A composite neonatal adverse outcome indicator using population-based data: an update.

INTRODUCTION: Severe morbidity rates in neonates can be estimated using diagnosis and procedure coding in linked routinely collected retrospective data as a cost-effective way to monitor quality and safety of perinatal services. Coding changes necessitate an update to the previously published composite neonatal adverse outcome indicator for identifying infants with severe or medically significant morbidity. OBJECTIVES: To update the neonatal adverse outcome indicator for identifying neonates with severe or medically significant morbidity, and to investigate the validity of the updated indicator. METHODS: We audited diagnosis and procedure codes and used expert clinician input to update the components of the indicator. We used linked birth, hospital and death data for neonates born alive at 24 weeks or more in New South Wales, Australia (2002-2014) to describe the incidence of neonatal morbidity and assess the validity of the updated indicator. RESULTS: The updated indicator included 28 diagnostic and procedure components. In our population of 1,194,681 live births, 5.44% neonates had some form of morbidity. The rate of morbidity was greater for higher-risk pregnancies and was lowest for those born at 39-40 weeks' gestation. Incidence increased over the study period for overall neonatal morbidity, and for individual components: intravenous infusion, respiratory diagnoses, and non-invasive ventilation. Severe or medically significant neonatal morbidity was associated with double the risk of hospital readmission and 10 times the risk of death within the first year of life. CONCLUSION: The updated composite indicator has maintained concurrent and predictive validity and is a standardised, economic way to measure neonatal morbidity when using population-based data. Changes within individual components should be considered when examining longitudinal data.

Improving Terrestrial Squamate Surveys with Camera-Trap Programming and Hardware Modifications.

Camera-traps are used widely around the world to census a range of vertebrate fauna, particularly mammals but also other groups including birds, as well as snakes and lizards (squamates). In an attempt to improve the reliability of camera-traps for censusing squamates, we examined whether programming options involving time lapse capture of images increased detections. This was compared to detections by camera-traps set to trigger by the standard passive infrared sensor setting (PIR), and camera-traps set to take images using time lapse in combination with PIR. We also examined the effect of camera trap focal length on the ability to tell different species of small squamate apart. In a series of side-by-side field comparisons, camera-traps programmed to take images at standard intervals, as well as through routine triggering of the PIR, captured more images of squamates than camera-traps using the PIR sensor setting alone or time lapse alone. Similarly, camera traps with their lens focal length set at closer distances improved our ability to discriminate species of small squamates. With these minor alterations to camera-trap programming and hardware, the quantity and quality of squamate detections was markedly better. These gains provide a platform for exploring other aspects of camera-trapping for squamates that might to lead to even greater survey advances, bridging the gap in knowledge of this otherwise poorly known faunal group.

Cortex dynamically modulates responses of thalamic relay neurons through prolonged circuit-level disinhibition in rat thalamus in vivo.

Cortex actively modulates the responses of thalamic relay neurons through corticothalamic (CT) projections. Here we investigated the temporal precision of CT modulation on sensory responses of relay neurons in rat ventral posterior medial thalamus (VPM) to direction-specific whisker stimuli. CT feedback levels were either augmented by cortical electrical microstimulation or depressed by cortical application of muscimol, a potent agonist of γ-aminobutyric acid A-type (GABAA) receptors. To evaluate the temporal specificity of CT influence, we compared the early (3-10 ms after stimulus onset) and late (10-100 ms) response components of VPM single units to whisker deflections in preferred or nonpreferred directions before and after altering CT feedback levels under urethane anesthesia. The data showed that cortical feedback most strongly affected the late responses of single VPM units to whisker stimulation. That is, cortical stimulation consistently increased the late responses of VPM units in the corresponding (homologous) barreloids to the stimulus direction preferred by neurons in the cortical locus stimulated. However, cortical stimulation could either increase or decrease the early response, depending on whether or not cortical and thalamic loci were tuned to the same direction. Such bidirectional regulation of the early and late VPM responses is consistent with a mechanism of circuit-level disinhibition in vivo. The results support the theory that CT feedback on thalamic sensory responses is mediated by a time-dependent shift of the excitation-inhibition balance in the thalamo-cortico-thalamic loop, such as would occur during sensory feature integration, plasticity, and learning in the awake state.

