Neuropsychological assessment and cortisol levels in biofluids from early Alzheimer's disease patients.

Cortisol dysregulation is proposed as a factor in the development of Alzheimer's disease (AD). AD patients can show high cortisol levels in prodromal phases of AD, early enough that neuropsychological alterations exist but activities of daily living remain unimpaired. Nevertheless, it is unknown if biofluid cortisol levels can have some AD predictive power together with neuropsychological assessment in prodromal stages in comparison with other cognitive disorders. In this work, an analytical method based on ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) was applied to determine the cortisol levels in different biofluids (urine, plasma, saliva, cerebrospinal fluid). Early AD patients and non-AD patients recruited at out-patient neurological unit were classified from the standard cerebrospinal fluid biomarkers levels (ß-amyloid, tau, phosphorylated tau), and studied with an extensive neuropsychological assessment including global, neuropsychological, functional and affective scales. We used a logistic regression model to discriminate between the AD and non-AD groups. Higher plasma cortisol levels were found in the AD group than in the non-AD group (p < 0.001). Regarding neuropsychological evaluation, delayed memory was used as representative of the neuropsychological status, and lower scores were obtained in the AD group (p < 0.001). The prediction model, including plasma cortisol levels and delayed memory scores, achieved an AUC of 0.93, as well as a sensitivity of 97% and a specificity of 69.4%. In conclusion, plasma cortisol levels and delayed memory scores were specifically impaired in early AD, allowing the development of a new diagnostic model which could be employed as a very satisfactory screening system.

Non-invasive monitoring of stress biomarkers in the newborn period.

The neonatal period is a highly sensitive time span during which stressful experiences may have an influence on later health outcomes. Medical procedures applied to newborn babies during hospitalization are stressors that trigger a physiological and psychological stress response. Stress response has been traditionally evaluated using scores based on behavioural signs such as facial expressions, limb movements, crying, etc., which are subjectively interpreted. Only few studies have employed measurable physiological signs to objectively evaluate the stress response to specific interventions. The aim of this review is to inform of recently developed biochemical methods that allow clinicians to evaluate the stress response to medical procedures performed in the neonatal period in biological samples non-invasively obtained. Stress biomarkers are based on the physiological stress response mediated by the hypophysis-pituitary-adrenal axis and the sympathetic-adreno-medullary systems. Cortisol is at present the most widely employed laboratory determination to measure stress levels. In recent years, sequentially determined salivary cortisol levels have allowed non-invasive monitoring of newborn infants under stressful conditions in the NICU.

Umbilical cord milking reduces the risk of intraventricular hemorrhage in preterm infants born before 32 weeks of gestation.

OBJECTIVE: Intraventricular hemorrhage (IVH) is a common complication in extremely preterm infants. We aimed to demonstrate that umbilical cord milking (UCM) would reduce the incidence of IVH in this at risk population. STUDY DESIGN: We compared the incidence of IVH in a prospective cohort of consecutively born preterm infants <32 weeks' gestation receiving UCM (n = 33) with a historical cohort that underwent immediate cord clamping (ICC) (n = 36). RESULTS: No significant differences regarding perinatal characteristics were present between both groups except for chorioamnionitis and preterm rupture of membranes which were more frequent in the UCM group. There was a significant reduction in the incidence of IVH in the UCM group as compared to the ICC group (UCM vs. ICC = 12 vs. 33%, p = 0.037; OR = 0.276 (95% CI 0.079-0.967; p = 0.033; NNT = 4.7) and a reduction in the number of transfusions (UCM vs. ICC = 56 vs. 30%, p = 0.035; OR = 0.348 (0.129-0.938; p = 0.033; NNT = 3.8). UCM was safe for mothers (similar decrease in maternal hemoglobin) and offspring. CONCLUSION: UCM significantly reduced the incidence of IVH in preterm infants < 32 weeks' gestation without associated complications for mother or offspring.

