Drug resistance in B and non-B subtypes amongst subjects recently diagnosed as primary/recent or chronic HIV-infected over the period 2013–2016: Impact on susceptibility to first-line strategies including integrase strand-transfer inhibitors

Objectives To characterize the prevalence of transmitted drug resistance mutations (TDRMs) by plasma analysis of 750 patients at the time of HIV diagnosis from January 1, 2013 to November 16, 2016 in the Veneto region (Italy), where all drugs included in the recommended first line therapies were prescribed, included integrase strand transfer inhibitors (InNSTI). Methods TDRMs were defined according to the Stanford HIV database algorithm. Results Subtype B was the most prevalent HIV clade (67.3%). A total of 92 patients (12.3%) were expected to be resistant to one drug at least, most with a single class mutation (60/68–88.2% in subtype B infected subjectsand 23/24–95.8% in non-B subjects) and affecting mainly NNRTIs. No significant differences were observed between the prevalence rates of TDRMs involving one or more drugs, except for the presence of E138A quite only in patients with B subtype and other NNRTI in subjects with non-B infection. The diagnosis of primary/recent infection was made in 73 patients (9.7%): they had almost only TDRMs involving a single class. Resistance to InSTI was studied in 484 subjects (53 with primary-recent infection), one patient had 143C in 2016, a total of thirteen 157Q mutations were detected (only one in primary/recent infection). Conclusions Only one major InSTI-TDRM was identified but monitoring of TDRMs should continue in the light of continuing presence of NNRTI-related mutation amongst newly diagnosed subjects, sometime impacting also to modern NNRTI drugs recommended in first-line therapy

Leptin fails to blunt the lipopolysaccharide-induced activation of the hypothalamic-pituitary-adrenal axis in rats

Copyright @ 2013 The authors. This work is licensed under a Creative Commons Attribution 3.0 Unported License.Obesity is a risk factor for sepsis morbidity and mortality, whereas the hypothalamic-pituitary-adrenal (HPA) axis plays a protective role in the body's defence against sepsis. Sepsis induces a profound systemic immune response and cytokines serve as excellent markers for sepsis as they act as mediators of the immune response. Evidence suggests that the adipokine leptin may play a pathogenic role in sepsis. Mouse endotoxaemic models present with elevated leptin levels and exogenously added leptin increased mortality whereas human septic patients have elevated circulating levels of the soluble leptin receptor (Ob-Re). Evidence suggests that leptin can inhibit the regulation of the HPA axis. Thus, leptin may suppress the HPA axis, impairing its protective role in sepsis.We hypothesised that leptin would attenuate the HPA axis response to sepsis.We investigated the direct effects of an i.p. injection of 2 mg/kg leptin on the HPA axis response to intraperitoneally injected 25 μg/kg lipopolysaccharide (LPS) in the male Wistar rat. We found that LPS potently activated the HPA axis, as shown by significantly increased plasma stress hormones, ACTH and corticosterone, and increased plasma interleukin 1β (IL1β) levels, 2 h after administration. Pre-treatment with leptin, 2 h before LPS administration, did not influence the HPA axis response to LPS. In turn, LPS did not affect plasma leptin levels. Our findings suggest that leptin does not influence HPA function or IL1b secretion in a rat model of LPS-induced sepsis, and thus that leptin is unlikely to be involved in the acute-phase endocrine response to bacterial infection in rats.The section is funded by grants from the MRC, BBSRC, NIHR and an Integrative Mammalian Biology (IMB) Capacity Building Award, and by a FP7-HEALTH-2009-241592 EuroCHIP grant and is supported by the NIHR Imperial Biomedical Research Centre Funding Scheme. This work is supported by a BBSRC Doctoral Training-Strategic Skills Award grant (BB/F017340/1)

Estudio de la zona con braquiópodos del Grupo de Lolén (Sierra de la Ventana, prov. Buenos Aires)

En el transcurso de los trabajos geológicos efectuados con el auspicio y medios otorgados por la Comisión de Investigación Científica de la provincia de Buenos Aires, en las Sierras Australes durante el período noviembre 1961 - mayo 1963 he tenido la oportunidad de recorrer y observar minuciosamente la porción inferior del grupo de Lolén. Ello me permitió conocer los pormenores de la distribución y contenido faunístico, como asimismo formular en base a nuevos hallazgos de evidente valor estratigráfico, una interpretación de la sucesión de elementos faunísticos, distinta de las precedentemente sugeridas en el caso al presente. En general, desde los primeros hallazgos reconocidos por Keidel en 1910 (Keidel, 1916), la investigación abarcó sectores de mejor acceso y en éstos, obviamente son los que he practicado en primer lugar mis observaciones, a la vez por tener a disposición un mayor número de datos geológicos. Como resultado de una primera visita al tramo fosilífero cerro Colorado al ex Club Hotel Ventana, luego prolongada hasta el abra de la Ventana y finalmente al área del abra del Chaco, en particular esta última, surgió el problema pertinente bajo una nueva faz de carácter geológico y estratigráfico

Petrografía de las sedimentitas psefíticas paleozoicas de las Sierras Australes bonaerenses

