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The ExoClock project is an inclusive, integrated, and interactive platform that was developed to monitor the ephemerides of the Ariel targets to increase the mission efficiency. The project makes the best use of all available resources, i.e., observations from ground telescopes, mid-time values from the literature and finally, observations from space instruments. Currently, the ExoClock network includes 280 participants with telescopes capable of observing 85\% of the currently known Ariel candidate targets. This work includes the results of $\sim$1600 observations obtained up to the 31st of December 2020 from the ExoClock network. These data in combination with $\sim$2350 mid-time values collected from the literature are used to update the ephemerides of 180 planets. The analysis shows that 40\% of the updated ephemerides will have an impact on future scheduling as either they have a significantly improved precision, or they have revealed biases in the old ephemerides. With the new observations, the observing coverage and rate for half of the planets in the sample has been doubled or more. Finally, from a population perspective, we identify that the differences in the 2028 predictions between the old and the new ephemerides have an STD that is double what is expected from gaussian uncertainties. These findings have implications for planning future observations, where we will need to account for drifts potentially greater than the prediction uncertainties. The updated ephemerides are open and accessible to the wider exoplanet community both from our Open Science Framework (OSF) repository and our website., Comment: 9 pages (47 with appendices and references), 8 figures, 2 tables. Submitted to ApJS. Revised based on the reviewer's comments

Introduction/Background* Pembrolizumab conferred a 57% objective response rate (ORR) in patients with mismatch repair deficient (MMRd) advanced endometrial cancer (EC). However, the majority of patients with advanced disease have no specific molecular profile (NSMP) tumours or p53-abnormal (p53abn). We hypothesized that pembrolizumab with an inducer of immunogenic cell death such as doxorubicin could improve clinical responses and survival in all EC molecular subtypes. Methodology The TOPIC study (NCT03276013) was an investigator-initiated, single-arm, multi-centre, phase II study in patients with recurrent/metastatic EC who received one prior line of platinum-based chemotherapy. Patients received doxorubicin 60 mg/m2 IV every 3 weeks for up to 9 cycles in combination with pembrolizumab 200 mg IV every 3 weeks up to 36 cycles, or until progression or toxicity. Tumour samples were analysed before treatment. Immunohistochemistry was performed for mismatch repair proteins and p53. Single-gene sequencing was used to detect polymerase-ɛ (POLE) exonuclease domain mutations. Primary outcome was progression-free survival rate at 6 months (PFS6). Subgroups were assessed relative to the primary outcome, ORR, median overall survival (OS), and 18-months OS rate. Result(s)* Molecular classification could be determined in 44 out of 48 patients included. As defined in the protocol, carcinosarcoma patients (n=6) were considered an exploratory cohort and were excluded from this analysis. In the non-carcinosarcoma cohort (n=38) median age was 66 years (range 37–80). Five (11.4%) patients were MMRd, 10 (22.7%) NSMP and 23 (52.3%) p53abn. No patient with POLE-mutated tumour was enrolled. Fifty-eight patients had endometroid EC, 42% serous carcinoma. Histologic grade at diagnosis: grade 1, 12.2%; grade 2, 21.1% and grade 3, 44.6%. Median follow-up at data cut-off was 19.1 months. Overall PFS6 was 59.3% (95%CI 45.4%-77.6%) with a median PFS of 6.5 months. Efficacy data according to patients’ molecular subtype are shown (see table 1). Overall, the NSMP subtype showed the better efficacy results (PFS6 of 78% and 40% ORR). Conclusion* Pembrolizumab plus doxorubicin exhibited promising antitumor activity in women with advanced EC after failure to platinum therapy, even in those patients that were not MMRd.

