was connected to the left main stem bronchus rather than the trachea, which is a rare presentation. This was however identified and divided, and an end to end oesophageal anastomosis was performed. There was minimal blood loss and no transfusion was given. During surgery, the mean (SD) end tidal CO2 (ET CO2) was: 4.2 (0.7) kPa and pCO2 was managed by pH stat [mean (SD):6.29 (1.42) kPa] (measured at 37 C), to maintain pCO2 in the normal range when corrected to Trec of 33.5 C (6).There were no arrhythmias. Heart rate, mean arterial blood pressure, oxygen requirement and Trec at HT were stable during surgery and post-surgery as shown in Fig. 1. He was ventilated and electively muscle relaxed with vecuronium for 5 days to protect the oesophageal anastomosis, which was under tension. On arrival back in the NICU, his Trec was 32.8 C. Active cooling was then continued for 72 h using a body wrap circulated with cold water servocontrolled to the Trec set at 33.5 C [Criticool; Medical ThermoRegulation Expertise (MTRE), Yavne, Israel]. Trec was stable at 33.5 ± 0.1 C Abbreviations aEEG, amplitude integrated electroencephalography; FFP, fresh frozen plasma; HT, Hypothermia; MRI, Magnetic resonance imaging; NE, Neonatal encephalopathy; NICU, neonatal intensive care unit; TEF, tracheoesophageal fistula; Trec, rectal temperature. Acta Paediatrica ISSN 0803–5253

This paper presents an overview of the architecture, design, and operation of a virtual network hardware emulation system. The primary motivation for creating the system was to allow operating system development engineers to create virtual network based hardware devices, which allows the developers to create support software for the devices. The system also allows test engineers to test the devices virtually before the devices are physically manufactured and available. The virtual network hardware emulation system consists of seven primary software components, such as a WLan Virtual Miniport component, which simulate the behavior of their physical counterparts. The system is designed in a modular way which allows a wide range of network based hardware devices to be virtualized and tested.

Medical EducationVolume 43, Issue 5 p. 394-395 ‘I will only work from 2.00 to 5.00…’ Ian Wilson, Ian Wilson Penrith South DC, New South Wales, AustraliaSearch for more papers by this authorDavid Harding, David Harding Penrith South DC, New South Wales, AustraliaSearch for more papers by this author Ian Wilson, Ian Wilson Penrith South DC, New South Wales, AustraliaSearch for more papers by this authorDavid Harding, David Harding Penrith South DC, New South Wales, AustraliaSearch for more papers by this author First published: 20 April 2009 https://doi.org/10.1111/j.1365-2923.2009.03312.xCitations: 6 Ian Wilson, School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith South DC, New South Wales 1797, Australia. Tel: 00 61 2 9852 4642; Fax: 00 61 2 9852 4701; E-mail: i.wilson@uws.edu.au Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume43, Issue5May 2009Pages 394-395 RelatedInformation

The main aim of identifying gene-environment interactions is to provide insight into mechanisms of disease development and to identify patients with an inherent vulnerability to certain conditions. This in turn may allow patients to be targeted with individualised treatment based on the knowledge of their inborn susceptibility to specific conditions. This review describes the possible effects of common genetic variation on outcome in various conditions affecting the neonate. It focuses predominantly on studies of positive association rather than non-association to illustrate this potential influence and to highlight the potential for further study and intervention. The shortcomings of published association studies and the place of such studies in future research are also discussed.

Objective: Post-traumatic stress disorder (PTSD) is a disabling condition, sometimes unresponsive to treatment. The aim of the present study was to examine the predictive utility of constructs from the transtheoretical model of behaviour change (TTM) known to predict outcome for other disorders. Method: A sample of 50 veterans presenting for a PTSD treatment programme provided data for this longitudinal study. Variables were assessed at four time-points during the treatment programme. Multiple regression and mixed-effects regression were utilized to determine the predictive utility of variables from the TTM. Results: Allocated stage of change at the time of a 2 day introduction programme predicted follow-up symptom severity, but changes therein during treatment did not predict changes in symptom severity. However, changes in the continuous readiness-to-change variable and behavioural processes of change were predictive of such changes. Conclusions: Despite some difficulties in the application of the TTM to PTSD, the model does appear to predict treatment outcome. Veterans who have increased readiness to change and who make more use of behavioural processes of change are likely to have improved outcomes.

How is success for Welfare‐to‐Work (WtW) programs defined, and is that definition adequate? This article assesses a snapshot of interagency communication in the 2000 Arkansas WtW program and its potential effects on the state's progress toward real welfare reform. Three key areas deemed necessary for successful implementation are explored: case management, inter‐agency communication, and goal congruence. Data for the evaluation were generated via surveys of agency personnel and program participants. The data reveal that interagency staff frequently disagree on responsibility for client assessment, that interagency staff do not always communicate effectively and seldom share data, and that staff from service providers and the Department of Human Services cite differing goals for the program they are charged with implementing. The authors reassess the adequacy of Arkansas' WtW program and suggest that in an era marked by systemic work‐related program reform, it is imperative that administrative linkages between state labor‐related agencies and personal welfare‐related agencies operate effectively.

Background: Cyclo-oxygenase (COX) inhibition by indomethacin does not result in an improvement in long-term neurocognitive outcome, despite reducing the incidence of both severe intraventricular haemorrhage and white matter injury visible on ultrasound. Diffuse brain injury after preterm birth may have inflammatory origins. These two points suggest that, in the preterm brain, COX inhibition may have a dominant proinflammatory or neuropathological role. The inducible form of the COX2 gene is polymorphic: the -765 C (rather than G) variant of the gene is associated with reduced COX2 activity.Objective: To test the hypothesis that the C allele of COX2 is associated with worse neurodevelopmental outcomes after premature birth.Outcomes: Cerebral palsy, disability, Griffith's developmental quotient at 2 years and British Ability Scales-11 general cognitive ability and motor performance (movement assessment battery for children) at 51/2 years were compared with COX2 genotype.Results: The C allele (GC 65 (31%), CC 3 (1%)) was independently associated with worse cognitive performance at 2 and 51/2 years: C allele mean (SEM) developmental quotient 92.7 (1.7), v GG 97.6 (1.5), p = 0.039; C allele mean (SEM) general cognitive ability, 943 (2.2) v GG 100.9 (1.7), p = 0.028.Conclusion: An antineuropathological role for COX2 in the preterm brain may kelp account for the lack of effect of indomethacin treatment in improving neurocognitive outcomes in children born preterm, despite reported reduction in apparent brain injury.

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ABSTRACT : BACKGROUND : Raised activity of the renin-angiotensin system (RAS) may both amplify inflammatory and free radical responses and decrease tissue metabolic efficiency and thus enhance cerebral injury in the preterm infant. The angiotensin-converting enzyme (ACE) DD genotype is associated with raised ACE and RAS activity as well as potentially adverse stimuli such as inflammation. The DD genotype has been associated with neurological impairments in the elderly, and thus may be also associated with poorer motor or cognitive development amongst children born preterm prematurely. METHODS : The association of DD genotype with developmental progress amongst 176 Caucasian children born at less than 33 weeks gestation (median birthweight 1475 g, range 645-2480 g; gestation 30 weeks, range 22-32; 108 male) was examined at 2 and 5 1/2 years of age. Measured neuro-cognitive outcomes were cranial ultrasound abnormalities, cerebral palsy, disability, Griffiths Developmental Quotient [DQ] at 2 yrs, and General Cognitive Ability [British Ability Scales-11] and motor performance [ABC Movement], both performed at 5 1/2 yrs. All outcomes were correlated with ACE genotype. RESULTS : The DD genotype was not associated with lower developmental quotients even after accounting for important social variables. CONCLUSION : These data do not support either a role for ACE in the development of cognitive or motor function in surviving infants born preterm or inhibition of ACE as a neuroprotective therapy.

有力的规范在实践中会是怎样的呢?Kellogg公司兼并了Keebler公司给我们了答案.在90年代,Kellogg曾是经济方面最成功的品牌之一,其产品像Kellogg牌玉米片在各家早餐桌边随处可见,公司利润相当可观,并达到最高值.但在90年代中期,Kellogg的经济开始进入低迷期.同时,零售商不再受控于Kellogg的高压模式,开始逐步增加自身品牌产品,消费者对谷类食品也逐渐失去了兴趣.