Algebraic treatment of PT\mathcal{PT}-symmetric coupled oscillators

The purpose of this paper is the discussion of a pair of coupled linear oscillators that has recently been proposed as a model of a system of two optical resonators. By means of an algebraic approach we show that the frequencies of the classical and quantum-mechanical interpretations of the optical phenomenon are exactly the same. Consequently, if the classical frequencies are real, then the quantum-mechanical eigenvalues are also real

Alarm-Based Prescriptive Process Monitoring

Predictive process monitoring is concerned with the analysis of events produced during the execution of a process in order to predict the future state of ongoing cases thereof. Existing techniques in this field are able to predict, at each step of a case, the likelihood that the case will end up in an undesired outcome. These techniques, however, do not take into account what process workers may do with the generated predictions in order to decrease the likelihood of undesired outcomes. This paper proposes a framework for prescriptive process monitoring, which extends predictive process monitoring approaches with the concepts of alarms, interventions, compensations, and mitigation effects. The framework incorporates a parameterized cost model to assess the cost-benefit tradeoffs of applying prescriptive process monitoring in a given setting. The paper also outlines an approach to optimize the generation of alarms given a dataset and a set of cost model parameters. The proposed approach is empirically evaluated using a range of real-life event logs

Risk prediction models for colorectal cancer in people with symptoms: a systematic review.

Colorectal cancer (CRC) is the fourth leading cause of cancer-related death in Europe and the United States. Detecting the disease at an early stage improves outcomes. Risk prediction models which combine multiple risk factors and symptoms have the potential to improve timely diagnosis. The aim of this review is to systematically identify and compare the performance of models that predict the risk of primary CRC among symptomatic individuals. We searched Medline and EMBASE to identify primary research studies reporting, validating or assessing the impact of models. For inclusion, models needed to assess a combination of risk factors that included symptoms, present data on model performance, and be applicable to the general population. Screening of studies for inclusion and data extraction were completed independently by at least two researchers. Twelve thousand eight hundred eight papers were identified from the literature search and three through citation searching. 18 papers describing 15 risk models were included. Nine were developed in primary care populations and six in secondary care. Four had good discrimination (AUROC > 0.8) in external validation studies, and sensitivity and specificity ranged from 0.25 and 0.99 to 0.99 and 0.46 depending on the cut-off chosen. Models with good discrimination have been developed in both primary and secondary care populations. Most contain variables that are easily obtainable in a single consultation, but further research is needed to assess clinical utility before they are incorporated into practice.JUS is funded by a National Institute of Health Research (NIHR) Clinica

Predicting the evolution of neck pain episodes in routine clinical practice.

BACKGROUND: The objective of this study was to develop models for predicting the evolution of a neck pain (NP) episode. METHODS: Three thousand two hundred twenty-five acute and chronic patients seeking care for NP, were recruited consecutively in 47 health care centers. Data on 37 variables were gathered, including gender, age, employment status, duration of pain, intensity of NP and pain referred down to the arm (AP), disability, history of neck surgery, diagnostic procedures undertaken, imaging findings, clinical diagnosis, and treatments used. Three separate multivariable logistic regression models were developed for predicting a clinically relevant improvement in NP, AP and disability at 3 months. RESULTS: Three thousand one (93.5%%) patients attended follow-up. For all the models calibration was good. The area under the ROC curve was ≥0.717 for pain and 0.664 for disability. Factors associated with a better prognosis were: a) For all the outcomes: pain being acute (vs. chronic) and having received neuro-reflexotherapy. b) For NP: nonspecific pain (vs. pain caused by disc herniation or spinal stenosis), no signs of disc degeneration on imaging, staying at work, and being female. c) For AP: nonspecific NP and no signs of disc degeneration on imaging. d) For disability: staying at work and no signs of facet joint degeneration on imaging. CONCLUSIONS: A prospective registry can be used for developing valid predictive models to quantify the odds that a given patient with NP will experience a clinically relevant improvement

Heat shock protein amplification improves cerebellar myelination in the Npc1nih mouse model.