Fungal secondary metabolites (SMs) include medically valuable compounds as well as compounds that are toxic, carcinogenic, and/or contributors to fungal pathogenesis. It is consequently important to understand the regulation of fungal secondary metabolism. McrA is a recently discovered transcription factor that negatively regulates fungal secondary metabolism. Deletion of mcrA (mcrAΔ), the gene encoding McrA, results in upregulation of many SMs and alters the expression of more than 1000 genes. One gene strongly upregulated by the deletion of mcrA is llmG, a putative methyl transferase related to LaeA, a major regulator of secondary metabolism. We artificially upregulated llmG by replacing its promoter with strong constitutive promoters in strains carrying either wild-type mcrA or mcrAΔ. Upregulation of llmG on various media resulted in increased production of the important toxin sterigmatocystin and compounds from at least six major SM pathways. llmG is, thus, a master SM regulator. mcrAΔ generally resulted in greater upregulation of SMs than upregulation of llmG, indicating that the full effects of mcrA on secondary metabolism involve genes in addition to llmG. However, the combination of mcrAΔ and upregulation of llmG generally resulted in greater compound production than mcrAΔ alone (in one case more than 460 times greater than the control). This result indicates that deletion of mcrA and/or upregulation of llmG can likely be combined with other strategies for eliciting SM production to greater levels than can be obtained with any single strategy.

This paper analyses the local and time-dependent behavior of large-scale structures responsible for liquid circulation in gas-water flow of a 3-D cylindrical bubble column of high aspect ratio with a multiple orifice for uniform aeration. The large-scale flow structures play an important role in the mixing and the mass transfer while coherent structures dominate hydrodynamic characteristics of the turbulent flow field. A three-dimensional Euler-Euler large eddy simulation (LES) model was used to calculate large-scale structures and their interaction with bubbles at inlet superficial gas velocities of U G = 6 and 8.4 cm/s where vortical-spiral and turbulent flow regimes occur. The two-phase model gives good agreements with experimental measurements. We use a conditional sampling procedure of liquid velocity and gas hold-up time series to identify and educe the development of coherent flow structures which consists in a pair of counter-rotating vortices convected in a staggered pattern along the column in both the vortical-spiral and central plume regions. On average, the detected instantaneous events for each template account for about 12–15% of the data recorded and may appear simultaneously. These events produce important fluctuations in the axial liquid velocity and gas void fraction. The sampling procedure yielded the averaged topology of the three-dimensional large-scale structures which was visualized using isosurfaces of the vorticity for different gas flow rates. The structures have spiral tube-shaped topology rotating along the column near the walls with a pair of counter-rotating cells sustained through the flow. This work provides deep insights into turbulent flow field in gas-liquid bubble column by LES and pattern recognition.

Fungi are a major source of valuable bioactive secondary metabolites (SMs). These compounds are synthesized by enzymes encoded by genes that are clustered in the genome. The vast majority of SM biosynthetic gene clusters are not expressed under normal growth conditions, and their products are unknown. Developing methods for activation of these silent gene clusters offers the potential for discovering many valuable new fungal SMs. While a number of useful approaches have been developed, they each have limitations and additional tools are needed. One approach, upregulation of SM gene cluster-specific transcription factors that are associated with many SM gene clusters, has worked extremely well in some cases, but it has failed more often than it has succeeded. Taking advantage of transcription factor domain modularity, we have developed a new approach. We have fused the DNA-binding domain of a transcription factor associated with a silent SM gene cluster with the activation domain of a robust SM transcription factor, AfoA. Expression of this hybrid transcription factor activated transcription of the genes in the target cluster and production of the antibiotic (+)-asperlin. Deletion of cluster genes confirmed that the cluster is responsible for (+)-asperlin production, and we designate it the aln cluster. Separately, co-induction of expression of two aln cluster genes revealed the pathway intermediate (2Z,4Z,6E)-octatrienoic acid, a compound with photoprotectant properties. Our findings demonstrate the potential of our novel synthetic hybrid transcription factor strategy to discover the products of other silent fungal SM gene clusters.