Identification of extracellular vesicles and characterization of miRNA expression profiles in human blastocoel fluid.

In this study, for the first time, we demonstrated the presence of microRNAs and extracellular vesicles in human blastocoel fluid. The bioinformatic and comparative analyses identified the biological function of blastocoel fluid microRNAs and suggested a potential role inside the human blastocyst. We found 89 microRNAs, expressed at different levels, able to regulate critical signaling pathways controlling embryo development, such as pluripotency, cell reprogramming, epigenetic modifications, intercellular communication, cell adhesion and cell fate. Blastocoel fluid microRNAs reflect the miRNome of embryonic cells and their presence, associated with the discovery of extracellular vesicles, inside blastocoel fluid, strongly suggests their important role in mediating cell communication among blastocyst cells. Their characterization is important to better understand the earliest stages of embryogenesis and the complex circuits regulating pluripotency. Moreover, blastocoel fluid microRNA profiles could be influenced by blastocyst quality, therefore, microRNAs might be used to assess embryo potential in IVF cycles.

A review of international clinical practice guidelines for the use of oxygen in the delivery room resuscitation of preterm infants.

AIM: To collate and assess international clinical practice guidelines (CPG) to determine current recommendations guiding oxygen management for respiratory stabilisation of preterm infants at delivery. METHODS: A search of public databases using the terms 'clinical practice guidelines', 'preterm', 'oxygen' and 'resuscitation' was made and complemented by direct query to consensus groups, resuscitation expert committees and clinicians. Data were extracted to include the three criteria for assessment: country of origin, gestation and initial FiO2 and target SpO2 for the first 10 minutes of life. RESULTS: A total of 45 CPGs were identified: 36 provided gestation specific recommendations (<28 to <37 weeks) while eight distinguished only between 'preterm' and 'term'. The most frequently recommended initial FiO2 were between 0.21 and 0.3 (n = 17). Most countries suggested altering FiO2 to meet SpO2 targets recommended by expert committees, However, specific five-minute SpO2 targets differed by up to 20% (70-90%) between guidelines. Five countries did not specify SpO2 targets. CONCLUSION: CPG recommendations for delivery room oxygen management of preterm infants vary greatly, particularly in regard to gestational ages, initial FiO2 and SpO2 targets and most acknowledge the lack of evidence behind these recommendations. Sufficiently large and well-designed randomised studies are needed to inform on this important practice.

Cumulus cells surrounding oocytes with high developmental competence exhibit down-regulation of phosphoinositol 1,3 kinase/protein kinase B (PI3K/AKT) signalling genes involved in proliferation and survival.

