A Novel Volume-Age-KPS (VAK) Glioblastoma Classification Identifies a Prognostic Cognate microRNA-Gene Signature.

BACKGROUND: Several studies have established Glioblastoma Multiforme (GBM) prognostic and predictive models based on age and Karnofsky Performance Status (KPS), while very few studies evaluated the prognostic and predictive significance of preoperative MR-imaging. However, to date, there is no simple preoperative GBM classification that also correlates with a highly prognostic genomic signature. Thus, we present for the first time a biologically relevant, and clinically applicable tumor Volume, patient Age, and KPS (VAK) GBM classification that can easily and non-invasively be determined upon patient admission. METHODS: We quantitatively analyzed the volumes of 78 GBM patient MRIs present in The Cancer Imaging Archive (TCIA) corresponding to patients in The Cancer Genome Atlas (TCGA) with VAK annotation. The variables were then combined using a simple 3-point scoring system to form the VAK classification. A validation set (N = 64) from both the TCGA and Rembrandt databases was used to confirm the classification. Transcription factor and genomic correlations were performed using the gene pattern suite and Ingenuity Pathway Analysis. RESULTS: VAK-A and VAK-B classes showed significant median survival differences in discovery (P = 0.007) and validation sets (P = 0.008). VAK-A is significantly associated with P53 activation, while VAK-B shows significant P53 inhibition. Furthermore, a molecular gene signature comprised of a total of 25 genes and microRNAs was significantly associated with the classes and predicted survival in an independent validation set (P = 0.001). A favorable MGMT promoter methylation status resulted in a 10.5 months additional survival benefit for VAK-A compared to VAK-B patients. CONCLUSIONS: The non-invasively determined VAK classification with its implication of VAK-specific molecular regulatory networks, can serve as a very robust initial prognostic tool, clinical trial selection criteria, and important step toward the refinement of genomics-based personalized therapy for GBM patients.

Astrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamate.

Astrocytes establish rapid cell-to-cell communication through the release of chemical transmitters. The underlying mechanisms and functional significance of this release are, however, not well understood. Here we identify an astrocytic vesicular compartment that is competent for glutamate exocytosis. Using postembedding immunogold labeling of the rat hippocampus, we show that vesicular glutamate transporters (VGLUT1/2) and the vesicular SNARE protein, cellubrevin, are both expressed in small vesicular organelles that resemble synaptic vesicles of glutamatergic terminals. Astrocytic vesicles, which are not as densely packed as their neuronal counterparts, can be observed in small groups at sites adjacent to neuronal structures bearing glutamate receptors. Fluorescently tagged VGLUT-containing vesicles were studied dynamically in living astrocytes by total internal reflection fluorescence (TIRF) microscopy. After activation of metabotropic glutamate receptors, astrocytic vesicles underwent rapid (milliseconds) Ca(2+)- and SNARE-dependent exocytic fusion that was accompanied by glutamate release. These data document the existence of a Ca(2+)-dependent quantal glutamate release activity in glia that was previously considered to be specific to synapses.

Rapid disease emergence through horizontal gene transfer between eukaryotes.

Among different species of eukaryotes, the extent and evolutionary significance of horizontal gene transfer remains poorly understood. A newly published study by Friesen and colleagues indicates that a recent gene transfer between two species of fungi has enabled the recipient to rapidly acquire high virulence on wheat. The study highlights a mechanism by which diseases can suddenly emerge, but also brings up the controversial issues of how horizontal gene transfer occurs and whether fungal incompatibility barriers to gene flow are more 'leaky' than was previously thought.

Hepatitis G virus infection in primary Sjögren's syndrome: analysis in a series of 100 patients.