Under the terms of the Creative Commons Attribution license.-- et al., The blocking of fine-capillary tubes used as flow impedances in He4 evaporation cryostats to achieve temperatures below 4.2 K is generally attributed to nitrogen or air impurities entering these tubes from the main bath. The failure of even the most rigorous low-temperature laboratory best practices aimed at eliminating the problem by maintaining the cleanliness of the helium bath and preventing impurities from entering the capillary tubes suggests that a different cause is responsible for the inexplicable reduction of impedance flow. Many low-temperature research laboratories around the world have suffered this nuisance at a considerable financial cost due to the fact that the affected systems have to be warmed to room temperature in order to recover their normal low-temperature operation performance. Here, we propose an underlying physical mechanism responsible for the blockages based upon the freezing of molecular H2 traces present in the liquid-helium bath. Solid H2 accumulates at the impedance low-pressure side, and, after some time, it produces a total impedance blockage. The presence of H2 traces is unavoidable due its occurrence in the natural gas wells where helium is harvested, forcing gas suppliers to specify a lower bound for impurity levels at about 100 ppb even in high-grade helium. In this paper, we present a simple apparatus to detect hydrogen traces present in liquid helium and easily check the quality of the liquid. Finally, we propose a solution to eliminate the hydrogen impurities in small- and large-scale helium recovery plants. The solution has been implemented in several laboratories that previously experienced a chronic occurrence of blocking, eliminating similar occurrences for more than one year., The authors are greatly appreciative and acknowledge the financial support from the Spanish Ministry of Economy and Competitiveness through the INNPACTO Projects No. IPT-2012-0442-420000 and No. MAT2015-64083-R, in addition to European Union FEDER funds.

In this study we present, analyze and compare the power spectral density of the wall shear stress in a turbulent plane channel flow obtained with different techniques. Experimentally the instantaneous wall shear stress was measured with the electrochemical technique using different probes, which give approximately the same results after applying the transfer function for correction of the probe’s inertia. Numerically, the time evolution of the wall shear stress has been determined using direct numerical simulations (DNS) and large eddy simulations (LES). The results of DNS are in a good agreement with the electrochemical flow measurements. However the power spectra of the wall shear stress obtained with LES shows deviations with respect to DNS at high frequencies because of the spatial filtering inherent to the LES technique.

A new ligand based on a ruthenocene moiety appended by a diyrromethene (Rc-dpm) was synthesized. Two copper complexes, Cu(Rc-dpm)2 (3) and Cu(Rc-dpm)acac (4), and one cobalt complex, Co(Rc-dpm)3, 5, were prepared from the ligand. These complexes were characterized by a combination of UV–Vis spectroscopy, elemental analysis, and X-ray crystallography. Copper(II) complex 3 was found to be coordinated by two dipyrromethene ligands in a distorted square planar environment around the copper while complex 4 had one dipyrromethene ligand and an acac coordinated in a nearly idealized square planar copper geometry. The cobalt(III) complex 5 has an octahedral geometry around the cobalt via the coordination of three dipyyromethene ligands.

The primary evaluation and management of 47 consecutive patients with 48 open calcaneal fractures was retrospectively analyzed. The fractures were treated over a 7year period. Forty-two fractures resulted from blunt trauma, and 6 followed penetrating trauma. The predominant mechanism of injury was a motor vehicle accident. Initial treatment consisted of emergent irrigation and debridement of the open wound with intravenous antibiotic prophylaxis. Most patients underwent a second debridement. More than two thirds of the wounds were >5 cm in length, degioving-type injuries, associated with a significant neurovascular deficit and/or required a freetissue transfer. Internal fixation of the os calcis was undertaken in 40% of patients. In addition, >40% of patients sustained concomitant foot and ankle fractures. Two patients underwent below-the-knee amputations as primary treatment. Five patients required a free-tissue transfer. Complications included two infections and one below-the-knee amputation. Two deaths occurred due to unrelated causes. Treatment standards for the optimal management of open calcaneal fractures remain controversial. A better understanding of this complex injury will help determine suitable treatment strategies.

Iatrogenic pneumocephalus is an uncommon complication observed after using the 'loss-of-resistance' technique with an air filled syringe. We report and review two cases of pneumocephalus: one subarachnoid and the other epidural.

