Phase transitions in atypical systems induced by a condensation transition on graphs

Random graphs undergo structural phase transitions that are crucial for dynamical processes and cooperative behavior of models defined on graphs. In this work we investigate the impact of a first-order structural transition on the thermodynamics of the Ising model defined on Erdős-Rényi random graphs, as well as on the eigenvalue distribution of the adjacency matrix of the same graphical model. The structural transition in question yields graph samples exhibiting condensation of degrees, characterized by a large number of nodes having degrees in a narrow interval. Although the condensed graph samples have correlated degrees, we demonstrate that the equations determining the thermodynamics of the Ising model and the eigenvalue distribution of the adjacency matrix both display their usual forms, characteristic of locally treelike ensembles. By solving these equations, we show that the condensation transition induces distinct thermodynamic first-order transitions between the paramagnetic and the ferromagnetic phases of the Ising model. The condensation transition also leads to an abrupt change in the global eigenvalue statistics of the adjacency matrix, which renders the second moment of the eigenvalue distribution discontinuous. As a side result, we derive the critical line determining the percolation transition in Erdõs-Rényi graph samples that feature condensation of degrees

Analytic solution of the two-star model with correlated degrees

Exponential random graphs are important to model the structure of real-world complex networks. Here we solve the two-star model with degree-degree correlations in the sparse regime. The model constraints the average correlation between the degrees of adjacent nodes (nearest neighbors) and between the degrees at the end-points of two-stars (next nearest neighbors). We compute exactly the network free energy and show that this model undergoes a first-order transition to a condensed phase. For non-negative degree correlations between next nearest neighbors, the degree distribution inside the condensed phase has a single peak at the largest degree, while for negative degree correlations between next nearest neighbors the condensed phase is characterized by a bimodal degree distribution. We calculate the degree assortativities and show they are nonmonotonic functions of the model parameters, with a discontinuous behavior at the first-order transition. The first-order critical line terminates at a second-order critical point, whose location in the phase diagram can be accurately determined. Our results can help to develop more detailed models of complex networks with correlated degrees

Tuberculosis Pleural: Trecho clínico de la sospecha al diagnóstico definitivo.

Descripción: Se presenta un caso de una paciente de 23 años sin antecedentes epidemiológicos de importancia, hospitalizada en el servicio de Medicina Interna, con diagnóstico clínico e imagenológico sugestivo de derrame pleural izquierdo asociado a manifestaciones respiratorias y generales. Resultados clínicos: Se practican exámenes de laboratorio complementarios y de esputo bacilos acidorresistentes (BAAR) no concluyentes pero por efecto mecánico y compresivo del derrame pleural, se solicita valoración con Cirugía General, decidiéndose realizar pleurostomía y toma de muestra para determinación de Adenosin Desaminasa (ADA), resultando finalmente positivo a tuberculosis pleural. Tratamiento: Se inicia terapia antituberculosis específica y se descarta esquema antibiótico empírico previamente iniciado. Resultados: El estado general evoluciona favorablemente, con mejoría evidente de los síntomas que motivaron su hospitalización y se decide finalmente egresar y continuar seguimiento por consulta externa. Relevancia clínica: Aún en ausencia de datos epidemiológicos a favor de infección por tuberculosis, la presencia de derrame pleural unilateral debe reorientar la sospecha diagnóstica, no obstante se debe enfatizar que en tales circunstancias la determinación del agente causal por esputos es limitada a un 25%, por lo que no existe en la actualidad ninguna prueba con mayor sensibilidad y especificidad que la determinación de ADA en líquido pleural, lo cual pudiera evitar demoras diagnósticas e inconvenientes relacionados con una terapia no específica

Caso clínico de trauma severo en región toracoabdominal izquierda con afectación de ambas cavidades.

Descripción: Se presenta un caso de un paciente joven con trauma en región toracoabdominal izquierda por accidente automovilístico, con evidencia inicial de hemotórax izquierdo mediano, evacuado por tubo pleural inserto en unidad de emergencia y posterior evidencia de signos de choque que motivan su inmediata intervención quirúrgica por laparotomía abdominal. Resultados clínicos: Se constata laceración de hemidiafragma izquierdo y de bazo, ambas grado IV, con penetración de varias estructuras abdominales en hemitórax izquierdo, las cuales se logran reducir con maniobras gentiles. Tratamiento: Se decide realizar esplenectomía de urgencia y frenorrafia así como peritoneostomía para relaparotomía programada, completándose además en este último tiempo operatorio con la inserción de una bioprótesis quirúrgica plana no absorbible, antiadherente de politetrafluoroetileno (PTFE) condensado en hemidiafragma izquierdo, drenaje de JacsonPratt en subfrénico izquierdo que se exterioriza por contraabertura y síntesis de la pared abdominal. Resultados: El estado general del paciente evoluciona favorablemente, decidiéndose dar alta de la institución pasado 10 días sin evidencia de complicaciones postquirúrgicas y con respuestas fisiológicas en parámetros normales. Relevancia clínica: La sospecha clínica de una posible lesión diafragmática se inicia desde la exploración física, siendo la vía abdominal la ideal para su abordaje, método no superado por ningún otro para establecer el diagnóstico, corregir defecto traumático y evaluar estado del resto de las estructuras intratorácicas e intrabdominales. La supervivencia depende en gran medida del pronto actuar, asociada a la instauración del resto de las medidas terapéuticas

Caso clínico de trauma severo en región toracoabdominal izquierda con afectación de ambas cavidades.

Descripción: Se presenta un caso de un paciente joven con trauma en región toracoabdominal izquierda por accidente automovilístico, con evidencia inicial de hemotórax izquierdo mediano, evacuado por tubo pleural inserto en unidad de emergencia y posterior evidencia de signos de choque que motivan su inmediata intervención quirúrgica por laparotomía abdominal. Resultados clínicos: Se constata laceración de hemidiafragma izquierdo y de bazo, ambas grado IV, con penetración de varias estructuras abdominales en hemitórax izquierdo, las cuales se logran reducir con maniobras gentiles. Tratamiento: Se decide realizar esplenectomía de urgencia y frenorrafia así como peritoneostomía para relaparotomía programada, completándose además en este último tiempo operatorio con la inserción de una bioprótesis quirúrgica plana no absorbible, antiadherente de politetrafluoroetileno (PTFE) condensado en hemidiafragma izquierdo, drenaje de JacsonPratt en subfrénico izquierdo que se exterioriza por contraabertura y síntesis de la pared abdominal. Resultados: El estado general del paciente evoluciona favorablemente, decidiéndose dar alta de la institución pasado 10 días sin evidencia de complicaciones postquirúrgicas y con respuestas fisiológicas en parámetros normales. Relevancia clínica: La sospecha clínica de una posible lesión diafragmática se inicia desde la exploración física, siendo la vía abdominal la ideal para su abordaje, método no superado por ningún otro para establecer el diagnóstico, corregir defecto traumático y evaluar estado del resto de las estructuras intratorácicas e intrabdominales. La supervivencia depende en gran medida del pronto actuar, asociada a la instauración del resto de las medidas terapéuticas

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline