Risks of Ventricular Arrhythmia and Heart Failure in Carriers of RBM20 Variants

BACKGROUND: Variants in RBM20 are reported in 2% to 6% of familial cases of dilated cardiomyopathy and may be associated with fatal ventricular arrhythmia and rapid heart failure progression. We sought to determine the risk of adverse events in RBM20 variant carriers and the impact of sex on outcomes. METHODS: Consecutive probands and relatives carrying RBM20 variants were retrospectively recruited from 12 cardiomyopathy units. The primary end point was a composite of malignant ventricular arrhythmia (MVA) and end-stage heart failure (ESHF). MVA and ESHF end points were also analyzed separately and males and females compared. Left ventricular ejection fraction (LVEF) contemporary to MVA was examined. RBM20 variant carriers with left ventricular systolic dysfunction (RBM20LVSD) were compared with variant-elusive patients with idiopathic left ventricular systolic dysfunction. RESULTS: Longitudinal follow-up data were available for 143 RBM20 variant carriers (71 male; median age, 35.5 years); 7 of 143 had an MVA event at baseline. Thirty of 136 without baseline MVA (22.0%) reached the primary end point, and 16 of 136 (11.8%) had new MVA with no significant difference between males and females (log-rank P=0.07 and P=0.98, respectively). Twenty of 143 (14.0%) developed ESHF (17 males and 3 females; log-rank P35%. At 5 years, 15 of 67 (22.4%) RBM20LVSD versus 7 of 197 (3.6%) patients with idiopathic left ventricular systolic dysfunction had reached the primary end point (log-rank P<0.001). RBM20 variant carriage conferred a 6.0-fold increase in risk of the primary end point. CONCLUSIONS: RBM20 variants are associated with a high risk of MVA and ESHF compared with idiopathic left ventricular systolic dysfunction. The risk of MVA in male and female RBM20 variant carriers is similar, but male sex is strongly associated with ESHF

Mucormycosis: an emerging disease?

ABSTRACTMucormycosis is the third invasive mycosis in order of importance after candidiasis and aspergillosis and is caused by fungi of the class Zygomycetes. The most important species in order of frequency is Rhizopus arrhizus (oryzae). Identification of the agents responsible for mucormycosis is based on macroscopic and microscopic morphological criteria, carbohydrate assimilation and the maximum temperature compatible with its growth. The incidence of mucormycosis is approximately 1.7 cases per 1000 000 inhabitants per year, and the main risk-factors for the development of mucormycosis are ketoacidosis (diabetic or other), iatrogenic immunosuppression, use of corticosteroids or deferoxamine, disruption of mucocutaneous barriers by catheters and other devices, and exposure to bandages contaminated by these fungi. Mucorales invade deep tissues via inhalation of airborne spores, percutaneous inoculation or ingestion. They colonise a high number of patients but do not cause invasion. Mucormycosis most commonly manifests in the sinuses (39%), lungs (24%), skin (19%), brain (9%), and gastrointestinal tract (7%), in the form of disseminated disease (6%), and in other sites (6%). Clinical diagnosis of mucormycosis is difficult, and is often made at a late stage of the disease or post-mortem. Confirmation of the clinical form requires the combination of symptoms compatible with histological invasion of tissues. The probable diagnosis of mucormycosis requires the combination of various clinical data and the isolation in culture of the fungus from clinical samples. Treatment of mucormycosis requires a rapid diagnosis, correction of predisposing factors, surgical resection, debridement and appropriate antifungal therapy. Liposomal amphotericin B is the therapy of choice for this condition. Itraconazole is considered to be inappropriate and there is evidence of its failure in patients suffering from mucormycosis. Voriconazole is not active in vitro against Mucorales, and failed when used in vivo. Posaconazole and ravuconazole have good activity in vitro. The overall rate of mortality of mucormycosis is approximately 40%

