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.

Large granulation cells on the surface of the giant star π1 Gruis.

Convection plays a major part in many astrophysical processes, including energy transport, pulsation, dynamos and winds on evolved stars, in dust clouds and on brown dwarfs. Most of our knowledge about stellar convection has come from studying the Sun: about two million convective cells with typical sizes of around 2,000 kilometres across are present on the surface of the Sun-a phenomenon known as granulation. But on the surfaces of giant and supergiant stars there should be only a few large (several tens of thousands of times larger than those on the Sun) convective cells, owing to low surface gravity. Deriving the characteristic properties of convection (such as granule size and contrast) for the most evolved giant and supergiant stars is challenging because their photospheres are obscured by dust, which partially masks the convective patterns. These properties can be inferred from geometric model fitting, but this indirect method does not provide information about the physical origin of the convective cells. Here we report interferometric images of the surface of the evolved giant star π1 Gruis, of spectral type S5,7. Our images show a nearly circular, dust-free atmosphere, which is very compact and only weakly affected by molecular opacity. We find that the stellar surface has a complex convective pattern with an average intensity contrast of 12 per cent, which increases towards shorter wavelengths. We derive a characteristic horizontal granule size of about 1.2 × 1011 metres, which corresponds to 27 per cent of the diameter of the star. Our measurements fall along the scaling relations between granule size, effective temperature and surface gravity that are predicted by simulations of stellar surface convection.

[The complete dislocation of the talus or «missing talus¼.] / L'image du mois. Dislocation complète du talus ou «missing talus¼.

The complete dislocation of the talus or «missing talus¼ corresponds to a simultaneous dislocation of the tibiotalar, talocalcaneal and talonavicular joints, without associated talar fracture. This lesion occurs as part of high energy trauma and accounts for 3 to 5 % of talus injuries. It is most frequently anterolateral and in more than 75 % of cases, this dislocation is open. Among the soft tissue lesions that are often associated with the dislocation, vascular lesions leading to avascular necrosis of the talus are found in almost 100 % of cases. This necrosis is generally well tolerated by the patient. A conservative treatment by reimplantation of the talus after debridement of the site should be performed as a first-line treatment as fast as possible. When the avascular necrosis of the talus is not well tolerated by the patient, a talectomy associated with tibiocalcaneal arthrodesis can be performed as a secondary procedure. Talectomy alone should not be done.

La dislocation complète du talus ou «missing talus¼ correspond à une dislocation simultanée des articulations tibiotalienne, talocalcanéenne et talonaviculaire, sans fracture talienne associée. Cette lésion survient dans le cadre d'un traumatisme à haute énergie et représente 3 à 5 % des lésions du talus. Elle est le plus fréquemment antéro-latérale et, dans plus de 75 % des cas, cette dislocation est ouverte. Parmi les lésions des tissus mous qui y sont souvent associées, les lésions vasculaires conduisant à une nécrose avasculaire du talus sont retrouvées dans presque 100 % des cas. Cette nécrose est généralement bien tolérée par le patient. Un traitement conservateur par réimplantation du talus après débridement du site doit être réalisé en première intention et ce, de manière urgente. Lorsque la nécrose avasculaire du talus n'est pas bien tolérée par le patient sur le long terme, une talectomie associée à une arthrodèse tibio-calcannénne peut être réalisée dans un second temps. La talectomie seule doit, quant à elle, être proscrite.

Test of the Einstein Equivalence Principle near the Galactic Center Supermassive Black Hole.

During its orbit around the four million solar mass black hole Sagittarius A* the star S2 experiences significant changes in gravitational potential. We use this change of potential to test one part of the Einstein equivalence principle: the local position invariance (LPI). We study the dependency of different atomic transitions on the gravitational potential to give an upper limit on violations of the LPI. This is done by separately measuring the redshift from hydrogen and helium absorption lines in the stellar spectrum during its closest approach to the black hole. For this measurement we use radial velocity data from 2015 to 2018 and combine it with the gravitational potential at the position of S2, which is calculated from the precisely known orbit of S2 around the black hole. This results in a limit on a violation of the LPI of |ß_{He}-ß_{H}|=(2.4±5.1)×10^{-2}. The variation in potential that we probe with this measurement is six magnitudes larger than possible for measurements on Earth, and a factor of 10 larger than in experiments using white dwarfs. We are therefore testing the LPI in a regime where it has not been tested before.

Spontaneous haemoperitoneum in pregnancy and endometriosis: a case series.