STUDY QUESTION: Is the phosphoinositol 1,3-kinase/protein kinase B (PI3K/AKT) pathway expression profile in cumulus cells (CCs) a potential marker of oocyte competence and predictive of pregnancy outcome? SUMMARY ANSWER: Eleven genes (AKT1, ARHGEF7, BCL2L1, CCND1, E2F1, HRAS, KCNH2, PIK3C2A, SHC1, SOS1 and SPP1) in the PI3K/AKT pathway were significantly down-regulated in CCs from oocytes that went on to produce a pregnancy compared to CCs associated with a negative outcome. WHAT IS KNOWN ALREADY: The PI3K/AKT pathway plays a pivotal role in the interdependence and continuous feedback between the oocyte and CCs. STUDY DESIGN SIZE, DURATION: The expression analysis of 92 transcripts in the PI3K/AKT pathway in CCs from patients with negative or positive pregnancy outcome, after single embryo transfer, was performed. Mouse CCs target gene expression was conducted to associate the expression profile of PI3K/AKT pathway to oocyte developmental profile. PARTICIPANTS/MATERIALS, SETTING, METHODS: Fifty-five good prognosis IVF patients who had been referred to IVF or intracytoplasmic sperm injection treatment for male-factor infertility or tubal disease were enroled. CCs from single cumulus-oocyte complexes (COCs) from 16 patients who underwent a single embryo transfer were analyzed. Twenty-five CD-1 mice were used to assess gene expression in CCs associated with oocytes with different competence in relation to hCG priming. A total 220 human COCs were collected. The RNA extracted from CCs of 16 selected patients was used to analyze PI3K/AKT pathway gene expression employing a 96-well custom TaqMan Array. Expression data of CCs associated to positive IVF outcome were compared to data from negative outcome samples. Mice were sacrificed after 9, 12, 15, 21 and 24 h post-hCG administration to obtain CCs from MII oocytes with different developmental competence. Akt1, Bcl2l2 and Shc1 expression were tested in the collected mouse CCs. In addition, the expression of upstream regulator ESR1, the gene encoding for the oestrogen receptor ERß, and the downstream effectors of the pathway FOXO1, FOXO3 and FOXO4 was evaluated in human and mouse samples. MAIN RESULTS AND THE ROLE OF CHANCE: Transcripts involved in the PI3K Signaling Pathway were selectively modulated according to the IVF/ICSI outcome of the oocyte. Eleven transcripts in this pathway were significantly down-regulated in all samples of CCs from oocytes with positive when compared those with a negative outcome. These outcomes were confirmed in mouse CCs associated with oocytes at different maturation stages. Expression data revealed that the down-regulation of ESR1 could be related to oocyte competence and is likely to be the driver of expression changes highlighted in the PI3K/AKT pathway. LIMITATIONS REASONS FOR CAUTION: Small sample size and retrospective design. WIDER IMPLICATIONS OF THE FINDINGS: The CCs expression profile of PI3K/AKT signaling genes, disclosed a specific CCs gene signature related to oocyte competence. It could be speculated that CCs associated with competent oocytes have completed their role in sustaining oocyte development and are influencing their fate in response to metabolic and hormonal changes by de-activating anti-apoptotic signals. STUDY FUNDING/COMPETING INTEREST(S): Supported by Merck Serono an affiliate of Merck KGaA, Darmstadt, Germany (research grant for the laboratory session; Merck KGaA reviewed the manuscript for medical accuracy only before journal submission. The authors are fully responsible for the content of this manuscript, and the views and opinions described in the publication reflect solely those of the authors). The authors declare no conflict of interest.

[More than three hours, less than three years. Safety of anesthetic procedures in children under three years, subject to surgeries of more than three hours]. / Más de tres horas y menos de tres años. Seguridad de procedimientos anestésicos en niños menores de tres años, sometidos a cirugías de más de tres horas.

The Food and Drug Administration (USA) warning (December 2016) on the safety of general anesthesia and sedation in patients younger that 3 years and pregnant women has raised many questions about the attitude that should be taken by professionals involved in the treatment of these patients. In view of this situation, the following Medical Scientific Societies: SEDAR, SECP, SECIP and SENeo have constituted a working group to analyze and clarify the safety of these techniques. In the present article, we conclude that at present both general anesthesia and deep sedation should continue to be considered safe techniques because there is no sufficient opposing evidence in clinical studies with humans. Despite this, we should not ignore the problem which must be followed carefully mainly in patients under three years of age undergoing anesthetic procedures longer than three hours or prolonged sedation in Neonatal or Pediatric Intensive Care Units.

La alerta de la FDA de diciembre 2016, sobre la seguridad de la anestesia general y las sedaciones en pacientes menores de 3 años y en mujeres embarazadas, ha suscitado numerosas dudas sobre la actitud que deben tomar los profesionales implicados en el tratamiento de estos pacientes. Ante esta situación, las siguientes Sociedades Científicas Médicas: SEDAR (Sociedad Española de Anestesia y Reanimación), SECP (Sociedad Española de Cirugía Pediátrica), SECIP (Sociedad Española de Cuidados Intensivos Pediátricos) y SENeo (Sociedad Española de Neonatología), han constituido un grupo de trabajo para analizar y clarificar la seguridad de estas técnicas. En este artículo concluimos que en el momento actual tanto la anestesia general como la sedación profunda deben seguir siendo consideradas como técnicas seguras, porque no existen evidencias de lo contrario en estudios con seres humanos. Esta seguridad no nos permite ignorar el problema, que debe ser seguido con atención, fundamentalmente en pacientes de menos de tres años, sometidos a procedimientos anestésicos de más de tres horas o a sedaciones prolongadas en las Unidades de Cuidados Intensivos Neonatales o Pediátricos.

Perinatal health services organization for preterm births: a multinational comparison.

OBJECTIVE: To explore population characteristics, organization of health services and comparability of available information for very low birth weight or very preterm neonates born before 32 weeks' gestation in 11 high-income countries contributing data to the International Network for Evaluating Outcomes of Neonates (iNeo). STUDY DESIGN: We obtained population characteristics from public domain sources, conducted a survey of organization of maternal and neonatal health services and evaluated the comparability of data contributed to the iNeo collaboration from Australia, Canada, Finland, Israel, Italy, Japan, New Zealand, Spain, Sweden, Switzerland and UK. RESULTS: All countries have nationally funded maternal/neonatal health care with >90% of women receiving prenatal care. Preterm birth rate, maternal age, and neonatal and infant mortality rates were relatively similar across countries. Most (50 to >95%) between-hospital transports of neonates born at non-tertiary units were conducted by designated transport teams; 72% (8/11 countries) had designated transfer and 63% (7/11 countries) mandate the presence of a physician. The capacity of 'step-down' units varied between countries, with capacity for respiratory care available in <10% to >75% of units. Heterogeneity in data collection processes for benchmarking and quality improvement activities were identified. CONCLUSIONS: Comparability of healthcare outcomes for very preterm low birth weight neonates between countries requires an evaluation of differences in population coverage, healthcare services and meta-data.

Development of a reliable analytical method to determine lipid peroxidation biomarkers in newborn plasma samples.

This paper describes a reliable analytical method based on ultra-performance liquid chromatography coupled to tandem mass spectrometry to determine F2-isoprostanes and other total byproducts (isoprostanes, isofurans, neuroprostanes and neurofurans) as lipid peroxidation biomarkers in newborn plasma samples. The proposed procedure is characterized by a simple sample treatment employing a reduced sample volume (100µL). Also, it shows a high throughput and high selectivity to determine simultaneously different isoprostane isomers in a large number of samples. The reliability of the described method was demonstrated by analysis of spiked plasma samples, obtaining recoveries between 70% and 130% for most of the analytes. Taking into account the implementation of further clinical studies, it was demonstrated the proper sensitivity of the method by means of the analysis of few human newborn plasma samples. In addition to this, newborn piglet plasma samples (n=80) were analyzed observing that the developed method was suitable to determine the analyte levels present in this kind of samples. Therefore, this analytical method could be applied in further clinical research about establishment of reliable lipid peroxidation biomarkers employing this experimental model.

Does the intravenous administration of frusemide reduce endolymphatic hydrops?

OBJECTIVE: To verify the hypothesis that intravenous frusemide reduces endolymphatic hydrops, as evaluated by three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging following intratympanic gadolinium administration. METHODS: The study comprised 12 patients (7 females and 5 males, aged 19-74 years) with Ménière's disease. Disease duration ranged from 0.5 to 8 years, with a frequency of 0.5 to 6 vertigo spells per month, as calculated in the last 6 months. Three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging was performed 24 hours after intratympanic injection of gadobutrol diluted eight-fold. Frusemide 20 mg was given intravenously immediately after imaging. Magnetic resonance imaging was repeated after 1 hour, using the same parameters and sequence. RESULTS: All patients showed enhancement defects, indicating endolymphatic hydrops of variable degrees. No modifications occurred at the second magnetic resonance imaging performed 1 hour after frusemide administration. CONCLUSION: There was no evidence of endolymphatic hydrops modification 1 hour after intravenously administered frusemide. Therefore, loop diuretics in Ménière's disease, which are today used on an empirical basis, must be reconsidered. Implications of these outcomes are discussed and related to the role of endolymphatic hydrops in the development of Ménière's disease.