Heated birthing pools as a source of Legionnaires' disease.

In June 2014 Public Health England confirmed a case of Legionnaires' disease (LD) in a neonate following birth at home in a hired birthing pool incorporating a heater and a recirculation pump which had been filled in advance of labour. The case triggered a public health investigation and a microbiological survey of an additional ten heated birthing pools hired or recently hired to the general public across England. The birthing pool used by the parent of the confirmed case was identified as the source of the neonate's infection following detection of Legionella pneumophila ST48 in both patient and environmental samples. Legionella species were detected by quantitative polymerase chain reaction but not culture in a further three pools together with other opportunistic pathogens identified by culture and matrix-assisted laser desorption ionization-time of flight (MALDI-ToF) mass spectrometry. A Patient Safety Alert from NHS England and Public Health England was issued stating that heated birthing pools filled in advance of labour should not be used for home births. This recommendation remains in place. This investigation in conjunction with other recent reports has highlighted a lack of awareness regarding the microbiological safety of heated birthing pools and their potential to be a source of LD and other opportunistic infections. Furthermore, the investigation raised important considerations with regards to microbiological sampling and testing in such incidents. Public health authorities and clinicians should consider LD in the differential diagnosis of severe respiratory infection in neonates within 14 days of a water birth.

Public health response to two incidents of confirmed MERS-CoV cases travelling on flights through London Heathrow Airport in 2014 ­ lessons learnt.

In May 2014, Public Health England was alerted to two separate laboratory-confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection who transited through London Heathrow Airport while symptomatic on flights from Saudi Arabia to the United States of America. We present the rationale for the public health response to both incidents, and report results of contact tracing. Following a risk assessment, passengers seated two seats around the cases were prioritised for contact tracing and a proactive media approach was used to alert all passengers on the planes of their possible exposure in both incidents. In total, 64 United Kingdom (UK) residents were successfully contacted, 14 of whom were sat in the priority area two seats all around the case(s). Five passengers reported respiratory symptoms within 14 days of the flight, but all tested were negative for MERS-CoV. Details of non-UK residents were passed on to relevant World Health Organization International Health Regulation focal points for follow-up, and no further cases were reported back. Different approaches were used to manage contact tracing for each flight due to variations in the quality and timeliness of the passenger contact information provided by the airlines involved. No evidence of symptomatic onward transmission was found.

Case of Legionnaires disease in a neonate following a home birth in a heated birthing pool, England, June 2014.

Public Health England was notified of Legionnaires' disease in a neonate following a home birth in a heated birthing pool filled from the domestic hot water supply two weeks earlier. We describe the incident, sampling results, and public health actions. It is recommended that heated birthing pools should not be used for home births. Neonates developing pneumonia within 14 days of labour or birth in any birthing pool should be tested for Legionnaires' disease.

Voltage-sensitive dye imaging reveals shifting spatiotemporal spread of whisker-induced activity in rat barrel cortex.

In rats, navigating through an environment requires continuous information about objects near the head. Sensory information such as object location and surface texture are encoded by spike firing patterns of single neurons within rat barrel cortex. Although there are many studies using single-unit electrophysiology, much less is known regarding the spatiotemporal pattern of activity of populations of neurons in barrel cortex in response to whisker stimulation. To examine cortical response at the population level, we used voltage-sensitive dye (VSD) imaging to examine ensemble spatiotemporal dynamics of barrel cortex in response to stimulation of single or two adjacent whiskers in urethane-anesthetized rats. Single whisker stimulation produced a poststimulus fluorescence response peak within 12-16 ms in the barrel corresponding to the stimulated whisker (principal whisker). This fluorescence subsequently propagated throughout the barrel field, spreading anisotropically preferentially along a barrel row. After paired whisker stimulation, the VSD signal showed sublinear summation (less than the sum of 2 single whisker stimulations), consistent with previous electrophysiological and imaging studies. Surprisingly, we observed a spatial shift in the center of activation occurring over a 10- to 20-ms period with shift magnitudes of 1-2 barrels. This shift occurred predominantly in the posteromedial direction within the barrel field. Our data thus reveal previously unreported spatiotemporal patterns of barrel cortex activation. We suggest that this nontopographical shift is consistent with known functional and anatomic asymmetries in barrel cortex and that it may provide an important insight for understanding barrel field activation during whisking behavior.

