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The article examines the accountability of clinical trials in terms of neurodevelopmental impairment and long-term morbidity. Topics discussed include use of validated psychometric instruments to quantify a child's developmental process, association of whole-body hypothermia with primary outcome of death or neurodisability and a chart that depicts the types of disability such as motor, hearing and vision.

Th cells are the major effector cells in transplant rejection and can be divided into Th1, Th2, Th17, and Treg subsets. Th differentiation is controlled by transcription factor expression, which is driven by positive and negative cytokine and chemokine stimuli at the time of T cell activation. Here we discovered that chemokine platelet factor 4 (PF4) is a negative regulator of Th17 differentiation. PF4-deficient and platelet-deficient mice had exaggerated immune responses to cardiac transplantation, including increased numbers of infiltrating Th17 cells and increased plasma IL-17. Although PF4 has been described as a platelet-specific molecule, we found that activated T cells also express PF4. Furthermore, bone marrow transplantation experiments revealed that T cell-derived PF4 contributes to a restriction in Th17 differentiation. Taken together, the results of this study demonstrate that PF4 is a key regulator of Th cell development that is necessary to limit Th17 differentiation. These data likely will impact our understanding of platelet-dependent regulation of T cell development which is important in many diseases, in addition to transplantation. [ABSTRACT FROM AUTHOR]

Activated platelets release many inflammatory molecules with important roles in accelerating vascular inflammation. Much is known about platelet and platelet-derived mediator interactions with endothelial cells and leukocytes, but few studies have examined the effects of platelets on components of the vascular wall. Vascular smooth muscle cells (VSMCs) undergo phenotypic changes in response to injury including the production of inflammatory molecules, cell proliferation, cell migration, and a decline in the expression of differentiation markers. In this study, we demonstrate that the platelet-derived chemokine platelet factor 4 (PF4/CXCL4) stimulates VSMC injury responses both in vitro and in vivo in a mouse carotid ligation model. PF4 drives a VSMC inflammatory phenotype including a decline in differentiation markers, increased cytokine production, and cell proliferation. We also demonstrate that PF4 effects are mediated, in part, through increased expression of the transcription factor Krüppel-like factor 4. Our data indicate an important mechanistic role for platelets and PF4 in VSMC injury responses both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Cerebral malaria continues to be a difficult to treat complication of Plasmodium falciparum infection in children. We have shown that platelets can have major deleterious immune functions in experimental cerebral malaria (ECM). One of the platelet derived mediators we have identified as particularly important is platelet factor 4/CXCL4. Our prior work demonstrated that PF4-/- mice are protected from ECM, have reduced plasma cytokines, and have reduced T-cell trafficking to the brain. We now show that PF4 drives monocyte cytokine production in a Kruppel like factor 4 (KLF4) dependent manner. Monocyte depleted Plasmodium berghei infected mice have improved survival, and KLF4 is greatly increased in control, but not monocyte depleted mice. PF4-/- mice have less cerebral monocyte trafficking and no change in KLF4 expression. These data indicate that PF4 induction of monocyte KLF4 expression may be an important step in the pathogenesis of ECM. [ABSTRACT FROM AUTHOR]

A number of neuroimaging techniques have been employed to understand how visual information is transformed along the visual pathway. Although each technique has spatial and temporal limitations, they can each provide important insights into the visual code. While the BOLD signal of fMRI can be quite informative, the visual code is not static and this can be obscured by fMRI's poor temporal resolution. In this study, we leveraged the high temporal resolution of EEG to develop an encoding technique based on the distribution of responses generated by a population of real-world scenes. This approach maps neural signals to each pixel within a given image and reveals location-specific transformations of the visual code, providing a spatiotemporal signature for the image at each electrode. Our analyses of the mapping results revealed that scenes undergo a series of nonuniform transformations that prioritize different spatial frequencies at different regions of scenes over time. This mapping technique offers a potential avenue for future studies to explore how dynamic feedforward and recurrent processes inform and refine high-level representations of our visual world. Author summary: The visual information that we sample from our environment undergoes a series of neural modifications, with each modification state (or visual code) consisting of a unique distribution of responses across neurons along the visual pathway. However, current noninvasive neuroimaging techniques provide an account of that code that is coarse with respect to time or space. Here, we present dynamic electrode-to-image (DETI) mapping, an analysis technique that capitalizes on the high temporal resolution of EEG to map neural signals to each pixel within a given image to reveal location-specific modifications of the visual code. The DETI technique reveals maps of features that are associated with the neural signal at each pixel and at each time point. DETI mapping shows that real-world scenes undergo a series of nonuniform modifications over both space and time. Specifically, we find that the visual code varies in a location-specific manner, likely reflecting that neural processing prioritizes different features at different image locations over time. DETI mapping therefore offers a potential avenue for future studies to explore how each modification state informs and refines the conceptual meaning of our visual world. [ABSTRACT FROM AUTHOR]

Two recent studies suggest that natural scenes and paintings show similar statistical properties. But does the content or region of origin of an artwork affect its statistical properties? We addressed this question by having judges place paintings from a large, diverse collection of paintings into one of three subject-matter categories using a forced-choice paradigm. Basic statistics for images whose caterogization was agreed by all judges showed no significant differences between those judged to be 'landscape' and 'portrait/still-life', but these two classes differed from paintings judged to be 'abstract'. All categories showed basic spatial statistical regularities similar to those typical of natural scenes. A test of the full painting collection (140 images) with respect to the works' place of origin (provenance) showed significant differences between Eastern works and Western ones, differences which we find are likely related to the materials and the choice of background color. Although artists deviate slightly from reproducing natural statistics in abstract art (compared to representational art), the great majority of human art likely shares basic statistical limitations. We argue that statistical regularities in art are rooted in the need to make art visible to the eye, not in the inherent aesthetic value of natural-scene statistics, and we suggest that variability in spatial statistics may be generally imposed by manufacture. [ABSTRACT FROM AUTHOR]

