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Background Ovarian cancer remains the most lethal gynecologic malignancy with high recurrence rates. Because recurrence involves primarily the peritoneum, intraperitoneal chemotherapy is being evaluated as a new approach to treat microscopic peritoneal disease. One trial showed that cisplatin–paclitaxel intraperitoneal chemotherapy with intravenous paclitaxel improved survival but increased morbidity. Another trial reported a significant improvement in overall survival (OS) and disease-free survival (DFS) without increasing the morbidity (P = 0.76) or mortality rates (hazard ratio 0.67, P = 0.02) after adding hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreduction. The current trial aims to evaluate the impact of adding HIPEC to primary or interval cytoreductive surgery for epithelial ovarian cancer (EOC) on the efficacy, safety, treatment feasibility, and quality of life. Patients and methods This is an international, multicenter, open-label, randomized (1 : 1), two-arm, phase III clinical trial that will enroll 432 patients with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage III EOC. Patients are randomized to receive or not HIPEC with the standard of care. Inclusion criteria include patients with FIGO stage III EOC, Fallopian tube carcinoma or primary peritoneal cancer who undergo complete primary or interval cytoreduction. The primary objective is to assess DFS of the addition of HIPEC. Secondary objectives are the assessment of OS, safety, return to intended oncologic treatment, quality of life and the trade-off between efficacy and morbidity. Conclusions The results might help extend the indications of HIPEC to include patients undergoing primary cytoreduction, providing a standardized protocol for HIPEC in EOC management and reliable information on the quality of life after adding HIPEC., Highlights • Ovarian cancer remains the most lethal gynecologic cancer with high rates of recurrence involving primarily the peritoneum. • Intraperitoneal chemotherapy is being evaluated as a new therapeutic approach to treat microscopic peritoneal disease. • This trial evaluates the impact of adding HIPEC to primary or interval cytoreductive surgery for EOC. • This trial evaluates the efficacy, safety, treatment feasibility and quality of life after the addition of HIPEC. • This is an international, multicenter, open label, randomized, phase III clinical trial.

Introduction Les modalites de l’antibiotherapie, notamment la date optimale du relais oral, ne sont pas definies au cours du traitement des abces cerebraux. L’objectif de cette etude est d’evaluer le pronostic des patients selon la date d’un eventuel relais oral de l’antibiotherapie. Materiels et methodes Etude retrospective monocentrique incluant des adultes hospitalises pour abces ou empyeme cerebral documentes (01/2007–06/2018). Etaient exclus : contexte d’endocardite, abces a Nocardia, Aspergillus, Toxoplama, Ecchinococcus, Mycobacterium. Les donnees recueillies concernaient : le terrain, les symptomes et scores de gravite a l’admission, les microorganismes identifies et l’antibiotherapie recue. Le pronostic etait evalue ≥ 3 mois apres arret du traitement. Les patients ayant recu une antibiotherapie orale pendant au moins la moitie de la duree totale de traitement (PO) etaient compares a ceux ayant recu un traitement intraveineux prolonge (IV). Les variables continues sont presentees avec leur mediane et intervalles interquartiles. Les groupes ont ete compares en analyse univariee. Resultats Sur 82 patients ayant des abces/empyemes cerebraux, 47 ont ete inclus dont 33 hommes (70 %), âge median 55 ans [42–68]. Le groupe PO comportait 16 (34 %) patients. Les abces etaient dus a des streptocoques (n = 25), anaerobies (n = 24), staphylocoques (n = 8), bacilles Gram negatif (n = 7) et actinomyces (n = 6). Le qSOFA etait ≥ 2 seulement chez 1 patient PO contre aucun IV. Les patients IV etaient davantage hospitalises en reanimation (20 vs 4 ; p = 0,01). L’antibiotherapie probabiliste initiale comportait une cephalosporine de 3e generation (n = 39, 83 %) et un nitroimidazole (n = 38, 81 %) dans les deux groupes. La duree mediane de l’antibiotherapie etait de 42 jours [42–54]. Un relais oral a ete realise chez 23 patients (49 %) dans un delai median de 21j [11–28] mais seulement 16 patients correspondaient au groupe PO, avec un delai median de relais oral apres 15j de traitement IV [9–19]. Les antibiotiques PO etaient : clindamycine (n = 8), cotrimoxazole (n = 4), metronidazole (n = 1) et l’association rifampicine et fluoroquinolone (n = 2). Le pronostic a ete evalue avec un delai median de 202j [18-645] et n’etait pas different entre les groupes IV et PO : 10 deces (9 vs 1 ; p = 0,09) dans un delai median de 27j [19–55], 3 recidives (2 vs 1), 10 reprises chirurgicales (4 vs 6 ; p = 0,051) et 17 patients avec sequelles neurologiques (12 vs 5 ; p = 0,61). Conclusion Les abces cerebraux sont des infections severes. Neanmoins un relais oral de l’antibiotherapie pourrait etre envisage apres 15 jours de voie IV sans modifier le pronostic. L’extension de la cohorte en multicentrique pourrait permettre de renforcer les resultats.