First M87 Event Horizon Telescope Results. II. Array and Instrumentation

The Event Horizon Telescope (EHT) is a very long baseline interferometry (VLBI) array that comprises millimeter- and submillimeter-wavelength telescopes separated by distances comparable to the diameter of the Earth. At a nominal operating wavelength of ~1.3 mm, EHT angular resolution (λ/D) is ~25 μas, which is sufficient to resolve nearby supermassive black hole candidates on spatial and temporal scales that correspond to their event horizons. With this capability, the EHT scientific goals are to probe general relativistic effects in the strong-field regime and to study accretion and relativistic jet formation near the black hole boundary. In this Letter we describe the system design of the EHT, detail the technology and instrumentation that enable observations, and provide measures of its performance. Meeting the EHT science objectives has required several key developments that have facilitated the robust extension of the VLBI technique to EHT observing wavelengths and the production of instrumentation that can be deployed on a heterogeneous array of existing telescopes and facilities. To meet sensitivity requirements, high-bandwidth digital systems were developed that process data at rates of 64 gigabit s−1, exceeding those of currently operating cm-wavelength VLBI arrays by more than an order of magnitude. Associated improvements include the development of phasing systems at array facilities, new receiver installation at several sites, and the deployment of hydrogen maser frequency standards to ensure coherent data capture across the array. These efforts led to the coordination and execution of the first Global EHT observations in 2017 April, and to event-horizon-scale imaging of the supermassive black hole candidate in M87

First M87 Event Horizon Telescope Results. I. The Shadow of the Supermassive Black Hole

When surrounded by a transparent emission region, black holes are expected to reveal a dark shadow caused by gravitational light bending and photon capture at the event horizon. To image and study this phenomenon, we have assembled the Event Horizon Telescope, a global very long baseline interferometry array observing at a wavelength of 1.3 mm. This allows us to reconstruct event-horizon-scale images of the supermassive black hole candidate in the center of the giant elliptical galaxy M87. We have resolved the central compact radio source as an asymmetric bright emission ring with a diameter of 42 ± 3 μas, which is circular and encompasses a central depression in brightness with a flux ratio 10:1. The emission ring is recovered using different calibration and imaging schemes, with its diameter and width remaining stable over four different observations carried out in different days. Overall, the observed image is consistent with expectations for the shadow of a Kerr black hole as predicted by general relativity. The asymmetry in brightness in the ring can be explained in terms of relativistic beaming of the emission from a plasma rotating close to the speed of light around a black hole. We compare our images to an extensive library of ray-traced general-relativistic magnetohydrodynamic simulations of black holes and derive a central mass of M = (6.5 ± 0.7) × 109 Me. Our radiowave observations thus provide powerful evidence for the presence of supermassive black holes in centers of galaxies and as the central engines of active galactic nuclei. They also present a new tool to explore gravity in its most extreme limit and on a mass scale that was so far not accessible

Eurotanais pyrenaensis Sanchez-Garcia, Penalver, Bird, Perrichot & Delclos, 2016, SP. NOV.

