A helium-burning white dwarf binary as a supersoft X-ray source.

Type Ia supernovae are cosmic distance indicators1,2, and the main source of iron in the Universe3,4, but their formation paths are still debated. Several dozen supersoft X-ray sources, in which a white dwarf accretes hydrogen-rich matter from a non-degenerate donor star, have been observed5 and suggested as Type Ia supernovae progenitors6-9. However, observational evidence for hydrogen, which is expected to be stripped off the donor star during the supernova explosion10, is lacking. Helium-accreting white dwarfs, which would circumvent this problem, have been predicted for more than 30 years (refs. 7,11,12), including their appearance as supersoft X-ray sources, but have so far escaped detection. Here we report a supersoft X-ray source with an accretion disk whose optical spectrum is completely dominated by helium, suggesting that the donor star is hydrogen-free. We interpret the luminous and supersoft X-rays as resulting from helium burning near the surface of the accreting white dwarf. The properties of our system provide evidence for extended pathways towards Chandrasekhar-mass explosions based on helium accretion, in particular for stable burning in white dwarfs at lower accretion rates than expected so far. This may allow us to recover the population of the sub-energetic so-called Type Iax supernovae, up to 30% of all Type Ia supernovae13, within this scenario.

Canadian Cancer Trials Group (CCTG) IND215: A phase Ib study of Selumetinib in patients with untreated advanced or metastatic NSCLC who are receiving standard chemotherapy regimens.

Introduction Selumetinib (AZD6244, ARRY-142886) is a potent inhibitor of MEK1/2, thereby inhibiting phosphorylation of ERK2. We investigated the toxicity and the recommended phase II dose of the combination of selumetinib with two platinum based first line chemotherapy combinations in non-small cell lung cancer. Methods This was a phase I trial of escalating doses of selumetinib with carboplatin (AUC 6), paclitaxel (200 mg/m2) (cohort 1) or pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) (cohort 2) in patients with chemotherapy naïve, advanced or metastatic NSCLC. Patients enrolled on cohort 2 had non-squamous histology. Dose escalation of selumetinib proceeded using a 3 + 3 design: 50 mg b.i.d. days 2-19 (dose level 1); 75 mg b.i.d. days 2-19 (dose level 2); and 75 mg b.i.d. continuously. Adverse events were evaluated using CTC AE v4 and response by RECIST 1.1. Results Thirty-nine patients were enrolled (cohort 1 n = 16; cohort 2, n = 23). There were no dose limiting toxicities in either cohort and the recommended phase II dose for both regimens was standard doses of carboplatin, paclitaxel or pemetrexed and cisplatin with continuous selumetinib at a dose of 75 mg b.i.d. Most adverse events were grade 1 or 2 and were predominantly diarrhea, nausea, stomatitis, peripheral edema, neutropenia, and skin rash. Response rate was 37.5% for cohort 1 and 30.4% for cohort 2. Conclusion Selumetinib at a dose of 75 mg b.i.d continuously can be safely combined with paclitaxel and carboplatin or pemetrexed and cisplatin in patients with advanced or metastatic NSCLC. This trial provided the dose for the regimens used in a randomized phase II trial in NSCLC (CCTG IND.219).

Experimental amine-epoxide sealer: a physicochemical study in comparison with AH Plus and EasySeal.

