Video Rate Molecular Imaging In Vivo with Stimulated Raman Scattering

Optical imaging in vivo with molecular specificity is important in biomedicine because of its high spatial resolution and sensitivity compared with magnetic resonance imaging. Stimulated Raman scattering (SRS) microscopy allows highly sensitive optical imaging based on vibrational spectroscopy without adding toxic or perturbative labels. However, SRS imaging in living animals and humans has not been feasible because light cannot be collected through thick tissues, and motion-blur arises from slow imaging based on backscattered light. In this work, we enable in vivo SRS imaging by substantially enhancing the collection of the backscattered signal and increasing the imaging speed by three orders of magnitude to video rate. This approach allows label-free in vivo imaging of water, lipid, and protein in skin and mapping of penetration pathways of topically applied drugs in mice and humans.Chemistry and Chemical Biolog

Unit-Level Variations in Healthcare Professionals' Availability for Preterm Neonates <29 Weeks' Gestation: An International Survey

INTRODUCTION The availability of and variability in healthcare professionals in neonatal units in different countries has not been well characterized. Our objective was to identify variations in the healthcare professionals for preterm neonates in 10 national or regional neonatal networks participating in the International Network for Evaluating Outcomes (iNeo) of neonates. METHOD Online, pre-piloted questionnaires about the availability of healthcare professionals were sent to the directors of 390 tertiary neonatal units in 10 international networks: Australia/New Zealand, Canada, Finland, Illinois, Israel, Japan, Spain, Sweden, Switzerland, and Tuscany. RESULTS Overall, 325 of 390 units (83%) responded. About half of the units (48%; 156/325) cared for 11-30 neonates/day and had team-based (43%; 138/325) care models. Neonatologists were present 24 h a day in 59% of the units (191/325), junior doctors in 60% (194/325), and nurse practitioners in 36% (116/325). A nurse-to-patient ratio of 1:1 for infants who are unstable and require complex care was used in 52% of the units (170/325), whereas a ratio of 1:1 or 1:2 for neonates requiring multisystem support was available in 59% (192/325) of the units. Availability of a respiratory therapist (15%, 49/325), pharmacist (40%, 130/325), dietitian (34%, 112/325), social worker (81%, 263/325), lactation consultant (45%, 146/325), parent buddy (6%, 19/325), or parents' resource personnel (11%, 34/325) were widely variable between units. CONCLUSIONS We identified variability in the availability and organization of the healthcare professionals between and within countries for the care of extremely preterm neonates. Further research is needed to associate healthcare workers' availability and outcomes

Country-Specific vs. Common Birthweight-for-Gestational Age References to Identify Small for Gestational Age Infants Born at 24-28 weeks: An International Study

BACKGROUND Controversy exists as to whether birthweight-for-gestational age references used to classify infants as small for gestational age (SGA) should be country specific or based on an international (common) standard. We examined whether different birthweight-for-gestational age references affected the association of SGA with adverse outcomes among very preterm neonates. METHODS Singleton infants (n = 23 788) of 24(0) -28(6) weeks' gestational age in nine high-resource countries were classified as SGA (<10th centile) using common and country-specific references based on birthweight and estimated fetal weight (EFW). For each reference, the adjusted relative risk (aRR) for the association of SGA with composite outcome of mortality or major morbidity was estimated. RESULTS The percentage of infants classified as SGA differed slightly for common compared with country specific for birthweight references [9.9% (95% CI 9.5, 10.2) vs. 11.1% (95% CI 10.7, 11.5)] and for EFW references [28.6% (95% CI 28.0, 29.2) vs. 24.6% (95% CI 24.1, 25.2)]. The association of SGA with the composite outcome was similar when using common or country-specific references for the total sample for birthweight [aRRs 1.47 (95% CI 1.43, 1.51) and 1.48 (95% CI 1.44, 1.53) respectively] and for EFW references [aRRs 1.35 (95% CI 1.31, 1.38) and 1.39 (95% CI 1.35, 1.43) respectively]. CONCLUSION Small for gestational age is associated with higher mortality and morbidity in infants born <29 weeks' gestational age. Although common and country-specific birthweight/EFW references identified slightly different proportions of SGA infants, the risk of the composite outcome was comparable

Trends, Characteristic, and Outcomes of Preterm Infants Who Received Postnatal Corticosteroid: A Cohort Study from 7 High-Income Countries

