Wave patterns in one-dimensional nonlinear degenerate diffusion equations

Several different types of wave patterns occur in physiology, chemistry and biology. In many cases such phenomena are modelled by reactive-diffusive parabolic systems (see, for example, Fisher 1937; Kolmogorov et al. 1937; Winfree 1988; Murray 1989; Swinney & Krinsky 1992). In many biological and physical situations, dispersal is modelled by a density-dependent diffusion coefficient, for example, the bacterium Rhizobium diffuses through the roots of some leguminosae plants according to a nonlinear diffusive law (Lara-Ochoa & Bustos 1990); nonlinear diffusion has been observed in the dispersion of some insects (Okubo 1980) and small rodents (Meyers & Krebs 1974)

Indicación Farmacéutica para el estreñimiento en pacientes con diabetes e hipertensión arterial.

Introducción: El estreñimiento en pacientes con hipertensión arterial o diabetes es un motivo frecuente de consulta al farmacéutico. La indicación farmacéutica no debe interferir con la medicación habitual de estos pacientes. Objetivos: Formular recomendaciones sobre indicación farmacéutica a pacientes con diabetes y/o hipertensión arterial que acuden a la oficina de farmacia solicitando tratamiento farmacológico para el estreñimiento. Material y métodos: Mediante revisión sistemática de Guías de Práctica Clínica sobre abordaje del estreñimiento, se han elaborado recomendaciones sobre indicación farmacéutica a pacientes con diabetes y/o hipertensión arterial que acuden a la oficina de farmacia solicitando tratamiento farmacológico. Tras diseñar una estrategia de búsqueda, se seleccionaron las fuentes bibliográficas y se llevó a cabo la recogida de información. La búsqueda bibliográfica se realizó en los siguientes recursos web: Medline, GuíaSalud, National Guideline Clearinghouse, Canadian Medical Association Infobase, Scottish Intercollegiate Guidelines Network, Australia’s Clinical Practice Guidelines Portal, Trip Database y National Health Service Evidence. Como fuentes complementarias, se consultó UpToDate, Base de Datos BOT plus 2.0 y un tratado de Farmacología Humana. Resultados: Las recomendaciones se refieren al manejo del estreñimiento idiopático no complicado en pacientes sin síntomas de alarma e incluyen, como tratamiento de primera línea, el consumo de fibra o de agentes formadores de masa. En pacientes que no toleran los laxantes formadores de masa o responden mal a suplementos de fibra, se recomienda el uso de laxantes osmóticos. Por último, si no hay una respuesta satisfactoria, las ecomendaciones incluyen los laxantes estimulantes. En pacientes hipertensos, debe tenerse en cuenta que el hidróxido de magnesio presenta potenciales interacciones con algunos fármacos antihipertensivos. Conclusión: La indicación farmacéutica incluye, como tratamiento de primera línea, suplementos de fibra o agentes formadores de masa. En quienes no los toleran o no responden satisfactoriamente, pueden recomendarse laxantes osmóticos o estimulantes

Indicación Farmacéutica para el estreñimiento en pacientes con diabetes e hipertensión arterial.