Paintings are the product of a process that begins with ordinary vision in the natural world and ends with manipulation of pigments on canvas. Because artists must produce images that can be seen by a visual system that is thought to take advantage of statistical regularities in natural scenes, artists are likely to replicate many of these regularities in their painted art. We have tested this notion by computing basic statistical properties and modeled cell response properties for a large set of digitized paintings and natural scenes. We find that both representational and nonrepresentational (abstract) paintings from our sample (124 images) show basic similarities to a sample of natural scenes in terms of their spatial frequency amplitude spectra, but the paintings and natural scenes show significantly different mean amplitude spectrum slopes. We also find that the intensity distributions of paintings show a lower skewness and sparseness than natural scenes. We account for this by considering the range of luminances found in the environment compared to the range available in the medium of paint. A painting's range is limited by the reflective properties of its materials. We argue that artists do not simply scale the intensity range down but use a compressive nonlinearity. In our studies, modeled retinal and cortical filter responses to the images were less sparse for the paintings than for the natural scenes. But when a compressive nonlinearity was applied to the images, both the paintings' sparseness and the modeled responses to the paintings showed the same or greater sparseness compared to the natural scenes. This suggests that artists achieve some degree of nonlinear compression in their paintings. Because paintings have captivated humans for millennia, finding basic statistical regularities in paintings' spatial structure could grant insights into the range of spatial patterns that humans find compelling. [ABSTRACT FROM AUTHOR]

A wide variety of papers have reviewed what is known about the function of primary visual cortex. In this review, rather than stating what is known, we attempt to estimate how much is still unknown about V1 function. In particular, we identify five problems with the current view of V1 that stem largely from experimental and theoretical biases, in addition to the contributions of nonlinearities in the cortex that are not well understood. Our purpose is to open the door to new theories, a number of which we describe, along with some proposals for testing them. [ABSTRACT FROM AUTHOR]

Abstract: When NO became available for clinical use, it seemed to hold enormous promise for newborn infants with lung disease. With regard to the term and near-term infant, the role of NO seems satisfactorily defined: Near-term and term infants with hypoxic respiratory failure unresponsive to current therapy, excluding infants with diaphragmatic hernia, should have a trial of inhaled nitric oxide. In the preterm infant, the situation is less clear with, as yet, no specific indication identified. [Copyright &y& Elsevier]

Several theoretical, computational, and experimental studies suggest that neurons encode sensory information using a small number of active neurons at any given point in time. This strategy, referred to as ‘sparse coding’, could possibly confer several advantages. First, it allows for increased storage capacity in associative memories; second, it makes the structure in natural signals explicit; third, it represents complex data in a way that is easier to read out at subsequent levels of processing; and fourth, it saves energy. Recent physiological recordings from sensory neurons have indicated that sparse coding could be a ubiquitous strategy employed in several different modalities across different organisms. [Copyright &y& Elsevier]

We describe two experiments that investigate the roles of polarity and symmetry in the perceptual grouping of contour fragments. Observers viewed, for one second on each presentation, arrays of oriented, spatial-frequency band-pass, elements, in which a subset of the elements was aligned along a twisting curve. In each of five conditions we measured observers' ability to detect aligned combinations of even- and odd-symmetric elements, of the same and different polarities, against a background of 'noise' elements. As with previous experiments we found that the 'path' could be reliably detected, even when the elements of the path were oriented at angles of up to ± 60 deg relative to each other. Detection of the path was still possible when the polarity of path elements alternated. However, the probability of detection of the path was raised significantly when the path elements were all of the same polarity. Perceptual grouping of even-symmetric elements was no different to perceptual grouping of odd-symmetric elements. The results provide evidence, that in achieving integration of contour fragments, the visual system uses a process that is to some degree phase selective. We use the results to describe how the visual system may resolve natural contours when they occur against backgrounds that vary over a wide range of intensities. The data presented here have been published in conference-abstract form (Hayes et al., 1993; Field et al., 1997). [ABSTRACT FROM AUTHOR]

Objective To assess changes in survival for infants born before 26 completed weeks of gestation. Design Prospective cohort study in a geographically defined population. Setting Former Trent health region of the United Kingdom. Subjects All infants born at 22+0 to 25+6 weeks' gestation to mothers living in the region. Terminations were excluded but all other births of babies alive at the onset of labour or the delivery process were included. Main outcome measures Outcome for all infants was categorised as stillbirth, death without admission to neonatal intensive care, death before discharge from neonatal intensive care, and survival to discharge home in two time periods: 1994-9 and 2000-5 inclusive. Results The proportion of infants dying in delivery rooms was similar in the two periods, but a significant improvement was seen in the number of infants surviving to discharge (P<0.001). Of 497 infants admitted to neonatal intensive care in 2000-5, 236 (47%) survived to discharge compared with 174/490 (36%) in 1994. These changes were attributable to substantial improvements in the survival of infants born at 24 and 25 weeks. During the 12 years of the study none of the 150 infants born at 22 weeks' gestation survived. Of the infants born at 23 weeks who were admitted to intensive care, there was no significant improvement in survival to discharge in 2000-5 (12/65 (18%) in 2000-5 v15/81 (19%) in 1994-9). Conclusions Survival of infants born at 24 and 25 weeks of gestation has significantly increased. Although over half the cohort of infants born at 23 weeks was admitted to neonatal intensive care, there was no improvement in survival at this gestation. Care for infants born at 22 weeks remained unsuccessful. [ABSTRACT FROM AUTHOR]

The article discusses the value and validity of neonatal disease severity scoring system. According to the authors, the scoring systems that exist in neonatal care have developed though a process that formalises the assessment of the risks attached to a particular baby. In neonatal care, the author notes that survival rate is chosen as the most significant outcome for comparison and hence most scores are designed to adjust for risk of death particularly in preterm babies.