[Five years after the Spanish neonatal resuscitation survey. Are we improving?]. / Encuesta española de reanimación neonatal 5 años después. ¿Vamos mejorando?

INTRODUCTION: An analysis is presented of delivery room (DR) neonatal resuscitation practices in Spanish hospitals. METHODS: A questionnaire was sent by e-mail to all hospitals attending deliveries in Spain. RESULTS: A total of 180 questionnaires were sent, of which 155 were fully completed (86%). Less than half (71, 46%) were level i or ii hospitals, while 84 were level iii hospital (54%). In almost three-quarters (74.2%) of the centres, parents and medical staff were involved in the decision on whether to start resuscitation or withdraw it. A qualified resuscitation team (at least two members) was available in 80% of the participant centres (63.9% level i-ii, and 94.0% level iii, P<.001). Neonatal resuscitation courses were held in 90.3% of the centres. The availability of gas blenders, pulse oximeters, manual ventilators, and plastic wraps was higher in level iii hospitals. Plastic wraps for pre-term hypothermia prevention were used in 63.9% of the centres (40.8% level i-iiand 83.3% level iii, P<.001). Term newborn resuscitation was started on room air in 89.7% of the centres. A manual ventilator (T-piece) was the device used in most cases when ventilation was required (42.3% level i-iiand 78.6% level iii, P<.001). Early CPAP in preterm infants was applied in 91.7% of the tertiary hospitals. In last 5 years some practices have improved, such neonatal resuscitation training, pulse oximeter use, or early CPAP support. CONCLUSIONS: There is an improvement in some practices of neonatal resuscitation. Significant differences have been found as regards the equipment or practices in the DR, when comparing hospitals of different levels of care.

[Pilot study on stress and resilience in families with premature newborns]. / Estudio piloto sobre el estrés y la resiliencia familiar en recién nacidos prematuros.

INTRODUCTION: Prematurity is associated with severe clinical conditions, long hospital stays, and uncertainty about patient outcomes. These circumstances lead to a stressful situation that may affect family functioning. The aim of this study was to study risk and protection factors affecting family functioning in preterm as compared to healthy term infants. POPULATION AND METHODS: Preterm infants with and without pathological conditions (n=40) were recruited at 24 months post-conception age, together with a control group of healthy term newborn infants (n=31). Parents or usual caregivers responded to the Inventory of Family Protection Factors and Parental Stress scales. The results were compared using the Student t test, unidirectional analysis of variance and the Tukey test. RESULTS: Parents of the control group attained higher scores than those of the preterm group for all the items studied; however, parents of preterm infants with pathological conditions perceived significantly less family resilience and more stress related to the upbringing of their child. CONCLUSIONS: Prematurity itself is a risk factor for family dysfunction because it causes an elevated degree of parental stress and difficulties in the development of protection factors such as resilience.

Ultra high performance liquid chromatography coupled to tandem mass spectrometry determination of lipid peroxidation biomarkers in newborn serum samples.

