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Environmental, social, and governance (ESG) issues have become a core business concern and a central focus of investors. The ESG reporting landscape is fragmented, with hundreds of reporting standards forming what has been called an alphabet soup of acronyms with no common framework to guide corporate disclosures. Companies’ ESG disclosures vary widely and investors complain that they do not have the comparable, decision-useful information that they need to properly factor ESG considerations into their investment decisions. For their part, companies express concern over the lack of guidance as to which disclosure standards to follow. The SEC’s reporting rules have remained essentially unchanged for decades even amid calls for reform. At the same time, organizations, including the World Economic Forum, have called for efforts to bring consistency and comparability to ESG disclosures. This chapter explores this dynamic landscape and anticipates significant change in the regulation of ESG reporting over the coming years.

Imaging using coherent extreme ultraviolet radiation from laser sources provides high-resolution images of biological samples., Microscopy with extreme ultraviolet (EUV) light can provide many advantages over optical, hard x-ray or electron-based techniques. However, traditional EUV sources and optics have large disadvantages of scale and cost. Here, we demonstrate the use of a laboratory-scale, coherent EUV source to image biological samples—mouse hippocampal neurons—providing quantitative phase and amplitude transmission information with a lateral resolution of 80 nm and an axial sensitivity of ~1 nm. A comparison with fluorescence imaging of the same samples demonstrated EUV imaging was able to identify, without the need for staining or superresolution techniques

The oral mucosa is an attractive site for mucosal vaccination, however the thick squamous epithelium limits antigen uptake. Here we utilize a modified needle-free injector to deliver immunizations to the sublingual and buccal (SL/B) tissue of rhesus macaques. Needle-free SL/B vaccination with modified vaccinia Ankara (MVA) and a recombinant trimeric gp120 protein generates strong vaccine-specific IgG responses in serum as well as vaginal, rectal and salivary secretions. Vaccine-induced IgG responses show a remarkable breadth against gp70-V1V2 sequences from multiple clades of HIV-1. In contrast, topical SL/B immunizations generates minimal IgG responses. Following six intrarectal pathogenic SHIV-SF162P3 challenges, needle-free but not topical immunization results in a significant delay of acquisition of infection. Delay of infection correlates with non-neutralizing antibody effector function, Env-specific CD4+ T-cell responses, and gp120 V2 loop specific antibodies. These results demonstrate needle-free MVA/gp120 oral vaccination as a practical and effective route to induce protective immunity against HIV-1., Oral vaccination is a potential option to elicit systemic and mucosal immunity against HIV. Here, Jones et al. show that oral vaccination with a modified needle-free injector induces protective immunity against SHIV in non-human primates and is superior to topical application of vaccines to oral tissues.

Objective To observe rates of returns and to identify trends in returns of potentially abused medications during medication take-back events. Methods A retrospective cross-sectional study was conducted of returned medications during medication take-back days from 2013 to 2016 based on a partnership between local law enforcement and a school of pharmacy in a rural South Carolina town. Data collected on returned items included active ingredients, estimated quantity, and prescription fill date if available. The medications were classified by therapeutic class and further identified drugs of potential abuse according to National Institute of Drug Abuse classifications. Descriptive statistics were used to analyze the data collected. Results In 2013, 742 different medications were returned, and 64 (8.63%) were potential drugs of abuse. In the years 2014-2016, 117 (11.43%) returned medications were potential drugs of abuse. In 2017, 40 (13.27%) returned medications were potentially abused drugs. Opioid analgesics were the most common potentially abused medication returned, accounting for 51.6%, 62.4%, and 65% of potentially abused medications returned in 2013, 2014-2016, and 2017, respectively. The other most common potentially abused returned medications were benzodiazepines (10.9%, 12.8%, 7.5%). The return of hypnotic medications increased over the study period from 0% in 2013 to 12.5% of potentially abused medications in 2017. The return of other medications such as loperamide and dextromethorphan varied over the study period. Conclusion The rate of potentially abused medications returned steadily rose over the period of the study. Heightened awareness and increased opportunities for proper disposal including the placement of permanent drug disposal locations may account for the decreased number of prescriptions returned following 2013.

We present a new phase characterization technique for ultrashort laser pulses that employs self-phase modulation (SPM) in the dispersion scan approach. The method can be implemented by recording a set of nonlinearly modulated spectra generated with a set of known chirp values. The unknown phase of the pulse is retrieved by linking the recorded spectra to the initial spectrum of the pulse via a phase function guessed by a function minimization iterative algorithm. This technique has many advantages over the dispersion scan techniques that use frequency conversion processes. Mainly, the use of SPM cancels out the phase and group velocity mismatch errors and dramatically widens the spectral acceptance of the nonlinear medium and the range of working wavelength. The robustness of the technique is demonstrated with smooth and complex phase retrievals using numerical examples. The method is shown to be not affected by the spatial distribution of the beam or the presence of nonlinear absorption process. In addition, we present an efficient method for phase representation based on a summation of a set of Gaussian functions. The independence of the functions from each other prevents phase coupling of any kind and facilitates a flexible phase representation.