Introducción: El estreñimiento en pacientes con hipertensión arterial o diabetes es un motivo frecuente de consulta al farmacéutico. La indicación farmacéutica no debe interferir con la medicación habitual de estos pacientes. Objetivos: Formular recomendaciones sobre indicación farmacéutica a pacientes con diabetes y/o hipertensión arterial que acuden a la oficina de farmacia solicitando tratamiento farmacológico para el estreñimiento. Material y métodos: Mediante revisión sistemática de Guías de Práctica Clínica sobre abordaje del estreñimiento, se han elaborado recomendaciones sobre indicación farmacéutica a pacientes con diabetes y/o hipertensión arterial que acuden a la oficina de farmacia solicitando tratamiento farmacológico. Tras diseñar una estrategia de búsqueda, se seleccionaron las fuentes bibliográficas y se llevó a cabo la recogida de información. La búsqueda bibliográfica se realizó en los siguientes recursos web: Medline, GuíaSalud, National Guideline Clearinghouse, Canadian Medical Association Infobase, Scottish Intercollegiate Guidelines Network, Australia’s Clinical Practice Guidelines Portal, Trip Database y National Health Service Evidence. Como fuentes complementarias, se consultó UpToDate, Base de Datos BOT plus 2.0 y un tratado de Farmacología Humana. Resultados: Las recomendaciones se refieren al manejo del estreñimiento idiopático no complicado en pacientes sin síntomas de alarma e incluyen, como tratamiento de primera línea, el consumo de fibra o de agentes formadores de masa. En pacientes que no toleran los laxantes formadores de masa o responden mal a suplementos de fibra, se recomienda el uso de laxantes osmóticos. Por último, si no hay una respuesta satisfactoria, las ecomendaciones incluyen los laxantes estimulantes. En pacientes hipertensos, debe tenerse en cuenta que el hidróxido de magnesio presenta potenciales interacciones con algunos fármacos antihipertensivos. Conclusión: La indicación farmacéutica incluye, como tratamiento de primera línea, suplementos de fibra o agentes formadores de masa. En quienes no los toleran o no responden satisfactoriamente, pueden recomendarse laxantes osmóticos o estimulantes

Yukawa Textures From Heterotic Stability Walls

A holomorphic vector bundle on a Calabi-Yau threefold, X, with h^{1,1}(X)>1 can have regions of its Kahler cone where it is slope-stable, that is, where the four-dimensional theory is N=1 supersymmetric, bounded by "walls of stability". On these walls the bundle becomes poly-stable, decomposing into a direct sum, and the low energy gauge group is enhanced by at least one anomalous U(1) gauge factor. In this paper, we show that these additional symmetries can strongly constrain the superpotential in the stable region, leading to non-trivial textures of Yukawa interactions and restrictions on allowed masses for vector-like pairs of matter multiplets. The Yukawa textures exhibit a hierarchy; large couplings arise on the stability wall and some suppressed interactions "grow back" off the wall, where the extended U(1) symmetries are spontaneously broken. A number of explicit examples are presented involving both one and two stability walls, with different decompositions of the bundle structure group. A three family standard-like model with no vector-like pairs is given as an example of a class of SU(4) bundles that has a naturally heavy third quark/lepton family. Finally, we present the complete set of Yukawa textures that can arise for any holomorphic bundle with one stability wall where the structure group breaks into two factors.Comment: 53 pages, 4 figures and 13 table

Numerical Hermitian Yang-Mills Connections and Vector Bundle Stability in Heterotic Theories

A numerical algorithm is presented for explicitly computing the gauge connection on slope-stable holomorphic vector bundles on Calabi-Yau manifolds. To illustrate this algorithm, we calculate the connections on stable monad bundles defined on the K3 twofold and Quintic threefold. An error measure is introduced to determine how closely our algorithmic connection approximates a solution to the Hermitian Yang-Mills equations. We then extend our results by investigating the behavior of non slope-stable bundles. In a variety of examples, it is shown that the failure of these bundles to satisfy the Hermitian Yang-Mills equations, including field-strength singularities, can be accurately reproduced numerically. These results make it possible to numerically determine whether or not a vector bundle is slope-stable, thus providing an important new tool in the exploration of heterotic vacua.Comment: 52 pages, 15 figures. LaTex formatting of figures corrected in version 2

Numerical Hermitian Yang-Mills Connections and Kahler Cone Substructure

We further develop the numerical algorithm for computing the gauge connection of slope-stable holomorphic vector bundles on Calabi-Yau manifolds. In particular, recent work on the generalized Donaldson algorithm is extended to bundles with Kahler cone substructure on manifolds with h^{1,1}>1. Since the computation depends only on a one-dimensional ray in the Kahler moduli space, it can probe slope-stability regardless of the size of h^{1,1}. Suitably normalized error measures are introduced to quantitatively compare results for different directions in Kahler moduli space. A significantly improved numerical integration procedure based on adaptive refinements is described and implemented. Finally, an efficient numerical check is proposed for determining whether or not a vector bundle is slope-stable without computing its full connection.Comment: 38 pages, 10 figure

Identifying barriers and finding solutions to implement best practices for cancer surgery at Maputo Central Hospital, Mozambique