Byproducts of arachidonic (AA) and docosahexaenoic acid (DHA) oxidation are highly relevant for the study of free radical associated conditions in the perinatal period. Plasma metabolites can provide the clinician with a snapshot of the oxidant status of patients before and after specific clinical interventions (e.g.: supplementation with oxygen). We describe a new andreliable ultra-performance liquid mass spectrometry method to determine F2-isoprostanes and other byproducts (isoprostanes, isofurans, neuroprostanes, neurofurans) in newborn serum samples. Cord blood samples were obtained from severely depressed newborn infants (Apgar score 1 min < 3; arterial cord pH < 7.00), and aliquoted for serum determination and stored at -80 °C. A UHPLC-MS/MS method was employed. It has a series of technical advantages: simple sample treatment; reduced sample volume (100 µL) which is essential for preterm neonates with low circulating blood volume, high throughput of sample analysis (96 samples in less than 24 h) and high selectivity for different isoprostanes isomers. Excellent sensitivity was achieved within limits of detection between 0.06 and 4.2 nmol L(-1), which renders this method suitable to monitoranalyte concentration in newborn samples. The method's precision was satisfactory; with coefficients of variation around 5-12% (intra-day) and 7-17% (inter-day). The reliability of the described method was assessed by analysis of spiked serum samples obtaining recoveries between 70% and 120%. The proposed method has rendered suitable for serum determination for newborn babies at risk of oxygen free radical associated conditions.

Detection of batch effects in liquid chromatography-mass spectrometry metabolomic data using guided principal component analysis.

Metabolomics based on liquid chromatography-mass spectrometry (LC-MS) is a powerful tool for studying dynamic responses of biological systems to different physiological or pathological conditions. Differences in the instrumental response within and between batches introduce unwanted and uncontrolled data variation that should be removed to extract useful information. This work exploits a recently developed method for the identification of batch effects in high throughput genomic data based on the calculation of a δ statistic through principal component analysis (PCA) and guided PCA. Its applicability to LC-MS metabolomic data was tested on two real examples. The first example involved the repeated analysis of 42 plasma samples and 6 blanks in three independent batches, and the second data set involved the analysis of 101 plasma and 18 blank samples in a single batch with a total runtime of 50h. The first and second data set were used to evaluate between and within-batch effects using the δ statistic, respectively. Results obtained showed the usefulness of using the δ statistic together with other approaches such as summary statistics of peak intensity distributions, PCA scores plots or the monitoring of IS peak intensities, to detect and identify instrumental instabilities in LC-MS.

[Factors associated with early weaning in a Spanish region]. / Factores asociados al abandono precoz de la lactancia materna en una región del este de España.

INTRODUCTION: Breastfeeding has undoubtedly great benefits. Previous studies have foundan early dropout. Only a few studies have investigated related factors. Our aim was to find out on-going breastfeeding rates along the first 12 months after birth and analyse factors associated with early weaning. MATERIAL AND METHODS: This is a prospective study including consecutive pairs (mother and newborn) till completion of the required sample. Variables were collected performing a structured program of surveys to the mothers. Bivariate and multivariate analysis of the data was performed. RESULTS: A total of 452 pairs were recruited. It was found that 81% of them started breastfeeding, with a prevalence of breastfeeding of 39% and 21% at 3 and 6 months after birth, respectively. Factors associated with early discontinuation of breastfeeding were: pregnancy induced by assisted reproduction methods (OR=5.58; 95% CI: 2.62-11.91), maternal smoking (OR=1.56; 95% CI: 1.10-2.22), poor maternal expectations about the duration of breastfeeding (OR=2.19; 95% CI: 1.49-3.23), use of nipple shields for breastfeeding (OR=2.57; 95% CI: 1.69-3.90), pacifier use on a regular basis during the first month after delivery (OR=1.39; 95% CI: 1.02-1.91), maternal university educational level (OR=0,59; 95% CI: 0,40-0,88), attending birth preparation programs during pregnancy (OR=0,68; 95% CI: 0,49-0,94), and believing having enough milk output at the time of discharge (OR=0,66; 95% CI: 0,47-0,92). CONCLUSIONS: International recommendations about duration of breastfeeding are not achieved in our country because of high rates of early weaning. We describe the known factors involved and other novel factors. The implementation of interventions to increase breastfeeding rates and to prevent early weaning are strongly recommended.