Our understanding of information processing by the mammalian visual system has come through a variety of techniques ranging from psychophysics and fMRI to single unit recording and EEG. Each technique provides unique insights into the processing framework of the early visual system. Here, we focus on the nature of the information that is carried by steady state visual evoked potentials (SSVEPs). To study the information provided by SSVEPs, we presented human participants with a population of natural scenes and measured the relative SSVEP response. Rather than focus on particular features of this signal, we focused on the full state-space of possible responses and investigated how the evoked responses are mapped onto this space. Our results show that it is possible to map the relatively high-dimensional signal carried by SSVEPs onto a 2-dimensional space with little loss. We also show that a simple biologically plausible model can account for a high proportion of the explainable variance (~73%) in that space. Finally, we describe a technique for measuring the mutual information that is available about images from SSVEPs. The techniques introduced here represent a new approach to understanding the nature of the information carried by SSVEPs. Crucially, this approach is general and can provide a means of comparing results across different neural recording methods. Altogether, our study sheds light on the encoding principles of early vision and provides a much needed reference point for understanding subsequent transformations of the early visual response space to deeper knowledge structures that link different visual environments. • Non-invasive brain imaging procedures, such as fMRI and EEG, form the backbone of our knowledge of human sensory systems. • In all imaging modalities, research has focused on the features of the response, such as the relative amplitudes of peaks and troughs in the evoked response, rather than the relative organization of entire responses across a variety of stimuli. • Here, we consider whole responses as points in a high-dimensional response space of possible alternatives and model the geometry of this space. • This global approach allows us to observe how the early visual system organizes information, to test the fit of biologically plausible computational models, and to estimate the information available in the signal. [ABSTRACT FROM AUTHOR]

Investigates the proposal that a coding strategy is employed in the primary visual cortex of mammals. Relationship of the properties of visual neurons to the statistical structure of natural images; Emergence of simple-cell receptive field properties through a sparse code for natural images.

Examines the cost of neonatal intensive care equipments in Great Britain. Introduction of budget holding contracts for perinatal services by the British Association of Pediatric Association and Perinatal Pediatrics; Impact of proposal on the guidelines for the selection of equipments; Requirement for intensive care level.

Thrombosis-associated pathologies, such as myocardial infarction and stroke, are major causes of morbidity and mortality worldwide. Because platelets are necessary for hemostasis and thrombosis, platelet directed therapies must balance inhibiting platelet function with bleeding risk. Glutamate receptor interacting protein 1 (GRIP1) is a large scaffolding protein that localizes and organizes interacting proteins in other cells, such as neurons. We have investigated the role of GRIP1 in platelet function to determine its role as a molecular scaffold in thrombus formation. Platelet-specific GRIP1-/- mice were used to determine the role of GRIP1 in platelets. GRIP1-/- mice had normal platelet counts, but a prolonged bleeding time and delayed thrombus formation in a FeCl3-induced vessel injury model. In vitro stimulation of WT and GRIP1-/- platelets with multiple agonists showed no difference in platelet activation. However, in vivo platelet rolling velocity after endothelial stimulation was significantly greater in GRIP1-/- platelets compared to WT platelets, indicating a potential platelet adhesion defect. Mass spectrometry analysis of GRIP1 platelet immunoprecipitation revealed enrichment of GRIP1 binding to GPIb-IX complex proteins. Western blots confirmed the mass spectrometry findings that GRIP1 interacts with GPIbα, GPIbβ, and 14-3-3. Additionally, in resting GRIP1-/- platelets, GPIbα and 14-3-3 have increased interaction compared to WT platelets. GRIP1 interactions with the GPIb-IX binding complex are necessary for normal platelet adhesion to a stimulated endothelium. [ABSTRACT FROM AUTHOR]

The article offers information on efficient coding principles in understanding the spontaneous activity in the LGN and V1 in the normative visual development. LGN/V1 spontaneous activity not only provides additional computational-level interpretation that can be understood through Marr's algorithmic level or Marr's computational level but also relates to the high-level coding objectives of V1. Also, natural visual environment techniques include sparse coding and independent component analysis.

Platelets are most recognized for their vital role as the cellular mediator of thrombosis, but platelets also have important immune functions. Platelets initiate and sustain vascular inflammation in many disease conditions, including arthritis, atherosclerosis, transplant rejection, and severe malaria. We now demonstrate that platelets express Τ cell costimulatory molecules, process and present Ag in MHC class I, and directly activate naive Τ cells in a platelet MHC class I-dependent manner. Using an experimental cerebral malaria mouse model, we also demonstrate that platelets present pathogen-derived Ag to promote Τ cell responses in vivo, and that platelets can be used in a cell-based vaccine model to induce protective immune responses. Our study demonstrates a novel Ag presentation role for platelets. [ABSTRACT FROM AUTHOR]

Background: UK-born infants of South Asian ethnic origin are known to have lower birthweights than their White British counterparts. When plotted on currently used birthweight charts they can be misclassified as small for gestational age. Similarly, large for gestational age infants can be missed. This has important clinical implications in their management. Objective: To create birthweight centile charts for the UK-born South Asian infants to identify true small and large for gestational age infants. Methods: A retrospective cross-sectional analysis of infants born 1 January 2003 to 31 December 2006 was undertaken. The birthweights of the South Asian and White British infants were compared. The LMS method was used to construct centile charts for the South Asian infants. Results: 24,274 White British and 7,190South Asian infants were included in the analysis. Overall, the South Asian males were 9-15% lighter than the White British males and the South Asian females were 9-13% lighter than the White British females. At term, the median birthweight for South Asian males was 329 g lower than that for White British males and for South Asian females 295 g less than the White British females. Conclusion: There are significant differences in the birthweights of White British and UK-born South Asian infants. Hence the standard birthweight centile charts which were designed using the birthweight data of White British infants appear to misclassify a proportion of South Asian infants. Use of ethnic specific birthweight charts would allow better detection of truly growth-restricted and macrosomic South Asian infants. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Wright JCE, Budd JLS, Field DJ, Draper ES. Epidemiology and outcome of congenital diaphragmatic hernia: a 9-year experience. Paediatric and Perinatal Epidemiology 2010. The aim of this study was to report the birth prevalence and short-term outcome of congenital diaphragmatic hernia (CDH) in a large geographically defined population, and to assess the feasibility of performing a randomised control trial (RCT) in this population. Data were collected on all cases of CDH reported to the East Midlands and South Yorkshire Congenital Anomalies Register between 1997 and 2005. A total of 194 cases of CDH were identified from 547 025 births; a birth prevalence of 3.5/10 000. Overall 1-year survival was 42%. In total, 69% of cases resulted in a live birth, of these 61% survived to 1 year; 73% were diagnosed antenatally and 22% postnatally, with 1-year survivals 30% and 71%, respectively. A total of 54% were isolated cases and 46% associated with another anomaly, with more live births (80% vs. 56%) and better 1-year survival (62% vs. 19%) with isolated CDH. Overall, only 83 babies were born alive with an isolated CDH: the only group suitable for inclusion in a RCT. In conclusion, given the small numbers of live isolated CDH cases it is impossible that any network alone would be able to perform a valid RCT of treatments, highlighting the need for collaborative international trials to address this complex condition. [ABSTRACT FROM AUTHOR]

