A dynamical measure of the black hole mass in a quasar 11 billion years ago.

Tight relationships exist in the local Universe between the central stellar properties of galaxies and the mass of their supermassive black hole (SMBH)1-3. These suggest that galaxies and black holes co-evolve, with the main regulation mechanism being energetic feedback from accretion onto the black hole during its quasar phase4-6. A crucial question is how the relationship between black holes and galaxies evolves with time; a key epoch to examine this relationship is at the peaks of star formation and black hole growth 8-12 billion years ago (redshifts 1-3)7. Here we report a dynamical measurement of the mass of the black hole in a luminous quasar at a redshift of 2, with a look back in time of 11 billion years, by spatially resolving the broad-line region (BLR). We detect a 40-µas (0.31-pc) spatial offset between the red and blue photocentres of the Hα line that traces the velocity gradient of a rotating BLR. The flux and differential phase spectra are well reproduced by a thick, moderately inclined disk of gas clouds within the sphere of influence of a central black hole with a mass of 3.2 × 108 solar masses. Molecular gas data reveal a dynamical mass for the host galaxy of 6 × 1011 solar masses, which indicates an undermassive black hole accreting at a super-Eddington rate. This suggests a host galaxy that grew faster than the SMBH, indicating a delay between galaxy and black hole formation for some systems.

Abnormalities in Cortical GABAergic Interneurons of the Primary Motor Cortex Caused by Lis1 (Pafah1b1) Mutation Produce a Non-drastic Functional Phenotype.

LIS1 (PAFAH1B1) plays a major role in the developing cerebral cortex, and haploinsufficient mutations cause human lissencephaly type 1. We have studied morphological and functional properties of the cerebral cortex of mutant mice harboring a deletion in the first exon of the mouse Lis1 (Pafah1b1) gene, which encodes for the LisH domain. The Lis1/sLis1 animals had an overall unaltered cortical structure but showed an abnormal distribution of cortical GABAergic interneurons (those expressing calbindin, calretinin, or parvalbumin), which mainly accumulated in the deep neocortical layers. Interestingly, the study of the oscillatory activity revealed an apparent inability of the cortical circuits to produce correct activity patterns. Moreover, the fast spiking (FS) inhibitory GABAergic interneurons exhibited several abnormalities regarding the size of the action potentials, the threshold for spike firing, the time course of the action potential after-hyperpolarization (AHP), the firing frequency, and the frequency and peak amplitude of spontaneous excitatory postsynaptic currents (sEPSC's). These morphological and functional alterations in the cortical inhibitory system characterize the Lis1/sLis1 mouse as a model of mild lissencephaly, showing a phenotype less drastic than the typical phenotype attributed to classical lissencephaly. Therefore, the results described in the present manuscript corroborate the idea that mutations in some regions of the Lis1 gene can produce phenotypes more similar to those typically described in schizophrenic and autistic patients and animal models.

Publisher Correction: Measuring the ionisation fraction in a jet from a massive protostar.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Measuring the ionisation fraction in a jet from a massive protostar.

It is important to determine if massive stars form via disc accretion, like their low-mass counterparts. Theory and observation indicate that protostellar jets are a natural consequence of accretion discs and are likely to be crucial for removing angular momentum during the collapse. However, massive protostars are typically rarer, more distant and more dust enshrouded, making observational studies of their jets more challenging. A fundamental question is whether the degree of ionisation in jets is similar across the mass spectrum. Here we determine an ionisation fraction of ~5-12% in the jet from the massive protostar G35.20-0.74N, based on spatially coincident infrared and radio emission. This is similar to the values found in jets from lower-mass young stars, implying a unified mechanism of shock ionisation applies in jets across most of the protostellar mass spectrum, up to at least ~10 solar masses.

Black hole physics. Black hole lightning due to particle acceleration at subhorizon scales.

Supermassive black holes with masses of millions to billions of solar masses are commonly found in the centers of galaxies. Astronomers seek to image jet formation using radio interferometry but still suffer from insufficient angular resolution. An alternative method to resolve small structures is to measure the time variability of their emission. Here we report on gamma-ray observations of the radio galaxy IC 310 obtained with the MAGIC (Major Atmospheric Gamma-ray Imaging Cherenkov) telescopes, revealing variability with doubling time scales faster than 4.8 min. Causality constrains the size of the emission region to be smaller than 20% of the gravitational radius of its central black hole. We suggest that the emission is associated with pulsar-like particle acceleration by the electric field across a magnetospheric gap at the base of the radio jet.

Retrospective case-control study of viral pathogen screening in proliferative verrucous leukoplakia lesions.

OBJECTIVE: This study aimed to survey the presence of known oncoviruses in oral biopsies from patients diagnosed with the aetiologically undetermined proliferative verrucous leukoplakia and compare results to those from milder oral leukoplakia (OL) cases, oral squamous cell carcinoma, a common outcome of the lesions of interest, and healthy controls. DESIGN: Blind, retrospective, case-control study. SETTING: A stomatology unit in an academic Hospital and a Public Health laboratory. PARTICIPANTS: Forty patients were divided in four groups. Ten patients had been diagnosed with proliferative verrucous leukoplakia, 10 with OL and 10 with OSCC, and 10 were healthy subjects. MAIN OUTCOME MEASURES: The presence or absence of oncovirus DNA was assayed with the amplification of viral genetic markers using PCR and subsequent gel electrophoresis confirmation. Amplified fragments were sequenced and identified bioinformatically. RESULTS: No DNA from the herpesvirus, papillomavirus or polyomavirus species was detected in the samples. CONCLUSIONS: No association between proliferative verrucous leukoplakia and target viruses was detected. A higher throughput viral metagenomic approach may prove valuable for future analyses, as it would not be restricted to a priori knowledge of potential targets.

[Pressure-sensitive neuropathy after obstetric delivery with epidural analgesia]. / Neuropatía sensible a la presión tras un parto bajo analgesia epidural.

We report the case of a woman who requested epidural analgesia for labor in whom catheterization of the epidural space was difficult, requiring multiple punctures; furthermore, the epidural block was followed by a long expulsion phase in the delivery room. Shortly after delivery the patient experienced paresthesia and weakness in her lower limbs. A diagnosis of pressure-sensitive, or tomaculous neuropathy was based on clinical observation and neurophysiologic and genetic studies. This hereditary disease, which affects peripheral nerve myelin, involves recurrent episodes of focal demyelination when nerves are injured slightly or compressed. This condition is probably underdiagnosed, as there are very few references to it in the literature on anesthesia.

[Spanish adaptation and diagnostic validity of the Yale Global Tics Severity Scale]. / Adaptación al español y validez diagnósticade la Yale Global Tics Severity Scale.

AIM: The aim of the study is to analyse the psychometric properties of the Spanish version of the Yale Global Tics Severity Scale (YGTSS). In addition, we analysed the sensitivity of this Scale for measuring change, as an instrument for quantifying the clinical evolution of patients with Tourette syndrome. PATIENTS AND METHODS: Analysis of the properties of the adapted version of the YGTSS questionnaire is focused on the validity of the concept (principal component factor analysis), internal consistency (Cronbach's alpha), intra-observer reliability (intraclass correlation coefficient) and sensitivity to change (Wilcoxon rank sum test). RESULTS: The factor analysis confirmed the existence of two dimensions on the scale, which account for 76.3% of the variability. The internal consistency, measured by Cronbach's alpha, was 0.997 for the motor tic dimension and 0.996 for the phonic tic dimension. The intra-observer reliability, assessed by intraclass correlation coefficient, was equal to or greater than 0.95, both for the 10 items related to tics (motor and phonic) and for the item related to disability. In the global scores for motor tics, phonic tics and disability, there were statistically significant differences between the mean score for the first interview (incorporation into the study group) and the second one (after 15 days' treatment). CONCLUSIONS: The Spanish version of the YGTSS adequately reflects the three psychometric properties examined in our study population. Its validity and reliability is greater in the motor and phonic tic dimensions than in that of disability.

Positional regulation of Pax2 expression pattern in mesencephalic and diencephalic alar plate.

Regionalization of the neural tube is a fundamental event in the development of the CNS. The isthmic organizer controls the development of the mesencephalic-rhombencephalic junction by means of fibroblast growth factor 8 (Fgf8) expression. The transcription factor paired box 2 (Pax2) is expressed early in the midbrain and is later progressively restricted to the mid-hindbrain region, playing an important role in the development of the mesencephalon and the cerebellum. In this study, by implanting Fgf8-beads in the chick neural tube, we show that Fgf8 induces a heterogeneous pattern of Pax2 expression in the diencephalon. To explore the mechanisms controlling this asymmetric induction and the down-regulation of Pax2 in the anterior mesencephalon we performed antero-posterior inversions of diencephalic and/or mesencephalic neuroepithelium, with or without Fgf8-bead implantation. We show that anterior factors do not play a role in Pax2 regionalization, while posterior factors could explain these expression patterns. We conclude that the anterior mesencephalon and the diencephalon are able to retain or activate Pax2 expression under caudal influences, and to develop as a tectal structure at later developmental stages.

[Prevalence of immunity to hepatitis viruses in pregnant women from the health area of Gijón (Spain)]. / Prevalencia de inmunidad frente a los virus de la hepatitis en gestantes del Area Sanitaria de Gijón.

INTRODUCTION: The objective of the study is to determine the prevalence of hepatitis B or C chronic infection, and hepatitis A or E immunity among pregnant women from Gijón, as well as their clinical and epidemiological antecedents. PATIENTS AND METHOD: HBsAg and anti-HCV were determined in 2287 pregnant women consecutively attended in the Cabueñes Hospital, Gijón. Ninety nine of them, non-European or Gipsy, were also tested for anti-HAV IgG and anti-HEV IgG as were a sample of 325 and 365 respectively of the remaining 2188. Several clinical and epidemiological parameters were checked in all of them. RESULTS: Hepatitis B virus: 10.8% (246/2287) were previously vaccinated. Among the 2043 non vaccinated, 0.8% (17 cases) were HBsAg+. None of them had HBV replication and in 59% (10/17) the HBV infection was unknown. Hepatitis C virus: 1.44% (33/2287) women were anti-VHC+, 1.26% (29/2287) anti-VHC and PCR+. In 28% of them (8/29) no parenteral risk factor was identified. Again, the infection was unknown in 58% (17/29) previously unknown. Hepatitis A virus: excluding non-European and Gipsy women, with a rate of immunity against HAV in younger than 29 years-old of 57% (12/21) and 89% (16/18), respectively, the anti-HAV IgG was positive in 17% (22/128) of the women younger than 29 years-old, 28% (60/214) between 29 and 36 years-old, and in 56% (13/23) of those older than 36 years-old. Hepatitis E virus: anti-HEC IgG was found in 2% (2/99) non European or Gipsy pregnant women and in 0.6% of the rest (2/325). CONCLUSIONS: a). Vaccination rate against hepatitis B virus is still low among pregnant women in Gijón; b). most of HBsAg+ or anti-VHC+ ignore it and many of them have not an evident risk factor; c). susceptibility to hepatitis A infection is high, with progress towards adult age, and d). remember the possibility of infection by hepatitis E virus.

[Epidemiology of chronic inflammatory bowel disease in Gijón, Asturias]. / Epidemiología de la enfermedad inflamatoria intestinal crónica en Gijón. Asturias.

AIMS: To determine several aspects of the epidemiology of chronic inflammatory bowel disease (IBD), including distribution of the various forms of IBD, sex, age at diagnosis considering lag-time to diagnosis, criteria used in the diagnosis, the relationship between educational level and activity, familial aggregation, phenotype (site and clinical type), number of admissions and mean hospital stay/year, surgical requirements and mortality. PATIENTS AND METHODS: We carried out a retrospective (1954-1993) and prospective (1994-97) descriptive epidemiologic population study, in the fifth health district of Gijón in Asturias (Spain), with 225,798 inhabitants. A total of 595 patients diagnosed with chronic IBD according to the diagnostic criteria described by Lennard-Jones and Truelove for Crohn's disease (CD) and ulcerative colitis (UC) and according to Ashley B. Price's criteria for indeterminate colitis (IC) were studied. In all patients a complete clinical follow-up was performed. RESULTS: During the study period, we diagnosed 595 patients with IBD [305 patients with UC (51.3%), 272 (45.7%) patients with CD and 18 (3%) with IC]. Sex distribution was 287 females (48.2%) and 308 males (51.8%), with a male/female ratio of 1.07. Mean age at presentation was 38.79 +/- 17.44 years (UC: 43.37 +/- 17.55; CD: 33.98 +/- 16.16; IC: 33.73 +/- 13.48), p = 0.000. Age at onset prior to diagnosis was as follows: UC: 42.03; CD: 30.47; IC: 30.99 (p = 0.000). Diagnostic criteria used in UC was symptomatic in 99.01% (p = ns), endoscopic in 95.04% (p = 0.000), and pathologic in 87.21% (p = 0.000); in CD diagnostic criteria used was radiologic in 85.29% (p = 0.000). A total of 29.1% of patients with UC and 66.7% of those with CD had higher education (p = 0.0005). Family history was found in 9.8%. Anatomical site was as follows: in UC: rectum 21%, 28.2% rectum and sigmoid, 22.3% left colitis, 4.2% distal to hepatic flexure and 24% pancolitis; in CD: 32.72% terminal ileum, 19.11% colon, 37.13% ileo-colon, 11.02% extensive intestinal and 3.67% gastro-duodenal. A total of 8.37% of patients with UC and 14.51% of those with CD had been hospitalized during the previous 4 years; mean hospital stay was 1.63 days in UC and 2.27 days in CD. The mean surgical requirements were 0.54 +/- 1.08 (31.59%); UC: 0.11 +/- 0.36 (10.2%); CD: 1.04 +/- 1.38 (56.25%), p = 0.000. The mortality rate was 48.73 deaths/1,000 inhabitants (UC: T = 65.57; CD: T = 33.08; IC:T= 0) p = ns. The standardized mortality ratio was 4.83 (UC: 6.51; CD: 3.28). CONCLUSIONS: We highlight the uniformity of the distribution of IBD in relation to types of disease and sex. Patients with CD had a higher level of education. Genetic components play an important role in these diseases and familial aggregation was high, especially in CD. Complicated situations are infrequent in this group of patients. Morbidity was higher in patients with CD as reflected by surgical requirements and hospital stay. Mortality was lower in CD than in UC.