The Optical Parametric Chirped Pulse Amplification is one of the most promising techniques to deliver 20PW laser system. The already available KD*P in large size is a good candidate as nonlinear crystal. In this article we report the experimental analysis of the spectral small signal gain for KD*P at 70% deuteration level for different phase matching and non-collinear angle. The data is also compared with a theoretical model.

An XUV interferometer composed of two inline high harmonic generation regions is used to characterize different ionized electron quantum paths. We unambiguously observe interference between long and short trajectories, revealing their attosecond-scale relative timing.

In this paper we present our plans for an auxiliary OPCPA beamline for the Vulcan PW laser facility. It will be capable of delivering 30J

Chirped pulses have important applications in [optical parametric] chirped pulse amplification ([OP]CPA), telecommunications, molecular alignment, chirp-assisted sum frequency generation, dispersive Fourier transform spectroscopy and coherent control [1, 2]. Knowledge of the nonlinear dispersion of these pulses is required for accurate extraction of information from experiments, as well as enabling optimal operation of [OP]CPA systems.

The complete characterisation of ultrashort optical pulses is a key capability in the design, optimisation and implementation of any ultrafast laser system or experiment and an accurate means to quantify the complex spectral or temporal amplitude of the field enables the maximum information to be extracted from dynamic measurements.

The topic is a national review of content and clinical experiences in undergraduate pediatric nursing education with recommendations for strengthening the pediatric nursing curriculum. American Association of Colleges of Nursing member programs ( N = 596) were surveyed with 344 schools responding. A 39-item survey collected school demographics, faculty characteristics, pediatric classroom and clinical information, and actual and perceived barriers to implementing the pediatric curriculum. Recommendations for change were offered by participants attending the 2011 Institute of Pediatric Nursing Nursing Forum. A mean of 33 ( SD = 27) total undergraduate faculty included an average of 3.1 ( SD = 3.11) faculty with graduate specialization and/or recent clinical experience in pediatrics. Within a mean of 43 (range = 0–136 hours) pediatric classroom hours, more than 59% of programs reported 2 hours or less in pediatric genetics, environmental health, and child nutrition. Content focused on acute and specialty care with programs using pediatric inpatient medical (68%) and surgical units (40%) for clinical learning. Recruiting pediatric faculty was a common issue and reported as extremely (23%) to moderately difficult (26%). Competition for clinical practice sites (76%) was a reported barrier. Adjustments in the pediatric undergraduate curriculum are recommended to highlight current health issues experienced by children including expansion of clinical learning experiences to settings where children live, learn, and play.

Objective Seizures are common among newborns with hypoxic-ischaemic encephalopathy (HIE) but the relationship between seizure burden and severity of brain injury among neonates receiving therapeutic hypothermia (TH) for HIE is unclear. We tested the hypothesis that seizure burden is associated with cerebral tissue injury independent of amplitude-integrated EEG (aEEG) background activity. Study design Term neonates undergoing 72 h of TH at four centres were selected for study if they had continuous aEEG and MRI. The aEEG with corresponding 2-channel raw EEG (aEEG/EEG), was classified by severity of background and seizure burden; MR images were classified by the severity of tissue injury. Results Of 85 neonates, 52% had seizures on aEEG/ EEG. Overall, 35% had high seizure burden, 49% had abnormal aEEG background in the first 24 h and 36% had severe injury on MRI. Seizures were most common on the first day, with significant recurrence during and after rewarming. Factors associated with severe injury on MRI were high seizure burden, poor aEEG background, 10 min Apgar and the need for more than one anticonvulsant. In multivariate logistic regression, high seizure burden was independently associated with greater injury on MRI (OR 5.00, 95% CI 1.47 to 17.05 p=0.01). Neither aEEG background, nor 10 min Apgar score were significant. Conclusions Electrographic seizure burden is associated with severity of brain injury on MRI in newborns with HIE undergoing TH, independent of degree of abnormality on aEEG background. Seizures are common during cooling, particularly on day 1, with a significant rebound on day 4.

We report the operation of an optical parametric amplifier (OPA) capable of producing gigawatt peak-power laser pulses with tunable wavelength in either the visible or near-infrared spectrum. The OPA has two distinct operation modes (i) generation of >350 uJ, sub 100 fs pulses, tunable between 1250 - 1550 nm; (ii) generation of >190 uJ, sub 150 fs pulses tunable between 490 - 530 nm. We have recorded high-order harmonic spectra over a wide range of driving wavelengths. This flexible source of femtosecond pulses presents a useful tool for exploring the wavelength-dependence of strong-field phenomena, in both the multi-photon and tunnel ionization regimes., 14 pages, 9 figures, This paper was published in Proceedings of SPIE 10088, Nonlinear Frequency Generation and Conversion: Materials and Devices XVI, doi 10.1117/12.2250775

We explore how the DiPOLE architecture, based on diode-pumped, cryo-cooled Yb:YAG, could be adapted for direct-CPA ps-pulse generation and conclude that generation of 2 ps, 70 J pulses at 10 Hz repetition rate is feasible.