We investigated sequential aerobic and anaerobic microbiologically induced corrosion of carbon steel to simulate deep geological disposal conditions. Under limited oxygen supply, lepidocrocite and magnetite corrosion products formed on the steel coupon, while under continuous oxygen supply, a mixture of lepidocrocite, maghemite and magnetite was identified. Upon oxygen consumption and establishment of sulphidogenic conditions, due to sulphate-reducing bacteria activity, all these oxides disappeared via transformation into pyrrhotite. Corrosion rate of steel in direct anaerobic cultures was higher than that of steel initially corroded in aerobic condition, suggesting a protective role of corrosion product layer formed under sequential aerobic–anaerobic conditions.

The concept of an ion-sensitive FET (ISFET) on diamond with boron delta-doped channel and oxygen-terminated surface for pH sensing has been successfully transferred to large-area nano-crystalline diamond on silicon substrates. The nano-crystalline diamond layers, including the boron delta-doped channels of the FETs, were grown by hot-filament CVD. The fabricated layers were characterised by their peak concentration of boron of 3 × 10 20 1/cm 3 and FWHM of about 1 nm. This allowed approx. 50% modulation of the channel current within the gate potential range corresponding to the potential window of water electrolysis on the diamond surface. The O-termination by combination of oxygen-plasma and wet chemical treatments resulted in a pH sensitivity of the ISFETs close to the Nernst's limit in the range between pH1 and pH13. The ISFET characteristics were stable even after anodic treatment in KOH. This allows using nano-crystalline diamond ISFETs with O-termination also as electrodes and even at anodic overpotentials.

The delta doping concept has been successfully applied to a diamond field effect transistor structure with an Al2O3 gate diode, resulting in full channel carrier activation at room temperature and channel current modulation with complete pinch-off. Using a gate recess configuration, a channel current density of 30 mA/mm with a gate length LG of 0.8 μm has been obtained with semi-enhancement mode operation. First RF measurements have resulted in fT and fmax cut-off frequencies of approx. 1 GHz and 3 GHz respectively.

Boron delta-doped profiles with peak concentrations above the full activation limit have been grown on (100)-oriented single crystal diamond substrates by microwave assisted CVD using a solid doping source technique. The growth process was optimized targeting electronic device applications. Up to now these profiles could only be analyzed by chemical/physical profiling and it had been difficult to relate these profiles to the electrical characteristics. For the first time, ERD (Electron Recoil Detection) profiles could be correlated with free carrier profiles extracted by electrochemical profiling based on electrochemical impedance analysis. The comparison shows, that it is possible to incorporate boron on acceptor site with high efficiency even for concentrations in the order of 1021 cm− 3 by the doping technique developed.

In this investigation an attempt has been made to incorporate a high temperature stable refractory metal ohmic contact deposited onto an oxygen terminated contact area into the surface channel field effect transistor concept based on a H-terminated surface in the channel area. First transistors were fabricated. A drain current density of 75 mA/mm and a threshold voltage of V th = −1.5 V was obtained for 1 µm gate length.

A concept of an ion sensitive FET (ISFET) on diamond using a thin and highly boron-doped channel is described. The doped channel is in direct contact to the electrolyte solution. The diamond surface is oxygen terminated to provide pH sensitivity and chemical stability. The first set of pH-sensitive ISFET microstructures with the extrinsically doped channel is fabricated on 100-oriented single crystal diamond substrate using a solid doping source technique and a wet chemical oxidation for the O termination. The fabricated structures show pH sensitivity close to the Nernst's limit of 59 mV/pH. The ISFET characteristics have been reproducible and did not degrade after repeated cycling between 0.1 M H2SO4 and 0.1 M KOH solutions. It is shown that only a part of the applied gate potential to the diamond–electrolyte interface drops within the delta-doped channel. The possible origin of this effect is discussed by analysing the electrochemical impedance characteristics of the boron-doped diamond electrode.