AIM: To compare selected physicochemical and biological properties of an experimental sealer with those of two commercially available sealers. METHODOLOGY: AH Plus and EasySeal were used as model materials for commercially available amine-epoxide sealers. They were mixed as stated by the manufacturer. The two components of experimental sealer EvoSeal A were mixed 1 : 1 vol%. The setting time was determined in two different ways: first, by setting of sealers in a temperature- and moisture-controlled environment followed by testing with a Gilmore needle and secondly, by oscillating measurements of setting behaviour using a rheometer. Differential scanning calorimetry (DSC) of the sealer was performed for comparison of thermal properties. Flow and film thickness were determined by applying pressures of 100 g and 15.3 kg, respectively, on the materials between two glass plates and measuring the diameters of the compressed sealer and the thickness with a micrometer gauge. Solubility of set materials was conducted by layering the samples with water, storing in a temperature- and humidity-controlled environment and evaporating the solvent. The solved sealer parts were then weighed. The radiopacity was measured in an X-ray experiment comparing radiopacity of a cured sealer to an aluminium step wedge. Volume shrinkage was defined by measuring the densities of samples before and after setting. The film thickness, fluidity, curing time, radiopacity and solubility of the test materials were performed as specified in DIN EN ISO 6876:2010 draft. The volume shrinkage was determined in a method adapted from standard DIN 13907:2007-01. Antibacterial activity was tested against Gram-positive Streptococcus oralis cultures in a contact test based on standard ISO 22196:2011 (E). Statistical analysis was performed using Mann-Whitney U-test where applicable. Significant differences were determined with P < 0.05. RESULTS: The experimental sealer, EvoSeal A, reached standard specifications. In terms of film thickness, the highest value was measured for EvoSeal A with a film thickness of 27 µm, comparing to 6 µm for EasySeal (P ≤ 0.001) and 8 µm for AH Plus (P ≤ 0.001). Comparing the flow, all values corresponded to EasySeal with a diameter of 17.3 mm. The only significant difference was determined for AH Plus compared to EvoSeal A (P = 0.0353). Volume shrinkage of EvoSeal A was 48% smaller compared to EasySeal and approximately 20% lower compared to AH Plus. The shortest curing time was determined for EvoSeal A (3.0 h) followed by EasySeal (4.1 h) and AH Plus (24 h). For all groups, significant differences were observed (P ≤ 0.001). EvoSeal A had a significantly higher radiopacity than EasySeal (P ≤ 0.001) but significantly lower values than AH Plus (P ≤ 0.001). The solubility of AH Plus and EvoSeal A was <0.5% (P = 0.2435). Compared to EasySeal with a solubility of 2.7%, significant differences were observed (P ≤ 0.02). Three weeks after setting, EasySeal and EvoSeal A still had an antibacterial effect against S. oralis in contrast to AH Plus. In this respect, comparing AH Plus with EvoSeal A and EasySeal, respectively, significant differences were observed (P ≤ 0.001). No significant differences between EasySeal with EvoSeal A (P = 0.540) were determined. CONCLUSIONS: The physical and chemical properties of the experimental sealer EvoSeal A were comparable to the two commercially established sealers EasySeal and AH Plus.

Heterozygous mutations in ANKH, the human ortholog of the mouse progressive ankylosis gene, result in craniometaphyseal dysplasia.

Craniometaphyseal dysplasia (CMD) is a bone dysplasia characterized by overgrowth and sclerosis of the craniofacial bones and abnormal modeling of the metaphyses of the tubular bones. Hyperostosis and sclerosis of the skull may lead to cranial nerve compressions resulting in hearing loss and facial palsy. An autosomal dominant form of the disorder (MIM 123000) was linked to chromosome 5p15.2-p14.1 (ref. 3) within a region harboring the human homolog (ANKH) of the mouse progressive ankylosis (ank) gene. The ANK protein spans the outer cell membrane and shuttles inorganic pyrophosphate (PPi), a major inhibitor of physiologic and pathologic calcification, bone mineralization and bone resorption. Here we carry out mutation analysis of ANKH, revealing six different mutations in eight of nine families. The mutations predict single amino acid substitutions, deletions or insertions. Using a helix prediction program, we propose for the ANK molecule 12 membrane-spanning helices with an alternate inside/out orientation and a central channel permitting the passage of PPi. The mutations occur at highly conserved amino acid residues presumed to be located in the cytosolic portion of the protein. Our results link the PPi channel ANK with bone formation and remodeling.

Sexual violence in post-conflict Liberia: survivors and their care.

Using routine data from three clinics offering care to survivors of sexual violence (SV) in Monrovia, Liberia, we describe the characteristics of SV survivors and the pattern of SV and discuss how the current approach could be better adapted to meet survivors' needs. There were 1500 survivors seeking SV care between January 2008 and December 2009. Most survivors were women (98%) and median age was 13 years (Interquartile range: 9-17 years). Sexual aggression occurred during day-to-day activities in 822 (55%) cases and in the survivor's home in 552 (37%) cases. The perpetrator was a known civilian in 1037 (69%) SV events. Only 619 (41%) survivors sought care within 72 h. The current approach could be improved by: effectively addressing the psychosocial needs of child survivors, reaching male survivors, targeting the perpetrators in awareness and advocacy campaigns and reducing delays in seeking care.