Differential hemodynamic effects of levosimendan in a porcine model of neonatal hypoxia-reoxygenation.

BACKGROUND: Neonatal asphyxia can be complicated by myocardial dysfunction with secondary alterations in pulmonary and regional hemodynamics. Levosimendan is a calcium-sensitizing inotrope that may support cardiac output, but little is known regarding its differential hemodynamic effects in asphyxiated neonates. METHODS: Mixed breed piglets (1-4 days old, weight 1.6-2.3 kg) were acutely instrumented. Normocapnic alveolar hypoxia (10-15% oxygen) was induced for 2 h, followed by reoxygenation with 100% (1 h) and then 21% oxygen (3 h). At 2 h of reoxygenation, after volume loading (Ringer's lactate 10 ml/kg), either levosimendan (0.1 or 0.2 µg/kg/min) or D(5)W (placebo) was infused for 2 h in a blinded, block-randomized fashion (n = 7-8/group). The systemic, pulmonary and regional (carotid, superior mesenteric and renal) hemodynamics were compared. RESULTS: At 0.1 and 0.2 µg/kg/min, levosimendan significantly increased cardiac output (121 and 123% of pretreatment, respectively) and heart rate, and decreased systemic vascular resistance without causing hypotension. Pulmonary arterial pressure and estimated pulmonary vascular resistance were significantly increased from pretreatment baseline in 0.1 but not 0.2 µg/kg/min levosimendan. Levosimendan infusion had no effects on regional hemodynamics. Myocardial efficiency but not oxygen consumption increased with 0.1 µg/kg/min levosimendan without significant effects on plasma troponin and myocardial lactate levels. CONCLUSIONS: In newborn piglets following hypoxia-reoxygenation injury, levosimendan improves cardiac output but has no marked effects in carotid, superior mesenteric and renal perfusion. It appears that various doses of levosimendan increase the cardiac output through different mechanisms. Further investigations are needed to examine the effectiveness of levosimendan as a cardiovascular supportive therapy either alone or in conjunction with other inotropes in asphyxiated neonates.

[Neuroprotection with hypothermia in the newborn with hypoxic-ischaemic encephalopathy. Standard guidelines for its clinical application]. / Neuroprotección con hipotermia en el recién nacido con encefalopatía hipóxico-isquémica. Guía de estándares para su aplicación clínica.

Standardisation of hypothermia as a treatment for perinatal hypoxic-ischaemic encephalopathy is supported by current scientific evidence. The following document was prepared by the authors on request of the Spanish Society of Neonatology and is intended to be a guide for the proper implementation of this therapy. We discuss the difficulties that may arise when moving from the strict framework of clinical trials to clinical daily care: early recognition of clinical encephalopathy, inclusion and exclusion criteria, hypothermia during transport, type of hypothermia (selective head or systemic cooling) and side effects of therapy. The availability of hypothermia therapy has changed the prognosis of children with hypoxic-ischaemic encephalopathy and our choices of therapeutic support. In this sense, it is especially important to be aware of the changes in the predictive value of the neurological examination and the electroencephalographic recording in cooled infants. In order to improve neuroprotection with hypothermia we need earlier recognition of to recognise earlier the infants that may benefit from cooling. Biomarkers of brain injury could help us in the selection of these patients. Every single infant treated with hypothermia must be included in a follow up program in order to assess neurodevelopmental outcome.

Coherent light with tunable polarization from single-pass free-electron lasers.

Tunable polarization over a wide spectral range is a required feature of light sources employed to investigate the properties of local symmetry in matter. In this Letter, we provide the first experimental characterization of the polarization of the harmonic light produced by a free-electron laser and demonstrate a method to obtain free-electron laser harmonics with tunable polarization. Experimental results are successfully compared with theory. Our findings can be expected to have a deep impact on the design and realization of experiments requiring full control of light polarization.