Experiencia de aplicación de modelos de seguimiento de cumplimiento del perfil de egreso en el plan de estudios en las carreras de la Facultad de Medicina de la Universidad Finis Terrae / Experience of applying models for monitoring compliance with the graduation profile in the study plan in the careers of the Faculty of Medicine of the Finis Terrae University

El Perfil de egreso constituye un modelo teórico y la imagen del profesional que la institución de educación superior aspira formar. Es un conjunto de atributos que son certificados y le permiten a una persona ser reconocida y aceptada por la sociedad como profesional. La emergencia de estándares de calidad, utilizados por las agencias de acreditación de carreras universitarias, hoy exigen la necesidad de evaluar y rendir cuentas acerca del logro de las competencias establecidas y declaradas en el perfil de egreso, sin embargo, hay escasa evidencia concreta que demuestre modelos operativos de cómo abordar ese proceso de evaluación en distintos programas. Dada la relevancia del Perfil de Egreso de una carrera de pregrado y considerando que constituye el eje fundamental para el desarrollo curricular de los programas educativos, para realizar el proceso de autoevaluación y la posterior acreditación de las carreras, diseñamos e implementamos un modelo de seguimiento del cumplimiento del perfil de egreso en el plan de estudios de las carreras de la Facultad de Medicina de la Universidad Finis Terrae.

The Graduate Profile constitutes the theoretical model and the professional image that higher education aspires to form. It is a set of certified attributes and allows a person to be recognized and accepted by society as a professional. The emergence of quality standards, used by university careers' accreditation agencies, demands the need to evaluate and be accountable for achieving the competencies established and declared in the Graduate Profile. However, the is limited concrete evidence to demonstrate operational models of how to approach this evaluation process in different programs. Given the relevance of the Graduate Profile of an undergraduate career and considering that it constitutes the fundamental axis for the curricular development of educational programs, to carry out the self-evaluation process and the subsequent accreditation of the degrees, we design and implement a model for monitoring the compliance with the graduation profile in the study plan of the Faculty of Medicine of Universidad Finis Terrae.

Mapeo del proceso clínico de pacientes con ideación suicida activa que consultan en el centro de salud familiar "San Alberto Hurtado" en Chile / Mapping of the clinical process of patients with active suicidal ideation who consult at the primary health care facility "San Alberto Hurtado" in Chile

Introducción: el suicidio es un fenómeno complejo y prevalente. En Chile, los centros de atención primaria pesquisan pacientes consideación suicida activa y los derivan a centros terciarios, pero el proceso es complejo y poco fluido. El objetivo de este trabajo fue mapear el proceso clínico que siguen los pacientes con ideación suicida activa derivados desde el centro de salud familiar Áncora San Alberto Hurtado en Santiago, Chile. Métodos: se realizaron reuniones con los principales protagonistas y se recolectaron protocolos de manejo. Se graficaron los procesos clínicos según la edad del paciente, identificando nudos, brechas y quiebres. Resultados: los pacientes menores de 15 años son derivados al servicio de urgencia pediátrica en el Complejo Asistencial Dr. Sótero del Río, donde son evaluados por un psiquiatra infanto-juvenil, quien determina si son dados de alta para continuar seguimiento en el nivel secundario o son hospitalizados. Los pacientes mayores de 15 años son referidos al servicio de urgencia psiquiátrica del Complejo Asistencial Barros Luco Trudeau para ser evaluados por un psiquiatra, quien evalúa si requieren seguimiento a nivel secundario u hospitalización. En este último caso, son derivados nuevamente al Hospital Sótero del Río. Se identificaron nudos, brechas y quiebres que dificultan la atención y seguimiento de los pacientes. Conclusión: existen condiciones que afectan el proceso clínico de pacientes con ideación suicida activa derivados desde un centro de atención primaria, y es fundamental reparar las dificultades identificadas para ofrecer a la población una atención en salud mental eficiente.(AU)