The case is described of a pregnant patient with Marfan's syndrome scheduled at 39 weeks' gestation for elective caesarean section carried out for the first time by total intravenous anaesthesia (TIVA) with continuous intravenous (i.v.) infusion of propofol. The diagnosis was based on a positive family history, classic phenotype, scoliosis, arachnodactyly, high narrow palate, hyperextensible joints, ectopia lentis and mitral valve prolapse, with a secondary low mitral insufficiency. Maternal and fetal surveillance did not detect complications during the course of pregnancy. Elective caesarean section was performed at 39 weeks due to high-risk pregnancy and to avoid the risk of haemodynamic alterations that take place during labour and delivery. The patient was given general anaesthesia with continuous i.v. infusion of propofol and boluses of atracurium and fentanyl after delivery. The haemodynamics and oxygen saturation remained stable during surgery. Apgar scores were 9 at 1 and 5 min. The post-delivery course was unremarkable and post partum echocardiography showed no changes from before caesarean section. The cardiovascular problems of Marfan's syndrome, the risk of haemodynamic changes associated with pregnancy and delivery, its anaesthetic implications and the possible advantages of TIVA with continuous i.v. infusion of propofol in the anaesthetic management of caesarean section in patients with this disease are discussed.

Regardless of treatment modality-operative or nonoperative - the goals ot Achilles tendon rupture management include restoration ot normal function of the muscle-tendon complex with normal plantar flexor power and endurance.

This report of carotid paraganglioma excision in three patients discusses differential diagnosis, preoperative assessment, preoperative embolization of the tumor, monitoring of anesthesia including cerebral oximetry, and postoperative complications. We consider cerebral protection to be essential during carotid paraganglioma surgery. Such protection may be provided by drugs such as sodium thiopental and by temporarily shunting the internal carotid artery. Preoperative angiography is also important for evaluating retrograde circulation through Willis's polygon and to examine the arteries irrigating the tumor. Information thus obtained helps establish the need for presurgical embolization of the tumor, thereby possibly reducing the risks, such as obstructive hematoma that are inherent to the procedure. Finally, in our opinion, full monitoring should include cerebral oximetry so that possible complications can be detected and resolved.

To evaluate the effects on postoperative pulmonary function and quality of analgesia of two protocols for epidural infusion of alfentanil after lung resection.After informed consent, 30 ASA I-IV patients undergoing chest surgery (lobectomy or pneumonectomy) were randomly assigned to two groups of 15. A catheter was inserted into the epidural space at T5-7 (group T) or L2-3 (group L). After a test dose, an initial bolus of alfentanil (10 micrograms/kg) was administered. After anesthetic induction, epidural analgesia was performed with an infusion of 400 micrograms/h of alfentanil (group L) during and after surgery. Endovenous patent-controlled anesthesia (PCA) was provided with morphine. During the first 24 h after surgery, the following variables were recorded: arterial blood gas concentrations, spirometric parameters, pain on a visual analog scale (VAS) and side effects. ANOVA and Scheffé and chi-square tests were used to analyze the results (por = 0.05).In group T, PaO2 was significantly higher at 6 and 18 h (por = 0.05), while FEV1 and FVC were significantly higher at 12 and 18 h. Pain assessed by VAS and PCA need for morphine was significantly less in group T.Thoracic epidural analgesia with alfentanil and lidocaine improves postoperative lung function and reduces the need for top-up analgesia in comparison with lumbar epidural infusion of alfentanil.