Mitosis in Barbulanympha. II. Dynamics of a two-stage anaphase, nuclear morphogenesis, and cytokinesis.

Anaphase in Barbulanympha proceeds in two discrete steps. In anaphase-A, chromosomal spindle fibers shorten and chromosomes move to the stationary centrosomes. In anaphase-B, the central spindle elongates and ("telophasic") bouquets of chromosomes, with kinetochores still connected by the shortened chromosomal fibers to the centrosomes, are moved far apart. The length, width, and birefringence of the central spindle remain unchanged throughout anaphase-A. In anaphase-B, the central spindle elongates up to fivefold. During elongation, the peripheral fibers of the central spindle splay, first anteriorly and then laterally. The remaining central spindle progressively becomes thinner and the retardation decreases; however, the coefficient of birefringence stays approximately constant. The nuclear envelope persists throughout mitosis in Barbulanympha and the nucleus undergoes an intricate morphological change. In prophase, the nucleus engulfs the spindle; in early anaphase-A, the nuclear envelope forms a seam anterior to the spindle, the nucleus thus transforms into a complete sleeve surrounding the central spindle. In late anaphase-A, the middle of the seam opens up in a cleft as the lips part; in anaphase-B, the cleft expands posteriorly, progressively exposing the central spindle. Finally, the cleft partitions the nucleus into two. The nuclear envelope shows an apparent elasticity and two-dimensional fluidity. Localized, transient deformations of the nuclear envelope indicate poleward and counter-poleward forces acting on the kinetochores embedded in the envelope. These forces appear responsible for nuclear morphogenesis as well as anaphase chromosome movement. At the end of anaphase-B, the two rostrate Barbulanympha may swim apart of be poked apart into two daughter cells by another organism cohabiting the host's hindgut.

Mitosis in Barbulanympha. I. Spindle structure, formation, and kinetochore engagement.

Successful culture of the obligatorily anaerobic symbionts residing in the hindgut of the wood-eating cockroach Cryptocercus punctulatus now permits continuous observation of mitosis in individual Barbulanympha cells. In Part I of this two-part paper, we report methods for culture of the protozoa, preparation of microscope slide cultures in which Barbulanympha survived and divided for up to 3 days, and an optical arrangement which permits observation and through-focus photographic recording of dividing cells, sequentially in differential interference contrast and rectified polarized light microscopy. We describe the following prophase events and structures: development of the astral rays and large extranuclear central spindle from the tips of the elongate-centrioles; the fine structure of spindle fibers and astral rays which were deduced in vivo from polarized light microscopy and seen as a particular array of microtubules in thin-section electron micrographs; formation of chromosomal spindle fibers by dynamic engagement of astral rays to the kinetochores embedded in the persistent nuclear envelope; and repetitive shortening of chromosomal spindle fibers which appear to hoist the nucleus to the spindle surface, cyclically jostle the kinetochores within the nuclear envelope, and churn the prophase chromosomes. The observations described here and in Part II have implications both for the evolution of mitosis and for understanding the mitotic process generally.

On the computations analyzing natural optic flow: quantitative model analysis of the blowfly motion vision pathway.

For many animals, including humans, the optic flow generated on the eyes during locomotion is an important source of information about self-motion and the structure of the environment. The blowfly has been used frequently as a model system for experimental analysis of optic flow processing at the microcircuit level. Here, we describe a model of the computational mechanisms implemented by these circuits in the blowfly motion vision pathway. Although this model was originally proposed based on simple experimenter-designed stimuli, we show that it is also capable to quantitatively predict the responses to the complex dynamic stimuli a blowfly encounters in free flight. In particular, the model visual system exploits the active saccadic gaze and flight strategy of blowflies in a similar way, as does its neuronal counterpart. The model circuit extracts information about translation velocity in the intersaccadic intervals and thus, indirectly, about the three-dimensional layout of the environment. By stepwise dissection of the model circuit, we determine which of its components are essential for these remarkable features. When accounting for the responses to complex natural stimuli, the model is much more robust against parameter changes than when explaining the neuronal responses to simple experimenter-defined stimuli. In contrast to conclusions drawn from experiments with simple stimuli, optimization of the parameter set for different segments of natural optic flow stimuli do not indicate pronounced adaptational changes of these parameters during long-lasting stimulation.