We demonstrate improved accuracy and consistency for spectral-shearing in-terferometry using multiple shears. Using a new algorithm, different spectral shears are combined to perform accurate spectral phase measurements of complicated pulses from a hollow-core ber system. © 2008 Optical Society of America.

We demonstrate an extremely accurate method for measuring ultrabroadband, sub-10 fs pulses even if they exhibit a highly modulated spectrum, space-time coupling, or both. The method uses a spatially encoded arrangement for spectral phase interferometry for direct electric field reconstruction, which allows a zero additional phase measurement to be performed with a relatively low signal-to-noise ratio in real time and single shot.

We review the requirements for achieving full phase and amplitude characterization of attosecond X-ray pulses and propose several methods for carrying out such measurements. We show via numerical simulation that these techniques are capable of retrieving full field information of attosecond pulses and compare their performance and ease of implementation.

The waveforms of attosecond pulses produced by high-harmonic generation carry information on the electronic structure and dynamics in atomic and molecular systems. Current methods for the temporal characterization of such pulses have limited sensitivity and impose significant experimental complexity. We propose a new linear and all-optical method inspired by widely-used multi-dimensional phase retrieval algorithms. Our new scheme is based on the spectral measurement of two attosecond sources and their interference. As an example, we focus on the case of spectral polarization measurements of attosecond pulses, relying on their most fundamental property -- being well confined in time. We demonstrate this method numerically reconstructing the temporal profiles of attosecond pulses generated from aligned $CO_2$ molecules., Comment: 4 pages 3 figures

Pulse characterisation methods based on non-collinear frequency mixing (NCFM) can introduce additional space-time coupling (STC) in the measurement. Thus it is necessary to re-examine the NCFM process in order to be able to measure STC accurately with these devices. SEA-SPIDER is one characterisation method that in principle can measure the temporal electric field of a pulse as a function of a single spatial dimension, thus measuring STC (but not the spatial phase). This method has been modelled specifically and found it is necessary to account for this additional ?geometric? STC for few-cycle pulses. SEA-SPIDER has already been demonstrated as an excellent candidate for measuring extremely large bandwidth pulses. In addition, it has been shown that it is possible to measure the STC of a pulse in one spatial dimension. However, the non-collinear sum-frequency generation used in the device introduces a small amount of additional STC coupling which can easily be corrected for. This analysis will prove invaluable as it allows one to obtain more complete and accurate information about their pulses. The ideas and analysis presented here can also be applied to other characterisation methods that claim to be able to measure STC.

On March 9, 2012, the New York Academy of Sciences brought together experts representing a variety of perspectives--including academic, industrial, regulatory, as well as those from physicians and consumers--to discuss considerations for the non-biological complex drug (NBCD) regulatory approval pathway, given the emerging regulatory guidelines for biosimilars (follow-on biological complex drugs). Some of the organizers of the conference expressed their belief that NBCDs share a number of characteristic features with biologicals: the structure cannot be fully defined by the available (physicochemical) analytical tests, and quality assurance is based on in-depth knowledge, consistency, and control of the production process. However, their view on NBCDs was not universally accepted among the experts who participated in the conference. Plenary sessions addressed the most recent regulatory developments, experimental design, interchangeability, and immunogenicity issues for follow-on versions of complex drugs from the perspective of key audiences, including industry, regulatory agencies, physicians, and consumers. This report summarizes these various perspectives on NBCDs and the scientific and regulatory considerations associated with complex drug categories.

Hypothermia is the first effective neuroprotective intervention for newborns who are critically ill following a life-threatening asphyxial insult. It is not surprising that it has raised complex and controversial ethical dilemmas for investigators and clinicians. Given the history of iatrogenic disasters in neonatology, there has been an understandable reluctance to incorporate hypothermia into routine clinical practice until there is persuasive evidence from high quality randomised trials. This article reviews ethical issues that arose during the design of the original clinical trials, the implications of accumulating evidence of safety and efficacy, and the problems of ensuring informed parental participation in treatment decisions.

Background: The 2007 Cochrane review of therapeutic hypothermia for neonatal encephalopathy (NE) indicates a significant reduction in adverse outcome. UK National Institute for Clinical Excellence guidelines are awaited.Objective: To benchmark current opinion and practice to inform future strategies for optimal knowledge transfer for therapeutic hypothermia.Methods: A web based questionnaire (30 sections related to opinion and practice of management of NE) sent to the clinical leads of Level I, II and III neonatal units throughout the UK in November/December 2007.Results: One hundred and twenty-five (out of 195) UK neonatal units responded (response rate 66%). Ten percent, 37.5% and 51.5% responses were from level I, II and III units respectively. Twenty eight percent of all units provided therapeutic hypothermia locally (52% of level III units), however 80% of responders would offer therapeutic hypothermia if there was the facility. Overall, 57% of responders considered therapeutic hypothermia effective or very effective - similar for all unit levels; 43% considered more data are required. Regional availability of therapeutic hypothermia exists in 55% of units and 41% of units offer transfer to a regional centre for therapeutic hypothermia.Conclusion: In the UK in 2007, access to therapeutic hypothermia was widespread although not universal. More than half of responders considered therapeutic hypothermia effective. Fifty-five percent of perinatal networks have the facility to offer therapeutic hypothermia. The involvement of national bodies may be necessary to ensure the adoption of therapeutic hypothermia according to defined protocols and standards; registration is important and will help ensure universal neurodevelopmental follow up.

SUMMARY Studies of cerebral oxidative metabolism were carried out by phosphorous magnetic resonance spectroscopy during the first week of life in 52 infants with clinical and/or biochemical evidence of birth asphyxia. 15 infants died and the 37 survivors were assessed by a wide range of neurodevelopmental tests at one year of age. The minimum recorded values for cerebral phosphocreatine/inorganic phosphate concentration ratio (an index of oxidative metabolism) were related to outcome. The results showed a significant relation between the extent of derangement of oxidative metabolism and the severity of adverse outcomes, including death, neurodevelopmental impairment and reduced head growth. RESUME Relation entre le metabolisme oxydatif cerebral apres asphyxie a la naissance, et le devenir neurodeveloppemental, la croissance cerebrale a un an Des etudes du metabolisme oxydatif cerebral par spectroscopic de resonance magnetique au phosphore ont ete entreprises durant la premiere semaine de vie chez 52 nourrissons presentant une evidence clinique et/ou biochimique d'asphyxie a la naissance. 15 nourrissons moururent et les 37 survivants subirent de nombreux tests neurodeveloppementaux a l'âge d'un an. Les taux minima enregistres pour le rapport de concentration phosphocreatine/phosphates inorganiques (index de metabolisme oxydatif) furent relies au devenir. Les resultats montrerent une relation significative entre l'importance de la perturbation du metabolisme oxydatif et la gravite des devenirs negatifs, incluant le deces, le retard neurodeveloppemental et la reduction de la croissance cranienne. ZUSAMMENFASSUNG Beziehung zwischen oxydativem Hirnstoffwechsel nach Geburtsasphyxie und entwicklungsneurologischem Befund und Hirnentwicklung im Alter von einem Jahr Bei 52 Kindern mit klinischem und/oder biochemischem Hinweis auf eine Geburtsasphyxie wurden in der ersten Lebenswoche anhand der Phosphor-MRS Untersuchungen des oxydativen Hirnstoff-wechsels durchgefuhrt. 15 Kinder starben und die 37 Uberlebenden wurden im Alter von einem Jahr mit einer Batterie von entwicklungsneurologischen Tests untersucht. Die niedrigsten Werte fur das Verhaltnis von cerebralem Phosphokreatinin/inorganischem Phosphat (ein Index fur oxydativen Metabolismus) wurden zum Endbefund in Relation gestellt. Die Ergebnisse zeigten eine signifikante Beziehung zwischen den Storungen des oxydativen Metabolismus und dem Schweregrad der pathologischen Befunde, die Tod, entwicklungsneurologische Storungen und vermindertes Kopfwachtum beinhalteten. RESUMEN Relacion entre el metabolismo oxidativo cerebral despues de una asfixia de parto y el desarrollo neuroevolutivo y el crecimiento del cerebral ano de edad Se realizaron estudios del metabolismo oxidativo cerebral utilizando la espectroscopia de resonancia magnetica con fosforo durante la primera semana de vida en 52 ninos lactantes con evidencia clinica y/o bioquimica de asfixia al nacer. 15 lactantes murieron y los 37 supervivientes fueron evaluados con un amplio abanico de tests de neurodesarrollo al ano de edad. Los valores minimos registrados de la relacion en el cerebro de fosfocreatina/fosfato inorganico (indice de metabolismo oxidativo) se relacionaron con el curso seguido. Los resultados mostraron una relacion significativa entre la extension de la alteracion del metabolismo oxidativo y la gravedad de los cursos posteriores adversos, incluyendo el exitus, la alteracion del neurodesarrollo y la reduccion en el crecimiento de la cabeza.

OBJECTIVE. The absence of cerebral autoregulation in preterm infants has been associated with adverse outcome, but its bedside assessment in the immature brain is problematic. We used spatially resolved spectroscopy to continuously measure cerebral oxygen saturation (expressed as a tissue-oxygenation index) and used the correlation of tissue-oxygenation index with spontaneous fluctuations in mean arterial blood pressure to assess cerebral autoregulation. PATIENTS AND METHODS. The tissue-oxygenation index and mean arterial blood pressure were continuously measured in very premature infants (n = 24) of mean (±SD) gestational age of 26 (±2.3) weeks at a mean postnatal age of 28 (±22) hours. The correlation between mean arterial blood pressure and tissue-oxygenation index in the frequency domain was assessed by using cross-spectral analysis techniques (coherence and transfer-function gain). Values of coherence reflect the strength of linear correlation, whereas transfer-function gain reflects the amplitude of tissue-oxygenation index changes relative to mean arterial blood pressure changes. RESULTS. High coherence (coherence ≥ 0.5) values were found in 9 infants who were of lower gestational age, lower birth weight, and lower mean arterial blood pressure than infants with coherence of CONCLUSIONS. High coherence between mean arterial blood pressure and tissue-oxygenation index indicates impaired cerebral autoregulation in clinically sick preterm infants and is strongly associated with subsequent mortality. Cross-spectral analysis of mean arterial blood pressure and tissue-oxygenation index has the potential to provide continuous bedside assessment of cerebral autoregulation and to guide therapeutic interventions.

