Treatment of gastrointestinal stromal tumor after imatinib and sunitinib.

Purpose of review Tyrosine kinase inhibitors (TKIs), such as imatinib and sunitinib, have changed the outcome of patients with gastrointestinal stromal tumor (GIST) and prolonged survival by many-fold. Unfortunately, treatment failure and tumor progression seem inevitable over time and constitute an unresolved clinical challenge. This article reviews current efforts to overcome drug resistance and progression. Recent findings The major mechanism of resistance toward imatinib and sunitinib is the development of secondary resistance mutations in the kinase domain of KIT. Recent efforts aim at inhibitors with increased activity against resistance mutations or a broader spectrum of activity. Other strategies include indirect KIT inhibition by modulating KIT chaperone proteins or inhibition of KIT-dependent and independent signaling pathways. Summary dThe rapid improvement of our understanding of GIST biology as well as resistance mechanisms towards imatinib and sunitinib will greatly facilitate the development of novel treatment strategies. This article summarizes the results of recently reported third and fourth-line clinical trials in patients with resistant GIST and reviews data of important proof-of-concept studies.

La reincidència en el Programa de Mediació i Reparació de menors

L’estudi actualitza la taxa de reincidència dels menors que durant l’any 2008 van finalitzar un programa de mediació o reparació (MRM) i als quals s’ha seguit fins el 30 de juny de 2011 per saber si han reincidit, és a dir, si han tornat a prendre contacte amb el sistema d’execució penal a Catalunya, ja sigui com a infractors juvenils o com a adults, en mesures d’execució penal a la comunitat o en el sistema penitenciari català. En total, la població estudiada ha estat de 2.022 subjectes. També s’han estudiat les poblacions d’altres tres mesures o programes que a priori es pensava que podrien correspondre a segments de població similars als del Programa de MRM i es volia comprovar si efectivament era així. Aquests tres grups de població estudiada són: 1) els menors i joves als que s’ha aplicat l’Art. 27.4 de la LORPM5/2000 (no continuar la tramitació de l’expedient), 2) aquells als que s’ha aplicat la mesura d’amonestació i 3) els joves per als quals l’informe tècnic proposava una mesura de prestacions en benefici de la comunitat. En l’informe es donen resultats del perfil dels infractors i de les víctimes; de les característiques del Programa de MRM; de la reincidència i les seves característiques; del perfil del jove reincident; es fa una anàlisi específica des de les perspectives de gènere i d’estrangeria; es comparen els programes i mesures esmentats i finalment es fan un seguit de recomanacions derivades dels resultats i de les conclusions.

Ten years of lung transplantation in Switzerland: results of the Swiss Lung Transplant Registry.

Lung transplantation has evolved from an experimental procedure to a viable therapeutic option in many countries. In Switzerland, the first lung transplant was performed in November 1992, more than ten years after the first successful procedure world-wide. Thenceforward, a prospective national lung transplant registry was established, principally to enable quality control. The data of all patients transplanted in the two Swiss Lung Transplant centres Zurich University Hospital and Centre de Romandie (Geneva-Lausanne) were analysed. In 10 years 242 lung transplants have been performed. Underlying lung diseases were cystic fibrosis including bronchiectasis (32%), emphysema (32%), parenchymal disorders (19%), pulmonary hypertension (11%) and lymphangioleiomyomatosis (3%). There were only 3% redo procedures. The 1, 5 and 9 year survival rates were 77% (95% CI 72-82), 64% (95% CI 57-71) and 56% (95% CI 45-67), respectively. The 5 year survival rate of patients transplanted since 1998 was 72% (95% CI 64-80). Multivariate Cox regression analysis revealed that survival was significantly better in this group compared to those transplanted before 1998 (HR 0.44, 0.26-0.75). Patients aged 60 years and older (HR 5.67, 95% CI 2.50-12.89) and those with pulmonary hypertension (HR 2.01, 95% CI 1.10-3.65) had a significantly worse prognosis The most frequent causes of death were infections (29%), bronchiolitis obliterans syndrome (25%) and multiple organ failure (14%). The 10-year Swiss experience of lung transplantation compares favourably with the international data. The best results are obtained in cystic fibrosis, pulmonary emphysema and parenchymal disorders.