Comparative clinical trial of granisetron and ondansetron in the prophylaxis of cisplatin-induced emesis. The Granisetron Study Group.

PURPOSE: To compare the efficacy and safety of granisetron and ondansetron, serotonin (5-HT3) receptor antagonists shown to be effective in the prevention of chemotherapy-induced emesis. PATIENTS AND METHODS: In a double-blind, randomized, stratified, parallel-group study, the efficacy and safety of granisetron and ondansetron were compared in 987 chemotherapy-naive patients who received cisplatin in doses > or = 60 mg/m2. Granisetron was administered as a single dose of 10 or 40 micrograms/kg before the start of chemotherapy. Ondansetron was administered in doses of 0.15 mg/kg before and 4 and 8 hours after the start of chemotherapy. The three treatment groups were well-matched with respect to demographic characteristics and the dose of cisplatin administered. RESULTS: For all evaluations, single doses of granisetron 10 or 40 micrograms/kg were as effective as three 0.15-mg/kg doses of ondansetron. Total control (no vomiting, no retching, no nausea, and no use of rescue) was attained by 38%, 41%, and 39% of all patients who received granisetron 10 microgram/kg, granisetron 40 micrograms/kg, and ondansetron, respectively. No vomiting or retching and no use of rescue antiemetics were reported in 47%, 48%, and 51% of patients who received granisetron 10 micrograms/kg, granisetron 40 micrograms/kg, and ondansetron, respectively; no nausea and no use of rescue antiemetics were reported in 39%, 42%, and 40% of patients, respectively. CONCLUSION: All three treatment regimens were well-tolerated. The results of this study indicate that a single dose of granisetron 10 or 40 micrograms/kg is as effective as three doses of ondansetron 0.15 mg/kg in the prevention of nausea and vomiting induced by cisplatin chemotherapy.

Neural architectures for robot intelligence.

We argue that direct experimental approaches to elucidate the architecture of higher brains may benefit from insights gained from exploring the possibilities and limits of artificial control architectures for robot systems. We present some of our recent work that has been motivated by that view and that is centered around the study of various aspects of hand actions since these are intimately linked with many higher cognitive abilities. As examples, we report on the development of a modular system for the recognition of continuous hand postures based on neural nets, the use of vision and tactile sensing for guiding prehensile movements of a multifingered hand, and the recognition and use of hand gestures for robot teaching. Regarding the issue of learning, we propose to view real-world learning from the perspective of data-mining and to focus more strongly on the imitation of observed actions instead of purely reinforcement-based exploration. As a concrete example of such an effort we report on the status of an ongoing project in our laboratory in which a robot equipped with an attention system with a neurally inspired architecture is taught actions by using hand gestures in conjunction with speech commands. We point out some of the lessons learnt from this system, and discuss how systems of this kind can contribute to the study of issues at the junction between natural and artificial cognitive systems.

3-Substituted 2-formylquinoxaline 1,4-dioxides.

The methylnitrone of 3-methyl-1,4-dioxidoquinoxaline-2-carboxaldehyde (1) has been exceptional antibacterial activity in vivo. Derivatives of 3-hydroxymethyl-1,4-dioxidoquinoxaline-2-carboxaldehyde and 3-acetoxymethyl-1,4-dioxidoquinoxaline-2-carboxaldehyde were prepared. Several of these compounds were found to be antibacterial agents of the same order of activity as I.

Beta-lactam antibiotics with N-oxide side chains. 1. Quinoxaline N-oxides.

A series of penicillin derivatives of quinoxaline di-N-oxide carboxylic acids was prepared. These compounds were prepared from the acid chlorides and mixed anhydrides of the quinoxaline di-N-oxides. The compounds prepared exhibited minimal antibacterial activity against gram-negative organisms.

Nitrones. 7. alpha-Quinoxalinyl-N-substituted nitrone 1,4-dioxides.

A series of alpha-quinoxalinyl-N-substitute nitrone 1,4-dioxides has been synthesize and evaluated as antibacterial and antiprotozoal agents. Structure-activity relationships are discussed. Of the compounds tested, alpha-(3-methyl-2-quinoxalinyl)-N-methylnitrone 1,4-dioxide (2) was the most active agent in vivo against the gram-negative and the gram-positive organisms.

Unusual association of bone marrow necrosis, disseminated intravascular coagulation, and a rare 8;16 chromosomal translocation in an adult patient with acute nonlymphocytic leukemia.

In a patient with acute nonlymphocytic leukemia of the classic type (FAB subtype M2), three infrequently observed phenomena occurred together; bone marrow necrosis, disseminated intravascular coagulation, and an 8;16 chromosomal translocation. All three resolved with antileukemic therapy, only to reemerge when the leukemia relapsed, suggesting a causal relationship among these phenomena. Such observations and the consistent application of cytogenetic studies to patients with leukemia may help elucidate the significance of specific chromosomal abnormalities in patients with leukemia.

[Embolisation techniques for renal tumors (author's transl)]. / Zur Technik der Embolisation bei Nierentumoren.

We have performed ten embolisations in nine patients with vascular renal tumours, eight of these pre-operatively. One patient had an inoperable hypernephroma which was embolised twice. We have used gelatine sponge particles (Gelaspon). In every patient it was possible to occlude the arterial supply. There were no complications.

[Isotope methods in the radiological diagnosis of venous disease. II. Indications and accuracy (author's transl)]. / Nuklearmedizinische Untersuchungsverfahren in der radiologischen Venendiagnostik. III. Indikationen und Stellenwert.

Radiological diagnostic methods for the diagnosis of abnormalities of veins were discussed in the light of 1,683 contrast venograms and isotope examinations in 650 patients with acute and chronic diseases of veins. For patients with increased thrombotic risks, the 125 I-fibrinogen test is recommended as a sensitive and simple method. Where there are symptoms of venous thrombosis, radionuclide venography, together with other noninvasive methods, may be used for establishing whether there are indications for contrast venography. These may also provide evidence of previous pulmonary emboli. These methods should also be used where there is clinical suspicion of previous pulmonary emboli. Non-invasive isotope methods have proved to be sensitive techniques for preliminary examinations and for follow-up. Contrast venography is necessary if definitive treatment is planned.

[Isotope methods in the diagnosis of venous disease. I. Methods of radionuclide venography (author's transl)]. / Nuklearmedizinische Untersuchungsverfahren in der radiologischen Venendiagnostik. I. Methoden der Radionuklidvenographie.

The method of radionuclide venography is best determined by the localisation and type of suspected venous abnormality. The authors describe four methods using 99mTc microspheres and 99mTc-pertechnetate. Correlation of the isotope and angiographic findings in 150 patients indicated an accuracy of 90% for the isotope methods. The risks of radionuclide venography are discussed. Isotope venography is recommended as a simple, non-invasive technique.

[Isotope methods in the diagnosis of venous disease. II. Results of radionuclide venography (author's transl)]. / Nuklearmedizinische Untersuchungsverfahren in der radiologischen Venendiagnostik. II. Ergebnisse der Radionuklidvenographie.

The frequency of scintigraphic findings in the presence of thromboses, post-thrombotic changes and in normal veins, was determined in 150 patients. The results of radionuclide venography and contrast venography in these patients have been compared. Abnormalities in veins can be detected by radionuclide venography with a high degree of accuracy. Differentiation between acute and chronic thrombosis and post-thrombotic changes can only be made by invasive contrast venography.

[99mTc marking of gel foam for catheter embolisation (author's transl)]. / 99mTc-Markierung von Gelatineschwamm für die Katheterembolisation.

A simple method is described for marking gel foam particles with 99mTc after reduction of the pertechnetate. This is carried out in the Luer lock syringe to be used for the injection. After embolisation and control angiography, the patient is placed under a scintillation camera. The position of the embolising material can then be demonstrated scintigraphically. In six patients marked emboli were found to be correctly placed. In another patient undergoing a second embolisation for a renal tumour, particles were found in the peripheral circulation.

[133Xe-labeling of tissue adhesives for catheter embolization]. / 133Xe-Markierung von Gewebekleber für die Katheterembolisation.

A method for radio-nuclide labelling of histo-acryl/lipiodol with 133Xe gas is described. The method consists of dissolving the gas in lipiodol under sterile conditions. After embolization and angiography, the localisation of the embolizing material can be determined by means of a scintillation camera. The labelling method was used in 15 patients. In all patients the position of the embolizing material, as demonstrated by scintigraphy, corresponded with the radiological findings. It was not possible to demonstrate escape of the material by scintigraphy.