Objective To see whether there was any difference in the effect of antenatal corticosteroids on neonatal outcomes according to different gestational ages at birth. Methods This was a prospective cohort study in a geographically defined population (Trent region, UK). All infants admitted for neonatal care, of 23-32 weeks' gestation, born to Trent resident mothers over the 15-year period between 1993 and 2007 were included. Antenatal corticosteroid treatment was given to pregnant women at risk of preterm birth. The primary outcome was survival until discharge from neonatal unit. Secondary outcomes included length of stay on the neonatal unit, duration of artificial respiratory support (mechanical ventilation and continuous positive airway pressure (CPAP)) and chronic lung disease (CLD). Results The overall mortality among babies born between 24 and 29 weeks with maternal steroids was lower (n=850 out of 4370; 19.4%) as compared to their counterparts whose mothers did not receive steroids (n=323 out of 920; 35.1%) The gestation-specific mortality figures (%) in the steroid treated group between 24 and 29 weeks' gestation were 61.5, 36.9, 28.5, 17.5, 10.2 and 5.1, respectively, and this was significantly lower than the group without steroid treatment. There was a 9.9% reduction in mortality among babies born at 23 weeks' gestation in the steroid treated group (n=81 out of 102; 79.4%) compared to the non-steroid group (n=75 out of 84; 89.3%), but this did not reach statistical significance (p=0.068). There was no significant effect of antenatal steroid treatment on length of stay, duration of respiratory support and CLD among infants who survived until discharge. There was no trend in survival in the two groups over the 15-year study period. Conclusions Antenatal corticosteroid treatment is associated with improved survival in babies born between 24 and 29 weeks' gestation. This, however, does not lead to any significant improvements in length of stay, duration of respiratory support and CLD among survivors. [ABSTRACT FROM AUTHOR]

Patterns of spontaneous activity in the developing retina, LGN, and cortex are necessary for the proper development of visual cortex. With these patterns intact, the primary visual cortices of many newborn animals develop properties similar to those of the adult cortex but without the training benefit of visual experience. Previous models have demonstrated how V1 responses can be initialized through mechanisms specific to development and prior to visual experience, such as using axonal guidance cues or relying on simple, pairwise correlations on spontaneous activity with additional developmental constraints. We argue that these spontaneous patterns may be better understood as part of an ''innate learning'' strategy, which learns similarly on activity both before and during visual experience. With an abstraction of spontaneous activity models, we show how the visual system may be able to bootstrap an efficient code for its natural environment prior to external visual experience, and we continue the same refinement strategy upon natural experience. The patterns are generated through simple, local interactions and contain the same relevant statistical properties of retinal waves and hypothesized waves in the LGN and V1. An efficient encoding of these patterns resembles a sparse coding of natural images by producing neurons with localized, oriented, bandpass structure-the same code found in early visual cortical cells. We address the relevance of higher-order statistical properties of spontaneous activity, how this relates to a system that may adapt similarly on activity prior to and during natural experience, and how these concepts ultimately relate to an efficient coding of our natural world. [ABSTRACT FROM AUTHOR]

Objective: To explore the differences in outcome of very preterm pregnancies between two geographically defined populations in Europe with similar socioeconomic characteristics and healthcare provision but different organisational arrangements for perinatal care. Design: Prospective cohort study. Setting: Nord Pas-de-Calais (NPC), France, and Trent, UK. Participants: All pregnancy outcomes 22+0 to 32+6 weeks' gestational age for resident mothers. Outcome measures: Mortality patterns (antepartum death, intrapartum death, labour ward death and neonatal unit death) among very preterm babies were analysed by region. Multinomial logistic regression was used to model regional differences for a variety of pregnancy outcomes and to adjust for regional differences in the organisation of perinatal care. Results: Delivery of very preterm infants was significantly higher in Trent compared with NPC (1.9% v 1.5% of all births, respectively (p<0.001 )). Stillbirth rate was significantly higher in NPC than in Trent (23.0%, 95% CI 20.0% to 26.5% v 14.4%, 95% CI 12.3% to 16.6%, respectively (p<0.001)) and survival to discharge was higher in Trent than in NPC (74.6%, 95% CI 71 .9% to 77.1% v 66.7%, 95% Cl 63.3% to 69.9%, respectively (p<0.001 )). Probability of intrapartum and labour ward death in NPC was more than five times higher than Trent (relative risk 5.3, 95% CI 2.2 to 13.1 (p<0.001)). Conclusion: The high rate of very preterm deliveries and the larger proportion of these infants recorded as live born in Trent appear to be the cause of the excess neonatal mortality seen in the routine statistics. Information about very preterm babies (not usually included in routine statistics) is vital to avoid inappropriate interpretation of international perinatal and infant data. This study highlights the importance of including deaths before transfer to neonatal care and emphasises the need to include the outcome of all pregnancies in a population in any comparative analysis. [ABSTRACT FROM AUTHOR]