Landscape genetics of an early successional specialist in a disturbance-prone environment.

Species that specialize in disturbed habitats may have considerably different dispersal strategies than those adapted to more stable environments. However, little is known of the dispersal patterns and population structure of such species. This information is important for conservation because many postfire specialists are at risk from anthropogenic changes to natural disturbance regimes. We used microsatellite markers to assess the effect of landscape variation and recent disturbance history on dispersal by a small mammal species that occupies the early seral stage of vegetation regeneration in burnt environments. We predicted that a postfire specialist would be able to disperse over multiple habitat types (generalist) and not exhibit sex-biased dispersal, as such strategies should enable effective colonization of spatially and temporally variable habitat. We found significant differentiation between sites that fitted an isolation-by-distance pattern and spatial autocorrelation of multilocus genotypes to a distance of 2-3 km. There was no consistent genetic evidence for sex-biased dispersal. We tested the influence of different habitat- and fire-specific landscape resistance scenarios on genetic distance between individuals and found a significant effect of fire. Our genetic data supported recently burned vegetation having greater conductance for gene flow than unburnt habitat, but variation in habitat quality between vegetation types and occupied patches had no effect on gene flow. Postfire specialists must evolve an effective dispersal ability to move over distances that would ensure access to early successional stage vegetation. Natural disturbance and natural heterogeneity may therefore not influence population genetic structure as negatively as expected.

Neonatal sensory deprivation and the development of cortical function: unilateral and bilateral sensory deprivation result in different functional outcomes.

The normal development of sensory perception in mammals depends on appropriate sensory experience between birth and maturity. Numerous reports have shown that trimming some or all of the large mystacial vibrissa (whiskers) on one side of the face after birth has a detrimental effect on the maturation of cortical function. The objective of the present study was to understand the differences that occur after unilateral whisker trimming compared with those that occur after bilateral deprivation. Physiological deficits produced by bilateral trimming (BD) of all whiskers for 2 mo after birth were compared with the deficits produced by unilateral trimming (UD) for the same period of time using extracellular recording under urethan anesthesia from single cells in rat barrel cortex. Fast spiking (FSUs) and regular spiking (RSUs) units were separated and their properties compared in four subregions identified by histological reconstructions of the electrode penetrations, namely: layer IV barrel and septum, and layers II/III above a barrel and above a septum. UD upregulated responses in layer IV septa and in layers II/III above septa and perturbed the timing of responses to whisker stimuli. After BD, nearly all responses were decreased, and poststimulus latencies were increased. Circuit changes are proposed as an argument for how inputs arising from the spared whiskers project to the undeprived cortex and, via commissural fibers, could upregulate septal responses after UD. Following BD, more global neural deficits create a signature difference in the outcome of UD and BD in rat barrel cortex.

Prenatal exposure to benzo(a)pyrene impairs later-life cortical neuronal function.

Prenatal exposure to environmental contaminants, such as benzo(a)pyrene [B(a)P] has been shown to impair brain development. The overarching hypothesis of our work is that glutamate receptor subunit expression is crucial for cortical evoked responses and that prenatal B(a)P exposure modulates the temporal developmental expression of glutamatergic receptor subunits in the somatosensory cortex. To characterize prenatal B(a)P exposure on the development of cortical function, pregnant Long Evans rats were exposed to low-level B(a)P (300 microg/kg BW) by oral gavage on gestational days 14-17. At this exposure dose, there was no significant effect of B(a)P on (1) the number of pups born per litter, (2) the pre-weaning growth curves and (3) initial and final brain to body weight ratios. Control and B(a)P-exposed offspring were profiled for B(a)P metabolites in plasma and whole brain during the pre-weaning period. No detectable levels of metabolites were found in the control offspring. However, a time-dependent decrease in total metabolite concentration was observed in B(a)P-exposed offspring. On PND100-120, cerebrocortical mRNA expression was determined for the glutamatergic NMDA receptor subunit (NR2B) in control and B(a)P-exposed offspring. Neural activity was also recorded from neurons in primary somatic sensory (barrel) cortex. Semiquantitative PCR from B(a)P-exposed offspring revealed a significant 50% reduction in NR2B mRNA expression in B(a)P-exposed offspring relative to controls. Recordings from B(a)P-exposed offspring revealed that N-methyl-d-aspartate (NMDA) receptor-dependent neuronal activity in barrel cortex evoked by whisker stimulation was also significantly reduced (70%) as compared to controls. Analysis showed that the greatest deficit in cortical neuronal responses occurred in the shorter latency epochs from 5 to 20 ms post-stimulus. The results suggest that in utero exposure to benzo(a)pyrene results in diminished mRNA expression of the NMDA NR2B receptor subunit to result in late life deficits in cortical neuronal activity in the offspring. The findings from this study lead to a strong prediction that in utero exposure to benzo(a)pyrene at a time when synapses are first formed and adjusted in strength by activity in the sensory pathways will produce a strong negative effect on brain function in offspring progeny.