To obtain high blocking voltages and low forward losses in power diode structures, a Schottky contact can be merged with a MIS contact or a pn-junction. In this configuration, the Schottky contact is responsible for a low forward threshold voltage and the MIS or pn-junction for a low reverse leakage current and a high breakdown voltage. In this study, a diamond merged diode structure has been fabricated and evaluated, containing simultaneously an Al or W:Si-Schottky contact and a boron/nitrogen pn-junction. The IV characteristics show a low forward barrier of 1.5 eV, a current rectification ratio of 10 9 at R.T., and a reverse breakdown at 2.5 MV/cm. Rectification has been obtained up to 1000 °C (in vacuum).

Rats chronically exposed to cold (5 degrees C for 5 weeks) develop hypertension. Isoprenaline-induced vascular smooth muscle relaxation is increased in these animals. Our main objective was to compare isoprenaline-induced relaxation of aortae isolated from control and cold-acclimated rats and attempt to relate the differences to changes in receptor parameters (affinity and reserve) and signaling mechanisms. Isoprenaline (10(-9)-10(-5) M)-induced relaxation was enhanced significantly (p0.05) in aorta segments from cold-acclimated rats. There was a significant (p0.05) increase in the potency of isoprenaline but with no change in affinity. Isoprenaline produced 50% of the maximum response while occupying about 50% and about 15% of the receptors in isolated rat aorta segments from control and cold-treated rats, respectively. Forskolin and db-cAMP also concentration-dependently relaxed aorta segments from control and cold-acclimated rats. There was no difference in potency or maximum response to forskolin (which directly activates adenylyl cyclase) and db-cAMP. cAMP concentrations in the presence of isoprenaline were significantly (p0.05) higher in aorta segments from rats chronically exposed to cold when compared with aorta segments from control rats. These findings suggested that altered mechanisms upstream of activation of adenylyl cyclase are involved in the increased beta-adrenoceptor-induced relaxation.

Summary Setting: Mycobacterium tuberculosis (M. tuberculosis) isolates from various parts of the USA which have few copies of the insertion sequence IS 6110 . Objective: To characterize the sites of insertion of IS 6110 among M. tuberculosis isolates that have one to six copies of the insertion sequence. Design: The mixed-linker polymerase chain reaction (ML-PCR) procedure was used to amplify the terminal repeats on the ends of IS 6110 and adjacent flanking sequences. From the ML-PCR products, sequences flanking 14 copies of IS 6110 in strains containing less than seven copies of the insertion were determined. Sequence information from the flanking deoxyribonucleic acid was used to construct flanking primers that can be used to indicate the presence of IS 6110 at a particular site when paired with outbound IS 6110 primers in a PCR. Over 200 strains of diverse origin were screened for the insertion of IS 6110 at several distinct sites using this procedure. Results: The direct repeat (DR) locus has been described as a highly preferred site for insertion of IS 6110 in strains of M. tuberculosis . Another highly preferred site of insertion of IS 6100 , DK1, is herein described. Insertions at DK1 are highly prevalent in M. tuberculosis strains harboring two to six copies of IS 6110 . The prevalence of insertions at this site decreases in strains with more than six copies of IS 6110 , even though the sequence itself is present in strains lacking a copy of IS 6110 at this site. Conclusion: In addition to the DR locus there are other conserved sites of insertion among M. tuberculosis strains. The data further suggest a separate lineage for the high copy and the low copy strains, and a possible sequential insertion of IS 6110 in strains of M. tuberculosis with less than seven copies.

A knowledge-based system for the design of the general layout of reinforced concrete spread footings is presented. A database, sorting previous design cases, is used to assist the user in obtaining different solutions for each problem. Plotting capability is also incorporated to show all the reinforcement details which could be obtained from a design office. The analysis of single and double footing is carried out using the conventional methods whereas the mat foundation is treated as a plate on elastic foundations and is analyzed by the bending theory of plates using the finite element method.