&lt;i&gt;EUROTANAIS PYRENAENSIS&lt;/i&gt; SANCHEZ- GARCIA, PE NALVER ~ &amp; PERRICHOT SP. NOV. (FIGS 2, 3) &lt;p&gt; &lt;i&gt;Etymology&lt;/i&gt;&lt;/p&gt; &lt;p&gt; The specific epithet &lt;i&gt;pyrenaensis&lt;/i&gt; is after the range of mountains in south-west Europe (natural border between France and Spain).&lt;/p&gt; &lt;p&gt; &lt;i&gt;Material&lt;/i&gt;&lt;/p&gt; &lt;p&gt; Holotype MNHN.F.A51529a, &male; (superbly preserved) and paratypes MNHN.F.A51529b, &male; (superbly preserved) and MNHN.F.A51529c, &male; (very incomplete; only antennulae, antennae, and some of the chelipeds are preserved). The darkened cuticle of the specimens makes resolving some detailed characters impossible with light microscopy. All type specimens are preserved as syninclusions in a small (greatest length 6.07 mm) dark-orange piece of amber. The sample was originally part of a single piece (#FOU-6) that was subsequently divided into four fragments for optimal study. Syninclusions comprised one Hemiptera, one Hymenoptera Falsiformicidae, one large undetermined Insecta, one Acari Stigmaeidae (A. Arillo, &lt;i&gt;pers. comm.&lt;/i&gt;), and the tanaidaceans MNHN.F.A51530, MNHN.F.A51531, and&lt;/p&gt; &lt;p&gt;MNHN.F.A51532.&lt;/p&gt; &lt;p&gt; MNHN.F.A51532 matches the diagnosis of &lt;i&gt;E. pyrenaensis&lt;/i&gt; for some characters. However, the specimen is highly degraded and preserved in brittle amber with multiple internal fractures that hinder examination, and we cannot attribute them to this species with full confidence.&lt;/p&gt; &lt;p&gt; &lt;i&gt;Occurrence&lt;/i&gt;&lt;/p&gt; &lt;p&gt; Middle Cenomanian Pyrenean amber, near Fourtou village, Aude department, north-eastern Pyrenees, southern France (Girard &lt;i&gt;et al.&lt;/i&gt;, 2013).&lt;/p&gt; &lt;p&gt; &lt;i&gt;Diagnosis&lt;/i&gt;&lt;/p&gt; &lt;p&gt; As for the genus with the following additions. Male. Cephalothorax subtriangular when viewed dorsally. Antennule with eight articles, with numerous aesthetascs. Antenna with subequal articles, never square. Blunt tooth of cheliped fixed finger bearing three distinctive setae. Pereopod basis with one long distal seta. Pereopod 1 much longer than following pereopods, with long dactylus plus unguis (not longer than propodus); pereopods 2 &lt;i&gt;&ndash;&lt;/i&gt; 3 with dactylus plus unguis much shorter than in pereopod 1; pereopods 4 &lt;i&gt;&ndash;&lt;/i&gt; 6 armed with weak spines, and with dactylus plus unguis slightly shorter and stouter than in pereopods 2 &lt;i&gt;&ndash;&lt;/i&gt; 3. Uropod biramous; endopod about 9.3 times the length of exopod; endopod with six articles; exopod with two articles, reaching half the length of endopodal article 1. Female. Unknown.&lt;/p&gt; &lt;p&gt; &lt;i&gt;Description&lt;/i&gt;&lt;/p&gt; &lt;p&gt; Based largely on the holotype MNHN.F.A51529a (Figs 2B &lt;i&gt;&ndash;&lt;/i&gt; E, 3G) and the paratype MNHN.F.A51529b (Fig. 3B &lt;i&gt;&ndash;&lt;/i&gt; F); differences with the paratype MNHN.F.A51529c (Fig. 3A) are noted.&lt;/p&gt; &lt;p&gt; Body (Figs 2A &lt;i&gt;&ndash;&lt;/i&gt; C, 3C) medium-sized, total length around 1.16 &lt;i&gt;&ndash;&lt;/i&gt; 1.25 mm, about 5.37 times as long as&lt;/p&gt; &lt;p&gt;wide; subcylindrical, slightly flattened dorsoventrally. All observed setae simple.&lt;/p&gt; &lt;p&gt; Cephalothorax subtriangular when viewed dorsally, gradually narrowing anteriorly (i.e. without a lateral constriction), 1.61 times longer than its maximum width; around 0.27 &lt;i&gt;&ndash;&lt;/i&gt; 0.31 times total body length, longer than combined length of pereonites 1 &lt;i&gt;&ndash;&lt;/i&gt; 4; posterior margin rounded, laterally swollen. Rostrum absent. Eyes (Fig. 3D) well developed, large, diameter 0.20 times the cephalothorax length, slightly bulging, anterolaterally placed on cephalothorax.&lt;/p&gt; &lt;p&gt; Pereon rather short, around 0.42 &lt;i&gt;&ndash;&lt;/i&gt; 0.45 times total body length. All pereonites wider than long, with fairly convex lateral margins when viewed dorsally, rectangular when viewed laterally; pereonite 1 shorter than pereonite 2, 4.02 times wider than long; pereonites 2 and 3 subequal in size, about 1.45 times the length of pereonite 1, 2.93 times wider than long; pereonites 4 &lt;i&gt;&ndash;&lt;/i&gt; 6 the longest, subequal in size, 2.15 times the length of pereonite 1, nearly twice as wide as long (1.92 times).&lt;/p&gt; &lt;p&gt; Pleon rather short, about 0.27 times total body length, with five free subequal pleonites each bearing pairs of pleopods; pleonites slightly wider than pereonites but much shorter (each about 0.46 times the length of each pereonite 4 &lt;i&gt;&ndash;&lt;/i&gt; 6), about 4.54 times wider than long. Pleotelson (Fig. 3F) short, not reaching the length of two pleonites together, gradually tapering distally, with broadly rounded posterior margin.&lt;/p&gt; &lt;p&gt; Antennule (Fig. 3B) eight-articled (nine-articled in MNHN.F.A51529c, Fig. 3A), fairly slender, tapering distally, 1.32 times the length of cephalothorax, with numerous aesthetascs although their distribution cannot be exactly determined owing to preservation; article 1 about 0.28 times the length of antennule, not reaching the length of articles 2 and 3 combined, about 3.96 times longer than thick, slightly expanded laterally at cephalothorax insertion, with one proximal, one medial, and one distal seta; article 2 about 0.73 times the length of article 1, 3.29 times longer than thick, with one proximal and one distal seta; article 3 about half the length of article 2 (0.56 times), about twice as long as thick (2.15 times), with three setae distally; articles 4 &lt;i&gt;&ndash;&lt;/i&gt; 8 slightly decreasing gradually in length and thickness towards the apex, articles 4 and 5 both with one seta distally, and article 7 with two setae distally; terminal article (article 8) as long as preceding article but thinner, bearing at least three short setae apically.