Advances in the generation of ultrashort laser pulses, and the emergence of new research areas such as attosecond science, nanoplasmonics, coherent control, and multidimensional spectroscopy, have led to the need for a new class of ultrafast metrology that can measure the electric field of complex optical waveforms spanning the ultraviolet to the infrared. Important examples of such waveforms are those produced by spectral control of ultrabroad bandwidth pulses, or by Fourier synthesis. These are typically tailored for specific purposes, such as to increase the photon energy and flux of high-harmonic radiation, or to control dynamical processes by steering electron dynamics on subcycle time scales. These applications demand a knowledge of the full temporal evolution of the field. Conventional pulse measurement techniques that provide estimates of the relative temporal or spectral phase are unsuited to measure such waveforms. Here we experimentally demonstrate a new, all-optical method for directly measuring the electric field of arbitrary ultrafast optical waveforms. Our method is based on high-harmonic generation (HHG) driven by a field that is the collinear superposition of the waveform to be measured with a stronger probe laser pulse. As the delay between the pulses is varied, we show that the field of the unknown waveform is mapped to energy shifts in the high-harmonic spectrum, allowing a direct, accurate, and rapid retrieval of the electric field with subcycle temporal resolution at the location of the HHG.

A LBO based OPG/OPA source is demonstrated with an energy exceeding 90mJ with a 6% RMS energy stability and tunability of 300nm between 750 to 1050nm. This novel source will facilitate the testing of MultiPetawatt OPCPA amplification schemes.

Children are directly exposed to bisphenol A (BPA) and other putative environmental obesogens through both diet and household products. The purpose of this study was to investigate sex- and genetic-dependent effects of BPA consumption on traits relevant to obesity and Type 2 diabetes in juveniles, using mice as models. Two strains of mice (C57BL/6J and DBA/2J) were chosen to represent distinct genetic backgrounds that differ in susceptibility to obesity and insulin resistance. Male and female mice of each strain consumed BPA at three doses in drinking water from four to eleven weeks of age. Male but not female mice of each strain consuming BPA were significantly fatter than controls. BPA induced corresponding changes in adipose tissue gene expression and metabolite abundance that indicate effects on adipogenesis and energy utilization. BPA consumption also altered the synthesis of adipokines, circulating factors that modulate insulin sensitivity and atherogenesis, in C57BL/6J but not DBA/2J males. Conversely, effects of BPA on plasma insulin were only observed in female mice, and with opposite effects in the two strains. These results suggest that dietary BPA may exacerbate childhood obesity and its consequences, and that sex and genetic background are important determinants of the physiological impact of BPA.

Objective: For optimal neuroprotection following transient perinatal hypoxia–ischaemia (HI), therapy should start before overt secondary energy failure and its irreversible neurotoxic cascade. Hypothermia is a promising neuroprotective intervention that also prolongs the therapeutic time window (“latent-phase”; the period between re-establishment of apparently normal cerebral metabolism after HI, and the start of secondary energy failure). The influences of HI severity on latent-phase duration and regional neuroprotection are unclear. Under normothermia and delayed whole-body cooling to 35 and 33 °C we aimed to assess relationships between HI severity and: (i) latent-phase duration; (ii) secondary-energy-failure severity; and (iii) neuronal injury 48 h following HI. Methods: Newborn piglets were randomized to: (i) HI-normothermia (n = 12), (ii) HI-35 °C (n = 7), and (iii) HI-33 °C (n = 10). HI-35 °C and HI-33 °C piglets were cooled between 2 and 26 h after HI. Insult and secondary-energy-failure severity and latent-phase duration were evaluated using phosphorus magnetic resonance spectroscopy and compared with neuronal death in cortical-grey and deep-grey matter. Results: More severe HI was associated with shorter latent-phase (p = 0.002), worse secondary energy failure (p = 0.023) and more cortical-grey-matter neuronal death (p = 0.016). Conclusions: Latent-phase duration is inversely related to insult severity; latent-phase brevity may explain the apparently less effective neuroprotection following severe cerebral HI.