Spirituality and religious practices among outpatients with schizophrenia and their clinicians

OBJECTIVES: Religious issues may be neglected by clinicians who are treating psychotic patients, even when religion constitutes an important means of coping. This study examined the spirituality and religious practices of outpatients with schizophrenia compared with their clinicians. Clinicians' knowledge of patients' religious involvement and spirituality was investigated. METHODS: The study sample included 100 patients of public psychiatric outpatient facilities in Geneva, Switzerland, with a diagnosis of nonaffective psychosis. Audiotaped interviews were conducted with use of a semistructured interview about spirituality and religious coping. The patients' clinicians (N=34) were asked about their own beliefs and religious activities as well as their patients' religious and clinical characteristics. RESULTS: Sixteen patients (16 percent) had positive psychotic symptoms reflecting aspects of their religious beliefs. A majority of the patients reported that religion was an important aspect of their lives, but only 36 percent of them had raised this issue with their clinicians. Fewer clinicians were religiously involved, and, in half the cases, their perceptions of patients' religious involvement were inaccurate. A few patients considered religious practice to be incompatible with treatment, and clinicians were seldom aware of such a conflict. CONCLUSIONS: Religion is an important issue for patients with schizophrenia, and it is often not related to the content of their delusions. Clinicians were commonly not aware of their patients' religious involvement, even if they reported feeling comfortable with such an issue.

Isolation and Identification of 9-methylgermacrene-B as the Putative Sex Pheromone of Lutzomyia cruzi (Mangabeira, 1938) (Diptera: Psychodidae)

Lutzomyia (Lutzomyia) cruzi has been named as a probable vector of Leishmania chagasi in Corumbá, Mato Grosso do Sul, Brazil. Taxonomically L. cruzi is closely related to the L. longipalpis species complex. Females of L. cruzi and L. longipalpis are morphologically indistinguishable and associated males must be examined carefully to confirm identifications. Chemical analysis hexane extracts of male L. cruzi has revealed the presence of a 9-methylgermacrene-B (C16), a homosesquiterpene (mw 218) previously shown to be the sex pheromone of one of the members of the L. longipalpis species complex.

Impact of an intervention to control risk associated with patient transfer.

QUESTION UNDER STUDY: Hospitals transferring patients retain responsibility until admission to the new health care facility. We define safe transfer conditions, based on appropriate risk assessment, and evaluate the impact of this strategy as implemented at our institution. METHODS: An algorithm defining transfer categories according to destination, equipment monitoring, and medication was developed and tested prospectively over 6 months. Conformity with algorithm criteria was assessed for every transfer and transfer category. After introduction of a transfer coordination centre with transfer nurses, the algorithm was implemented and the same survey was carried out over 1 year. RESULTS: Over the whole study period, the number of transfers increased by 40%, chiefly by ambulance from the emergency department to other hospitals and private clinics. Transfers to rehabilitation centres and nursing homes were reassigned to conventional vehicles. The percentage of patients requiring equipment during transfer, such as an intravenous line, decreased from 34% to 15%, while oxygen or i.v. drug requirement remained stable. The percentage of transfers considered below theoretical safety decreased from 6% to 4%, while 20% of transfers were considered safer than necessary. A substantial number of planned transfers could be "downgraded" by mutual agreement to a lower degree of supervision, and the system was stable on a short-term basis. CONCLUSION: A coordinated transfer system based on an algorithm determining transfer categories, developed on the basis of simple but valid medical and nursing criteria, reduced unnecessary ambulance transfers and treatment during transfer, and increased adequate supervision.

The mycobacterial cord factor adjuvant analogue trehalose-6,6'-dibehenate (TDB) activates the Nlrp3 inflammasome.

The success of a vaccine consists in the induction of an innate immune response and subsequent activation of the adaptive immune system. Because antigens are usually not immunogenic, the addition of adjuvants that activate innate immunity is required. The mycobacterial cord factor trehalose-6,6'-dimycolate (TDM) and its synthetic adjuvant analogue trehalose-6,6'-dibehenate (TDB) rely on the C-type lectin Mincle and the signaling molecules Syk and Card9 to trigger innate immunity. In this study, we show that stimulation of bone marrow-derived dendritic cells (BMDCs) with TDB induces Nlrp3 inflammasome-dependent IL-1β secretion. While Card9 is required for NF-κB activation by TDB, it is dispensable for TDB-induced activation of the Nlrp3 inflammasome. Additionally, efflux of intracellular potassium, lysosomal rupture, and oxygen radical (ROS) production are crucial for caspase-1 processing and IL-1β secretion by TDB. In an in vivo inflammation model, we demonstrate that the recruitment of neutrophils by TDB is significantly reduced in the Nlrp3-deficient mice compared to the wild-type mice, while the production of chemokines in vitro is not influenced by the absence of Nlrp3. These results identify the Nlrp3 inflammasome as an essential mediator for the induction of an innate immune response triggered by TDB.