Abstract: To account for the spatial and temporal response properties of the retina, a number of studies have proposed that these properties serve to “whiten” the visual input. In particular, it has been argued that the sensitivity of retinal ganglion cells is matched to the spatial frequency spectrum of natural scenes, resulting in a flattened or “whitened” response spectrum across a range of frequencies. However, we argue that there are two distinct hypotheses regarding the flattening of the spectrum. The decorrelation hypothesis proposes that the magnitude of each ganglion cell tuning curve rises with spatial frequency, resulting in a flattened response spectrum for natural scene stimuli. With appropriate sampling, this scheme allows neighboring neurons to be uncorrelated with each other. The response equalization hypothesis proposes that the overall response magnitude of neurons increases with spatial frequency. The proposed goal of this model is to allow neurons with different receptive field sizes to produce the same average response to natural scenes. The response equalization hypothesis proposes an explanation for the relative gain of different ganglion cells and we show that this proposal fits well with published data. We suggest that both hypotheses are important in understanding the tuning and sensitivity of ganglion cells. However, using a simulation, both models are shown to be insufficient to explain the center-surround receptive field organization of ganglion cells. We discuss other factors, including representational sparseness, which could be related to the goals of ganglion cell spatial processing. We suggest three constraints needed to describe the basic linear properties of P-type ganglion cells: decorrelation, response equalization, and a minimal wiring or minimal size constraint. [Copyright &y& Elsevier]

: ObjectiveTo record the maternal morbidity and pregnancy outcome in this cohort.: DesignRetrospective data collection from a prospectively defined cohort.: SettingThe 37 largest perinatal centres in the UK.: Population258 in utero transfers recorded during a three-month census (1/4/99–30/6/99).: MethodsA questionnaire regarding the outcome of each mother was sent to the perinatal centre and receiving hospital.: ResultsData were returned on 242/258 (94%) mothers. Fifty-eight percent were transferred out of their perinatal centre in preterm labour and 38% had coexisting disease necessitating early delivery. The median gestational age at transfer was 32 weeks (range 23–41). Sixty-one percent delivered at the receiving hospital; 12% were transferred on to a third hospital and 29% ultimately returned to deliver at the original perinatal centre. Fifty-two percent of mothers received postnatal care in hospitals other than those defined as a major perinatal centre. One mother delivered during transfer and a further nine within one hour of arrival. One mother received intensive care after delivery and later died, a further 7% required high dependency care postnatally. Data were available on 273/333 (82%) babies. The median gestational age at delivery was 34 weeks (range 24–41). Six infants were stillborn and 187/264 (71%) infants were admitted to a neonatal unit.: ConclusionsThis study has documented the maternal morbidity, potential risks and pregnancy outcome of a cohort of mothers transferred out of the largest perinatal centres in the UK because of a shortage of neonatal cots. A national standard for the delivery of high risk perinatal services is needed to uphold good clinical practice guidelines in the care of high risk mothers and their infants. [Copyright &y& Elsevier]

Extracorporeal membrane oxygenation (ECMO) is a supportive intensive-care technique used for babies with acute respiratory failure. We examined morbidity at age 4 years in surviving children recruited to the UK Collaborative ECMO Trial, and provide long-term data on ECMO support compared with contemporary conventional care. The neonatal ECMO policy resulted in improved survival and a favourable outcome. We therefore advocate the safety and efficacy of this intervention. [ABSTRACT FROM AUTHOR]

From the earliest stages of sensory processing, neurons show inherent non-linearities: the response to a complex stimulus is not a sum of the responses to a set of constituent basis stimuli. These non-linearities come in a number of forms and have been explained in terms of a number of functional goals. The family of spatial non-linearities have included interactions that occur both within and outside of the classical receptive field. They include, saturation, cross orientation inhibition, contrast normalization, end-stopping and a variety of non-classical effects. In addition, neurons show a number of facilitatory and invariance related effects such as those exhibited by complex cells (integration across position). Here, we describe an approach that attempts to explain many of the non-linearities under a single geometric framework. In line with Zetzsche and colleagues (e.g., Zetzsche et al., 1999) we propose that many of the principal non-linearities can be described by a geometry where the neural response space has a simple curvature. In this paper, we focus on the geometry that produces both increased selectivity (curving outward) and increased tolerance (curving inward). We demonstrate that overcomplete sparse coding with both low-dimensional synthetic data and high-dimensional natural scene data can result in curvature that is responsible for a variety of different known non-classical effects including end-stopping and gain control. We believe that this approach provides a more fundamental explanation of these non-linearities and does not require that one postulate a variety of explanations (e.g., that gain must be controlled or the ends of lines must be detected). In its standard form, sparse coding does not however, produce invariance/tolerance represented by inward curvature. We speculate on some of the requirements needed to produce such curvature. [ABSTRACT FROM AUTHOR]

Objective: This study explores the associations between lifestyle factors and late and moderate preterm birth (LMPT: 32(+0)-36(+6) weeks' gestation), a relatively under-researched group.Study Design: A population-based case-cohort study was undertaken involving 922 LMPT and 965 term (37+ weeks' gestation) singleton live and stillbirths born between 1 September 2009 and 31 December 2010 to women residing in Leicestershire and Nottinghamshire, UK. Poisson multivariable regression models were fitted to estimate relative risks (RR) of LMPT birth associated with maternal smoking, alcohol and recreational drug use, and diet.Results: Women who smoked during pregnancy were at 38% increased risk of LMPT birth compared with non-smokers (RR 1.38, 95% CI (1.04 to 1.84)). Low consumption of fruit and vegetables was associated with a 31% increased risk compared with those who reported eating higher consumption levels (RR 1.31 (1.03 to 1.66)). Women who did not have any aspects of a Mediterranean diet were nearly twice as likely to deliver LMPT compared with those whose diet included more Mediterranean characteristics (RR 1.81 (1.04 to 3.14)). Women who smoked and consumed low levels of fruit and vegetables (5% of women) were at particularly high risk (RR=1.81 (1.29 to 2.55)). There was no significant effect of alcohol or recreational drug use on LMPT birth.Conclusions: Smoking and poor diet during pregnancy, factors that strongly impact on very preterm birth, are also important at later gestations and experienced together are associated with an elevated rate of risk. Our findings suggest early cessation of smoking during pregnancy may be an effective strategy to reduce LMPT births. [ABSTRACT FROM AUTHOR]