&lt;/p&gt; &lt;p&gt;Antenna (Fig. 3D) at least five-articled (proximal area obscured), approximately half the length of antennule and much thinner; visible articles subequal in size, about 3.35 times longer than thick, without visible setae; terminal article with long setae apically, difficult to enumerate as preserved.&lt;/p&gt; &lt;p&gt;Mouthparts and maxilliped (Fig. 3D) apparently reduced or lacking.&lt;/p&gt; &lt;p&gt;Cheliped robust; sclerite not visible; basis fairly robust, widening distally, nearly twice as long as thick (1.95 times), about 0.81 times the length of carpus, without visible setae; merus subtriangular, with up to two long setae ventrally; carpus about 2.18 times longer than thick, about 0.88 times the length of propodus, without visible setae; propodus (Figs 2E, 3E) robust, fixed finger deflexed almost perpendicular to palm, with dactylus directed medially, with one seta near the insertion of dactylus; fixed finger and dactylus unequal in length, widely separated at base forming a distinct gap between them (i.e. forcipate); fixed finger with three inner setae subdistally arising from a blunt tooth, unguis not visible; dactylus strongly developed, extending beyond fixed finger, gradually curving, with rounded end, unguis not visible.&lt;/p&gt; &lt;p&gt; Pereopod 1 (Fig. 2D) much longer than following pereopods; coxa present; basis fairly slender, cylindrical, about 4.06 times longer than thick, longer than combined length of merus and carpus, with one long seta distally; ischium short; merus and carpus subequal in length, not widening distally, without visible setae; propodus longer than carpus, tapering distally, with one dorsodistal and one ventrodistal long seta; dactylus plus unguis curved and very long, about as long as propodus; unguis not distinguishable. Pereopods 2 &lt;i&gt;&ndash;&lt;/i&gt; 3 (Fig. 2D) as pereopod 1 but shorter; merus together with carpus about half the length (0.56 times) of the combined length of merus and carpus 1, with up to one and two distal short setae, respectively; propodus about half the length of propodus 1 (0.57 times), with one dorsodistal and one ventrodistal short seta; dactylus plus unguis about 0.39 times the length of dactylus plus unguis 1, about 0.69 times the length of propodus; unguis not distinguishable.&lt;/p&gt; &lt;p&gt; Pereopods 4 &lt;i&gt;&ndash;&lt;/i&gt; 6 similar in length to pereopods 2 and 3 but sturdier; coxa present; basis fairly robust, more inflated than in pereopods 1 &lt;i&gt;&ndash;&lt;/i&gt; 3, about 2.85 times longer than thick, longer than combined length of merus and carpus, with one long seta distally; ischium short; merus and carpus subequal in size, not widening distally, merus without visible spines and carpus with up to two minute spines; propodus longer than carpus, tapering distally, with up to two dorsodistal minute spines; dactylus plus unguis slightly shorter and stouter than in pereopods 2 &lt;i&gt;&ndash;&lt;/i&gt; 3, claw-like; unguis not distinguishable.&lt;/p&gt; &lt;p&gt;Pleopods all alike; basal article rounded, without visible setae; endopod and exopod subovate, with long setae bundled together in a pointed process sticking out under the pleon.&lt;/p&gt; &lt;p&gt;Uropod (Fig. 3F, G) biramous, the endopod about 9.29 times the length of exopod; basal article elongated, about 2.48 times longer than thick, longer than exopod, without visible setae; endopod greatly elongated but shorter than pleon, with six subequal articles, each article about 2.60 times longer than thick, with up to two setae distally (difficult to exactly enumerate as preserved) except for the terminal article, which ends with four long setae; exopod very short, thinner than endopod, reaching slightly beyond half the length of endopodal article 1, with two subequal articles, article 1 with one short seta distally, article 2 ending with two long setae.&lt;/p&gt; &lt;p&gt; &lt;i&gt;Remarks&lt;/i&gt;&lt;/p&gt; &lt;p&gt; Paratype MNHN.F.A51529c of &lt;i&gt;E. pyrenaensis&lt;/i&gt; sp. nov. has a nine-articled antennule instead of eightarticled as in the other type specimens of the species. However, this may be intraspecific variation; note that in Recent species with a large number of flagellar segments (more than five) there may be differences of one or more (an example being males of &lt;i&gt;Leptochelia acrolophus&lt;/i&gt; Bird, 2015, with six to ten flagellar articles depending on body size; Bird, 2015).&lt;/p&gt; &lt;p&gt; As mouthparts are apparently reduced or lacking in paratype MNHN.F.A51529b, the specimen should be considered a terminal male stage, devoted solely to reproduction. In fact, in mature, especially natatory, males of most tanaidomorphan genera [e.g. &lt;i&gt;Cryptocopoides&lt;/i&gt; (Sieg, 1973 in M.S.) Sieg, 1977, &lt;i&gt;Leptochelia&lt;/i&gt; Dana, 1849, &lt;i&gt;Leptognathia&lt;/i&gt; Sars, 1882, &lt;i&gt;Paratanais&lt;/i&gt; Dana, 1852, &lt;i&gt;Sinelobus&lt;/i&gt; Sieg, 1980, and &lt;i&gt;Tanaissus&lt;/i&gt; Stebbing, 1891], the mouthparts (including the maxilliped) undergo different degrees of reduction, in extreme cases rendering the animal a nonfeeding individual (Larsen, 2005; B&lstrok;a zewicz- _ Paszkowycz &lt;i&gt;et al.&lt;/i&gt;, 2014). Mouthparts cannot be examined in the specimens of &lt;i&gt;E. terminator&lt;/i&gt; and &lt;i&gt;E. seilacheri&lt;/i&gt; owing to fossilization position. However, it is worth noting that the alavatanaid males of &lt;i&gt;Al. carabe&lt;/i&gt; were described as having well-developed mouthparts (Sanchez-Garc&imath;a &lt;i&gt;et al.&lt;/i&gt;, 2015).&lt;/p&gt;Published as part of &lt;i&gt;Sanchez-Garcia, Alba, Penalver, Enrique, Bird, Graham J., Perrichot, Vincent &amp; Delclos, Xavier, 2016, Palaeobiology of tanaidaceans (Crustacea: Peracarida) from Cretaceous ambers: extending the scarce fossil record of a diverse peracarid group, pp. 492-522 in Zoological Journal of the Linnean Society 178 (3)&lt;/i&gt; on pages 497-501, DOI: 10.1111/zoj.12427, &lt;a href="http://zenodo.org/record/5368955"&gt;http://zenodo.org/record/5368955&lt;/a&gt