[Incidence and prevalence of inflammatory bowel disease in Gijon, Asturias, Spain]. / Incidencia y prevalencia de la enfermedad inflamatoria intestinal en Gijón (Asturias).

AIM: To determine the incidence and prevalence of inflammatory bowel disease in our area and to compare our results with those of other series from Spain and other parts of the world. PATIENTS AND METHODS: Descriptive epidemiologic population study, retrospective (1954-1993) and prospective (1994-1997) in health district V of Gijón in Asturias (Spain) with 225,798 inhabitants. Diagnostic criteria used were those described by Lennard-Jones and Truelove for Crohn's disease and ulcerative colitis and those described by Ashley B. Price for indeterminate colitis. Annual incidence was expressed per 100,000 inhabitants. Prevalence was calculated excluding cured patients: proctocolectomized in ulcerative colitis (10 cases) and deaths (29 cases). RESULTS: During the period studied, 595 patients were diagnosed with bowel disease (305 patients with ulcerative colitis, 272 with Crohn's disease and 18 with indeterminate colitis). Mean annual incidence (1954-1997) was 6.128 (95% CI: 2.90-9.36). In the 4-year prospective study the incidence was 15.49 (95% CI: 11.19-21.79), 9.36 for ulcerative colitis, 6.08 for Crohn's disease and 0.77 for indeterminate colitis (UC/CD: 1.58). Prevalence was 246.23 (95% CI: 225.6-226.70, 212.79 for ulcerative colitis, 116.47 for Crohn's disease and 7.97 for indeterminate colitis. CONCLUSIONS: Incidence and prevalence obtained in our environment were higher than those described in other areas of Spain and were similar to those found in areas of Europe and other parts of the world with a higher incidence. Incidence and prevalence have increased since 1980, probably due to the widespread use of endoscopy as a diagnostic technique. Rates were higher in the prospective study than in the retrospective one.

Mortality and causes of death in patients with chronic inflammatory bowel disease in Gijón, Asturias (Spain).

OBJECTIVE: to review mortality, survival, influence of age at diagnosis and at death, cause of death, and relation with the extent of chronic inflammatory bowel disease, in a city in northern Spain. METHOD: descriptive retrospective epidemiological study of 516 patients diagnosed in Gijón (Asturias) between 1954 and 1997. RESULTS: of the 26 patients who died (5.03%), 18 had ulcerative colitis, 8 had Crohn's disease, and none had indeterminate colitis. Mortality was higher than in the general population, with a standard mortality ratio (SMR) of 5 (95% confidence interval 1.6-11.6). We found no differences in sex ratio (p = 0.63). Mean duration of the disease was 10 +/- 8 years in surviving patients, and 6 +/- 6 years in patients who died (p = 0.02). Duration was longer in Crohn's disease than in ulcerative colitis (p = 0.014). Mean age at diagnosis for chronic inflammatory bowel disease was 37.5 +/- 17 years in patients who survived, and 58 +/- 18 years in patients who died (p = 0.0005). Mean age at death was 64 +/- 20 years. In Crohn's disease, the most frequent cause of death was the primary disease (50%), followed by tumors of different origin (37.5%). In ulcerative colitis the primary disease was also the most frequent cause of death (38.%), followed by thromboembolic disease (22.2%) and tumors (22.2%). CONCLUSIONS: mortality among patients with chronic inflammatory bowel disease is higher than in the general population in our setting, decreases as duration of the disease increases, and is higher in patients diagnosed at older ages. Fewer than half the deaths were due to the primary disease; many patients with Crohn's disease died from tumors or thromboembolic disease.