INTRODUCTION Our objective was to evaluate the temporal trend of systemic postnatal steroid (PNS) receipt in infants of 24-28 weeks' gestational age, identify characteristics associated with PNS receipt, and correlate PNS receipt with the incidence of bronchopulmonary dysplasia (BPD) and BPD/death from an international cohort included in the iNeo network. METHODS We conducted a retrospective study using data from 2010 to 2018 from seven international networks participating in iNeo (Canada, Finland, Israel, Japan, Spain, Sweden, and Switzerland). Neonates of 24 and 28 weeks' gestational age who survived 7 days and who received PNS were included. We assessed temporal trend of rates of systemic PNS receipt and BPD/death. RESULTS A total of 47,401 neonates were included. The mean (SD) gestational age was 26.4 (1.3) weeks and birth weight was 915 (238) g. The PNS receipt rate was 21% (12-28% across networks) and increased over the years (18% in 2010 to 26% in 2018; p &lt; 0.01). The BPD rate was 39% (28-44% across networks) and remained unchanged over the years (35.2% in 2010 to 35.0% in 2018). Lower gestation, male sex, small for gestational age status, and presence of persistent ductus arteriosus (PDA) were associated with higher rates of PNS receipt, BPD, and BPD/death. CONCLUSION The use of PNS in extremely preterm neonates increased, but there was no correlation between increased use and the BPD rate. Research is needed to determine the optimal timing, dose, and indication for PNS use in preterm neonates

Neonatal Outcomes in Very Preterm Infants With Severe Congenital Heart Defects: An International Cohort Study

Background Very preterm infants are at high risk of death or severe morbidity. The objective was to determine the significance of severe congenital heart defects (CHDs) for these risks.Methods and Results This cohort study included infants from 10 countries born from 2007-2015 at 24 to 31 weeks' gestation with birth weights <1500 g. Severe CHDs were defined by International Classification of Diseases, Ninth Revision (ICD-9) and Tenth (ICD-10) codes and categorized as those compromising systemic output, causing sustained cyanosis, or resulting in congestive heart failure. The primary outcome was in-hospital mortality. Secondary outcomes were neonatal brain injury, necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity. Adjusted and propensity score-matched odds ratios (ORs) were calculated. Analyses were stratified by type of CHD, gestational age, and network. A total of 609 (0.77%) infants had severe CHD and 76 371 without any malformation served as controls. The mean gestational age and birth weight were 27.8 weeks and 1018 g, respectively. The mortality rate was 18.6% in infants with CHD and 8.9% in controls (propensity score-matched OR, 2.30; 95% CI, 1.61-3.27). Severe CHD was not associated with neonatal brain injury, necrotizing enterocolitis, or retinopathy of prematurity, whereas the OR for bronchopulmonary dysplasia increased. Mortality was higher in all types, with the highest propensity score-matched OR (4.96; 95% CI, 2.11-11.7) for CHD causing congestive heart failure. While mortality did not differ between groups at <27 weeks' gestational age, adjusted OR for mortality in infants with CHD increased to 10.9 (95% CI, 5.76-20.70) at 31 weeks' gestational age. Rates of CHD and mortality differed significantly between networks.Conclusions Severe CHD is associated with significantly increased mortality in very preterm infants

Preventive strategies and factors associated with surgically treated necrotising enterocolitis in extremely preterm infants: an international unit survey linked with retrospective cohort data analysis

Objectives To compare necrotising enterocolitis (NEC) prevention practices and NEC associated factors between units from eight countries of the International Network for Evaluation of Outcomes of Neonates, and to assess their association with surgical NEC rates.Design Prospective unit-level survey combined with retrospective cohort study.Setting Neonatal intensive care units in Australia/New Zealand, Canada, Finland, Israel, Spain, Sweden, Switzerland and Tuscany (Italy).Patients Extremely preterm infants born between 240 to 286 weeks’ gestation, with birth weightsExposures NEC prevention practices (probiotics, feeding, donor milk) using responses of an on-line pre-piloted questionnaire containing 10 questions and factors associated with NEC in literature (antenatal steroids, c-section, indomethacin treated patent ductus arteriosus and sepsis) using cohort data.Outcome measures Surgical NEC rates and death following NEC using cohort data.Results The survey response rate was 91% (153 units). Both probiotic provision and donor milk availability varied between 0%–100% among networks whereas feeding initiation and advancement rates were similar in most networks. The 9792 infants included in the cohort study to link survey results and cohort outcomes, revealed similar baseline characteristics but considerable differences in factors associated with NEC between networks. 397 (4.1%) neonates underwent NEC surgery, ranging from 2.4%–8.4% between networks. Standardised ratios for surgical NEC were lower for Australia/New Zealand, higher for Spain, and comparable for the remaining six networks.Conclusions The variation in implementation of NEC prevention practices and in factors associated with NEC in literature could not be associated with the variation in surgical NEC incidence. This corroborates the current lack of consensus surrounding the use of preventive strategies for NEC and emphasises the need for research

Preventive strategies and factors associated with surgically treated necrotising enterocolitis in extremely preterm infants: an international unit survey linked with retrospective cohort data analysis

OBJECTIVES To compare necrotising enterocolitis (NEC) prevention practices and NEC associated factors between units from eight countries of the International Network for Evaluation of Outcomes of Neonates, and to assess their association with surgical NEC rates. DESIGN Prospective unit-level survey combined with retrospective cohort study. SETTING Neonatal intensive care units in Australia/New Zealand, Canada, Finland, Israel, Spain, Sweden, Switzerland and Tuscany (Italy). PATIENTS Extremely preterm infants born between 24$^{0}$ to 28$^{6}$ weeks' gestation, with birth weights<1500 g, and admitted between 2014-2015. EXPOSURES NEC prevention practices (probiotics, feeding, donor milk) using responses of an on-line pre-piloted questionnaire containing 10 questions and factors associated with NEC in literature (antenatal steroids, c-section, indomethacin treated patent ductus arteriosus and sepsis) using cohort data. OUTCOME MEASURES Surgical NEC rates and death following NEC using cohort data. RESULTS The survey response rate was 91% (153 units). Both probiotic provision and donor milk availability varied between 0%-100% among networks whereas feeding initiation and advancement rates were similar in most networks. The 9792 infants included in the cohort study to link survey results and cohort outcomes, revealed similar baseline characteristics but considerable differences in factors associated with NEC between networks. 397 (4.1%) neonates underwent NEC surgery, ranging from 2.4%-8.4% between networks. Standardised ratios for surgical NEC were lower for Australia/New Zealand, higher for Spain, and comparable for the remaining six networks. CONCLUSIONS The variation in implementation of NEC prevention practices and in factors associated with NEC in literature could not be associated with the variation in surgical NEC incidence. This corroborates the current lack of consensus surrounding the use of preventive strategies for NEC and emphasises the need for research

Variations in Oxygen Saturation Targeting, and Retinopathy of Prematurity Screening and Treatment Criteria in Neonatal Intensive Care Units: An International Survey

BACKGROUND Rates of retinopathy of prematurity (ROP) and ROP treatment vary between neonatal intensive care units (NICUs). Neonatal care practices, including oxygen saturation (SpO2) targets and criteria for the screening and treatment of ROP, are potential contributing factors to the variations. OBJECTIVES To survey variations in SpO2 targets in 2015 (and whether there had been recent changes) and criteria for ROP screening and treatment across the networks of the International Network for Evaluating Outcomes in Neonates (iNeo). METHODS Online prepiloted questionnaires on treatment practices for preterm infants were sent to the directors of 390 NICUs in 10 collaborating iNeo networks. Nine questions were asked and the results were summarized and compared. RESULTS Overall, 329/390 (84%) NICUs responded, and a majority (60%) recently made changes in upper and lower SpO2 target limits, with the median set higher than previously by 2-3% in 8 of 10 networks. After the changes, fewer NICUs (15 vs. 28%) set an upper SpO2 target limit > 95% and fewer (3 vs. 5%) a lower limit < 85%. There were variations in ROP screening criteria, and only in the Swedish network did all NICUs follow a single guideline. The initial retinal examination was carried out by an ophthalmologist in all but 6 NICUs, and retinal photography was used in 20% but most commonly as an adjunct to indirect ophthalmoscopy. CONCLUSIONS There is considerable variation in SpO2 targets and ROP screening and treatment criteria, both within networks and between countries

Towards an Economy of Higher Education

This paper draws a distinction between ways thinking and acting, and hence of policy and practice in higher education, in terms of different kinds of economy: economies of exchange and economies of excess. Crucial features of economies of exchange are outlined and their presence in prevailing conceptions of teaching and learning is illustrated. These are contrasted with other possible forms of practice, which in turn bring to light the nature of an economy of excess. In more philosophical terms, and to expand on the picture, economies of excess are elaborated with reference, first, to the understanding of alterity in the work of Emmanuel Levinas and, second, to the idea of Dionysian intensity that is to be found in Nietzsche. In the light of critical comment on some current directions in policy and practice, the implications of these ways of thinking for the administrator, the teacher and the student in higher education are explored

The International Network for Evaluating Outcomes of very low birth weight, very preterm neonates (iNeo): a protocol for collaborative comparisons of international health services for quality improvement in neonatal care

The International Network for Evaluating Outcomes of very low birth weight, very preterm neonates (iNeo): a protocol for collaborative comparisons of international health services for quality improvement in neonatal care. Abstract Background: The International Network for Evaluating Outcomes in Neonates (iNeo) is a collaboration of population-based national neonatal networks including Australia and New Zealand, Canada, Israel, Japan, Spain, Sweden, Switzerland, and the UK. The aim of iNeo is to provide a platform for comparative evaluation of outcomes of very preterm and very low birth weight neonates at the national, site, and individual level to generate evidence for improvement of outcomes in these infants. Methods/design: Individual-level data from each iNeo network will be used for comparative analysis of neonatal outcomes between networks. Variations in outcomes will be identified and disseminated to generate hypotheses regarding factors impacting outcome variation. Detailed information on physical and environmental factors, human and resource factors, and processes of care will be collected from network sites, and tested for association with neonatal outcomes. Subsequently, changes in identified practices that may influence the variations in outcomes will be implemented and evaluated using quality improvement methods. Discussion: The evidence obtained using the iNeo platform will enable clinical teams from member networks to identify, implement, and evaluate practice and service provision changes aimed at improving the care and outcomes of very low birth weight and very preterm infants within their respective countries. The knowledge generated will be available worldwide with a likely global impact. BM