The handling of upper gastrointestinal hemorrhage (UGH) usually includes the hospitalization of all patients, regardless of severity and prognosis. The aim of this paper is to assess the security of the outpatient control of some UGH, after their assessment in the hospital emergency room.Prospective cohort of 533 patients who attended over 1994 and 1995 hospital emergency room for an episode of UGH not linked to portal hypertension. After clinical and endoscopical assessment in the emergency department, 422 cases (79%) were admitted and 111 (21%) discharged for outpatient care. An analysis is presented of the characteristics of both groups, their clinical outcomes and a multivariate analysis to assess the factors associated with the decision to admit the patient.Outpatients were young, with less comorbidity and better haemodynamic status than hospitalized patients. Most of outpatient cases UGH was due to gastroduodenitis, oesophagitis and Mallory-Weiss syndrome, as opposed to the greater importance of peptic ulcer in those admitted. All outpatients presented clean lesions or haematic remains. 25 (5.9%) hospitalized patients presented rebleeding, vs. only 1 (0.9%) outpatient (p0.05). When more severity cases were excluded from hospital group, the differences were not significant. All cases with active bleeding, severe haemodynamic repercussion or without endoscopy were admitted. For the remainder, the decision to admit was associated with the presence of bleeding stigmata, haemodynamic repercussion, some causes of hemorrhage, older age, and urea levels.Although the scarce sample do not permit definitive conclusions, results guide towards that a substantial part of UGH not linked to portal hypertension may be monitored without hospitalizing the patient, thereby minimizing care costs and increasing the productive capacity of the hospital, without increasing risks for the patient.

To analyze the quality of several anesthetic techniques used for major outpatient surgery in our hospital, by quantifying for each the relative risk (RR) of adverse events during anesthesia and in the postoperative period.One thousand seventeen patients who underwent surgery between 18 May 1998 and 23 October 1998 were studied retrospectively.The mean age of the patients was 52.27 +/- 24.65 yr; 44.18% were ASA I, 40.56% were ASA II, 14.56% ASA III and 0.67% ASA IV. Mean time of surgery was 33 +/- 16.49 min and mean recovery time until discharge was 77.3 +/- 93.4 min. Admission was necessary for 0.6% of the patients and re-admission for 0.3%. General anesthesia was used with 19%, anesthetic monitoring with 17%, regional anesthesia (including peribulbar) with 46% and local anesthesia plus sedation with 16.6%. In 95% of the cases, no adverse events occurred during anesthesia; in 94.8% no such events occurred during the early recovery period. During surgery and postoperative recovery, intradural anesthesia was associated with significantly greater RR of adverse events in comparison with general anesthesia (6.6 and 2.2 respectively) and in comparison with monitored anesthesia (7.2 and 3.3). No differences in RR were found between general anesthesia and monitored anesthesia. Problems were slight to moderate in severity and mainly related to nausea and vomiting (2%).Recording perioperative events permits evaluation of the quality of anesthesic procedures. Intradural anesthesia is associated with more complications.

We describe our experience in managing single lung ventilation (SLP) with the Univent bronchial blocker tube from 1993 to the present.Patients were grouped based on the following criteria: use of a double lumen tube as an alternative to SLP (group 1), use of SLP and tracheotomy (group 2), or difficult or dangerous orotracheal intubation (group 3).The mean age of the 32 patients (22 men and 10 women) studied was 45.7 +/- 12.2 years. Mean weight was 67.9 +/- 13.4 kg. Ten patients were physical status ASA I, 10 were ASA II, 10 were ASA III and 2 were ASA IV. Group 1 contained 28 patients (18 receiving right SLP and 10 receiving left SLP; use of SLP failed to collapse the lung in 4 patients [14.3%]). Group 2 consisted of 5 patients and group 3 contained 11. The Univent tube was used in 4 patients in group 3 who did not require use of SLP but whose intubation was considered difficult and in whom laryngoscopic findings were consistent with a Cormack-Lehane group III classification. The Univent bronchial blocker tube was used as a guide, such that intubation was achieved on the first try. The tube was removed from 3 patients (8%) in the intensive care recovery ward. The remaining 29 tracheas were extubated in the operating room. No side effects attributable to the Univent tube were recorded.The advantages and disadvantages of this new tool for the management of SLP mean that it may be useful for specific situations (such as for SLP with difficult intubation or in patients with tracheotomies or aneurysms of the descending thoracic aorta), but that it does not replace conventional methods. We believe that the Univent bronchial blocker tube should be available as part of operating room equipment.