OBJECTIVE: To report pregnancy outcomes of SHiP (spontaneous haemoperitoneum in pregnancy) and the association with endometriosis. DESIGN: Retrospective case note review. SETTING: Dutch referral hospitals for endometriosis. SAMPLE: Eleven women presenting with 15 events of SHiP. METHODS: In collaboration with the Dutch Working Group on Endometriosis, unpublished cases of SHiP that occurred in the Netherlands between 2010 and 2015 were retrieved. MAIN OUTCOME MEASURES: Maternal and perinatal mortality and morbidity. RESULTS: SHiP occurred predominantly in the second and third trimester of pregnancy. The earliest and major presenting symptom was an acute onset of abdominal pain, often combined with low haemoglobin levels or signs of fetal distress. Imaging was a diagnostic tool when free peritoneal fluid could be observed. For surgical treatment of the bleeding site, a midline laparotomy was mostly needed, the median estimated amount of blood loss was 2000 mL. No fetomaternal or perinatal mortality was reported, despite a high rate of preterm births (54.5%). In all women, endometriosis was diagnosed at a certain moment in time and therefore was probably involved in the pathogenesis of SHiP. Four women showed recurrence of SHiP. In one of these cases the second event of SHiP occurred in a subsequent pregnancy. CONCLUSION: Pregnancy outcomes of SHiP are improving when compared with previous reports, with absent fetomaternal and perinatal mortality in this recent series. Growing knowledge and adequate multidisciplinary intervention may have contributed to these favourable results. Increasing awareness of this serious complication of pregnancy is advocated, especially in women diagnosed with endometriosis. TWEETABLE ABSTRACT: Growing awareness of SHiP is advocated, especially in women diagnosed with endometriosis.

[History of cancer and chemotherapy before chemotherapy]. / Histoire du cancer et de la chimiothérapie avant la chimiothérapie.

Chemotherapy stands today for cancer. In 1909, Paul Ehrlich (1854-1915) advocates the use of arsphenamine by infusion. So, he is considered as the father of chemotherapy. In fact, the first to have thought through chemotherapy was Sir Christopher Wren (1632-1723). In 1676, ideas and experiments on animals had sufficiently progressed to allow Michel Ettmuller (1644-1683) to publish the first edition of his book and several others were printed until 1753. In this book, he describes the first intravenous treatment, it sets the first indications, dosages and different products which can be used. However this method has been forgotten until the late 19th century.

RNAi-mediated germline knockdown of FABP4 increases body weight but does not improve the deranged nutrient metabolism of diet-induced obese mice.

OBJECTIVE: To investigate the impact of reduced adipocyte fatty acid-binding protein 4 (FABP4) in control of body weight, glucose and lipid homeostasis in diet-induced obese (DIO) mice. METHODS: We applied RNA interference (RNAi) technology to generate FABP4 germline knockdown mice to investigate their metabolic phenotype. RESULTS: RNAi-mediated knockdown reduced FABP4 mRNA expression and protein levels by almost 90% in adipocytes of standard chow-fed mice. In adipocytes of DIO mice, RNAi reduced FABP4 expression and protein levels by 70 and 80%, respectively. There was no increase in adipocyte FABP5 expression in FABP4 knockdown mice. The knockdown of FABP4 significantly increased body weight and fat mass in DIO mice. However, FABP4 knockdown did not affect plasma glucose and lipid homeostasis in DIO mice; nor did it improve their insulin sensitivity. CONCLUSION: Our data indicate that robust knockdown of FABP4 increases body weight and fat mass without improving glucose and lipid homeostasis in DIO mice.

Additive action of 11beta-HSD1 inhibition and PPAR-gamma agonism on hepatic steatosis and triglyceridemia in diet-induced obese rats.

Both 11beta-hydroxysteroid dehydrogenase (11beta-HSD1) inhibition and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonism reduce liver and plasma lipids in rodents through partly distinct mechanisms. This study aimed to assess their additivity of action on liver and plasma lipids in a model of diet-induced steatosis. Rats were fed an obesogenic diet and were treated either with an 11beta-HSD1 inhibitor (Compound A, 3 mg kg(-1) day(-1)) or rosiglitazone (RSG, 5 mg kg(-1) day(-1)) or both for 6 weeks. Compound A and RSG reduced liver steatosis and triglyceridemia, and did so additively when given in combination. The 11beta-HSD1 inhibitor had no effect on serum adiponectin, but increased liver adiponectin receptor type 2 (Adipo-R2) mRNA levels. Conversely, RSG increased serum adiponectin, a likely mediator of its antisteatotic action, but had no effect per se on the Adipo-R2 expression. mRNA levels of representative genes of fatty acid oxidation tended to be increased by both compounds. The study shows that combined 11beta-HSD1 inhibition and PPAR-gamma agonism additively reduce liver steatosis and triglyceridemia, which may eventually prove therapeutically useful.