Objective: To describe neonatal outcomes and explore variation in delivery of care for infants born late (34-36  weeks) and moderately (32-33 weeks) preterm (LMPT).Design/setting: Prospective population-based study comprising births in four major maternity centres, one midwifery-led unit and at home between September 2009 and December 2010. Data were obtained from maternal and neonatal records.Participants: All LMPT infants were eligible. A random sample of term-born infants (≥37 weeks) acted as controls.Outcome Measures: Neonatal unit (NNU) admission, respiratory and nutritional support, neonatal morbidities, investigations, length of stay and postnatal ward care were measured. Differences between centres were explored.Results: 1146 (83%) LMPT and 1258 (79% of eligible) term-born infants were recruited. LMPT infants were significantly more likely to receive resuscitation at birth (17.5% vs 7.4%), respiratory (11.8% vs 0.9%) and nutritional support (3.5% vs 0.3%) and were less likely to be fed breast milk (64.2% vs 72.2%) than term infants. For all interventions and morbidities, a gradient of increasing risk with decreasing gestation was evident. Although 60% of late preterm infants were never admitted to a NNU, 83% required medical input on postnatal wards. Clinical management differed significantly between services.Conclusions: LMPT infants place high demands on specialist neonatal services. A substantial amount of previously unreported specialist input is provided in postnatal wards, beyond normal newborn care. Appropriate expertise and planning of early care are essential if such infants are managed away from specialised neonatal settings. Further research is required to clarify optimal and cost-effective postnatal management for LMPT babies. [ABSTRACT FROM AUTHOR]

Background--Platelets have a pathophysiologic role in the ischemic microvascular environment of acute coronary syndromes. In comparison with platelet activation in normal healthy conditions, less attention is given to mechanisms of platelet activation in diseased states. Platelet function and mechanisms of activation in ischemic and reactive oxygen species-rich environments may not be the same as in normal healthy conditions. Extracellular regulated protein kinase 5 (ERK5) is a mitogen-activated protein kinase family member activated in hypoxic, reactive oxygen species-rich environments and in response to receptor-signaling mechanisms. Prior studies suggest a protective effect of ERK5 in endothelial and myocardial cells after ischemia. We present evidence that platelets express ERK5 and that platelet ERK5 has an adverse effect on platelet activation via selective receptor-dependent and receptor-independent reactive oxygen species-mediated mechanisms in ischemic myocardium. Methods and Results--Using isolated human platelets and a mouse model of myocardial infarction (MI), we found that platelet ERK5 is activated post-MI and that platelet-specific ERK5-/- mice have less platelet activation, reduced MI size, and improved post-MI heart function. Furthermore, the expression of downstream ERK5-regulated proteins is reduced in ERK5-/- platelets post-MI. Conclusions--ERK5 functions as a platelet activator in ischemic conditions, and platelet ERK5 maintains the expression of some platelet proteins after MI, leading to infarct expansion. This demonstrates that platelet function in normal healthy conditions is different from platelet function in chronic ischemic and inflammatory conditions. Platelet ERK5 may be a target for acute therapeutic intervention in the thrombotic and inflammatory post-MI environment. [ABSTRACT FROM AUTHOR]

Objective There is a paucity of data relating to neurodevelopmental outcomes in infants born late and moderately preterm (LMPT; 32+0-36+6 weeks). This paper present the results of a prospective, population-based study of 2-year outcomes following LMPT birth. Design 1130 LMPT and 1255 term-born children were recruited at birth. At 2 years corrected age, parents completed a questionnaire to assess neurosensory (vision, hearing, motor) impairments and the Parent Report of Children's Abilities-Revised to identify cognitive impairment. Relative risks for adverse outcomes were adjusted for sex, socio-economic status and small for gestational age, and weighted to account for over-sampling of term-born multiples. Risk factors for cognitive impairment were explored using multivariable analyses. Results Parents of 638 (57%) LMPT infants and 765 (62%) controls completed questionnaires. Among LMPT infants, 1.6% had neurosensory impairment compared with 0.3% of controls (RR 4.89, 95% CI 1.07 to 22.25). Cognitive impairments were the most common adverse outcome: LMPT 6.3%; controls 2.4% (RR 2.09, 95% CI 1.19 to 3.64). LMPT infants were at twice the risk for neurodevelopmental disability (RR 2.19, 95% CI 1.27 to 3.75). Independent risk factors for cognitive impairment in LMPT infants were male sex, socio-economic disadvantage, non-white ethnicity, preeclampsia and not receiving breast milk at discharge. Conclusions Compared with term-born peers, LMPT infants are at double the risk for neurodevelopmental disability at 2 years of age, with the majority of impairments observed in the cognitive domain. Male sex, socio-economic disadvantage and preeclampsia are independent predictors of low cognitive scores following LMPT birth. [ABSTRACT FROM AUTHOR]

Background Understanding length of stay for babies in neonatal care is vital for planning services and for counselling parents. While previous work has focused on the length of stay of babies who survive to discharge, when investigating resource use within neonatal care, it is important to also incorporate information on those babies who die while in care. We present an analysis using competing risks methodology which allows the simultaneous modelling of babies who die in neonatal care and those who survive to discharge. Methods Data were obtained on 2723 babies born at 24-28 weeks gestational age in 2006-10 and admitted to neonatal care. Death and discharge alive are two mutually exclusive events and can be treated as competing risks. A flexible parametric modelling approach was used to analyse these two competing events and obtain estimates of the absolute probabilities of death or discharge. Results The absolute probabilities of death or discharge are presented in graphical form showing the cause-specific cumulative incidence over time by gender, gestational age and birthweight. The discharge of babies alive generally occurred over a longer time period for babies of lower gestational age and smaller birthweight than for bigger babies. Conclusion This study has presented a useful statistical method for modelling the length of stay where there are significant rates of in-unit mortality. In health care systems that are increasingly focusing on costs and resource planning, it is essential to consider not only length of stay of survivors but also for those patients who die before discharge. [ABSTRACT FROM AUTHOR]