OBJECTIVE To determine the prevalence and clinical significance of hepatitis G virus (HGV) infection in a large cohort of patients with primary Sjögren¿s syndrome (SS). PATIENTS AND METHODS The study included 100 consecutive patients (92 female and eight male), with a mean age of 62 years (range 31¿80) that were prospectively visited in our unit. All patients fulfilled the European Community criteria for SS and underwent a complete history, physical examination, as well as biochemical and immunological evaluation for liver disease. Two hundred volunteer blood donors were also studied. The presence of HGV-RNA was investigated in the serum of all patients and donors. Aditionally, HBsAg and antibodies to hepatitis C virus were determined. RESULTS Four patients (4%) and six volunteer blood donors (3%) presented HGV-RNA sequences in serum. HGV infection was associated with biochemical signs of liver involvement in two (50%) patients. When compared with primary SS patients without HGV infection, no significant differences were found in terms of clinical or immunological features. HCV coinfection occurs in one (25%) of the four patients with HGV infection. CONCLUSION The prevalence of HGV infection in patients with primary SS is low in the geographical area of the study and HCV coinfection is very uncommon. HGV infection alone does not seen to be an important cause of chronic liver injury in the patients with primary SS in this area.

Control of Concrete Deterioration Due to Trace Compounds in Deicers, HR-299, 1992

This report describes the research completed under the research contract entitled "Development of a Conductometric Test for Frost Resistance of Concrete" undertaken for the Iowa Highway Research Board. The objective of the project was to develop a test method which can be reasonably and rapidly performed in the laboratory and in the field to predict, with a high degree of certainty, the behavior of concrete subjected to the action of alternate freezing and thawing. The significance of the results obtained, and recommendations for use and the continued development of conductometric testing are presented in this final report. In this project the conductometric evaluation of concrete durability was explored with three different test methods. The test methods and procedures for each type of test as well as presentation of the results obtained and their significance are included in the body of the report. The three test methods were: (1) Conductometric evaluation of the resistance of concrete to rapid freezing and thawing, (2) Conductometric evaluation of the resistance of concrete to natural freezing and thawing, and (3) Conductometric evaluation of the pore size distribution of concrete and its correlation to concrete durability. The report also includes recommendations for the continued development of these test methods.

Continuous electroencephalographic monitoring in critically ill patients with central nervous system infections.

OBJECTIVES: To determine the prevalence, predictors, and clinical significance of electrographic seizures (ESz) and other continuous electroencephalographic monitoring findings in critically ill patients with central nervous system infections. DESIGN: Retrospective cohort study. SETTING: Eighteen-bed neurocritical care unit. PATIENTS: We identified 42 consecutive patients with primary central nervous system infection (viral, 27 patients [64%]; bacterial, 8 patients [18%]; and fungal or parasitic, 7 patients [17%]) who underwent continuous electroencephalographic monitoring between January 1, 1996, and February 28, 2007. MAIN OUTCOME MEASURES: Presence of ESz or periodic epileptiform discharges (PEDs). RESULTS: Electrographic seizures were recorded in 14 patients (33%), and PEDs were recorded in 17 patients (40%). Twenty patients (48%) had either PEDs or ESz. Of the 14 patients with ESz, only 5 (36%) had a clinical correlate. Periodic epileptiform discharges (odds ratio=13.4; P=.001) and viral cause (odds ratio=13.0; P=.02) were independently associated with ESz. Both ESz (odds ratio=5.9; P=.02) and PEDs (odds ratio=6.1; P=.01) were independently associated with poor outcome at discharge (severe disability, vegetative state, or death). CONCLUSIONS: In patients with central nervous system infections undergoing continuous electroencephalographic monitoring, ESz and/or PEDs were frequent, occurring in 48% of our cohort. More than half of the ESz had no clinical correlate. Both ESz and PEDs were independently associated with poor outcome. Additional studies are needed to determine whether prevention or treatment of these electrographic findings improves outcome.

Towards the identification of a genetic basis for Landau-Kleffner syndrome.

OBJECTIVE: To establish the genetic basis of Landau-Kleffner syndrome (LKS) in a cohort of two discordant monozygotic (MZ) twin pairs and 11 isolated cases. METHODS: We used a multifaceted approach to identify genetic risk factors for LKS. Array comparative genomic hybridization (CGH) was performed using the Agilent 180K array. Whole genome methylation profiling was undertaken in the two discordant twin pairs, three isolated LKS cases, and 12 control samples using the Illumina 27K array. Exome sequencing was undertaken in 13 patients with LKS including two sets of discordant MZ twins. Data were analyzed with respect to novel and rare variants, overlapping genes, variants in reported epilepsy genes, and pathway enrichment. RESULTS: A variant (cG1553A) was found in a single patient in the GRIN2A gene, causing an arginine to histidine change at site 518, a predicted glutamate binding site. Following copy number variation (CNV), methylation, and exome sequencing analysis, no single candidate gene was identified to cause LKS in the remaining cohort. However, a number of interesting additional candidate variants were identified including variants in RELN, BSN, EPHB2, and NID2. SIGNIFICANCE: A single mutation was identified in the GRIN2A gene. This study has identified a number of additional candidate genes including RELN, BSN, EPHB2, and NID2. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Iowa Historic Property Study: Iowana Farms Milk Company, 1416 State Street, City of Bettendorf, Scott County, Iowa, 2012

The Iowana Farms Milk Company factory building was considered to retain sufficient integrity and possess sufficient significance to be considered eligible for the National Register of Historic Places under Criteria A and C for its historical and architectural significance in the Bettendorf community. The Iowana Farms Milk Company was an important early to mid-twentieth-century business in Bettendorf, and was among the few that was not owned or operated by the Bettendorf Company. It was a strong and thriving business for many years, and its products were well known in the Quad Cities region. The importance of this property becomes even more significant when one considers that most of the buildings once associated with the actual Bettendorf Company, which was undeniably the most important business and industry in town, are now gone. As a result, the Iowana Farms Milk Company factory building was a physical vestige of the once-thriving commercial industries that made Bettendorf into a city in the twentieth century. This property was further significant for its representation of the evolution of the dairy industry in the twentieth century from farm to factory production. It also reflected the changes to the industry based on scientific discoveries, mechanical innovations, and governmental regulations related to improved sanitation and the pure milk movement. The Iowana Farms Milk Company represented a model plant for the time, and the marketing strategies it employed followed the trends of the industry. The Iowana Farms Milk Company plant had to be removed to make room for a new I-74 bridge over the Mississippi River at Bettendorf. The construction of the new bridge also required removal of the historic Iowa-Illinois Memorial Bridge. The documentation reported herein and for that of the Iowa-Illinois Memorial Bridge fulfills the requirements of the Memorandum of Agreement regarding the removal of these historic properties.

El significado de las ocupaciones en las personas mayores-jóvenes: algunas tendencias

Con la llegada del nuevo paradigma del “envejecimiento activo” planteado por la Organización Mundial de la Salud (OMS, 2002), estamos asistiendo a una nueva manera de enfocar el progresivo envejecimiento de la población. Este enfoque trata de fomentar la consecución de una esperanza de vida saludable y libre de discapacidad, gracias a la promoción de políticas y programas cuyos objetivos principales se centran en la independencia y en la autonomía a lo largo del proceso de envejecimiento. Acorde con este enfoque pensamos que las ocupaciones significativas son una buena herramienta para mantener la autonomía de estas personas al fomentar la prevención y la promoción de su salud, motivo por el cual desarrollamos este estudio. Los objetivos principales del presente estudio son conocer y comprender que ocupaciones adquieren un significado y satisfacción personal en las personas mayores-jóvenes, que han concluido su etapa laboral, que cuentan con buena salud y condiciones psicofísicas favorables y que viven de manera autónoma en la comunidad, así como explorar también si se establece en estas personas alguna vinculación entre las actividades que eligen desarrollar en la actualidad con su perfil e historia ocupacional previa. Por último, este estudio pretende conocer el tipo de gestión que cada persona prefiere para llevar a cabo las actividades cotidianas que les son más significativas, a partir de los contextos en los que se inscribe. El marco teórico se desarrolla a partir de la conceptualización aportada por diversos autores sobre el envejecimiento activo y la ciencia de la ocupación. La metodología utilizada es de carácter cualitativo, enfocado desde un paradigma constructivista. Los resultados del estudio muestran que se inicia tímidamente un cambio de tendencias en la elección y el significado que las personas mayores-jóvenes atribuyen a sus ocupaciones. Muestran también que las ocupaciones elegidas como más significativas por estas personas mantienen una vinculación con las que ya realizaban con anterioridad a la jubilación, con su historia o perfil 6 ocupacional previo. Y finalmente demuestran que el tipo de gestión que eligen para efectuarlas influye en la elección del entorno donde las llevan a término.

In situ RHAMM protein expression in acute myeloid leukemia blasts suggests poor overall survival.