Little information is available on long-term neurodevelopmental outcome of preterm infants with unilateral cerebral lesions detected by neonatal cranial ultrasound. This study aims to investigate the long-term outcome in a cohort of very preterm infants with unilateral cerebral lesions acquired in the perinatal period.A prospective cohort study of 668 preterm infants (33 weeks gestation; birth years 1985-1991) at a single tertiary perinatal centre in the UK. All infants had serial cranial ultrasound examination in the neonatal period. Outcome was assessed at age 8 years with the Wechsler Intelligence Scales for Children (WISC-R), Test of Visuo-motor Integration (VMI) and the Test of Motor Impairment (TOMI).Of the 668 infants, 369 infants had normal ultrasound scans. Two hundred and ninety nine children had bilateral parenchymal or non-parenchymal lesions (57 left-sided, 41 right-sided, 201 bilateral). Five hundred and thirty four (79%) children attended follow-up at age 8 years. Mean Full Scale IQ (FSIQ) was 101 (SD+/-16), 93 (SD+/-17), 102 (SD+/-17) and 91 (SD+/-21) for normal, left-sided, right-sided and bilateral lesion groups respectively. In all groups verbal IQ (VIQ) was higher than performance IQ (PIQ). Scores of FSIQ, VIQ and PIQ, VMI and TOMI were significantly different between the groups. After exclusion of children with parenchymal lesions, however, the difference was only significant for the TOMI scores. In all tests, children with left-sided lesions performed poorer than children with right-sided lesions.In this cohort of preterm infants with unilateral cerebral lesions, verbal function was preserved over non-verbal function independently of the side of lesion. Furthermore, the results suggest that the neurodevelopmental outcome of children with left-sided lesions is less favourable than that of children with right-sided lesions.

This study investigated whether in preterm children who had ventricular dilatation (VD) on neonatal cranial ultrasound outcome at age 8 years was influenced by the additional presence of germinal matrix haemorrhage--intraventricular haemorrhage (GMH-IVH). Six-hundred and ninety-nine preterm infants (

INTRODUCTION. Very preterm birth (VPT; METHODS. We assessed 108 VPT individuals and 67 term-born controls at ages 18 to 19 years with the Eysenck Personality Questionnaire-Revised, short form (EPQ-RS). This questionnaire rates 3 dimensions of personality: extraversion (sociability, liveliness, sensation seeking); neuroticism (anxiety, low mood, low self-esteem); and psychoticism (coldness, aggression, predisposition to antisocial behavior). A fourth scale, “lie,” which measures dissimulation, is also derived. RESULTS. VPT individuals had significantly lower extraversion scores, higher neuroticism scores, and higher lie scores than term-born controls, after controlling for age at assessment and socioeconomic status. P scores were not significantly different between the 2 groups. There was a gender difference in that the increased neuroticism and decreased extraversion scores were accounted for mainly by VPT females. Associations between EPQ-RS scores and neonatal status, adolescent behavioral ratings, and body size at 18 to 19 years were assessed by using Kendall partial correlations, correcting for age at assessment and socioeconomic status. Gestational age, indices of neonatal hypoxia, and neonatal ultrasound ratings were not correlated with EPQ-RS scores. Birth weight was weakly associated with increased lie scores. Rutter Parents' Scale score, a measure of adolescent psychopathology, was associated with an increased neuroticism score. Poor social adjustment in adolescence was associated with an increased lie score. Height and weight at 18 to 19 years were not associated with EPQ-RS, but reduced occipitofrontal circumference was associated with both decreased extraversion and increased lie scores. CONCLUSIONS. Young adults who are born VPT have different personality styles from their term-born peers. This may be associated with an increased risk of psychiatric difficulties.

Solid tumours are often treated with external beams of photons generated by Bremsstrahlung radiation. These beams are shaped and filtered to optimise the dose to specific regions defined by the treatment plans, which may involve irradiations from multiple angles. It is important that doses to healthy tissue do not exceed tolerance doses and that the dose to the tumour is maximised. To accomplish these objectives, commercially available 3-D treatment planning software is used to calculate doses to healthy tissue and to the tumour. It is generally believed that these commercial software packages calculate doses through the patient to within a few per cent. In order to examine this claim, dose calculations obtained from ADAC software for external beam treatment to the pelvic region of a RANDO phantom are compared with 37 thermoluminescence dosemeters placed into several slices of a RANDO phantom. The phantom was irradiated to obtain a prescription dose of 180 cGy at the tumour location. Data from homogeneous regions agree within several per cent with results obtained from ADAC software, whereas this comparison is less favourable in regions of heterogeneity. Results from Monte Carlo calculations in a homogeneous phantom are comparable to results from ADAC treatment planning software.

Studies in encephalopathic infants have demonstrated a brief phase of normal cerebral energetics following hypoxia-ischaemia prior to development of delayed energy failure. In experimental models, mild hypothermia has shown a consistent neuroprotective action, although its efficacy is critically dependent on the severity of the primary insult, the delay in initiating cooling, and the duration and depth of hypothermia. Early electroencephalographic assessment of encephalopathic infants has the potential to provide objective information about the preceding insult, aiding the selection of infants for enrollment to clinical trials. Preliminary results from a large randomised trial of selective head cooling suggest that early intervention can lead to significantly improved outcome in a subgroup of encephalopathic infants with intermediate electroencephalographic abnormalities. Further research in established experimental models is essential to improve the identification of suitable infants for treatment, to investigate the importance of variations in regional brain temperature, and to examine the therapeutic potential of hypothermia combined with other neuroprotective agents.

A recent online article in the Journal of Medical Ethics, which received wide media coverage, raised the possibility that children are being ‘subjected to torture’ due to the ‘fervent or fundamentalist views’ of their parents. However, the quality of argument in that article was inadequate to sustain such a radical thesis. There was no engagement with the perspectives of different religious traditions about end-of-life care. Instead the authors invoked practices such as male infant circumcision which are wholly irrelevant to the end-of-life theme. There were serious failings in relation to core principles of social and epide-miological research practice: the study based its conclusion on a sample of only six cases and failed to consider even the more obvious confounding features. Rather than demonizing the religious beliefs of parents there should be recognition of the need for mutual respect, dialogue based on an ‘expert-expert relationship’ and collaboration based on ‘shared understanding’.

