A temperate super-Jupiter imaged with JWST in the mid-infrared.

Of the ~25 directly imaged planets to date, all are younger than 500Myr and all but 6 are younger than 100Myr1. Eps Ind A (HD209100, HIP108870) is a K5V star of roughly solar age (recently derived as 3.7-5.7Gyr2 and 3.5 - 1.3 + 0.8 Gyr3). A long-term radial velocity trend 4,5 as well as an astrometric acceleration6,7 led to claims of a giant planet2,8,9 orbiting the nearby star (3.6384±0.0013pc10). Here we report JWST coronagraphic images that reveal a giant exoplanet which is consistent with these radial and astrometric measurements, but inconsistent with the previously claimed planet properties. The new planet has temperature ~275K, and is remarkably bright at 10.65µm and 15.50µm. Non-detections between 3.5-5µm indicate an unknown opacity source in the atmosphere, possibly suggesting a high metallicity, high carbon-to-oxygen ratio planet. The best-fit temperature of the planet is consistent with theoretical thermal evolution models, which are previously untested at this temperature range. The data indicates that this is likely the only giant planet in the system and we therefore refer to it as "b", despite it having significantly different orbital properties than the previously claimed planet "b".

Experimental and theoretical investigation of 2D nanoplatelet-based conversion layers for color LED microdisplays.

In the field of augmented reality, there is a need for very bright color microdisplays to meet the user specifications. Today, one of the most promising technology to manufacture such displays involves a blue micro-LED technology and quantum dots-based color conversion layers. Despite recent progress, the external power conversion efficiencies (EPCE) of these layers remain under ∼25%, below the needs (>40%) to reach a white luminance of 100,000 cd/m2. In this work, we have synthesized CdSexS1-x nanoplatelet-based conversion layers for red and green conversion, and measured their absorption properties and EPCE performances with respect to layer thickness. On this basis, a model was developed that reliably predicts the layer EPCE while using only few input data, namely the layer absorption coefficients and the photoluminescence quantum yield (PLQY) of color photoresist. It brings a new insight into the conversion process at play at a micro-LED level and provides a simple method for extensive optimization of conversion materials. Finally, this study highlights the outstanding red conversion efficiency of photoresist layers made of core-double shell CdSexS1-x nanoplatelets with 31% EPCE (45% external PLQY) for 8 µm-thick conversion layer.

Two families of exocomets in the ß Pictoris system.

The young planetary system surrounding the star ß Pictoris harbours active minor bodies. These asteroids and comets produce a large amount of dust and gas through collisions and evaporation, as happened early in the history of our Solar System. Spectroscopic observations of ß Pictoris reveal a high rate of transits of small evaporating bodies, that is, exocomets. Here we report an analysis of more than 1,000 archival spectra gathered between 2003 and 2011, which provides a sample of about 6,000 variable absorption signatures arising from exocomets transiting the disk of the parent star. Statistical analysis of the observed properties of these exocomets allows us to identify two populations with different physical properties. One family consists of exocomets producing shallow absorption lines, which can be attributed to old exhausted (that is, strongly depleted in volatiles) comets trapped in a mean motion resonance with a massive planet. Another family consists of exocomets producing deep absorption lines, which may be related to the recent fragmentation of one or a few parent bodies. Our results show that the evaporating bodies observed for decades in the ß Pictoris system are analogous to the comets in our own Solar System.

Gaps at the interface between dentine and self-adhesive resin cement in post-endodontic restorations quantified in 3D by phase contrast-enhanced micro-CT.

AIM: To assess the extent of gaps between root dentine and titanium or fibreglass post restorations following cementation with a self-adhesive resin cement. METHODOLOGY: Fourteen root filled maxillary central incisors restored with prefabricated posts made of Fibreglass (n = 7) or Titanium (n = 7) and cemented with RelyX Unicem 2 were imaged by rapid, high-resolution phase contrast-enhanced micro-CT (PCE-CT) in a synchrotron X-ray imaging facility (ID19, ESRF, 34 KeV, 0.65 µm pixel resolution). Reconstructions were used to measure canal, cement and post perimeters and cross-sectional areas and interfacial gaps at 0.1 mm increments in the root canal space, along the cervical region of the tooth. Remnants of endodontic sealer (AH Plus), when present, were also quantified. Mann-Whitney and 2-way ANOVA tests were used to compare findings within slices and between the two post groups. Pearson correlation coefficients (r) were determined between the interfacial gaps and the other measured parameters. RESULTS: Clearly detectable gaps were found in 45% (±14%) of the interfaces between dentine and cement, along the canal in the cervical area of the tooth beneath the core. The length of interfacial gaps was moderately correlated to the canal cross-sectional area, to the canal perimeter and to the canal area filled by cement (R = 0.52 ~ 0.55, P < 0.001). There was no significant difference between samples with fibreglass or titanium (P > 0.01). Both post types had defect-free interfaces with cement. Endodontic sealer remnants were found on ~10% of the canal walls and were moderately correlated to the presence of gaps. Approximately 30% of the sealer-affected interfaces exhibited no detachment between dentine, sealer and cement. CONCLUSIONS: Self-adhesive cements had interfacial gaps along substantial regions of the root canal surface, which was not correlated with the amount of cement in the canal. PCE-CT proved to be an excellent non-destructive method to study root canal restorations of hydrated samples in 3D.

Serum protein electrophoresis: an interesting diagnosis tool to distinguish viral from bacterial community-acquired pneumonia.

29-69 % of pneumonias are microbiologically documented because it can be considered as an invasive procedure with variable test sensitivity. However, it drastically impacts therapeutic strategy in particular the use of antibiotics. Serum protein electrophoresis (SPEP) is a routine and non-invasive test commonly used to identify serum protein disorders. As virus and bacteria may induce different globulins production, we hypothesize that SPEP can be used as an etiological diagnosis test. Retrospective study conducted from 1/1/13 until 5/1/15 among patient hospitalized for an acute community-acquired pneumonia based on fever, crackles and radiological abnormalities. α/ß, α/γ, ß/γ globulins and albumin/globulin (A/G) ratio were calculated from SPEP. Data were analyzed in 3 groups: documented viral (DVP) or bacterial pneumonia (DBP) and supposedly bacterial pneumonia (SBP). We used ANOVA statistic test with multiple comparisons using CI95 and ROC curve to compare them. 109 patients included divided into DBP (n = 16), DVP (n = 26) and SBP (n = 67). Mean age was 62 ± 18 year-old with a sex ratio M/F of 1.3. Underlying conditions (e.g. COPD, diabetes) were comparable between groups in multivariate analysis. Means of A/G ratio were 0.80 [0.76-0.84], 0.96 [0.91-1.01], 1.08 [0.99-1.16] respectively for DBP, SBP and DVP (p = 0.0002). A/G ratio cut-off value of 0.845 has a sensitivity of 87.5 % and a specificity of 73.1 %. A/G ratio seems to be an easy diagnostic tool to differentiate bacterial from viral pneumonia. A/G ratio cut-off value below 0.845 seems to be predictable of a bacterial origin and support the use of antibiotics.

Large changes in Pluto's atmosphere as revealed by recent stellar occultations.

Pluto's tenuous nitrogen atmosphere was first detected by the imprint left on the light curve of a star that was occulted by the planet in 1985 (ref. 1), and studied more extensively during a second occultation event in 1988 (refs 2-6). These events are, however, quite rare and Pluto's atmosphere remains poorly understood, as in particular the planet has not yet been visited by a spacecraft. Here we report data from the first occultations by Pluto since 1988. We find that, during the intervening 14 years, there seems to have been a doubling of the atmospheric pressure, a probable seasonal effect on Pluto.

Outcomes of concurrent radiotherapy with weekly docetaxel and platinum-based chemotherapy in stage III non-small-cell lung cancer.

