Evaluation of palliative therapy, alone or in combination with toceranib phosphate, in dogs diagnosed with metastatic or recurrent beta-cell neoplasia.

AIMS: To compare survival in dogs with recurrent or metastatic insulinomas that were treated with palliative therapy, alone or in combination with toceranib phosphate and to assess tolerability of the combined therapy in dogs. MATERIALS AND METHODS: Dogs diagnosed with insulinoma were retrospectively identified in the records of the Veterinary Teaching Hospital Complutense (Madrid, Spain). Diagnosis of insulinoma was based on clinical signs of hypoglycaemia, concentrations in serum of glucose <3.3 mmol/L and insulin >10 µIU/mL and presence of a pancreatic mass on diagnostic imaging. Dogs were treated surgically or medically, according to clinical stage established by imaging techniques, and monitored with blood and urine analyses monthly and abdominal ultrasonography every 3 months until death. Dogs that presented with metastatic disease at diagnosis or with recurrent hypoglycaemia after surgery were treated, according to the owner's decision, with one of two treatment protocols: palliative therapy alone (control group, n=7: diet, prednisone, famotidine or omeprazole, ±octreotide) or palliative therapy in combination with toceranib (treatment group, n=5; median dose of toceranib 2.52 mg/kg). Overall survival time (OST) and adverse events were compared between the two treatment groups. RESULTS: The OST was longer in the treatment group (median 399, min 125, max 476 days) compared to the control group (median 67, min 23, max 387 days; p=0.042). Dogs in the treatment group had a higher incidence of grade 1-2 gastrointestinal toxicity (diarrhoea) than dogs in the control group (p=0.010). In all cases, gastrointestinal toxicity was solved by temporarily discontinuing toceranib. CONCLUSIONS AND CLINICAL RELEVANCE: The use of toceranib combined with palliative treatment in dogs with suspect metastatic or recurrent insulinomas increased survival time and was adequate tolerated.

Mirage Andreev Spectra Generated by Mesoscopic Leads in Nanowire Quantum Dots.

We study transport mediated by Andreev bound states formed in InSb nanowire quantum dots. Two kinds of superconducting source and drain contacts are used: epitaxial Al/InSb devices exhibit a doubling of tunneling resonances, while, in NbTiN/InSb devices, Andreev spectra of the dot appear to be replicated multiple times at increasing source-drain bias voltages. In both devices, a mirage of a crowded spectrum is created. To describe the observations a model is developed that combines the effects of a soft induced gap and of additional Andreev bound states both in the quantum dot and in the finite regions of the nanowire adjacent to the quantum dot. Understanding of Andreev spectroscopy is important for the correct interpretation of Majorana experiments done on the same structures.

Toward the Mutational Landscape of Autosomal Dominant Retinitis Pigmentosa: A Comprehensive Analysis of 258 Spanish Families.

Purpose: To provide a comprehensive overview of the molecular basis of autosomal dominant retinitis pigmentosa (adRP) in Spanish families. Thus, we established the molecular characterization rate, gene prevalence, and mutational spectrum in the largest European cohort reported to date. Methods: A total of 258 unrelated Spanish families with a clinical diagnosis of RP and suspected autosomal dominant inheritance were included. Clinical diagnosis was based on complete ophthalmologic examination and family history. Retrospective and prospective analysis of Spanish adRP families was carried out using a combined strategy consisting of classic genetic techniques and next-generation sequencing (NGS) for single-nucleotide variants and copy number variation (CNV) screening. Results: Overall, 60% of our families were genetically solved. Interestingly, 3.1% of the cohort carried pathogenic CNVs. Disease-causing variants were found in an autosomal dominant gene in 55% of the families; however, X-linked and autosomal recessive forms were also identified in 3% and 2%, respectively. Four genes (RHO, PRPF31, RP1, and PRPH2) explained up to 62% of the solved families. Missense changes were most frequently found in adRP-associated genes; however, CNVs represented a relevant disease cause in PRPF31- and CRX-associated forms. Conclusions: Implementation of NGS technologies in the adRP study clearly increased the diagnostic yield compared with classic approaches. Our study outcome expands the spectrum of disease-causing variants, provides accurate data on mutation gene prevalence, and highlights the implication of CNVs as important contributors to adRP etiology.