Introduction: suicide is a complex and prevalent phenomenon. In Chile, primary health care centers detect most cases of patients with active suicidal ideation and refer them to hospitals, however, this process is complex and not very fluid. The objective was to map the clinical process of patients with active suicidal ideation referred from a primary care center in Santiago, Chile. Methods: we held multiple meetings with the principal persons in charge, and collected management protocols. We mapped the clinical process according to patient age, identifying knots, breaches, and breaks. Results: Patients 14 years or younger attend the pediatric emergency service in Dr. Sótero del Río Welfare Complex, where they receive an assessment by a child and adolescent psychiatrist who determines whether they are hospitalized or discharged to continue to follow up at the secondary level. Patients 15 years or older attend the psychiatric emergencyservice in Hospital Barros Luco Trudeau, where they undergo a psychiatric evaluation which determines whether they are hospitalized or require to follow up at the outpatient setting. If, however, the patient needs to be hospitalized, he/she must return to Hospital Sóterodel Río. Multiple knots, breaches, and breaks were identified, that make health care and follow up of these patients difficult. Conclusion:multiple determinants affect the clinical process of patients with active suicidal ideation referred from a primary health care center. The difficulties identified must be repaired in order to offer the population efficient mental health care.(AU)

[New aspects of immunotherapy in multiple sclerosis]. / Neues aus der Immuntherapie bei Multipler Sklerose.

The spectrum of therapeutic options for immunotherapy of multiple sclerosis is continuously broadening. After the approval of cladribine and ocrelizumab in Europe, two new drugs are now available with ocrelizumab being the first approved option for treatment of primary progressive multiple sclerosis; however, the increased use of highly effective therapies is accompanied by a rise in severe side effects. During recent months, special attention was paid to the new progressive multifocal leukoencephalopathy (PML) risk assessment in natalizumab-treated patients, cardiac side effects of fingolimod, cases of idiopathic thrombocytopenic purpura and listeria meningitis associated with alemtuzumab and cases of daclizumab-treated patients with liver failure or encephalitis. These case reports highlight the importance of careful monitoring of all patients treated with immunomodulatory therapies.

Insights from mathematical modelling for T cell migration into the central nervous system.

The migration of immune cells from peripheral immune organs into the central nervous system (CNS) through the blood-brain barrier (BBB) is a tightly regulated process. The complex interplay between cells of the BBB and immune cells coordinates cell migration as a part of normal immune surveillance while its dysregulation is critically involved in the pathogenesis of various CNS diseases. To develop tools for a deeper understanding of distribution and migratory pattern of immune cells regulated by the BBB, we made use of a mathematical modelling approach derived from Markov chain theory. We present a data-driven model using a derivation of kinetic differential equations from a particle game. According to the theory of gases, these equations allow one to predict the mean behaviour of a large class of cells by modelling cell-cell interactions. We used this model to assess the distribution of naive, central memory and effector memory T lymphocytes in the peripheral blood and cerebrospinal fluid. Our model allows us to evaluate the impact of activation status, migratory capacity and cell death for cell distribution in the peripheral blood and the CNS.

[Actual medical care situation and therapeutic needs in multiple sclerosis: Impact of the Pharmaceutical Market Restructuring Act (AMNOG)]. / Versorgungsrealität und therapeutischer Bedarf bei Multipler Sklerose : Auswirkungen des AMNOG.

BACKGROUND: The treatment of patients with multiple sclerosis (MS) is associated with constantly rising costs for the healthcare system and pharmaceuticals constitute 60 % of the direct medical costs. The Pharmaceutical Market Restructuring Act (Arzneimittelmarkt-Neuordnungsgesetz, AMNOG) came into force on 1 January 2011 with the aim of limiting the costs of pharmaceuticals by obligating newly approved products to be subjected to an early evaluation of the additional benefits by the Federal Joint Committee (FJC, Gemeinsamer Bundesausschuss, G­BA). The majority of products evaluated up to October 2015 in neurology (5 out of 8) were approved for treatment of MS. OBJECTIVE: Has the AMNOG been able to fulfill the original aims? MATERIAL AND METHODS: Analysis of available information on MS therapies evaluated by the FJC between December 2010 and October 2015. RESULTS: For various reasons an additional benefit could be shown in only 2 out of 5 assessment procedures for MS drugs. It is obvious that some methodological shortcomings of the process have to be improved. Additionally requirements for pivotal clinical trials have to be harmonized with AMNOG requirements taking the best available evidence and real-life data into consideration (e.g. non-interventional studies) and a closer collaboration between the FJC, healthcare providers and the neurological societies is necessary. CONCLUSION: The AMNOG procedure currently only partially fulfills the original aims, which could be the reason why guidelines play a more important role for therapy decision-making than FJC decisions. As the early evaluation procedure is an adaptive process methodological shortcomings might be overcome in the future; however, this requires a much closer collaboration between the FJC and neurological societies.