Judgments of trained observers on adverse drug reactions.

Patients (672) admitted to a department of medicine during five consecutive months were followed by an investigator who identified 110 clinical manifestations which could have been considered adverse drug reactions. From these, 42 were excluded because they did not correspond to the definition of adverse reaction or they were inadequately documented. The remaining 68 cases were submitted to three independent observers who had to reply to a series of questions; from these replies five degrees of probability for the reaction itself were deduced. Reactions (54; 49% of the manifestations reported) were considered as certain or probable by at least two observers, but only 27 rections of these (25%) were attributed to the same drug by all three observers. There was a low level of agreement between any two observers (paired agreement ratio: 0.6 to 0.7) and little difference of agreement between any one observer and each of the others (personal agreement ratio: 0.6 to 0.7).

An integrative genomics approach to the reconstruction of gene networks in segregating populations.

The reconstruction of genetic networks in mammalian systems is one of the primary goals in biological research, especially as such reconstructions relate to elucidating not only common, polygenic human diseases, but living systems more generally. Here we propose a novel gene network reconstruction algorithm, derived from classic Bayesian network methods, that utilizes naturally occurring genetic variations as a source of perturbations to elucidate the network. This algorithm incorporates relative transcript abundance and genotypic data from segregating populations by employing a generalized scoring function of maximum likelihood commonly used in Bayesian network reconstruction problems. The utility of this novel algorithm is demonstrated via application to liver gene expression data from a segregating mouse population. We demonstrate that the network derived from these data using our novel network reconstruction algorithm is able to capture causal associations between genes that result in increased predictive power, compared to more classically reconstructed networks derived from the same data.

Cerebrospinal fluid lactate in 78 cases of adult meningitis.

In a retrospective study of 78 cases of adult meningitis, the CSF lactate was measured on the first spinal tap (ST); 25 had a bacterial meningitis, 28 a viral meningitis; 22 other cases had been on antibiotics prior to admission; 3 cases had meningitis of rare aetiology. The median CSF lactate level among the 25 bacterial cases amounted to 13.6 mmol/l (range: 3.5-24.5) whereas it remained low in the 28 viral cases: 2.7 mmol/l (range: 1.4-4.2). These differences are highly significant. The comparison of the CSF lactate level with the other tests routinely performed showed that the CSF lactate level had the highest sensitivity, specificity and predictive values. The CSF lactate level on the first ST had no prognostic value, but a rapid decrease of the CSF lactate during the treatment is indicative of good prognosis. Among the pretreated cases, a high lactate level could be an indication that bacteria were the causal agents. In conclusion, the measurement of the CSF lactate, quickly performed and inexpensive, is worth performing when a meningitis is suspected, as it appears to be the best way of distinguishing bacterial from non-bacterial meningitis.

Ultrasonography as an aid to diagnosis and treatment in a rural African hospital: a prospective study of 1,119 cases.

The aim of this study was to assess the utility of ultrasonography in a rural African hospital in Cameroon with scarce resources. A prospective questionnaire was administered and completed for each of the 1,119 consecutive cases included in the study. Among these 1,119 cases, the diagnosis made by clinicians and by echography could be verified by another means for 323 patients. Ultrasonography showed abnormal findings in 78% of the cases. In the group of 323 patients in which the diagnosis made by echography could be verified, it was correct in 95.4% of the cases, erroneous in 4.6% of the cases, judged useful for diagnosis in 67.8% of the cases, and not contributive in 27.6% of the cases. Ultrasonography was judged useful when treatment was decided upon in 62% of the cases. This study demonstrated the value of ultrasonography in the context of a developing country and the conditions by which its use could be delineated.

Anterior elbow dislocation with recurrent instability.

Anterior elbow dislocations are often associated with severe soft tissue lesions. The mechanism of dislocation is usually an anteriorly directed blow on the proximal ulna after a fall on a flexed elbow. Simple anterior elbow dislocations are traditionally treated by closed reduction followed by a short period of immobilisation. Fracture-dislocations are usually unstable after reduction and necessitate surgical management. The authors report a case of acute anterior dislocation with a concomitant radial head fracture that was complicated by recurrent instability. The literature is reviewed to discuss a treatment strategy.

[Hemi-arthroplasty of the shoulder: radiological, functional and dynamic studies]. / L'hémi-arthroplastie d'épaule: étude radiologique, fonctionnelle et dynamique.