BACKGROUND: Niemann-Pick disease type C (NPC) is a rare prematurely fatal lysosomal lipid storage disease with limited therapeutic options. The prominent neuropathological hallmarks include hypomyelination and cerebellar atrophy. We previously demonstrated the efficacy of recombinant human heat shock protein 70 (rhHSP70) in preclinical models of the disease. It reduced glycosphingolipid levels in the central nervous system (CNS), improving cerebellar myelination and improved behavioural phenotypes in Npc1nih (Npc1-/-) mice. Furthermore, treatment with arimoclomol, a well-characterised HSP amplifier, attenuated lysosomal storage in NPC patient fibroblasts and improved neurological symptoms in Npc1-/- mice. Taken together, these findings prompted the investigation of the effects of HSP amplification on CNS myelination. METHODS: We administered bimoclomol daily or rhHSP70 6 times per week to Npc1-/- (BALB/cNctr-Npc1m1N/J, also named Npc1nih) mice by intraperitoneal injection from P7 through P34 to investigate the impact on CNS myelination. The Src-kinase inhibitor saracatinib was administered with/without bimoclomol twice daily to explore the contribution of Fyn kinase to bimoclomol's effects. FINDINGS: Treatment with either bimoclomol or rhHSP70 improved myelination and increased the numbers of mature oligodendrocytes (OLs) as well as the ratio of active-to-inactive forms of phosphorylated Fyn kinase in the cerebellum of Npc1-/- mice. Additionally, treatment with bimoclomol preserved cerebellar weight, an effect that was abrogated when co-administered with saracatinib, an inhibitor of Fyn kinase. Bimoclomol-treated mice also exhibited increased numbers of immature OLs within the cortex. INTERPRETATION: These data increase our understanding of the mechanisms by which HSP70 regulates myelination and provide further support for the clinical development of HSP-amplifying therapies in the treatment of NPC. FUNDING: Funding for this study was provided by Orphazyme A/S (Copenhagen, Denmark) and a Pathfinder Award from The Wellcome Trust

Unbiased yeast screens identify cellular pathways affected in Niemann-Pick disease type C

Niemann–Pick disease type C (NPC) is a rare lysosomal storage disease caused by mutations in either the NPC1 or NPC2 genes. Mutations in the NPC1 gene lead to the majority of clinical cases (95%); however, the function of NPC1 remains unknown. To gain further insights into the biology of NPC1, we took advantage of the homology between the human NPC1 protein and its yeast orthologue, Niemann–Pick C–related protein 1 (Ncr1). We recreated the NCR1 mutant in yeast and performed screens to identify compensatory or redundant pathways that may be involved in NPC pathology, as well as proteins that were mislocalized in NCR1-deficient yeast. We also identified binding partners of the yeast Ncr1 orthologue. These screens identified several processes and pathways that may contribute to NPC pathogenesis. These included alterations in mitochondrial function, cytoskeleton organization, metal ion homeostasis, lipid trafficking, calcium signalling, and nutrient sensing. The mitochondrial and cytoskeletal abnormalities were validated in patient cells carrying mutations in NPC1, confirming their dysfunction in NPC disease

Cumplimiento, conocimiento y automedicación como factores asociados a los resultados clínicos negativos de la farmacoterapia

The patient plays a fundamental role in the attainment of good results in pharmacotherapy. Noncompliance,self-medication, or insufficient knowledge of the therapy being employed may provide asource for the causes of these negative clinical outcomes, otherwise known as medicine related problems(MRP). he Dader method was used in the evaluation, identification and classification of MRP. Theassociation of variables was established through the statistical Chi square test. Patient knowledge of themedicine, degree of compliance to therapy and self-medication were studied as causes of the negativeoutcomes encountered. 2556 patients were interviewed throughout the year that the study took place,giving a total of 2261 of valid cases. 33% presented an MRP as the cause of his/her visit to the hospitalemergency ward. Knowledge of the medicine, compliance and self-medication were only studied in thepopulation that presented an MRP and in this work it is demonstrated that these are aspects that areassociated with different dimensions of MRP. It is not possible to establish an association between theexistence or not of negative clinical outcomes in patients with the factors of knowledge of medication,compliance and self-medication. This is due to the fact that these variables are not attributable to thepatient himself, but rather are associated with the characteristics of each medicine.El paciente juega un papel primordial en la consecución de los resultados terapéuticos. El incumplimiento,la automedicación, o la falta de conocimiento del la farmacoterapia pueden ser causas de esosresultados clínicos negativos, denominados en ocasiones problemas relacionados con medicamentos(PRM). El método Dáder se utilizó para la evaluación, identificación y clasificación de PRM. Laasociación de variables se estableció mediante el estadístico chi cuadrado. El conocimiento de la medicación,el cumplimiento y la automedicación fueron estudiados como causa de estos resultados negativosde la medicación. Fueron entrevistados 2556 pacientes durante el año de estudio, resultando 2261 casosválidos. El 33 % presentaron un PRM como causa de visita a urgencias. El conocimiento de la medicación,el cumplimiento y la automedicación fueron estudiados solo en la población que presentó unPRM y se demuestra que son aspectos asociados a las distintas dimensiones de PRM. No es posibleestablecer asociación entre la existencia o no de resultados clínicos negativos en los pacientes con elconocimiento de la medicación, el cumplimiento y la automedicación, debido a que estas variables noson atributos del paciente sino que están asociadas a cada medicamento

Non-specific low back pain in primary care in the Spanish National Health Service: a prospective study on clinical outcomes and determinants of management