Diverse assemblages of tanaids (Crustacea) related to Albian-Cenomanian resin-producing forests in Western Europe and their paleobiological implications

International audienceAttempts at reconstructing amber forest habitats have sometimes neglected some aspects concerning arthropod communities in the soil, particularly those related to humid terrestrial conditions with, at least, certain proximity to partially flooded areas. The improving knowledge of the Spanish and French amber-bearing localities (AlbianCenomanian) has allowed the discovery of organisms that lived close to or in aquatic environments. Among these, small crustaceans belonging to the peracaridan Order Tanaidacea are exceptionally preserved. Except for a few rare freshwater and brackish species, Recent tanaids are marine organisms which occur over the full range of depths, and they typically hide in crevices or interstices, or construct tubes or burrows. Tanaids are exceedingly sparse in the geological record, with only 13 fossil species recorded to date. These are mostly rock-impressions, and only few specimens have been found as bioinclusions in ancient resins from some deposits around the world. The history of tanaids goes back to Lower Carboniferous, with the oldest species discovered in Scotland. Paleozoic taxa are also known from the Upper Carboniferous of Illinois and Lower Permian of Germany. Various Mesozoic tanaids were described from Lower Jurassic of Germany, Middle Jurassic of Bulgaria, Germany and Switzerland, Upper Jurassic of Germany, and Lower Cretaceous of Germany, but until recently, the only fossils known as bioinclusions were three species from Lower Cretaceous amber of Spain, placed in Alavatanaidae (Suborder Tanaidomorpha). The new findings include 19 tanaids in Albian Spanish amber from Alava (Perïacerrada 1 outcrop, Burgos Province), with at least two new morphotypes. A single specimen from El Soplao amber (Cantabria Province) has been tentatively assigned to Alavatanais carabe Vonk and Schram, 2007. Furthermore, Albian-Cenomanian French amber has provided 17 tanaids among which three potential new morphotypes. These specimens were found in am ber from various localities in the Charentes region (Archingeay-Les Nouillers and La Buzinie), and in the departments of Vendée (La Garnache) and Aude (Fourtou). The new fossils ail belong to the Suborder Tanaidomorpha and are remarkably modern in appearance, which is of great interest in understanding the history of the Order and their relationships with extant families. These tanaid assemblages from palaeogeographically close Spanish and French Cretaceous amber bearing-deposits, suggest that this group was relatively common in or around the ancient resin-producing forests, and often some of them have been found together in the same amber piece. Moreover, taphonomic and palaeobiological approaches showed that Spanish tanaids were preserved together with diverse nonaquatic syninclusions originating from the litter, i.e. inorganic soil components, decayed plant debris, arthropod remains, fungal hyphae, coprolites, and body-fossils such as isopods, mites, and thysanurans. French tanaids, however, were generally preserved in a mixture of terrestrial, often litter-inhabiting arthropods and fungi, but also marine organisms like centric diatoms and sponge spicules. This provides evidence for the early adaptation of tanaids to various habitats, from edaphic conditions in moist terrestrial or freshwater habitats, as suggested by Spanish fossils, to brackish or even marine habitats, as suggested by French fossils

Palaeobiology of tanaidaceans (Crustacea: Peracarida) from Cretaceous ambers: extending the scarce fossil record of a diverse peracarid group

International audienceDiverse assemblages of tanaidacean peracarid crustaceans from western Tethyan continental deposits suggest that the group was relatively common in or around ancient resin-producing forests. Here we report the results of an examination of 13 tanaidacean specimens from three Cretaceous (Albian to Turonian) French amber deposits. Two new species of the fossil family Alavatanaidae are placed in the previously described Early Cretaceous genus Eurotanais: Eurotanais pyrenaensis sp. nov. from Cenomanian Pyrenean amber (Fourtou, Aude) and Eurotanais seilacheri sp. nov. from Turonian Vendean amber (La Garnache, Vendée). The remaining specimens are placed in three newly erected genera and species (but family incertae sedis): Arcantitanais turpis gen. et sp. nov. from Albian–Cenomanian Charentese amber (Archingeay, Charente-Maritime), and Tytthotanais tenvis gen. et sp. nov. and Armadillopsis rara gen. et sp. nov. from Pyrenean amber. These are the first formally described fossils that might be related to the paratanaoidean families Nototanaidae and Paratanaidae, sharing with these some putatively derived features and providing possible evidence for the antiquity and morphological stability of these families and the suborder Tanaidomorpha. The distinctive features and character combinations of these fossil taxa are discussed in connection with possible relationships to the living lineages of tanaidaceans. Propagation phase-contrast X-ray synchrotron microtomography was used to obtain high-quality 3D images for some fossils. A discussion is provided on the putative palaeobiology of tanaidaceans and the French resiniferous forest ecosystem. The discovery of these new tanaidaceans extends the palaeogeographical distribution and stratigraphical range of the family Alavatanaidae and sheds new light on the palaeoecology and diversity of tanaidaceans in pre-angiospermous woodlands