To evaluate the efficacy and incidence of side effects of two types of lumbar epidural analgesia with morphine, preemptive or postincisional, combined with total intravenous anesthesia in chest surgery.This double-blind prospective study enrolled 20 patients (ASA I-IV) undergoing lobectomy or pneumonectomy. Anesthetic induction and maintenance was provided with propofol, atracurium and alfentanil. Lumbar epidural analgesia (L2-L3) with morphine was provided for group A patients with 2 to 4 mg upon excision of tissue and for group B with 2 to 4 mg during anesthetic induction. The following variables were recorded: arterial blood gas concentrations, heart rate, SpO2, EtCO2, postanesthetic recovery, arterial gases, side effects and pain on a visual analogue scale. Top-up analgesia was provided by intravenous metamizole and/or epidural morphine. For statistical analysis we used ANOVA, chi-square tests and Student-Newman-Keuls tests.The need for propofol and alfentanil during anesthesia, and for morphine and metamizole after surgery were statistically greater in group A. Pain 18 hours after surgery was also greater in group A. No significant differences between groups for other variables was observed.Preemptive analgesia with lumbar epidural morphine in addition to the general anesthesia described here seems to provide higher-quality analgesia with few side effects, reducing the need for propofol and alfentanil during surgery and for postoperative morphine and metamizole.

To evaluate the monitoring of intramucosal pH (pHi) and standard pH (pHs) during heart surgery with extracorporeal circulation (ECC) and moderate hypothermia. The correlations of pHi and pHs and the postoperative APACHE III score after surgery were analyzed.Sixteen patients with cardiac output0.4 scheduled for coronary bypass surgery, or aortic or mitral valve replacement were studied. Arterial pH (pHa), pHi and pHs were measured and the difference between pHa and pHi was calculated before starting ECC (T0), during ECC and hypothermia (T1) and after termination of ECC (T2). The APACHE III score was recorded 18 h after surgery.No significant differences between the pHi and pHs were observed in these patients. pHi was significantly higher during ECC with hypothermia (T1) than at baseline (T0). pHi and pHs were significantly correlated during the study period. There was no correlation between the APACHE III score in the immediate postoperative period and either pHi or pHs during surgery.Periods of splanchnic hypoxia (pHi7.32) during heart surgery with moderate hypothermia were not seen in patients with cardiac output0.4. pHs is a reliable measurement of pHi. There is no relation between APACHE III scores in the early postoperative period and pHi or pHs levels during surgery.

The diagnosis of chronic pancreatitis continues to present difficulties. The nonspecific nature of the symptomatology, its low prevalence and the limited value of morphological and functional tests in the early stages are the most common causes of delay in diagnosis. Our aim was to analyze the most significant clinical manifestations and the diagnostic features of chronic pancreatitis, distinguishing between alcoholic and nonalcoholic etiologies. We studied 158 patients, 136 (86.1%) with alcoholic and 22 (13.9%) with nonalcoholic chronic pancreatitis. The initial symptomatology, the age at diagnosis, the delay in diagnosis from the onset of the clinical signs and the type of diagnosis (incidental or suspected) were considered for each patient. Men predominated in both the alcoholic and the nonalcoholic pancreatitis groups (97.8% and 68.2%, respectively). The mean ages at onset and diagnosis were 38 and 50.6 years, respectively, in alcoholic chronic pancreatitis and 44 and 55 years in the nonalcoholic group; the differences between the two parameters were statistically significant. The most common clinical signs in alcoholic chronic pancreatitis were abdominal pain (81.6%) and episodes of acute pancreatitis (64%), while patients with nonalcoholic pancreatitis presented abdominal pain (59%), diarrhea (40.9%) and weight loss (36.4%). The delay in diagnosis from the onset of the clinical manifestations was 5.8 years (6.1 years in alcoholic and 4.3 years in nonalcoholic pancreatitis. The diagnosis was incidental in 34% of cases of alcoholic chronic pancreatitis and in 50% of cases in the nonalcoholic group.