Topological π Junctions from Crossed Andreev Reflection in the Quantum Hall Regime.

We consider a two-dimensional electron gas (2DEG) in the quantum Hall regime in the presence of a Zeeman field, with the Fermi level tuned to a filling factor of ν=1. We show that, in the presence of spin-orbit coupling, contacting the 2DEG with a narrow strip of an s-wave superconductor produces a topological superconducting gap along the contact as a result of crossed Andreev reflection (CAR) processes across the strip. The sign of the topological gap, controlled by the CAR amplitude, depends periodically on the Fermi wavelength and strip width and can be externally tuned. An interface between two halves of a long strip with topological gaps of opposite sign implements a robust π junction, hosting a pair of Majorana zero modes that do not split despite their overlap. We show that such a configuration can be exploited to perform protected non-Abelian tunnel-braid operations without any fine tuning.

Magnetically-driven colossal supercurrent enhancement in InAs nanowire Josephson junctions.

The Josephson effect is a fundamental quantum phenomenon where a dissipationless supercurrent is introduced in a weak link between two superconducting electrodes by Andreev reflections. The physical details and topology of the junction drastically modify the properties of the supercurrent and a strong enhancement of the critical supercurrent is expected to occur when the topology of the junction allows an emergence of Majorana bound states. Here we report charge transport measurements in mesoscopic Josephson junctions formed by InAs nanowires and Ti/Al superconducting leads. Our main observation is a colossal enhancement of the critical supercurrent induced by an external magnetic field applied perpendicular to the substrate. This striking and anomalous supercurrent enhancement cannot be described by any known conventional phenomenon of Josephson junctions. We consider these results in the context of topological superconductivity, and show that the observed critical supercurrent enhancement is compatible with a magnetic field-induced topological transition.

Identification of the Photoreceptor Transcriptional Co-Repressor SAMD11 as Novel Cause of Autosomal Recessive Retinitis Pigmentosa.

Retinitis pigmentosa (RP), the most frequent form of inherited retinal dystrophy is characterized by progressive photoreceptor degeneration. Many genes have been implicated in RP development, but several others remain to be identified. Using a combination of homozygosity mapping, whole-exome and targeted next-generation sequencing, we found a novel homozygous nonsense mutation in SAMD11 in five individuals diagnosed with adult-onset RP from two unrelated consanguineous Spanish families. SAMD11 is ortholog to the mouse major retinal SAM domain (mr-s) protein that is implicated in CRX-mediated transcriptional regulation in the retina. Accordingly, protein-protein network analysis revealed a significant interaction of SAMD11 with CRX. Immunoblotting analysis confirmed strong expression of SAMD11 in human retina. Immunolocalization studies revealed SAMD11 was detected in the three nuclear layers of the human retina and interestingly differential expression between cone and rod photoreceptors was observed. Our study strongly implicates SAMD11 as novel cause of RP playing an important role in the pathogenesis of human degeneration of photoreceptors.

Stacking boundaries and transport in bilayer graphene.

Pristine bilayer graphene behaves in some instances as an insulator with a transport gap of a few millielectronvolts. This behavior has been interpreted as the result of an intrinsic electronic instability induced by many-body correlations. Intriguingly, however, some samples of similar mobility exhibit good metallic properties with a minimal conductivity of the order of 2e(2)/h. Here, we propose an explanation for this dichotomy, which is unrelated to electron interactions and based instead on the reversible formation of boundaries between stacking domains ("solitons"). We argue, using a numerical analysis, that the hallmark features of the previously inferred many-body insulating state can be explained by scattering on boundaries between domains with different stacking order (AB and BA). We furthermore present experimental evidence, reinforcing our interpretation, of reversible switching between a metallic and an insulating regime in suspended bilayers when subjected to thermal cycling or high current annealing.

