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Objectives: To assess the prevalence of positive screens using the Modified Checklist for Autism in Toddlers (M-CHAT) questionnaire and follow-up interview in late and moderately preterm (LMPT; 32-36 weeks) infants and term-born controls., Study Design: Population-based prospective cohort study of 1130 LMPT and 1255 term-born infants. Parents completed the M-CHAT questionnaire at 2-years corrected age. Parents of infants with positive questionnaire screens were followed up with a telephone interview to clarify failed items. The M-CHAT questionnaire was re-scored, and infants were classified as true or false positives. Neurosensory, cognitive, and behavioral outcomes were assessed using parent report., Results: Parents of 634 (57%) LMPT and 761 (62%) term-born infants completed the M-CHAT questionnaire. LMPT infants had significantly higher risk of a positive questionnaire screen compared with controls (14.5% vs 9.2%; relative risk [RR] 1.58; 95% CI 1.18, 2.11). After follow-up, significantly more LMPT infants than controls had a true positive screen (2.4% vs 0.5%; RR 4.52; 1.51, 13.56). This remained significant after excluding infants with neurosensory impairments (2.0% vs 0.5%; RR 3.67; 1.19, 11.3)., Conclusions: LMPT infants are at significantly increased risk for positive autistic screen. An M-CHAT follow-up interview is essential as screening for autism spectrum disorders is especially confounded in preterm populations. Infants with false positive screens are at risk for cognitive and behavioral problems., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Edges in natural scenes can result from a number of different causes. In this study, we investigated the statistical differences between edges arising from occlusions and nonocclusions (reflectance differences, surface change, and cast shadows). In the first experiment, edges in natural scenes were identified using the Canny edge detection algorithm. Observers then classified these edges as either an occlusion edge (one region of an image occluding another) or a nonocclusion edge. The nonocclusion edges were further subclassified as due to a reflectance difference, a surface change, or a cast shadow. We found that edges were equally likely to be classified as occlusion or nonocclusion edges. Of the nonocclusion edges, approximately 33% were classified as reflectance changes, 9% as cast shadows, and 58% as surface changes. We also analyzed local statistical properties like contrast, average edge profile, and slope of the edges. We found significant differences between the contrast values for each category. Based on the local contrast statistics, we developed a maximum likelihood classifier to label occlusion and nonocclusion edges. An 80%-20% cross validation demonstrated that the human classification could be predicted with 83% accuracy. Overall, our results suggest that for many edges in natural scenes, there exists local statistical information regarding the cause of the edge. We believe that this information can potentially be used by the early visual system to begin the process of segregating objects from their backgrounds., (© 2014 ARVO.)

Studies of visual masking have provided a wide range of important insights into the processes involved in visual coding. However, very few of these studies have employed natural scenes as masks. Little is known on how the particular features found in natural scenes affect visual detection thresholds and how the results obtained using unnatural masks relate to the results obtained using natural masks. To address this issue, this paper describes a psychophysical study designed to obtain local contrast detection thresholds for a database of natural images. Via a three-alternative forced-choice experiment, we measured thresholds for detecting 3.7 cycles/° vertically oriented log-Gabor noise targets placed within an 85 × 85-pixels patch (1.9° patch) drawn from 30 natural images from the CSIQ image database (Larson & Chandler, Journal of Electronic Imaging, 2010). Thus, for each image, we obtained a masking map in which each entry in the map denotes the root mean squared contrast threshold for detecting the log-Gabor noise target at the corresponding spatial location in the image. From qualitative observations we found that detection thresholds were affected by several patch properties such as visual complexity, fineness of textures, sharpness, and overall luminance. Our quantitative analysis shows that except for the sharpness measure (correlation coefficient of 0.7), the other tested low-level mask features showed a weak correlation (correlation coefficients less than or equal to 0.52) with the detection thresholds. Furthermore, we evaluated the performance of a computational contrast gain control model that performed fairly well with an average correlation coefficient of 0.79 in predicting the local contrast detection thresholds. We also describe specific choices of parameters for the gain control model. The objective of this database is to provide researchers with a large ground-truth dataset in order to further investigate the properties of the human visual system using natural masks., (© 2014 ARVO.)

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.

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.

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., (© 2010 Blackwell Publishing Ltd.)