Using a zero-offset carrier-envelope locking technique, we have synthesized an octave-spanning composite frequency comb exhibiting 132-attosecond timing jitter between the constituent pulses over a one-second observation window. In the frequency domain, this composite comb has a modal structure and coherence which are indistinguishable from those of a comb that might be produced by a hypothetical single mode locked oscillator of equivalent bandwidth. The associated phase stability enables the participating multi-color pulse sequences to be coherently combined, representing an example of multi-pulse synthesis using a femtosecond oscillator.

Objective. Juvenile idiopathic arthritis (JIA) can affect a child's performance across a range of activities necessary to normal childhood development. Although there are now several available measures of disability in JIA, none have been validated for use with children in the UK. Consequently, a study was undertaken to compare and validate four such measures, together with a locally developed function test. Methods. Fifty-three children between the ages of 5 and 16 yr were recruited into the study. The mean age was 10.4 yr and mean duration of disease 4 yr. Seventy per cent were female. Results. Internal consistency was adequate in three of five measures. Four of five measures showed the expected associations between disease activity and function (P < 0.05). The level of reliability was poor for tests that involved direct assessment by therapists. Most showed poor levels of unidimensionality. Conclusion. Until new measures become available, the CHAQ appears to be the current best buy' for measuring function in children with arthritis.

Two methods of neonatal cranial ultrasound (US) scanning, linear-array and mechanical-sector, were compared for their accuracy in predicting neurodevelopmental outcome in a cohort of 854, of whom 782 (92%) infants, all born less than 33 weeks of gestation and cared for on the Neonatal Intensive Care Unit at University College Hospital, London between 1979 and 1988, were included in the analysis. A total of 205 infants were studied by linear-array and 577 infants by mechanical-sector scan. Ultrasound findings were grouped into three risk categories on the basis of the US diagnosis. Outcome was assessed at 8 years of age. The probability estimates for neurologically disabling and nondisabling impairments, extra education and mean IQ were compared for the two US methods. There was no significant difference between the two methods in the accuracy of prediction of neurodevelopmental outcome.

Transient perinatal hypoxia-ischemia (HI) can lead to delayed cerebral damage beginning 8-24 h after resuscitation. Cerebroprotective therapies applied soon after HI may thus reduce the severity of brain injury. We have previously shown that MgSO4 administration to newborn piglets after HI fails to prevent the delayed global impairment in cerebral energy metabolism characteristic of severe brain damage. However, high extracellular concentrations of magnesium ions have been found to prevent specific excitotoxic neural cell death in vivo and in vitro. This study therefore examined the hypothesis that MgSO4 administration after HI reduces damage in some regions of the brain even though global energy metabolism is unaffected. Twelve newborn piglets were subjected to global cerebral HI by transient occlusion of both common carotid arteries and reduction of the inspired oxygen fraction to 0.12 until cerebral high-energy phosphates, measured by magnetic resonance spectroscopy, were significantly depleted. Subjects were randomly assigned to two groups of six: the first received MgSO4 (three doses, 400 mg/kg 1 h after resuscitation and 200 mg/kg at 12 and 24 h), and the second received placebo infusions. At 48 h after the start of the experiment, the piglets were killed and their brains were perfused, fixed, and embedded in paraffin wax. Five-micrometer sections were stained with hematoxylin and eosin to allow semiquantitative analysis of the severity and extent of injury to the hippocampus, cerebellum, cerebral cortex, caudate nucleus, thalamus, and striatum and the white matter tracts. There was no difference in the severity of tissue damage between the MgSO4-treated group and the placebo-treated animals in any brain region.

Life-sustaining treatment may be ethically withdrawn or withheld in critically ill or dying newborns if the action is genuinely in the best interests of the patient. This may occur in situations where life-sustaining treatment is futile because of a hopeless prognosis, or if the burdens of intensive treatment clearly outweigh its likely benefits. There is no fundamental ethical difference between the withholding of resuscitation and the withdrawing of life-sustaining treatment once it has commenced. However the actions may have different emotional and psychological implications. A decision to withdraw treatment should only be taken with the consensus of experienced staff caring for the baby and with the unpressurized agreement of the parents. Palliative care and symptomatic relief should always continue after life-support has been withdrawn. Emotional and practical support should be provided for parents and adequate training and support is essential for obstetric and neonatal unit staff.

The Hippocratic tradition of medical ethics enshrines respect for the sanctity of all human life, combined with a medical duty of care, and a duty to act according to the sole interests of the patient. The fundamental role of the doctor is to preserve and protect life. Intentional killing by commission or omission is therefore never appropriate. The doctor is called on to evaluate treatment options to withhold or withdraw any treatment in which the burdens outweigh the benefits. In the presence of significant uncertainty about the prognosis, or about the value of intensive treatment, the doctor should act to preserve life, and the withdrawal of life-sustaining treatment should only occur if the hopeless prognosis is ‘beyond reasonable doubt’. The withdrawal of futile or burdensome intensive treatment is neither morally nor practically equivalent to intentional killing.