Optic nerve transection affects development and use-dependent plasticity in neocortex of the rat: Quantitative acetylcholinesterase imaging.

We investigated the effects of neonatal optic nerve transection on cortical acetylcholinesterase (AChE) activity in hooded rats during postnatal development and following behavioral manipulation after weaning. AChE reaction product was quantified on digitized images of histochemically stained sections in layer IV of primary somatic sensory, primary visual and visual association cortex. Rats with optic nerve transection were compared to sham-operated littermates. In all cortical regions of both types of animal, AChE reaction product was increased to peak 2 weeks after birth and decreased thereafter, reaching adult levels at the end of the third postnatal week. During postnatal development, reaction product in primary visual cortex was lower in rats deprived of retinal input than in sham-operated littermates and the area delineated by reaction product was smaller. However, optic nerve transection did not modify the time course of postnatal development or statistically significantly diminish adult levels of AChE activity. Behavioral manipulations after weaning statistically significantly increased enzyme activity in sham-operated rats in all cortical areas examined. Compared with cage rearing, training in a discrimination task with food reward had a greater impact than environmental enrichment. By contrast, in the rats with optic nerve transection enrichment and training resulted in statistically significantly increased AChE activity only in lateral visual association cortex. Our findings provide evidence for intra- and supramodal influences of the neonatal removal of retinal input on neural activity- and use-dependent modifications of cortical AChE activity. The laminar distribution of the AChE reaction product suggests that the observed changes in AChE activity were mainly related to cholinergic basal forebrain afferents. These afferents may facilitate the stabilization of transient connections between the somatic sensory and the visual pathway.

Cortical modulation of spatial and angular tuning maps in the rat thalamus.

The massive feedback projections from cortex to the thalamus modulate sensory information transmission in many ways. We investigated the role of corticothalamic feedback projections on the directional selectivity (angular tuning) of neurons in the rat ventral posterior medial (VPM) nucleus to stimulation of their principal whisker. The angular tuning properties of single VPM neurons were compared before and after epochs of electrical stimulation of layer VI feedback neurons in the ipsilateral cortex under urethane anesthesia. Microstimulation of layer VI in "matched" (homologous) barrel columns sharpens the angular tuning curves of single VPM neurons that are tuned to the same direction as the stimulation site in the cortex. Further, microstimulation rotates the angular preference of VPM neurons initially tuned to a different direction toward the direction that cortical neurons prefer. Stimulation in "mismatched" (nonhomologous) barrel columns suppresses responses without consistent effects on angular tuning. We conclude that the primary sensory cortex exerts a significant influence on both spatial and angular tuning maps in the relay nuclei that project to it. The results suggest that the tuning properties of VPM cells in the behaving animal are continually modified to optimize perception of the most salient incoming messages.

Rapid plasticity follows whisker pairing in barrel cortex of the awake rat.