Treatment options for patients with high-risk acute myeloid leukemia (AML) include high-dose chemotherapy regimens in combination with allogeneic hematopoietic stem cell transplantation, which takes advantage of the donor T-cell-mediated graft-versus-leukemia effect. Together with beneficial responses observed in assays targeted at leukemia-associated antigens (LAA), this encouraged research on cancer vaccines and adoptive cellular therapies in AML. The receptor for hyaluronic acid-mediated motility (RHAMM, CD168) was identified as one of the most promising LAA in AML. Thus far, little is known about in situ expression in leukemic bone marrow blasts or the prognostic role of RHAMM and its interaction partners in AML. We immunohistochemically analyzed the expression and prognostic significance of RHAMM on trephine bone marrow biopsies from 71 AML cases that had been evaluated for cytogenetics and presence of FLT3-internal tandem duplications and NPM1 mutations. Fifty-five patients (77%) were treated with curative intent, while 16 (23%) received the most appropriate supportive care. Twenty of 71 (28%) AML cases were considered RHAMM+. Receiver operating characteristic curves showed significant discriminatory power considering overall survival (OS) in AML patients treated curatively for RHAMM (p = 0.015). Multivariable analysis revealed that expression of RHAMM in >5% of leukemic blasts identifies a subgroup of curatively treated cases with adverse OS independent of failures to achieve complete remission. RHAMM not only represents a promising LAA with specific T-cell responses in AML but, if assessed in situ on blasts, also a probable prognostic factor.

Seguiment de la diagnosi socioambiental del Camí de Cavalls: sector nord-est

El Camí de Cavalls és un element característic amb una importància històrica, cultural i recreativa considerable a Menorca. Aquesta illa va ser declarada Reserva de la Biosfera per l UNESCO l’any 1993; com a conseqüència, a l’any 2000 es va implantar el Pla Especial del Camí de Cavalls amb diversos objectius: definir les característiques del Camí i els seus instruments de gestió i aplicació; implantar mecanismes i normes que permetin l’ús públic que garanteixin la seva protecció i conservació; i finalment definir polítiques de sostenibilitat i conscienciació ambiental. Al llarg dels anys, la seva gestió ha permès que el Camí presenti una millora del seu estat de conservació i fer-ne un ús favorable a nivell socioambiental. L’any 2008 es va realitzar una diagnosi del Sector nord-est de la illa, aplicant-ne diversos indicadors per tal de determinar l’estat del Cam,í coincidint amb l’aplicació dels criteris plantejats pel Pla Especial del 2000 (Diagnosi Socioambiental del Camí de Cavalls de Menorca 2008). En aquest document s’explica la realització de la segona diagnosi, a partir del protocol dissenyat cinc anys abans, per tal de valorar l’estat actual del Camí i observar i definir les variacions que s’han produït en aquest període de temps. Els resultats mostren una tendència global positiva de millora del Camí, tal i com es planteja en la hipòtesis del projecte, tot i presentar-se una sèrie d’inconvenients a l’hora d’aplicar i valorar qualitativament els indicadors utilitzats. L’estudi s’ha realitzat amb la col·laboració dels centres de estudis ambientals de l’ICTA (Institut de Ciència i Tecnologia Ambientals) amb seu a la UAB (Universitat Autònoma de Barcelona), i l’OBSAM (Observatori Socioambiental de Menorca) amb seu a l’IME (Institut Menorquí d’Estudis).

Hepatitis G virus infection in primary Sjögren's syndrome: analysis in a series of 100 patients.

OBJECTIVE To determine the prevalence and clinical significance of hepatitis G virus (HGV) infection in a large cohort of patients with primary Sjögren¿s syndrome (SS). PATIENTS AND METHODS The study included 100 consecutive patients (92 female and eight male), with a mean age of 62 years (range 31¿80) that were prospectively visited in our unit. All patients fulfilled the European Community criteria for SS and underwent a complete history, physical examination, as well as biochemical and immunological evaluation for liver disease. Two hundred volunteer blood donors were also studied. The presence of HGV-RNA was investigated in the serum of all patients and donors. Aditionally, HBsAg and antibodies to hepatitis C virus were determined. RESULTS Four patients (4%) and six volunteer blood donors (3%) presented HGV-RNA sequences in serum. HGV infection was associated with biochemical signs of liver involvement in two (50%) patients. When compared with primary SS patients without HGV infection, no significant differences were found in terms of clinical or immunological features. HCV coinfection occurs in one (25%) of the four patients with HGV infection. CONCLUSION The prevalence of HGV infection in patients with primary SS is low in the geographical area of the study and HCV coinfection is very uncommon. HGV infection alone does not seen to be an important cause of chronic liver injury in the patients with primary SS in this area.