Purpose: The aim of this study was to assess the surgical resources and surgical oncology team skills at the Surgical Department of Maputo Central Hospital (MCH) in Mozambique in order to define an educational program to support surgical oncology practice. Methods: From January 2017 to December 2017, a general evaluation of the resources of MCH was carried out, as well as its offerings in oncological care in different services. Data were obtained by reviewing documents, visiting surgical services and interviewing key informants and others informally. In addition, a group of seven surgeons of the Surgical Department of MCH answered a questionnaire about the quality of the cancer units (The Cancer Units Assessment Checklist for low- or middle-income African countries). Subsequently, surgical, anaesthesiology and intensive care facilities were evaluated according to the Portuguese-speaking African Countries Assessment of Surgical Oncology Capacity Survey (PSAC-Surgery). All the data were triangulated in order to identify gaps, develop an action plan and define an educational program. Results: Breast, oesophagus and colorectal cancers were the most commonly treated neoplasms in MCH. A range of technical and resource needs as well as the gaps in knowledge and skills were identified. All surgeons recognised the need to create a training program in oncology at the undergraduate level, specific training for residents and continuing oncological education for general surgeons to improve the practice of surgical oncology. It was evident that all these interventions needed to be formalised, appropriately certified and count for professional career progression. Based on the local epidemiological data and on these study findings, oncology education programs were developed for surgeons. Conclusions: The findings of this study contributed to the development of an educational program in surgical oncology, considered essential to the training of surgeons at MCH. The cancer educational programs and the mobilisation of adequate resources will ensure the provision of adequate surgical oncology treatments for MCH. The training requirements should be tailored to suit the local needs based on the most prevalent malignancies diagnosed in the region. In our view, this methodology may apply to other countries with similar realities in the formation of surgical oncologists.publishersversionpublishe

Patient-centric trials for therapeutic development in precision oncology

An enhanced understanding of the molecular pathology of disease gained from genomic studies is facilitating the development of treatments that target discrete molecular subclasses of tumours. Considerable associated challenges include how to advance and implement targeted drug-development strategies. Precision medicine centres on delivering the most appropriate therapy to a patient on the basis of clinical and molecular features of their disease. The development of therapeutic agents that target molecular mechanisms is driving innovation in clinical-trial strategies. Although progress has been made, modifications to existing core paradigms in oncology drug development will be required to realize fully the promise of precision medicine

A phase II study of cell cycle inhibitor UCN-01 in patients with metastatic melanoma: a California Cancer Consortium trial

Background Genetic abnormalities in cell cycle control are common in malignant melanoma. UCN-01 (7-hydroxystaurosporine) is an investigational agent that exhibits antitumor activity by perturbing the cancer cell cycle. A patient with advanced melanoma experienced a partial response in a phase I trial of single agent UCN-01. We sought to determine the activity of UCN-01 against refractory metastatic melanoma in a phase II study. Patients and methods Patients with advanced melanoma received UCN-01 at 90 mg/m2 over 3 h on cycle 1, reduced to 45 mg/m2 over 3 h for subsequent cycles, every 21 days. Primary endpoint was tumor response. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). A two-stage (17 + 16), single arm phase II design was employed. A true response rate of ≥20% (i.e., at least one responder in the first stage, or at least four responders overall) was to be considered promising for further development of UCN-01 in this setting. Results Seventeen patients were accrued in the first stage. One patient was inevaluable for response. Four (24%) patients had stable disease, and 12 (71%) had disease progression. As there were no responders in the first stage, the study was closed to further accrual. Median PFS was 1.3 months (95% CI, 1.2–3.0) while median OS was 7.3 months (95% CI, 3.4–18.4). One-year and two year OS rates were 41% and 12%, respectively. A median of two cycles were delivered (range, 1–18). Grade 3 treatment-related toxicities include hyperglycemia (N = 2), fatigue (N = 1), and diarrhea (N = 1). One patient experienced grade 4 creatinine elevation and grade 4 anemia possibly due to UCN-01. No dose modification was required as these patients had disease progression. Conclusion Although well tolerated, UCN-01 as a single agent did not have sufficient clinical activity to warrant further study in refractory melanoma