Non-Abelian gauge potentials in graphene bilayers.

We study the effect of spatial modulations in the interlayer hopping of graphene bilayers, such as those that arise upon shearing or twisting. We show that their single-particle physics, characterized by charge accumulation and recurrent formation of zero-energy bands as the pattern period L increases, is governed by a non-Abelian gauge potential arising in the low-energy electronic theory due to the coupling between layers. We show that such gauge-type couplings give rise to a potential that, for certain discrete values of L, spatially confines states at zero energy in particular regions of the moiré patterns. We also draw the connection between the recurrence of the flat zero-energy bands and the non-Abelian character of the potential.

Electron-induced rippling in graphene.

We show that the interaction between flexural phonons, when corrected by the exchange of electron-hole excitations, may drive the graphene sheet into a quantum critical point characterized by the vanishing of the bending rigidity of the membrane. Ripples arise then due to spontaneous symmetry breaking, following a mechanism similar to that responsible for the condensation of the Higgs field in relativistic field theories, and leading to a zero-temperature buckling transition in which the order parameter is given by the square of the gradient of the flexural phonon field.

Zero Landau level in folded graphene nanoribbons.

Graphene nanoribbons can be folded into a double layer system keeping the two layers decoupled. In the quantum Hall regime folds behave as a new type of Hall bar edge. We show that the symmetry properties of the zero Landau level in metallic nanoribbons dictate that the zero energy edge states traversing a fold are perfectly transmitted onto the opposite layer. This result is valid irrespective of fold geometry, magnetic field strength, and crystallographic orientation of the nanoribbon. Backscattering suppression on the N=0 Hall plateau is ultimately due to the orthogonality of forward and backward channels, much like in the Klein paradox.

Pseudospin valve in bilayer graphene: towards graphene-based pseudospintronics.

We propose a nonmagnetic, pseudospin-based version of a spin valve, in which the pseudospin polarization in neighboring regions of a graphene bilayer is controlled by external gates. Numerical calculations demonstrate a large on-off ratio of such a device. This finding holds promise for the realization of pseudospintronics: a form of electronics based upon the manipulation of pseudospin analogous to the control of physical spin in spintronics applications.

Tendinitis aquílea en el anciano / Tendinitis in the achilles in the elderly

No disponible

Actitud diagnóstica y terapéutica ante el paciente que acude con hemoptisis / Diagnostic and therapeutic attitude in patient with hemoptysis

La hemoptisis es un síntoma que requiere un estudio exhaustivo ya que puede ser secundaria a una enfermedad grave y/o dar lugar a una hemorragia fatal o incluso a un síndrome asfíctico. Por ello debemos confirmar el diagnóstico en el menor tiempo posible, así como evaluar la gravedad del cuadro, localizar la lesión responsable y tratarla adecuadamente porque la evolución clínica es impredecible. El objeto de este trabajo es repasar el manejo de esta entidad, así como establecer un modelo que coordine los Servicios de Atención Primaria y Neumología (AU)

Resonant radiation pressure on neutral particles in a waveguide.

A theoretical analysis of electromagnetic forces on neutral particles in a hollow waveguide is presented. We show that the effective scattering cross section of a very small (Rayleigh) particle can be strongly modified inside a waveguide. The coupling of the scattered dipolar field with the waveguide modes induces a resonant enhanced backscattering state of the scatterer-guide system close to the onset of new modes. The particle effective cross section can then be as large as the wavelength even far from any transition resonance. As we will show, a small particle can be strongly accelerated along the guide axis while being highly confined in a narrow zone of the cross section of the guide.