Electrical pharyngeal stimulation increases substance P level in saliva.

BACKGROUND: Substance P (SP) is a neuropeptide known to enhance the swallow response. It likely acts as a neurotransmitter in the pharyngeal mucosa in response to local stimuli. It has been proposed that dysphagia after stroke may be related to reduced levels of SP, which therefore constitutes a therapeutic target. In the present pilot study, we evaluated whether electrical pharyngeal stimulation (EPS), a neuromodulation device to enhance cortical reorganization for the restoration of swallowing function after brain injury, is able to increase SP in saliva or serum. METHODS: In a randomized crossover study design, 20 healthy volunteers were treated with 10 min of real (0.2-ms pulses, 5 Hz, 280 V, stimulation intensity (mA) individually adjusted to tolerance level) or sham EPS on two separate sessions. Stimulation was delivered via a pair of bipolar ring electrodes mounted on an intraluminal catheter positioned in the pharynx. Blood and saliva samples were taken prior to, during, and up to 1 h after EPS and analyzed for their SP concentration by ELISA. KEY RESULTS: Following real EPS but not sham stimulation, SP levels in saliva increased immediately and significantly about 28% (p < 0.01) compared to baseline. Serum levels remained unchanged. CONCLUSIONS & INFERENCES: Electrical pharyngeal stimulation is able to induce pharyngeal SP release in healthy subjects.

Dielectric square resonator investigated with microwave experiments.

We present a detailed experimental study of the symmetry properties and the momentum space representation of the field distributions of a dielectric square resonator as well as the comparison with a semiclassical model. The experiments have been performed with a flat ceramic microwave resonator. Both the resonance spectra and the field distributions were measured. The momentum space representations of the latter evidenced that the resonant states are each related to a specific classical torus, leading to the regular structure of the spectrum. Furthermore, they allow for a precise determination of the refractive index. Measurements with different arrangements of the emitting and the receiving antennas were performed and their influence on the symmetry properties of the field distributions was investigated in detail, showing that resonances with specific symmetries can be selected purposefully. In addition, the length spectrum deduced from the measured resonance spectra and the trace formula for the dielectric square resonator are discussed in the framework of the semiclassical model.

Localized lasing modes of triangular organic microlasers.

We investigated experimentally the ray-wave correspondence in organic microlasers of various triangular shapes. Triangular billiards are of interest since they are the simplest cases of polygonal billiards and the existence and properties of periodic orbits in triangles are not yet fully understood. The microlasers with symmetric shapes that were investigated exhibited states localized on simple periodic orbits, and their lasing characteristics like spectra and far-field distributions could be well explained by the properties of the periodic orbits. Furthermore, asymmetric triangles that do not feature simple periodic orbits were studied. Their lasing properties were found to be more complicated and could not be explained by periodic orbits.

XIAP-targeting drugs re-sensitize PIK3CA-mutated colorectal cancer cells for death receptor-induced apoptosis.

Mutations in the oncogenic PIK3CA gene are found in 10-20% of colorectal cancers (CRCs) and are associated with poor prognosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and agonistic TRAIL death receptor antibodies emerged as promising anti-neoplastic therapeutics, but to date failed to prove their capability in the clinical setting as especially primary tumors exhibit high rates of TRAIL resistance. In our study, we investigated the molecular mechanisms underlying TRAIL resistance in CRC cells with a mutant PIK3CA (PIK3CA-mut) gene. We show that inhibition of the constitutively active phosphatidylinositol-3 kinase (PI3K)/Akt signaling pathway only partially overcame TRAIL resistance in PIK3CA-mut-protected HCT116 cells, although synergistic effects of TRAIL plus PI3K, Akt or cyclin-dependent kinase (CDK) inhibitors could be noted. In sharp contrast, TRAIL triggered full-blown cell death induction in HCT116 PIK3CA-mut cells treated with proteasome inhibitors such as bortezomib and MG132. At the molecular level, resistance of HCT116 PIK3CA-mut cells against TRAIL was reflected by impaired caspase-3 activation and we provide evidence for a crucial involvement of the E3-ligase X-linked inhibitor of apoptosis protein (XIAP) therein. Drugs interfering with the activity and/or the expression of XIAP, such as the second mitochondria-derived activator of caspase mimetic BV6 and mithramycin-A, completely restored TRAIL sensitivity in PIK3CA-mut-protected HCT116 cells independent of a functional mitochondrial cell death pathway. Importantly, proteasome inhibitors and XIAP-targeting agents also sensitized other CRC cell lines with mutated PIK3CA for TRAIL-induced cell death. Together, our data suggest that proteasome- or XIAP-targeting drugs offer a novel therapeutic approach to overcome TRAIL resistance in PIK3CA-mutated CRC.