Objective: To investigate time trends in socioeconomic inequalities in cause specific neonatal mortality in order to assess changing patterns in mortality due to different causes, particularly prematurity, and identify key areas of focus for future intervention strategies., Design: Retrospective cohort study., Setting: England., Participants: All neonatal deaths in singleton infants born between 1 January 1997 and 31 December 2007., Main Outcome Measure: Cause specific neonatal mortality per 10 000 births by deprivation tenth (deprivation measured with UK index of multiple deprivation 2004 at super output area level)., Results: 18 524 neonatal deaths occurred in singleton infants born in the 11 year study period. Neonatal mortality fell between 1997-9 and 2006-7 (from 31.4 to 25.1 per 10 000 live births). The relative deprivation gap (ratio of mortality in the most deprived tenth compared with the least deprived tenth) increased from 2.08 in 1997-9 to 2.68 in 2003-5, before a fall to 2.35 in 2006-7. The most common causes of death were immaturity and congenital anomalies. Mortality due to immaturity before 24 weeks' gestation did not decrease over time and showed the widest relative deprivation gap (2.98 in 1997-9; 4.14 in 2003-5; 3.16 in 2006-7). Mortality rates for all other causes fell over time. For congenital anomalies, immaturity, and accidents and other specific causes, the relative deprivation gap widened between 1997-9 and 2003-5, before a slight fall in 2006-7. For intrapartum events and sudden infant deaths (only 13.5% of deaths) the relative deprivation gap narrowed slightly., Conclusions: Almost 80% of the relative deprivation gap in all cause mortality was explained by premature birth and congenital anomalies. To reduce socioeconomic inequalities in mortality, a change in focus is needed to concentrate on these two influential causes of death. Understanding the link between deprivation and preterm birth should be a major research priority to identify interventions to reduce preterm birth.

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.

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 v 15/81 (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.

One of the fundamental unanswered questions in visual science regards how the visual system attains a high degree of invariance (e.g., position invariance, size invariance, etc.) while maintaining high selectivity. Although a variety of theories have been proposed, most are distinguished by the degree to which information is maintained or discarded. To test whether information is maintained or discarded, we have compared the ability of the human visual system to detect a variety of wide-field changes to natural images. The changes range from simple affine transforms and intensity changes common to our visual experience to random changes as represented by the addition of white noise. When sensitivity was measured in terms of the Euclidean distance (L(2) norm) between image pairs, we found that observers were an order of magnitude less sensitive to the geometric transformations than to added noise. A control experiment ruled out that the sensitivity difference was caused by the statistical properties of the image difference created by this transformation. We argue that the remarkable difference in sensitivity relates to the processes used by the visual system to build invariant relationships and leads to the unusual result that observers are least sensitive to those transformations most commonly experienced in the natural world.

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% CI 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.

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 non-representational (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.

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.

Background: It is likely that the imbalance between the pro- and anti-inflammatory cytokines will determine the outcome in infants with severe respiratory failure receiving extracorporeal membrane oxygenation (ECMO)., Aims: We determined if there was an imbalance between pro- and anti-inflammatory cytokines in serial bronchoalveolar lavage (BAL) fluid obtained from survivors and non-survivors of ECMO., Methods: We therefore measured the cellular changes and the molar ratios of pro-inflammatory and anti-inflammatory cytokines in serial BAL fluid obtained from survivors and non-survivors of ECMO. Fifteen infants surviving ECMO (median age 1 day, range 1-120) and 7 who did not (28 days, range 1-402) were studied., Results: In the lungs of survivors, the increased proportion of airway neutrophils at presentation decreased with time and was matched by a parallel increase in percent alveolar macrophages as the infants' condition improved. The pro- and anti-inflammatory pulmonary cytokine ratios were static in the survivors. In the non-survivors, the ratio of tumour necrosis factor-alpha (TNF-alpha) against soluble TNF-receptor 1 (sTNF-R1) and soluble TNF receptor 2 (sTNF-R2) was increased at days 2-3 when compared to the survivors, but the molar ratio interleukin-1beta (IL-1beta)/soluble IL-1 receptor antagonist (sIL-1RA) was largely undetectable due to undetectable IL-1beta., Conclusions: These data suggest that the infants who survive ECMO resolve their pulmonary inflammation and that in non-survivors the ratio of TNF-alpha against its receptor antagonists is increased and is associated with a poor outcome. Furthermore, this group of infants were unable to produce significant concentrations of IL-1beta.

Objective: To record the maternal morbidity and pregnancy outcome in this cohort., Design: Retrospective data collection from a prospectively defined cohort., Setting: The 37 largest perinatal centres in the UK., Population: 258 in utero transfers recorded during a three-month census (1/4/99-30/6/99)., Methods: A questionnaire regarding the outcome of each mother was sent to the perinatal centre and receiving hospital., Results: Data 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., Conclusions: This 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.