BACKGROUND: The Spanish National Health Service is a universal and free health care system. Non-specific low back pain (LBP) is a prevalent disorder, generating large health and social costs. The objectives of this study were to describe its management in primary care, to assess patient characteristics that influence physicians' decisions, and to describe clinical outcome at 2 months. METHODS: A cross-sectional sample of 648 patients with non-specific low back pain was recruited by 75 physicians (out of 361 – 20.8%) working in 40 primary care centers in 10 of the 17 administrative regions in Spain, covering 693,026 out of the 40,499,792 inhabitants. Patients were assessed on the day they were recruited, and prospectively followed-up 14 and 60 days later. The principal patient characteristics that were analyzed were: sex, duration of the episode, history of LBP, working status, severity of LBP, leg pain and disability, and results of straight leg raising test. Descriptors of management were: performance of the straight leg raising test, ordering of diagnostic procedures, prescription of drug treatment, referral to physical therapy, rehabilitation or surgery, and granting of sick leave. Regression analysis was used to analyze the relationship between patients' baseline characteristics and physicians' management decisions. Only workers were included in the models on sick leave. RESULTS: Mean age (SD) of included patients was 46.5 (15.5) years, 367 (56.6%) were workers, and 338 (52.5%) were females. Median (25th–75th interquartile range) duration of pain when entering the study was 4 (2–10) days and only 28 patients (4.3%) had chronic low back pain. Diagnostic studies included plain radiographs in 43.1% of patients and CT or MRI scans in 18.8%. Drug medication was prescribed to 91.7% of patients, 19.1% were sent to physical therapy or rehabilitation, and 9.6% were referred to surgery. The main determinants of the clinical management were duration of the episode and, to a lesser extent, the intensity of the pain (especially leg pain), a positive straight leg raising test, and degree of disability. The main determinant of sick leave was the degree of disability, followed by the characteristics of the labor contract and the intensity of leg pain (but not low back pain). After at least 2 months of treatment, 37% of patients were still in pain and approximately 10% of patients had not improved or had worsened. CONCLUSION: Although the use of X-Rays is high, determinants of physicians' management of LBP in primary care made clinical sense and were consistent with patterns suggested by evidence-based recommendations. However, after 2 months of treatment more than one third of patients continued to have back pain and about 10% had worsened

Study protocol of effectiveness of a biopsychosocial multidisciplinary intervention in the evolution of non-speficic sub-acute low back pain in the working population : cluster randomised trial

Background: Non-specific low back pain is a common cause for consultation with the general practitioner, generating increased health and social costs. This study will analyse the effectiveness of a multidisciplinary intervention to reduce disability, severity of pain, anxiety and depression, to improve quality of life and to reduce the incidence of chronic low back pain in the working population with non-specific low back pain, compared to usual clinical care. Methods/Design: A Cluster randomised clinical trial will be conducted in 38 Primary Health Care Centres located in Barcelona, Spain and its surrounding areas. The centres are randomly allocated to the multidisciplinary intervention or to usual clinical care. Patients between 18 and 65 years old (n = 932; 466 per arm) and with a diagnostic of a non-specific sub-acute low back pain are included. Patients in the intervention group are receiving the recommendations of clinical practice guidelines, in addition to a biopsychosocial multidisciplinary intervention consisting of group educational sessions lasting a total of 10 hours. The main outcome is change in the score in the Roland Morris disability questionnaire at three months after onset of pain. Other outcomes are severity of pain, quality of life, duration of current non-specific low back pain episode, work sick leave and duration, Fear Avoidance Beliefs and Goldberg Questionnaires. Outcomes will be assessed at baseline, 3, 6 and 12 months. Analysis will be by intention to treat. The intervention effect will be assessed through the standard error of measurement and the effect-size. Responsiveness of each scale will be evaluated by standardised response mean and receiver-operating characteristic method. Recovery according to the patient will be used as an external criterion. A multilevel regression will be performed on repeated measures. The time until the current episode of low back pain takes to subside will be analysed by Cox regression. Discussion: We hope to provide evidence of the effectiveness of the proposed biopsychosocial multidisciplinary intervention in avoiding the chronification of low back pain, and to reduce the duration of non-specific low back pain episodes. If the intervention is effective, it could be applied to Primary Health Care Centres

Model for resource allocation in decentralized networks using Interaction nets

This article presents the description of a model for allocating resources using Interaction Nets and a strategy for playing public goods. In the description of the model first shows the behavior of the allocation of resources towards the nodes depending on the usefulness of the network and the satisfaction of the agents. Then the generalization of the model with Interaction Nets is described, and a simulation of this behavior is made. It is found that there is an emerging behavior condition in the dynamics of the interaction when assigning resources. To test the model, the interaction of sharing the Internet in an ad hoc network is done. The interaction is shown in the general model obtained