Hankinnan tietojärjestelmäintegraatiot raskaassa konepajateollisuudessa

Tässä diplomityössä tarkastellaan sähköisen liiketoiminnan mukanaan tuomia mahdollisuuksia yrityksen hankintatoimen prosessien tehostamiseksi. Työ keskittyy erityisesti raskaassa konepajateollisuudessa toimivan yrityksen, Metso Paperin, hankinnan tietojärjestelmien integroimiseen. Pääasiallinen tutkimusmenetelmä on kirjallisuustutkimus, jota lisäksi täydennetään empiirisesti tutkittujen case-tapauksien avulla, joissa tarkastellaan sähköisen hankintatoimen käytännön toteutusta Metso Paperin ja sen alihankkijan, Toijala Worksin välillä. Diplomityön tavoitteena on esittää yrityksen hankintaverkoston ja siihen kuuluvien alihankkijoiden toiminnan uudelleen organisoiminen ja hallitseminen, minkä lisäksi työssä käsitellään myös hankintastrategian merkitystä yrityksen liiketoiminnan kannalta. Työn tietotekninen osuus keskittyy sähköisen liiketoiminnan edellyttämän tietojärjestelmän suunnittelemiseen, mutta ei sen käytännön toteuttamiseen. Työn tärkein tulos on sähköisenliiketoiminnan aloittamisen mahdollistava kaksivaiheinen tiedonsiirtomalli, jonka ensimmäinen vaihe perustuu jo olemassa olevien tietojärjestelmien, eli Extranet- ja Notes -työpöytien, hyödyntämiseen uudella, aiempaa tehokkaammalla tavalla. Mallin toinen vaihe jakautuu yrityksen sisäisen ja ulkoisen tiedonsiirtoon. Toisen vaiheen keskeinen tulos on ratkaisuehdotus sisäisten ja ulkoisten tietojärjestelmien toimintojen ja tietojen saumattomaksi integroimiseksi toisiinsa, eli tutkimuskohteena olevan yrityksen hankintaverkostoon ja sen erityispiirteisiin sopiva sähköisen kaupankäynnin sovellutus.

Team Effectiveness in Patient Health Management: An Overview of Reviews

Background: The desire to improve the quality of health care for an aging population with multiple chronic diseases is fostering a rapid growth in inter-professional team care, supported by health professionals, governments, businesses and public institutions. However, the weight of evidence measuring the impact of team care on patient and health system outcomes has not, heretofore, been clear. To address this deficiency, we evaluated published evidence for the clinical effectiveness of team care within a chronic disease management context in a systematic overview. Methods: A search strategy was built for Medline using medical subject headings and other relevant keywords. After testing for perform- ance, the search strategy was adapted to other databases (Cinhal, Cochrane, Embase, PsychInfo) using their specific descriptors. The searches were limited to reviews published between 1996 and 2011, in English and French languages. The results were analyzed by the number of studies favouring team intervention, based on the direction of effect and statistical significance for all reported outcomes. Results: Sixteen systematic and 7 narrative reviews were included. Diseases most frequently targeted were depression, followed by heart failure, diabetes and mental disorders. Effective- ness outcome measures most commonly used were clinical endpoints, resource utilization (e.g., emergency room visits, hospital admissions), costs, quality of life and medication adherence. Briefly, while improved clinical and resource utilization endpoints were commonly reported as positive outcomes, mixed directional results were often found among costs, medication adherence, mortality and patient satisfaction outcomes. Conclusions: We conclude that, although suggestive of some specific benefits, the overall weight of evidence for team care efficacy remains equivocal. Further studies that examine the causal interactions between multidisciplinary team care and clinical and economic outcomes of disease management are needed to more accurately assess its net program efficacy and population effectiveness.