Aims Dried blood spots ( DBS) alongside micro-analytical techniques are a potential solution to the challenges of performing pharmacokinetic ( PK) studies in children. However, DBS methods have received little formal evaluation in clinical settings relevant to children. The aim of the present study was to determine a PK model for caffeine using a ' DBS/microvolume platform' in preterm infants. Methods DBS samples were collected prospectively from premature babies receiving caffeine for treatment of apnoea of prematurity. A non-linear mixed effects approach was used to develop a population PK model from measured DBS caffeine concentrations. Caffeine PK parameter estimates based on DBS data were then compared with plasma estimates for agreement. Results Three hundred and thirty-eight DBS cards for caffeine measurement were collected from 67 preterm infants (birth weight 0.6-2.11 kg). 88% of cards obtained were of acceptable quality and no child had more than 10 DBS samples or more than 0.5 ml of blood taken over the study period. There was good agreement between PK parameters estimated using caffeine concentrations from DBS samples ( CL = 7.3 ml h−1 kg−1; V = 593 ml kg−1; t1/2 = 57 h) and historical caffeine PK parameter estimates based on plasma samples ( CL = 4.9-7.9 ml h−1 kg−1; V = 640-970 ml kg−1; t1/2 = 101-144 h). We also found that changes in blood haematocrit may significantly confound estimates of caffeine PK parameters based on DBS data. Conclusions This study demonstrates that DBS methods can be applied to PK studies in a vulnerable population group and are a practical alternative to wet matrix sampling techniques. [ABSTRACT FROM AUTHOR]

Objective To assess the care given to the babies born at the threshold of viability over the last 20 years using regional and national data. Design Population-based retrospective study. Setting Former 'Trent' health region. Participants Babies born between 1 January 1991 and 31 December 2010 at 22+0 to 25+6 weeks gestational age. Main outcome measure Survival and use of respiratory support. Methods Data of all babies born between 1 January 1991 and 31 December 2010 with a gestational age of 22+0 to 25+6 weeks and admitted to a neonatal unit were extracted from The Neonatal Survey. Use of respiratory support in terms of ventilation and continuous positive airway pressure (CPAP) for this group of babies was calculated as a proportion of the total used by the whole neonatal intensive care population within the defined study area. Results The proportion of babies surviving to discharge increased significantly over time in those born at 24 and 25 weeks ( p<0.01) but failed to achieve statistical significance for those at 23 weeks ( p=0.08). No babies born at 22 weeks survived. The babies born at 22-25 weeks accounted for 26.3% of all ventilation and 21.5% of CPAP given. Conclusion Our work concurs with the current UK guidelines. There could be advantages in focusing the care of babies born at 23 weeks to a small number of intensive care units to allow specialist expertise to develop in all aspects of the management of these babies. However, focusing care will not necessarily improve survival or reduce morbidity. [ABSTRACT FROM AUTHOR]

The authors tested the hypothesis that the birth prevalence of gastroschisis is positively associated with use of recreational drugs in early pregnancy. A matched case-control study was carried out in three regions of the United Kingdom over the period January 2001 through August 2003. For each case, three liveborn controls were matched by initial intended place of delivery, region, and maternal age. Maternal hair analysis provided independent verification of recreational drug use. Conditional logistic regression was used to estimate mutually adjusted odds ratios. Estimates were revised using data from hair analysis. Statistically significant adjusted odds ratios for gastroschisis were associated with first-trimester use of 1) any recreational drug (odds ratio (OR) = 2.2, 95% confidence interval (CI): 1.2, 4.3) and 2) vasoconstrictive recreational drugs (defined as cocaine, amphetamines, and ecstasy) (OR = 3.3, 95% CI: 1.0, 10.5). Other significant exposures included aspirin use (OR = 20.4, 95% CI: 2.2, 191.5), cigarette smoking (OR = 1.7, 95% CI: 1.1, 2.6), and prior history of gynecologic infection/disease (OR = 2.6, 95% CI: 1.2, 5.6). Recreational drug use is a significant risk factor for gastroschisis and is one of a constellation of potentially preventable exposures which include cigarette smoking, aspirin use, and history of gynecologic infection/disease. Maternal hair analysis proved an acceptable and valuable method of independently verifying recreational drug use. [ABSTRACT FROM PUBLISHER]

Objective: To explore the relationship between infection and socioeconomic deprivation among mothers of spontaneous very preterm infants to contribute to the understanding of the deprivation gap in the incidence of very preterm birth. Methods: We used comprehensive data from a large retrospective study of very preterm birth in a U. K. health region (representing approximately 1 in 12 U.K. births) between 1994 and 2005. We report the relationship between fetal or maternal infection before birth and deprivation quintile of all singleton live births at 22 0/7 to 32 6/7 weeks of gestation associated with spontaneous onset of labor. Results: Overall, 24% of the 4,987 spontaneous very preterm singleton births had recorded evidence of maternal or fetal infection. Rates of infection increased significantly with increasing deprivation. Spontaneous very preterm births to mothers from the most deprived quintile were at 43% increased odds of being associated with infection compared with those from the least deprived quintile (odds ratio 1.43, 95% confidence interval 1.13-1.80) after adjusting for gestation, year of birth, and mother's age. Conclusion: Spontaneous very preterm births to mothers from more deprived areas are more likely to be associated with infection before birth. Level Of Evidence: II. [ABSTRACT FROM AUTHOR]

The article studies the relationship between infection and socioeconomic deprivation among mothers of spontaneous very preterm infants. The authors found that rates of infection increased significantly with increasing deprivation. The authors concluded that spontaneous very preterm births to mothers from deprived areas are more likely to be associated with infection before birth.