En este trabajo se estudian la composición mineralógica esencial y la fábrica de las sedimentitas psefíticas que integran, en parte, los grupos de La Lola (Silúrico) y Bravard (Eodevónico), y la serie de Sauce Grande (Carbónico superior), en las Sierras Australes de la provincia de Buenos Aires. Estos depósitos son considerados como ortoconglomerados (La Lola y Bravard) y paraconglomerados (Sauce Grande), reconociéndose la naturaleza cuarzosa de los primeros y cuarzo-feldespática de los segundos. La deformación tectónica observada varía en sus características, según la intensidad de la misma y la competencia de las sedimentitas afectadas y ha modificado parcialmente la fábrica sedimentaria, especialmente en los conglomerados de La Lola y Bravard. Como complemento, se analizan la génesis, condiciones ambientales y, en el caso de Sauce Grande, la procedencia del material lítico. Se señala además la posible existencia de una discordancia angular entre el grupo eodevónico de Lolén y la serie de Sauce Grande, y se sugiere la unión de la serie de Piedra Azul con la de Sauce Grande.This paper deais with essential mineralogical composition and fabric of the psephitic rocks which partially make up the La Lola (Siluriana and Bravard (Eodevonian) Groups and the Sauce Grande Series (Upper Carboniferous), all in the Sierra de la Ventana range in Southern Buenos Aires Province. The La Lola and Bravard psephites are shown to be orthoconglo- merates on the basis of their quartzose nature, whilst the Sauce Grande ones, on the main quartz-felspathic, are classified as paraconglomerates. Depending on the intensity of deformation and competence of the sedi- ments, the tectonic deformation has partially altered the original depo- sition fabric and imposed a grain orientation, specially in the La Lola and Bravard conglomerates. The study also ineludes provenance of lithic fragments (Sauce Grande Series), enviromental conditions and génesis of the rocks. The presence of a probable angular unconformity between the Lolén Group (Eodevonian) and Sauce Gande Series is mentioned, and the reunión of the Piedra Azul Series to Sauce Grande is suggested

A large-deviations approach to gelation

A large-deviations principle (LDP) is derived for the state at fixed time, of the multiplicative coalescent in the large particle number limit. The rate function is explicit and describes each of the three parts of the state: microscopic, mesoscopic and macroscopic. In particular, it clearly captures the well known gelation phase transition given by the formation of a particle containing a positive fraction of the system mass. Via a standard map of the multiplicative coalescent onto a time-dependent version of the Erdős-Rényi random graph, our results can also be rephrased as an LDP for the component sizes in that graph. The proofs rely on estimates and asymptotics for the probability that smaller Erdős-Rényi graphs are connected

A large-deviations principle for all the cluster sizes of a sparse Erdős–Rényi graph

Let (Formula presented.) be the Erdős–Rényi graph with connection probability (Formula presented.) as N → ∞ for a fixed t ∈ (0, ∞). We derive a large-deviations principle for the empirical measure of the sizes of all the connected components of (Formula presented.), registered according to microscopic sizes (i.e., of finite order), macroscopic ones (i.e., of order N), and mesoscopic ones (everything in between). The rate function explicitly describes the microscopic and macroscopic components and the fraction of vertices in components of mesoscopic sizes. Moreover, it clearly captures the well known phase transition at t = 1 as part of a comprehensive picture. The proofs rely on elementary combinatorics and on known estimates and asymptotics for the probability that subgraphs are connected. We also draw conclusions for the strongly related model of the multiplicative coalescent, the Marcus–Lushnikov coagulation model with monodisperse initial condition, and its gelation phase transition

Petrología del Grupo Eodevónico de Lolén, Sierras Australes (Provincia de Buenos Aires)

La composición mineralógica y petrología del Grupo de Lolén, el más alto de la Serie eodevónica de la Ventana, es descripta con cierto detalle, en un perfil paralelo a la ruta 76. El grupo está constituido por psamitas (grauvacas cuarzosas, cuarcitas y cuarcitas feldespáticas) y pelitas, con algunos conglomerados finos lenticulares y otros de naturaleza intraformacional intercalados. El intenso plegamiento ha afectado todo el grupo, de tal manera que todas las sedimentitas han sido re- cristalizadas con intensidad variable, más marcada hacia las zonas básales. Del análisis microscópico (texturas y composición) se infiere que tres han sido las etapas que caracterizan los procesos metamórficos : cristalización sintectónica (responsable del clivaje de flujo), cristalización postectónica (crecimiento cristalino) y deformación postcristalina (fenómenos cataclásticos). A pesar del carácter metamòrfico de esta serie sedimentaria, es posible inferir con cuidado, la naturaleza primitiva de las sedimentitas y su ambiente de sedimentación

Reliability of a cranial window for chronic epidural recordings from the pig primary somatosensory cortex

Chronically implanted microelectrodes face adverse biological responses and various kinds of device failure. To overcome these challenges, a cranial window was developed allowing repeated access to the primary somatosensory cortex (S1) of the pig. This study evaluated the reliability of the signals recorded using repeated temporary placement of a micro-electrocorticography (µECoG) array via a cranial window. Seven pigs were implanted with a cranial window, which was accessed twice after implantation at 2-3 week intervals. Brain responses were evoked by electrical stimulation to the ulnar nerve. At each session, three trials were recorded, consisting of a hundred stimulations. Averaged responses of P1 amplitude, latency, and variance between channels were obtained. Signal characteristics were stable within and between sessions. No systematic errors were found for the P1 amplitude and channel variability. For the P1 latency, a systematic decrease in latency was found between session 1 (25±2 ms) and sessions 2 and 3 (24±2 ms). These results show that the temporary placement of microelectrodes to record brain signals is a good alternative to permanent implantation

Large deviations for Markov jump processes with uniformly diminishing rates

We prove a large-deviation principle (LDP) for the sample paths of jump Markov processes in the small noise limit when, possibly, all the jump rates vanish uniformly, but slowly enough, in a region of the state space. We further discuss the optimality of our assumptions on the decay of the jump rates. As a direct application of this work we relax the assumptions needed for the application of LDPs to, e.g., Chemical Reaction Network dynamics, where vanishing reaction rates arise naturally particularly the context of mass action kinetics