Synaptic plasticity can be induced easily throughout life in the rodent somatic sensory cortex. Trimming all but two whiskers on one side of an adult rat's face, called 'whisker pairing', causes the active (intact) whiskers to develop a stronger drive on cortical cells in their respective barrel columns, while inactive (trimmed) whisker efficacy is down-regulated. To date, this type of activity-dependent plasticity has been induced by trimming all but two whiskers, letting the rats explore their environment from 1 day to 1 month, after which cortical responses were analyzed physiologically under anesthesia. Such studies have enhanced our understanding of cortical plasticity, but the anesthesia complicates the examination of changes that occur in the first few hours after whisker trimming. Here we assayed the short-term changes that occur in alert, active animals over a period of hours after whisker trimming. The magnitude of barrel cortex evoked responses was measured in response to stimulation of the cut and paired whiskers of rats under several conditions: (a) whisking in air (control), (b) active whisking of an object by the rat, and (c) epochs of passive whisker stimulation to identify the onset of whisker pairing plasticity changes in cortex. The main difference between whisking in air without contact and passive whisker stimulation is that the former condition induces an increased response to stimulation of inactive cut whiskers, while the latter condition increases the responses to the stimulated whiskers. The results support the conclusion that whisker pairing plasticity in barrel cortex occurs within 4 h after whisker trimming in an awake, alert animal.

Stimulus frequency processing in awake rat barrel cortex.

In awake rats, we examined the relationship between neural spiking activity in primary somatic sensory cortex and the frequency of whisker stimulation. Neural responses were recorded extracellularly in barrel cortex while single whiskers were deflected with 0.5-18 air puffs per second (apps), a range that includes the whisk rates observed when rats explore their environment and discriminate surfaces with their whiskers. Twenty-nine neurons in layers III and IV were isolated in three rats (23 in barrel columns and 6 in septum columns). At < or = 9 apps, cortical neurons responded with one to two spikes per stimulus, whereas at > 9 apps, the response efficacy was reduced to only 0.2-0.4 spikes per stimulus. Several mechanisms are discussed that could account for the decrement in responsiveness. Despite this adaptation, neural spike rates increased in direct proportion with stimulus frequency when cast on logarithmic scales. At > 9 apps, however, this relationship deteriorated in barrel columns in which the response approximately halved. In contrast, septum column cells continued to increase their spike rates linearly up to 18 apps, although they responded at lower magnitude than the barrel column cells. Our findings suggest that septum column neurons are potential candidates to encode stimulus frequency using spike rate across the entire frequency range relevant to rats' whisking behavior.

Gestational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure effects on sensory cortex function.

Gestational exposure to environmental contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) poses a significant threat to normal growth and differentiation of the developing brain. To characterize the impact of gestational TCDD exposure on subsequent cortical function, pregnant Long Evans rats were exposed to a single acute dose (100 or 700ng/kg b.w. via gavage) on gestational day 15. This dosing regimen had no significant effect on birth index. After the TCDD-exposed animals were born and reached maturity, neural activity was recorded under urethane anesthesia from neurons in primary somatic sensory cortex. Spontaneous activity was reduced by approximately 50% in barrel cortex compared to corn oil vehicle controls. The magnitude of neuronal response to sensory (whisker) stimuli also was significantly reduced, and responses did not achieve control levels at any stimulus intensity. The greatest deficit was in the short latency component of the cortical responses. These decrements in cortical responsiveness were present in young F1 generation TCDD-exposed animals and persisted for up to 180 days. Because glutamate receptors are crucial to the evoked responses and show developmental regulation, selected iontotropic glutamate receptor subunits (NMDA NR2A+NR2B and GluR1) were profiled for RNA levels in the cortex of F1 generation rats. The expression of NR2B (NMDA receptor) and GluR1 (AMPA receptor) subunits was significantly reduced in the TCDD-exposed F1 generation animals compared to vehicle controls. The results indicate that gestational TCDD exposure results in cortical deficits that are paralled by diminished expression of certain NMDA and AMPA receptor subunits at a time when synapses are being formed for the first time in cortex.

A combined deficiency of vitamins E and C causes severe central nervous system damage in guinea pigs.