The aim of our study was to analyze the influence of alcohol consumption on the early clinical manifestations of alcoholic chronic pancreatitis of the 517 patients in whom chronic pancreatitis was initially suspected, 158 were diagnosed with this disease; of these, alcohol was considered the cause in 136 (86.1%). Alcohol was considered a major etiologic factor when mean consumption wasor = 60 grams per day for at least 4 years. Alcohol consumption, initial clinical manifestations and time of onset were considered up until the moment of diagnosis in all patients. The sex distribution was 133 men (97.8%) and 3 women (2.2%). The average age was 22 +/- 6.5 years at onset of alcoholism, 38 +/- 9.4 years at onset of clinical features, and 44 +/- 9.4 years at diagnosis. The interval between the onset of alcoholism and the initial clinical manifestations was 15.8 +/- 8.8 years, and the interval between the latter and diagnosis was 6.1 +/- 4.9 years. Average alcohol consumption was 162 +/- 8 grams/day and total consumption was 1312 +/- 1017 kg. A statistically significant relationship was found only for mean alcohol consumption and abdominal pain. We found a higher frequency of acute pancreatitis outbreaks, calcifications, steatorrhea and diabetes until the moment of diagnosis in the higher alcohol consumption groups, although the relationship was not statistically significant.

We report the case of a 49-year-old man who suffered anaphylactic/anaphylactoid shock within the first few minutes of reaching the recovery room after unremarkable coronary surgery and revascularization. Adequate monitoring permitted differential diagnosis and establishment of specific treatment Monitoring also allowed us to document hemodynamic changes and oxygen consumption during this instance of anaphylactic/anaphylactoid shock. Anaphylactic/anaphylactoid shock caused significant vasoparalysis with decreases in arterial pressures, reduction of oxygen consumption and discrete changes in oxygen exchange. The reposition of volume and administration of adrenaline were insufficient. Appropriate management of noradrenaline perfusion, which was made possible by complete monitoring, was essential for reestablishing normal hemodynamic and oximetric readings and preventing myocardial ischemia.

Primary ventricular arrhythmias are rarely seen in children. Some of them have a poor prognosis; they should be diagnosed because adequate treatment can prevent sudden death.Twenty children (11 male, nine female), aged 3 to 16 years (mean: 7.7 +/- 4), with apparently normal hearts and normal QTc intervals were referred for stress or emotion-induced syncope. Primary ventricular arrhythmia, consisting of isolated polymorphic ventricular extrasystoles followed by salvos eventually degenerating into ventricular fibrillation, was reproducibly induced by physical exertion. The syncopal events and "torsades de pointe" disappeared with beta-blocking therapy. A total of four syncopal events and two sudden deaths occurred during a mean follow-up of 8 years, probably due to discontinuation of treatment.Fifty-four-cases of stress-induced severe polymorphous ventricular arrhythmia have been reported in the literature. There were four sudden deaths in 37 patients on beta-blocking therapy, and ten sudden deaths in 21 untreated patients.Clinically close to the congenital long QT syndrome, this primary ventricular arrhythmia must be looked for in cases of stress or emotion-induced syncope. The diagnosis relies on Holter monitoring and a stress test. Life-long beta blocker therapy is required.

The purpose of the experiment was to determine whether diaphragmatic circulation could be compared to other skeletal muscle circulation or whether it has an originality of its own. Diaphragmatic (phrenic and costophrenic arcade arteries), coronary, femoral and cerebral arteries were taken up from anaesthetized pigs, cut into rings and suspended in organ chambers for isometric tension recording. Vasopressin induced a maximal contraction of the femoral artery, no significant changes in tone in cerebral and coronary arteries, and only minimal contraction (30% of the maximum) in diaphragmatic arteries. These results were obtained in a state of basal level of tension or in vessels contracted with prostaglandin F2 alpha. The endothelium did not influence the response in any of the vessels investigated. Norepinephrine induced a contraction in the femoral artery and a relaxation in the coronary artery which was not influenced by the endothelium. Isoproterenol could relax the coronary but not the femoral or the diaphragmatic arteries. The alpha 2-adrenoceptor agonist UK 14304 induced endothelium-dependent relaxation in the diaphragmatic and coronary arteries, but not in the femoral arteries. Phenoxybenzamine unmasked a small alpha-adrenoceptor reserve in the diaphragmatic arteries. These results suggest that diaphragmatic circulation has protective mechanisms in order to preserve a correct supply to the vital respiratory muscle it subserves.