PURPOSE: The present study evaluated the outcomes of concurrent weekly docetaxel and platinum-based drug doublet in association with concurrent thoracic radiotherapy (TR) in the curative treatment of stage III locally advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with stage IIIA/B NSCLC were retrospectively included. Patients received weekly docetaxel and either cisplatin or carboplatin intravenous injections during concurrent TR (60 to 66Gy). Patients who received induction chemotherapy with the same drug doublet were also included. The endpoints were: disease control rate (DCR), overall recurrence rate, survival rates [disease-free survival (DFS) and overall survival (OS)] and toxicity. RESULTS: Eighty-nine consecutive patients treated with this association were included. Median follow-up time was 57.8 months. DCR was 76.5% at the first follow-up CT scan (6 to 12 weeks after the end of concurrent treatment). Median DFS and OS was 14.3 and 29.9 months respectively. Three-year survival was 43%. The overall recurrence rate was 65.9%. During overall treatment, grade 3 to 4 adverse events occurred in 29.2% of patients, the most common being esophagitis (12.4% of patients). Only 13.5% of patients presented with a grade 3 or higher adverse event after the end of concurrent treatment. CONCLUSIONS: Weekly docetaxel and platinum-based drug doublet combined with TR yielded promising results in stage III NSCLC, with high survival rates. The toxicity of this association is acceptable, with mainly manageable esophagitis. These findings warrant validation in a prospective study before considering this association for standard of care.

Achieving synaptically relevant pulses of neurotransmitter using PDMS microfluidics.

Fast synaptic transmission is mediated by post-synaptic ligand-gated ion channels (LGICs) transiently activated by neurotransmitter released from pre-synaptic vesicles. Although disruption of synaptic transmission has been implicated in numerous neurological and psychiatric disorders, effective and practical methods for studying LGICs in vitro under synaptically relevant conditions are unavailable. Here, we describe a novel microfluidic approach to solution switching that allows for precise temporal control over the neurotransmitter transient while substantially increasing experimental throughput, flexibility, reproducibility, and cost-effectiveness. When this system was used to apply ultra-brief ( approximately 400micros) GABA pulses to recombinant GABA(A) receptors, members of the cys-loop family of LGICs, the resulting currents resembled hippocampal inhibitory post-synaptic currents (IPSCs) and differed from currents evoked by longer, conventional pulses, illustrating the importance of evaluating LGICs on a synaptic timescale. This methodology should therefore allow the effects of disease-causing mutations and allosteric modulators to be evaluated in vitro under physiologically relevant conditions.

HSP110 promotes colorectal cancer growth through STAT3 activation.

Heat shock protein 110 (HSP110) is induced by different stresses and, through its anti-apoptotic and chaperoning properties, helps cells survive these adverse situations. In colon cancers, HSP110 is abnormally abundant. We have recently shown that colorectal cancer patients with microsatellite instability (MSI) had an improved response to chemotherapy because they harbor an HSP110-inactivating mutation (HSP110DE9). In this work, we used patient biopsies, human colorectal cancer cells grown in vitro and in vivo (xenografts), and intestinal crypts to demonstrate that HSP110 is also involved in colon cancer growth. We showed that HSP110 induces colon cancer cell proliferation and that this effect is associated with STAT3 activation, specifically an increase in STAT3 phosphorylation, nuclear translocation and transcription factor activity. STAT3 inhibition blocks the proliferative effect of HSP110. From a molecular standpoint, we demonstrated that HSP110 directly binds to STAT3, thereby facilitating its phosphorylation by JAK2. Finally, we showed a correlation between HSP110 expression and STAT3 phosphorylation in colon cancer patient samples. Thus, the expression of HSP110 in colon cancer contributes to STAT3-dependent tumor growth and the frequent inactivating mutation of this chaperone is probably an important event underlying the improved prognosis in colon cancer displaying MSI.

Etanercept reduces late endotoxin-induced pulmonary hypertension in the pig.

To evaluate whether etanercept, a tumor necrosis factor (TNF)-blocking agent, may counteract hemodynamic deterioration in endotoxemic shock, we designed a prospective, randomized placebo-controlled trial with parallel groups, consisting of 13 pigs aged 10-14 weeks receiving general anesthesia. Five pigs were given 25 mg of etanercept, 1 h before the start of a 4-h continuous infusion of endotoxin. Another 5 pigs were given the corresponding volume of saline, 1 h before the start of a 4-h continuous infusion of endotoxin. Three pigs were given 25 mg of etanercept, 1 hr before the start of a 4-h continuous infusion of saline. At 1 h of endotoxemia, mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance index (PVRI) increased identically in both groups of pigs receiving endotoxin. Thereafter, two distinct different patterns in hemodynamics were observed. TNF-blocked pigs showed significantly lower MPAP and PVRI compared to controls. In the etanercept-treated endotoxemic pigs, Doppler analysis of the diastolic mitral inflow demonstrated a significantly increased E/A-ratio (early mitral wave inflow was divided by the atrial wave) at 2 h. The TNFblocking agent etanercept normalized two hemodynamic features of endotoxin-induced septic shock in pigs: (1) the sustained pulmonary hypertension and (2) diastolic dysfunction.

Cross-polarization/magic-angle-spinning nuclear magnetic resonance in selectively 13C-labeled synthetic eumelanins.

We report a solid-state NMR study of synthetic eumelanins prepared by oxidation of 5,6-dihydroxyindole (DHI) selectively 13C-labeled at positions 2 or 3 of the indole ring. The 13C-1H couplings have been used to quantify the carbons by selecting the non-protonated and protonated carbon resonances. By comparing the data of non-labeled melanin to that obtained using [2-(13)C]- and [3-(13)C]-enriched DHI, it was possible to clearly demonstrate the high chemical reactivity of position 2 and, to a lesser extent, position 3 of the DHI unit. These two sites together are responsible for three-quarters of the proton loss during polymerization. The cross-polarization/magic-angle-spinning spectra likewise point to a partial oxidation of positions 2 and 3 to the carboxyl and carbonyl oxidation states during the formation of melanin. Furthermore, it is shown that 13C-13C dipolar interactions in [2-(13)C]-enriched DHI melanins can be observed using radiofrequency-driven dipolar recoupling (RFDR) 2D experiments. An upper limit of about 4 A for the distance between the C-2 carbons is deduced from the RFDR experiments. This result is in agreement with the basic arrangement of the different atoms expected in the DHI melanins.

Estradiol-17 beta and mu-opioid peptides rapidly hyperpolarize GnRH neurons: a cellular mechanism of negative feedback?

Control of the HPG axis involves a rapid (30 min) inhibition of LH (GnRH) release by E2. The time course of this effect is faster than expected for a purely transcriptional mechanism of E2 action. To elucidate the mechanism of E2 action, intracellular recordings in TTX were performed in guinea pig hypothalamic GnRH neurons. These neurons were directly hyperpolarized by both the mu-opioid agonist, DAMGO (Tyr-D-Ala-Gly-MePhe-Gly-ol, 9 mV) and the GABAB agonist, baclofen (18 mV) by opening K+ channels. Schild analysis with naloxone (Ke = 2.4 nM) confirmed that mu-opioid receptors mediated the effect of DAMGO. E2 also directly hyperpolarized GnRH neurons by opening K+ channels. Coupled with previous work showing a rapid effect of E2 to alter mu-opioid potency (1), a model is presented in which E2 rapidly inhibits GnRH neurons through parallel, possibly synergistic pathways.

Effects of basic fibroblast growth factor on survival and choline acetyltransferase development of spinal cord neurons.

To investigate the biological role of basic fibroblast growth factor (bFGF) for the development of the spinal cord we studied the in vitro and in vivo effects of this protein on survival and choline acetyltransferase (ChAT)-activity of embryonic chick and rat spinal cord neurons. In vitro, bFGF (ED50 1-2.8 ng/ml) supported the survival of embryonic neurons from the ventral part of the rat spinal cord (ventral spinal cord, vsc), including motoneurons. Addition of bFGF (100 ng/ml) increased the ChAT-activity in embryonic chick vsc cultures to 150% as compared to untreated cultures (100%). The effect of bFGF was dose-dependent. In vivo-application of bFGF resulted in a similar increase of ChAT-activity in chick spinal cord. Since bFGF stimulates the ChAT-activity of spinal cord neurons in vivo and in vitro we therefore conclude that this protein may have a physiological function for the transmitter development of cholinergic spinal cord neurons.

Basic fibroblast growth factor prevents ontogenetic neuron death in vivo.

Basic fibroblast growth factor (bFGF) is a mitogen and a potent neurotrophic protein for ciliary ganglionic (CG) neurons in vitro. Recombinant bFGF was administered to the chorionic-allantoic membrane of chick embryos during the period of ontogenetic neuron death in the cholinergic CG between embryonic days (E) 8 and E14. Neuronal losses in untreated chicks and in embryos that received the vehicle only (phosphate-buffered saline plus cytochrome c) amounted to 44%. Basic FGF permitted the survival of 87% of the neurons present at E8. There were no apparent differences in the size and number of non-neuronal cells in CG. These data add to the increasing body of evidence that bFGF is an important multifunctional growth factor with a neurotrophic capacity.

Rapid effects of estrogen to modulate G protein-coupled receptors via activation of protein kinase A and protein kinase C pathways.

17Beta-estradiol (E2) rapidly (<20 min) attenuates the ability of mu-opioids to hyperpolarize guinea pig hypothalamic neurons. We have used intracellular recordings from female guinea pig hypothalamic slices to characterize the receptor and intracellular pathway(s) mediating E2's rapid effects. E2 acts stereospecifically with physiologically relevant concentration-dependence (EC50 = 8 nM) to cause a fourfold reduction in the potency of the mu-opioid agonist (D-Ala2-N-Me-Phe4-Gly5-ol)-enkephalin and the GABA(B) agonist baclofen to activate an inwardly rectifying K+ conductance in hypothalamic neurons. Both the nonsteroidal estrogen diethylstilbestrol and the anti-estrogen ICI 164,384 blocked E2 actions to uncouple mu-opioid receptors. Using a pharmacological Schild analysis, we found that ICI 164,384 competed for this E2 receptor with a Ke of approximately 0.3 nM. The protein synthesis inhibitor cycloheximide did not block the estrogenic uncoupling of the mu-opioid receptor from its K+ channel, implying a rapid, nongenomic mechanism of E2 action. The effects of E2 were mimicked by the bath application of the protein kinase A (PKA) activators, forskolin and Sp-cAMP, and the protein kinase C (PKC) activator phorbol-12,13-dibutyrate. Furthermore, the selective PKA antagonists Rp-cAMP and KT5720, which have different chemical structures and modes of action, both blocked the effects of E2. In addition, the actions of E2 were blocked by the selective PKC inhibitor Calphostin C. Therefore, it appears that E2 can activate both PKA and PKC to cause a heterologous desensitization of both mu-opioid and GABA(B) receptors, which has the potential to alter synaptic transmission in many regions of the CNS.

[Slow ventricular tachycardia presenting in the antenatal period]. / Tachycardie ventriculaire lente de révélation anténatale.

The authors report two cases of slow ventricular tachycardia presenting in the antenatal period. One foetus had anasarca at 38 weeks' gestation. After birth, improved myocardial function contributed to the rapid resorption of the effusions. The other case was well tolerated in the foetal and neonatal periods. In both cases, Holter ECG recorded an intermittent ventricular arrhythmia with salvos of sustained ventricular tachycardia with a maximum rate of 185/min, only 10% higher than the underlying sinus rhythm, disappearing on acceleration of the sinus rhythm. The aetiological investigation was negative. Therapeutic abstention was supported by the spontaneously favourable outcome after 3 and 5 months. Slow ventricular tachycardia or accelerated idioventricular rhythms are usually considered to be benign but the case with foetal anasarca suggests that they should be carefully followed up in the neonatal period. In the absence of a consensus on management, therapeutic abstention implies regular cardiological examination until the arrhythmia has disappeared.

[Atrial flutter: a possible early sign of acute rejection in heart transplantation. A case report]. / Le flutter atrial: un témoin précoce possible du rejet aigu chez le transplanté cardiaque. A propos d'une observation.