Scattering experiments with microwave billiards at an exceptional point under broken time-reversal invariance.

Scattering experiments with microwave cavities were performed and the effects of broken time-reversal invariance (TRI), induced by means of a magnetized ferrite placed inside the cavity, on an isolated doublet of nearly degenerate resonances were investigated. All elements of the effective Hamiltonian of this two-level system were extracted. As a function of two experimental parameters, the doublet and the associated eigenvectors could be tuned to coalesce at a so-called exceptional point (EP). The behavior of the eigenvalues and eigenvectors when encircling the EP in parameter space was studied, including the geometric amplitude that builds up in the case of broken TRI. A one-dimensional subspace of parameters was found where the differences of the eigenvalues are either real or purely imaginary. There, the Hamiltonians were found to be PT invariant under the combined operation of parity (P) and time reversal (T) in a generalized sense. The EP is the point of transition between both regions. There a spontaneous breaking of PT occurs.

Long-term effects of dalfampridine in patients with multiple sclerosis.

BACKGROUND/OBJECTIVE: Dalfampridine is the extended-release formulation of 4-aminopyridine and is approved for the symptomatic treatment of impaired mobility in patients with multiple sclerosis. Our aim was to examine the short- and long-term effects of treatment with dalfampridine on motoric and cognitive assessment parameters of multiple sclerosis (MS) patients over 9-12 months. METHODS: Fifty-two patients with MS with an EDSS between 4.0 and 7.0 and impaired mobility were evaluated for parameters of walking ability, MSFC, cognitive and motor fatigue and evoked potentials at treatment initiation with dalfampridine as well as 2 weeks and after 9-12 months later. RESULTS: Thirty out of fifty-two patients (~60%) were still on treatment after 9-12 months. Two weeks after treatment initiation, significant ameliorations could be found for T25FW, maximum walking distance as well as motoric and cognitive fatigue which still persisted after 9-12 months. In contrast significant effects for velocity were observed only after 2 weeks, for improvement in PASAT only after 9-12 months. A tendency for improvement of somatosensory evoked potentials was found in a subset of patients. CONCLUSION: Dalfampridine shows positive short- and long-term effects on motoric and cognitive assessment parameters in an open-label observational study in a cohort of patients with MS.

Bound states in sharply bent waveguides: analytical and experimental approach.

Quantum wires and electromagnetic waveguides possess common features since their physics is described by the same wave equation. We exploit this analogy to investigate experimentally with microwave waveguides and theoretically with the help of an effective potential approach the occurrence of bound states in sharply bent quantum wires. In particular, we compute the bound states, study the features of the transition from a bound to an unbound state caused by the variation of the bending angle, and determine the critical bending angles at which such a transition takes place. The predictions are confirmed by calculations based on a conventional numerical method as well as experimental measurements of the spectra and electric field intensity distributions of electromagnetic waveguides.

Experimental observation of localized modes in a dielectric square resonator.

We investigated the frequency spectra and field distributions of a dielectric square resonator in a microwave experiment. Since such systems cannot be treated analytically, the experimental studies of their properties are indispensable. The momentum representation of the measured field distributions shows that all resonant modes are localized on specific classical tori of the square billiard. Based on these observations a semiclassical model was developed. It shows excellent agreement with all but a single class of measured field distributions that will be treated separately.

Trace formula for chaotic dielectric resonators tested with microwave experiments.