Este trabajo forma parte del capítulo central de la tesis doctoral "Señorío y propiedad en el País Valenciano. Los dominios de la Casa Ducal de Medinaceli", leída en Valencia en noviembre de 1993 En la Sierra de Eslida, los establecimientos de los bienes que habían pertenecido a los moriscos se realizaron exclusivamente bajo régimen enfitéutico. Los repartos iniciales de 1612-1614 originaron unas comunidades rurales si no igualitarias sí relativamente homogéneas. Pese al paulatino incremento que experimentó su diferenciación interna, y que se debió más a factores intrínsecos a su propia dinámica que a la actuación de grupos sociales extraños a ellas, hasta el primer tercio del siglo XVIII seguían constituyendo ejemplos típicos de sociedades agrarias con un escaso grado de movilidad social. In the Sierra de Eslida, the sttelments of the properties that had belonged to the moslems were exclusively re-allocated under «unfitéutico» règime. The initial distributions of 1612-1614 originated rural comunities if not igualitarian, relatively homogeneous. Although, the gradual increase of internal differences than was due more to inherent dynamic that to the action of other social groups, until the first third of the XVIII century they continued being typical examples of agrarian comunities with a small degree of social mobility.

We announce the discovery of GPX-1 b, a transiting brown dwarf with a mass of $19.7\pm 1.6$ $M_{\mathrm{Jup}}$ and a radius of $1.47\pm0.10$ $R_{\mathrm{Jup}}$, the first sub-stellar object discovered by the Galactic Plane eXoplanet (GPX) survey. The brown dwarf transits a moderately bright ($V$ = 12.3 mag) fast-rotating F-type star with a projected rotational velocity $v\sin{ i_*}=40\pm10$ km/s. We use the isochrone placement algorithm to characterize the host star, which has effective temperature $7000\pm200$ K, mass $1.68\pm0.10$ $M_{\mathrm{Sun}}$, radius $1.56\pm0.10$ $R_{\mathrm{Sun}}$ and approximate age $0.27_{-0.15}^{+0.09}$ Gyr. GPX-1 b has an orbital period of $\sim$1.75 d, and a transit depth of $0.90\pm0.03$ %. We describe the GPX transit detection observations, subsequent photometric and speckle-interferometric follow-up observations, and SOPHIE spectroscopic measurements, which allowed us to establish the presence of a sub-stellar object around the host star. GPX-1 was observed at 30-min integrations by TESS in Sector 18, but the data is affected by blending with a 3.4 mag brighter star 42 arcsec away. GPX-1 b is one of about two dozen transiting brown dwarfs known to date, with a mass close to the theoretical brown dwarf/gas giant planet mass transition boundary. Since GPX-1 is a moderately bright and fast-rotating star, it can be followed-up by the means of Doppler tomography., 13 pages, 13 figures, accepted to MNRAS in May 2021

Escherichia coli K-12 vinylglycolate-resistant mutants have been isolated and characterized. Two of the mutants, JSH 150 and JSH 151, have been determined to be double mutants, lacking both membrane-bound L-and D-lactate dehydrogenases. The lactate transport system is intact in all strains; both radioactive lactate and vinylglycolate are actively taken up. Likewise, the phosphoenolypyruvate-dependent phosphotransferase system for hexose uptake is active. Vinylglycolate, previously shown to inhibit the phosphoenolpyruvate-dependent phosphotransferase system, has very little effect in the double mutants. The extent of vinylglycolate inhibition in other mutants seems directly related to the activity of the lactate dehydrogenases. This indicates that vinylglycolate is oxidized to 2-keto-3-butenoate before inactivating the phosphoenolpyruvate-dependent phosphotransferase system. These results were found in whole cells and confirmed in isolated membrane vesicles.