BACKGROUND. It is known that extremely premature infants do less well than more mature infants, and this fact has led some countries to adopt a "cutoff for viability" using birth weight or gestation. Infants affected by intrauterine growth retardation are at additional risk of poor outcome. There are few data to inform decisions about viability and (dis)continuation of intensive care when both extreme pre-maturity and severe growth retardation are present. OBJECTIVE. We focused on (1) premature infants affected by marked intrauterine growth retardation to determine if there was a cutoff weight centile below which the mortality sharply increased and (2) the short-term outcome of extremely premature and growth-retarded infants to determine a cutoff for viability. METHODS. We evaluated preterm infants of 22-32 weeks' gestation if they were alive at the onset of labor and born to European mothers resident in the Trent (United Kingdom) health region between 1994 and 2003. Infants were categorized into 6 weight centiles, and infants in each category were assessed for survival to discharge from the neonatal unit, duration of respiratory support, length of stay in the neonatal unit, and the age at death in nonsurvivors. RESULTS. We identified a total of 8228 infants who met the study criteria. Of these, 4448 infants were male, 6194 were front singleton pregnancies, and 2887 were born at ≤28 completed weeks of gestation. Survival to discharge was markedly reduced in the infants born at ≤28 weeks of gestation with a birth weight less than the 2nd centile. Stillbirth was inversely related to birth weight centile in infants born before 29 weeks of gestation. CONCLUSIONS. The survival for infants born at ≤28 weeks' gestation and having a birth weight in less than the 2nd centile is poor, and consideration should be given to modifying their management. [ABSTRACT FROM AUTHOR]

Summary: The growth of the eye, unlike other parts of the body, is not ballistic. It is guided by visual feedback with the eventual aim being optimal focus of the retinal image or emmetropization . It has been shown in animal models that interference with the quality of the retinal image leads to a disruption to the normal growth pattern, resulting in the development of refractive errors and defocused retinal images . While it is clear that retinal images rich in pattern information are needed to control eye growth, it is unclear what particular aspect of image structure is relevant. Retinal images comprise a range of spatial frequencies at different absolute and relative contrasts and in different degrees of spatial alignment. Here we show, by using synthetic images, that it is not the local edge structure produced by relative spatial frequency alignments within an image but rather the spatial frequency composition per se that is used to regulate the growth of the eye. Furthermore, it is the absolute energy at high spatial frequencies regardless of the spectral slope that is most effective. Neither result would be expected from currently accepted ideas of how human observers judge the degree of image “blur” in a scene where both phase alignments and the relative energy distribution across spatial frequency (i.e., spectral slope) are important. [Copyright &y& Elsevier]

Objective. To determine the risk of chronic lung disease (CLD) in small for gestational age (SGA) preterm infants in comparison to appropriately grown and large for gestational age (LGA) infants. Methods. Observational study derived from a geographically defined population (Trent Health Region, United Kingdom). All preterm infants of ≤32 completed weeks' gestation born to Trent resident mothers admitted to neonatal units between 1995 and 1999 (inclusive) were included. Birth weight percentiles were created for the whole population, and infants were classified as SGA infants (if <10th percentile), appropriately grown (if between 25th and 75th percentiles--reference group), and LGA infants (if ≥90th centile). Both mortality and CLD rates (using both 28 days' and 36 weeks' postmenstrual age [PMA] definitions) were determined for these groups of infants. Results. Four thousand fifty-one preterm infants ≤<32 weeks' gestation were identified. SGA infants showed higher mortality before 28 days' postnatal age and 36 weeks' PMA as compared with reference group infants (odds ratio [OR]: 2.01, 95% confidence interval [CI]: 1.49-2.72; and OR: 2.00, 95% CI: 1.49-2.69), respectively. SGA infants showed a significantly greater risk of developing CLD, both at 28 days' and 36 weeks' PMA as compared with the reference group infants (OR: 1.34, 95% CI: 1.03-1.74; and OR: 1.87, 95% CI: 1.39-2.51), respectively. LGA infants showed a trend toward a reduced incidence of CLD in comparison to the reference group, which was statistically significant for the 36 weeks' definition (OR: 0.76 -28 weeks, 95% CI: 0.57-1.01; and OR: 0.55-36 weeks, 95% CI: 0.37-0.81). Conclusions. Fetal growth seems to influence mortality in general and morbidity, attributable to CLD, in particular in preterm infants. SGA preterm infants are at higher risk of death before 28 days' and 36 weeks' PMA and CLD by both definitions. LGA infants show reduced risk of CLD. Pediatrics 2003;111:483-487; prematurity; ch [ABSTRACT FROM AUTHOR]

The article discusses the cohort study which examines the adverse effects on infants with moderate or late and early term weeks of gestational age. The study examines the effects of gestation on the health outcomes at three and five years, which measures the hospital admissions, growth, and wheezing. Result shows that the infants with less gestation in hospital admissions has the poor outcome and infants that were born late has worst adverse health outcome.

The article presents a study which examines the socioeconomic variations in the result of pregnancies affected with congenital anomalies with a poor prognosis. The study has audited all registered cases of nine selected congenital anomalies with poor prognostic results in Great Britain. It reveals that antenatal detection has made a wide socioeconomic inequalities in liveborn infants with an anomaly and subsequent neonatal mortality.

Presents a letter to the editor regarding tables published in a 1999 issue of the "British Medical Journal" and discussed efforts to predict the survival of premature infants.

The article focuses on a study which investigated the association between neonatal death and socioeconomic inequalities in neonatal mortality. The study included all neonatal deaths of singleton infants in England, who were born between January 1, 1997 and December 31, 2007. It discovered that preterm birth and congenital anomalies accounted for nearly 80 percent of the deprivation gap in all-cause neonatal mortality.

The article offers information on a study which determined evidence of socioeonomic inequalities in the survival and provision of neonatal care among very preterm infants. Data was collected from all infants born between January 1, 1998 and December 1, 2007 in the former Trent health region in England. The researchers measured the survival to discharge from neonatal care per 1000 total births and per 1000 very preterm births. An overview of the research findings is offered.