From September 1973 to October 1992, forty-three shoulder arthroplasties were performed in forty-one patients with complicated fractures or degenerative disease. Radiological and functional assessment with a mean follow-up time of forty-five months permitted us to review twenty patients with fifteen Neer II prosthesis, three isoelastic prosthesis and two total shoulder replacements. Of these, eleven presented with traumatic injuries and four with degenerative disease. The mean age at operative time was 61 years. Radiological evaluation showed that all cases had a retroversion of about 30 degrees. Normal humeral length and lateral shifting were not achieved in most patients; in fact only one had a restored length and lateral shifting. The mean scapulothoracic range of motion was found to be half that of a normal gliding shoulder (angle 30 degrees instead of 60 degrees). The subacromial space was diminished by one third in all cases. Relief of shoulder pain was the most significant finding. Mobility was restored to a level of about 75% of normal according to Constant's Scale. Dynamometric measures showed an important loss of force (47% of normal) despite a normal external rotation force. Recent improvements in implant conception (modular prosthesis) and a better understanding of physiological shoulder mechanisms should improve the functional results of this arthroplasty in the future.

[Hepatitis C: from pathogenesis to treatment]. / L'hépatite C: de la pathogénie au traitement.

Hepatitis C virus (HCV) belongs to the greater family of Flaviviridae. It is probably responsible for the majority of NANB hepatitis. Serologic evidence in the term of antibodies against certain parts of HCV persists in 60 to 100% of patients with NANB hepatitis after blood transfusion. The evidence for the existence of a second virus responsible for NANB has not been excluded as inactivation-studies would suggest. HCV is also a common cause for sporadic acute hepatitis. It is the purpose of this article to present diagnosis, course and treatment of this form of hepatitis.

Imaging the surface of Altair.

Spatially resolving the surfaces of nearby stars promises to advance our knowledge of stellar physics. Using optical long-baseline interferometry, we constructed a near-infrared image of the rapidly rotating hot star Altair with a resolution of <1 milliarcsecond. The image clearly reveals the strong effect of gravity darkening on the highly distorted stellar photosphere. Standard models for a uniformly rotating star cannot explain our findings, which appear to result from differential rotation, alternative gravity-darkening laws, or both.

[Pressure determination in tachycardia. Improved approximation using a stage-by-stage technic]. / Mesure de pression lors de tachyarythmie. Approximation meilleure par la technique de mesure par paliers.

In heart arrhythmia, and especially tachyarrhythmia, blood pressure measurements are known to be approximate. The current recommendations proved to be unsatisfactory in a group of 23 patients in whom they were tested systematically. A simple atraumatic bedside method, developed from the standard method of measuring blood pressure by sphygmomanometer and called the "stage by stage" measurement method, is presented.

[Therapeutic approach to a cerebrovascular accident]. / Attitude thérapeutique devant un accident cérébro-vasculaire

The therapeutic approach to vascular lesions, which in fact represents the effective prevention of potential or recurrent brain damage, is discussed. The following problems are considered: asymptomatic localized vascular bruit; transient ischemic attack; minor strokes; progressive strokes; total strokes; and hemorrhages. Supportive therapy in the patient with brain damage is presented.

Role of PPARs in the regulation of obesity-related insulin sensitivity and inflammation.

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptor isoforms with key roles in the regulation of lipid and glucose metabolism. Synthetic ligands for PPAR gamma (and PPAR alpha) have effects of promoting insulin sensitization in the context of obesity. Recent evidence suggests that activation of PPAR delta might produce similar effects. Both PPAR gamma and PPAR alpha have also been shown to produce selected anti-inflammatory effects and to reduce the progression of atherosclerosis in animals (alpha and gamma) or in humans (alpha). Mechanisms underlying insulin-sensitizing effects are complex. For PPAR gamma, direct effects on adipose tissue lipid metabolism with secondary benefits in liver and/or muscle (lipid levels and insulin signaling) have been implicated. For PPAR alpha, accelerated lipid catabolism may contribute to reduced muscle or liver 'steatosis'. Anti-inflammatory mechanisms as contributors to the beneficial metabolic effects of PPAR activation are also worth considering for the following reasons: (1) obesity and insulin resistance are associated with a proinflammatory milieu. (2) PPAR gamma has clear effects to oppose the effects of tumor necrosis factor-alpha (TNFalpha) in adipocytes. (3) effects of PPAR ligands on cytokine-mediated signaling (eg via NF-kappa B) may be expected to enhance insulin action. (4) Adipose production of several molecules that are implicated as markers or mediators of inflammation is reduced. (5) In humans, treatment with either PPAR alpha or PPAR gamma agonists has been shown to reduce circulating levels of proteins that serve as markers of inflammation. (6) Adiponectin, a fat-derived circulating factor that has been implicated as having anti-inflammatory activity, is induced by PPAR gamma agonism.