We measured the resonance spectra of two stadium-shaped dielectric microwave resonators and tested a semiclassical trace formula for chaotic dielectric resonators proposed by Bogomolny et al. [Phys. Rev. E 78, 056202 (2008)]. We found good qualitative agreement between the experimental data and the predictions of the trace formula. Deviations could be attributed to missing resonances in the measured spectra in accordance with previous experiments [Phys. Rev. E 81, 066215 (2010)]. The investigation of the numerical length spectrum showed good qualitative and reasonable quantitative agreement with the trace formula. It demonstrated, however, the need for higher-order corrections of the trace formula. The application of a curvature correction to the Fresnel reflection coefficients entering the trace formula yielded better agreement, but deviations remained, indicating the necessity of further investigations.

Application of a trace formula to the spectra of flat three-dimensional dielectric resonators.

The length spectra of flat three-dimensional dielectric resonators of circular shape were determined from a microwave experiment. They were compared to a semiclassical trace formula obtained within a two-dimensional model based on the effective index of refraction approximation and a good agreement was found. It was necessary to take into account the dispersion of the effective index of refraction for the two-dimensional approximation. Furthermore, small deviations between the experimental length spectrum and the trace formula prediction were attributed to the systematic error of the effective index of refraction approximation. In summary, the methods developed in this article enable the application of the trace formula for two-dimensional dielectric resonators also to realistic, flat three-dimensional dielectric microcavities and -lasers, allowing for the interpretation of their spectra in terms of classical periodic orbits.

PT symmetry and spontaneous symmetry breaking in a microwave billiard.

We demonstrate the presence of parity-time (PT) symmetry for the non-Hermitian two-state Hamiltonian of a dissipative microwave billiard in the vicinity of an exceptional point (EP). The shape of the billiard depends on two parameters. The Hamiltonian is determined from the measured resonance spectrum on a fine grid in the parameter plane. After applying a purely imaginary diagonal shift to the Hamiltonian, its eigenvalues are either real or complex conjugate on a curve, which passes through the EP. An appropriate basis choice reveals its PT symmetry. Spontaneous symmetry breaking occurs at the EP.

Double-slit experiments with microwave billiards.

Single and double-slit experiments are performed with two microwave billiards with the shapes of a rectangle and a quarter stadium, respectively. The classical dynamics of the former is regular, whereas that of the latter is chaotic. Microwaves can leave the billiards via slits in the boundary, forming interference patterns on a screen. The aim is to determine the effect of the billiard dynamics on their structure. For this the development of a method for the construction of a directed wave packet by means of an array of multiple antennas was crucial. The interference patterns show a sensitive dependence not only on the billiard dynamics but also on the initial position and direction of the wave packet.

[Pregabalin and gabapentin in multiple sclerosis: clinical experiences and therapeutic implications]. / Ionenkanalmodulatoren bei Multipler Sklerose : Bestandsaufnahme der Anwendung in der Praxis.

BACKGROUND: Due to a plethora of additional symptoms patients with multiple sclerosis (MS) receive symptomatic treatment besides disease-modifying therapies. Among the substances which are commonly used are ion channel modulators (e. g. pregabalin, gabapentin, carbamazepine). The aim of this study was to investigate the use of these drugs in clinical practice in a larger patient cohort. PATIENTS: Data from 533 MS patients [439 without and 94 patients with add-on therapy (treatment group)] were evaluated retrospectively. All patients received a detailed neurological examination including evaluation of EDSS scores. RESULTS: Pregabalin and gabapentin are used most commonly. Abnormal sensations are the most frequent reason for therapy initiation. Patients with higher EDSS values and/or under mitoxantrone treatment most frequently receive additional therapy. CONCLUSION: So far, it is not known whether the investigated agents exert a beneficial influence on the disease course of MS itself beyond a mere symptomatic treatment. Further research efforts and clinical studies are necessary to address this question.

Experimental test of a trace formula for two-dimensional dielectric resonators.

Resonance spectra of two-dimensional dielectric microwave resonators of circular and square shapes have been measured. The deduced length spectra of periodic orbits were analyzed and a trace formula for dielectric resonators recently proposed by Bogomolny [Phys. Rev. E 78, 056202 (2008)] was tested. The observed deviations between the experimental length spectra and the predictions of the trace formula are attributed to a large number of missing resonances in the measured spectra. We show that by taking into account the systematics of observed and missing resonances the experimental length spectra are fully understood. In particular, a connection between the most long-lived resonances and certain periodic orbits is established experimentally.