The authors report the case of a cardiac transplant patient with a recurrence of atrial flutter two months after electrical cardioversion and despite long-term preventive treatment with amiodarone. Early investigation for signs of rejection with 4 endomyocardial biopsies was negative. Aggravation of the haemodynamic status due to flutter with a rapid ventricular response led to an attempted radio-frequency ablation. Endocavitary mapping confirmed persistence of sinus activity in the native atrium and the presence of a circuit of type I isthmic flutter (anticlockwise circuit) in the donor atrium. Ablation by radio-frequency in the same procedure was successful. A fifth myocardial biopsy the same day finally confirmed stage 3A acute rejection. No signs of recurrent rejection or arrhythmia have been observed after 24 months' follow-up in this patient. This preliminary experience confirms the need to look for graft rejection by repeated myocardial biopsies in cardiac transplant, patients with atrial flutter and the efficacy of radio-frequency ablation in cases of resistance to conventional therapy.

[Ventricular tachycardia by branch to branch re-entry. Familial case with Steinert's disease]. / Tachycardie ventriculaire par réentrée de branche à branche. Cas familial avec maladie de Steinert.

Ventricular tachycardia by branch to branch reentry is a rare arrhythmia. It occurs in cardiomyopathies associated with conduction defects. During tachycardia a His potential precedes each QRS complex which usually has a left bundle branch block appearance. The authors report two familial cases of ventricular branch to branch tachycardia (son and mother) without cardiomyopathy. The diagnosis of Steinert's disease was made post-mortem in these two patients. In cases of branch to branch ventricular tachycardia, the diagnosis of myotonic dystrophy should be excluded. Conversely, endocavitary electrophysiological investigation with ventricular stimulation should be proposed for symptomatic patients (dizzy spells, syncope) to diagnose branch to branch ventricular tachycardia, even in cases with conduction defects which could also explain the symptoms.

[Radiofrequency ablation in auricular flutter. Predictive factors of primary success and medium term results]. / Ablation par radiofréquence du flutter auriculaire. Facteurs prédictifs du succès primaire et devenir à moyen terme.

Ninety-one consecutive patients underwent radiofrequency ablation of chronic or paroxysmal atrial flutter. The average age of the patients was 66. There was a previous history of atrial fibrillation in 38% of cases and of cardiac surgery in 14.3% of cases. The primary success rate was 79% (92% in cases of common flutter). The predictive factors of success were the type of flutter (p < 0.001), left ventricular (p < 0.01) and left atrial dimensions (p < 0.01) at echocardiography. The length of the cavo-tricuspid isthmus measured by echocardiography had no influence on the initial result but, in primary success, did affect the parameters of the procedure (duration and number of applications of radiofrequency energy). After an average of 11 +/- 2 months, sinus rhythm was maintained in 67% of patients. There were recurrences of flutter in 27.5% of cases and of atrial fibrillation in 5.5% of cases: 85% of these episodes occurred during the first six months after ablation. A second procedure was carried out in 12 patients for recurrence of flutter (92% primary success rate). After an average follow-up of 8.4 months, 4 patients had a recurrence and required a third procedure (100% success rate). In cases of failure of ablation, the rhythm was converted by a shock or atrial pacing: 47.3% of these patients remained in sinus rhythm with antiarrhythmic therapy with a 12 month follow-up. Radiofrequency ablation of atrial flutter is, therefore, a safe method, the difficulty of which is mainly related to anatomical factors: the medium-term results are better than those of other therapeutic methods.

[Occupational asthma caused by organic substances]. / L'asthme professionnel aux produits organiques.

Occupational asthma (OA) to organic substances is frequently related to IgE-dependent hypersensitivity. New etiological agents are latex and vegetal gums, in health care personnel as in carpet-making manufactures. Bakers are exposed to numerous allergens: wheat and cereal flours, sesame and other seed proteins, alpha-amylase and other enzymes. Alpha-amylase extracted from Aspergillus orizae is a potent allergen. Plant derived materials have been identified as allergens in the floral industry (Ficus, Ginseng, Gypsophila, etc). The accurate diagnosis relies upon a thorough history, completed by measurements of peak expiratory flows during the work. Sensitization can be confirmed by prick tests and immuno assays for IgE antibodies. Bronchial provocation tests documenting OA are advisable. The early detection of OA might be evaluated by skin tests to occupational allergens repeated yearly. The prevention of OA relies on air sampling technologies controlling the allergenic density of the atmosphere and removing asthmatics from exposed areas. There are no scientific grounds for discarding atopics from occupations at risk for OA.