Anàlisi del riu Llobregat com a via de transport del Baix Llobregat a l'època romana, amb eines SIG

Desenvolupament d'un Sistema d'Informació Geogràfica (SIG), que permeti analitzar les funcions dels jaciments romans de la zona del riu Llobregat i consultar els jaciments, emmagatzemats en una base de dades de forma espacial.

Wissensvermehrung durch Konzeptentwicklung? Das Beispiel Vergänglichkeit [The contibution of concept development to nursing knowledge? The example of Transitoriness].

To provide nursing practice with evidence, it is important to understand nursing phenomena in detail. Therefore, good descriptions including the identification of characteristics and attributes of nursing phenomena on various levels of abstraction, i. e., concepts, are needed. In this article the significance of concept development for nursing science will be demonstrated by drawing on the example of 'transitoriness'. The evolutionary concept analysis proposed by Rodgers (2000) is introduced in more detail. Drawing on transitoriness, the phenomenon is presented with the help of the evolutionary concept analysis by Rodgers (2000). The phenomenon's characteristics and attributes are identified, as well as potential areas of application. Moreover, areas are outlined, in which interventions for nursing practice can be developed, implemented and evaluated. Thus, nursing practice is updated to include new findings and innovation. Through concept analysis nursing phenomena can be described in more detail, enhanced or broadened for use in nursing practice. Such structured processes as concept analysis can be employed successfully for other nursing phenomena. Concept analyses can lead to the identification of tasks for the respective scientific discipline and professionals. Thus, concept analyses can lead to the concretisation of tasks in nursing.

SIG i Arqueologia : el riu Llobregat i la seva relació amb el territori en l'època romana

Aquest treball se centra en la utilització i aplicació de les tecnologies dels Sistemes d'Informació Geogràfica; en concret es realitza una pràctica sobre el traçat del riu Llobregat a l'època romana.

Multiple non-ossifying fibromas as a cause of pathological femoral fracture in Jaffe-Campanacci syndrome.

BACKGROUND: Jaffe-Campanacci is a rare syndrome characterised by the association of café-au-lait spots, axillary freckles, multiple non-ossifying fibromas of the long bones and jaw, as well as some features of type 1 neurofibromatosis. There are less than 30 reported cases, and a genetic profile has not yet been determined. Furthermore, it has not been clarified whether it is a subtype of type 1 neurofibromatosis or a separate syndrome. The risk of pathological fracture is over 50%, due to substantial cortical thinning of the weight-bearing bones. CASE PRESENTATION: A 17-year-old female patient, known for type 1 neurofibromatosis, presented with a low-energy distal femoral fracture due to disseminated large non-ossifying fibromas. Investigations revealed all of the distinctive signs of Jaffe-Campanacci syndrome. Both her distal femurs and proximal tibias exhibited multiple non-ossifying fibromas. The fracture was treated by open reduction and internal plate fixation. Some of the bony lesions were biopsied to confirm the diagnosis. The fracture healed eventless, as did the lesions biopsied or involved in the fracture. The other ones healed after curettage and bone grafting performed at the time of plate removal. CONCLUSION: Jaffe-Campanacci is a rare syndrome having unclear interactions with type 1 neurofibromatosis, which still needs to be characterised genetically. It is associated with a high risk of pathological fracture, due to the presence of multiple large non-ossifying fibromas of the long bones, with an expected normal healing time. Curettage and bone grafting promote healing of the lesions and should be considered to prevent pathological fracture. We agree with other authors that all patients with newly-diagnosed type 1 neurofibromatosis should undergo an osseous screening to detect disseminated non-ossifying fibromas, and evaluate the inherent risk of pathological fracture.

Construcció d'una aplicació web utilitzant el mètode Rational Unified Process

Construcció d'una aplicació web a partir de les especificacions d'un client imaginari. Estudi i utilització del mètode Rational Unified Process, el més habitual actualment en la construcció de software. Disseny d'una base de dades i implementació del model lògic mitjançant un SGBD punter al mercat com Oracle.