We report the anaesthetic management of vaginal delivery in a woman with Friedreich's ataxia, who had hypertrophic cardiomyopathy and had previously undergone thoracic spinal fusion with Harrington rod fixation. Combined spinal-epidural analgesia was used. Options for the anaesthetic management of labour and delivery are discussed.

To many people, especially writers of science fiction interested in preserving brains for narrative purposes, it seems self evident that cooling the brain protects it against hypoxic–ischaemic damage. Indeed, every day, cardiac surgeons and anaesthetists cool the brains of children during surgery to protect them against the effects of cardiac arrest or cardiopulmonary bypass. However there has long been a hope that cooling the brain after hypoxia–ischaemia might lessen cerebral injury. Observational data in support of this were collected by Westin and colleagues 40 years ago,1 but experimental studies in animal models at that time failed to support the hypothesis and it fell from favour.2 Now the belief is gaining ground again among basic researchers that moderate brain cooling to around 32oC is one of several interventions which can be applied after hypoxia–ischaemia to modify the process of brain cell death and so lessen cerebral damage. A cornerstone of this growing consensus was the realisation that not only do some cells die during hypoxia–ischaemia, but many more may die hours or days later.3 In the 1980s this delayed cerebral injury was shown in infants with birth asphyxia using31P magnetic resonance spectroscopy (MRS): asphyxiated infants were usually found to have normal cerebral energy metabolism soon after resuscitation, but oxidative phosphorylation became impaired 9 to 24 hours later and remained low for many days.4 The delayed impairment of energy metabolism was not contingent on continued hypoxia–ischaemia, nor was it associated with intracellular acidosis,5 but its magnitude was linearly related to the severity of later neurodevelopmental impairment and reduced brain growth.6 This was clear evidence that the effects of birth asphyxia might become manifest only some days after resuscitation, and indeed more recent data suggest that abnormal cerebral energy metabolism and cell death …

Quantitative techniques have been derived for the measurement of global cerebral blood flow, cerebral blood volume, its reponse to changing arterial carbon dioxide tension and mixed cerebral venous saturation in the human newborn undergoing intensive care. Normal ranges have been established and significant disturbances of cerebral oxygenation and perfusion have been demonstrated in a variety of pathological conditions. Recently, absolute cerebral deoxyhaemoglobin concentration has been obtained in the newborn using second differential spectroscopy. When combined with the measurement of total cerebral haemoglobin concentration, the mean saturation of cerebral blood (SmcO2) may be obtained, allowing global cerebral oxygenation to be determined continuously in the intensive care unit.Marked changes in the concentrations of cerebral oxy– and deoxyhaemoglobin have been observed in foetuses undergoing labour. Measurements of SmcO2from the foetal brain prior to delivery have shown the unexpected close correlation with acid–base status at birth Although movement artefact remains a theoretical risk during uterine contractions, preliminary measurements of optical path length by intensity–modulated spectroscopy have demonstrated only small fluctuations. In future the clinical application of time, phase and spatially resolved spectroscopy is likely to improve both the quantitative accuracy and the regional specificity of physiological measurements in the foetal and neonatal brain.

Magnetic resonance spectroscopy (MRS) and near-infrared spectroscopy (NIRS) are capable of providing detailed information on cerebral oxidative metabolism in infants who have been resuscitated following an acute asphyxial episode. In severely affected infants studied by phosphorus and proton MRS, a consistent observation has been the development of deranged cerebral energy metabolism 12-48 hours after resuscitation, despite the maintenance of cardiovascular and respiratory homeostasis. Follow-up studies have indicated that the development of delayed energy failure is closely associated with the development of microcephaly and an adverse neurodevelopmental outcome. This pathophysiologic sequence has been modelled in newborn animals, allowing the mechanisms of delayed energy failure to be elucidated and cerebroprotective treatments to be tested. New developments in MRS and magnetic resonance imaging will enable quantitative and highly localised information on cerebral metabolism to be obtained in asphyxiated infants, increasing the accuracy of early clinical assessment. Significant cerebral vasodilatation and vasoparalysis of the cerebral circulation have been observed by NIRS in asphyxiated infants following resuscitation, but the prognostic value of this observation remains uncertain. Technical advances. in NIRS are likely to improve the reproducibility and accuracy of the technique, allowing the assessment of regional cerebral haemodynamics and metabolism at the bedside. (C) 1997 Wiley-Liss, Inc.

Ultrafast optics has changed dramatically in the last twenty years, driven by new laser sources, as well as new methods of manipulation and measurement for broadband coherent optical fields. In this article we address the means and technologies that enable experimental characterisation of short electromagnetic pulses, indicating the general principles involved, how these have been implemented in various approaches, and how the most popular methods encode the temporal electric field of a short optical pulse in the measured signal and extract the field reliably from the data. We provide a more detailed design for one of the popular methods, SPIDER.