A short period of combined deficiency of vitamins E and C causes profound central nervous system (CNS) dysfunction in guinea pigs. For this report, CNS histopathology was studied to define the nature and extent of injury caused by this double deficiency. Weanling guinea pigs were fed a vitamin E-deficient or -replete diet for 14 d. Then vitamin C was withdrawn from the diet of some guinea pigs. Four diet groups were thus formed: replete, vitamin E deficient, vitamin C deficient, and both vitamin E and C deficient. From 5 to 11 d after institution of the doubly deficient diet, 9 of 12 guinea pigs developed paralysis, and 2 more were found dead. The remaining guinea pig in the doubly deficient group and all animals in the other 3 groups survived without clinical impairment until the experiment was terminated at 13-15 d. Brains and spinal cords were serially sectioned and stained for examination. Only the combined deficiency produced damage in the CNS. The damage consisted mainly of nerve cell death, axonal degeneration, vascular injury, and associated glial cell responses. The spinal cord and the ventral pons in the brainstem were most severely affected, often exhibiting asymmetric cystic lesions. Several features of the lesions suggest that the primary damage was to blood vessels. These results indicate that the paralysis and death caused by combined deficiency of vitamins E and C in guinea pigs is caused by severe damage in the brainstem and spinal cord.

Rate code and temporal code for frequency of whisker stimulation in rat primary and secondary somatic sensory cortex.

We recorded responses to frequencies of whisker stimulation from 479 neurons in primary (S1) and secondary (S2) somatic sensory cortex of 26 urethane-anesthetized rats. Five whiskers on the right side of the snout were deflected with air puffs at seven frequencies between 1 and 18/s. In left S1 (barrels and septa) and S2, subsets of neurons (5%) responded to whisker stimulation across the entire range of frequencies with > or = 1 electrical discharges/ten stimuli (full responders). In contrast, 60% of the recorded cells responded above threshold only at stimulus frequencies below 6/s and 35% remained subthreshold at all frequencies tested. Thus, the full responders are unique in that they were always responsive and appeared particularly suited to facilitate a dynamic, broadband processing of stimulus frequency. Full responders were most responsive at 1 stimulus/s, and showed greatest synchrony with whisker motion at 18 stimuli/s. The barrel cells responded with the greatest temporal accuracy between 3 and 15 stimuli/s. The septum cells responded less accurately, but maintained their accuracy at all frequencies. Only septum cells continued to increase their discharge rate with increasing stimulus frequency. The S2 cells discharged with lowest temporal accuracy modulated only by stimulus frequencies < or = 6/s and exhibited the steepest decrease in discharge/stimulus with increasing stimulus frequency. Our observations suggest that full responders in the septa are well suited to encode high frequencies of whisker stimulation in timing and rate of discharge. The barrel cells, in contrast, showed the strongest temporal coding at stimulus frequencies in the middle range, and S2 cells were most sensitive to differences in low frequencies. The ubiquitous decline in discharge/stimulus in S1 and S2 may explain the decrease in blood flow observed at increasing stimulus frequency with functional imaging.

Balancing bilateral sensory activity: callosal processing modulates sensory transmission through the contralateral thalamus by altering the response threshold.

Rats tactually explore a nearly spherical space field around their heads with their whiskers. The information sampled by the two sets of whiskers is integrated bilaterally at the cortical level in an activity dependent manner via the corpus callosum. We have recently shown that sensory activity in one barrel field cortex (BFC) modulates the processing of incoming sensory information to the other BFC. Whether interhemispheric integration is dynamically linked with corticothalamic modulation of incoming sensory activity is an important hypothesis to test, since subcortical relay neurons are directly modulated by cortical neurons through top-down processes. In the present study, we compared the direct sensory responses of single thalamic relay neurons under urethane anesthesia before and after inactivating the BFC contralateral to a thalamic neuron. The data show that silencing one BFC reduces response magnitude in contralateral thalamic relay neurons, significantly and reversibly, in response to test stimuli applied to the principal whisker at two times response threshold (2T) intensity for each unit. Neurons in the ventral posterior medial (VPM) nucleus and the medial division of the posterior nucleus (POm) react in a similar manner, although POm neurons are more profoundly depressed by inactivation of the contralateral BFC than VPM neurons. The results support the novel idea that the subcortical relay of sensory information to one hemisphere is strongly modulated by activity levels in the contralateral as well as in the ipsilateral SI cortex. The mechanism of the modulation appears to be based on shifting the stimulus-response curves of thalamic neurons, thereby rendering them more or less sensitive to sensory stimuli. We conclude that global sensory processing is created by combining activity in each cerebral hemisphere and continually balancing the flow of information to cortex by adjusting the responsiveness of ascending sensory pathways.