Good manufacturing practice-compliant validation and preparation of BM cells for the therapy of acute myocardial infarction

BACKGROUND: Intracoronary application of BM-derived cells for the treatment of acute myocardial infarction (AMI) is currently being studied intensively. Simultaneously, strict legal requirements surround the production of cells for clinical studies. Thus good manufacturing practice (GMP)-compliant collection and preparation of BM for patients with AMI was established by the Cytonet group. METHODS: As well as fulfillment of standard GMP requirements, including a manufacturing license, validation of the preparation process and the final product was performed. Whole blood (n=6) and BM (n=3) validation samples were processed under GMP conditions by gelafundin or hydroxyethylstarch sedimentation in order to reduce erythrocytes/platelets and volume and to achieve specifications defined in advance. Special attention was paid to the free potassium (<6 mmol/L), some rheologically relevant cellular characteristics (hematocrit <0.45, platelets <450 x 10(6)/mL) and the sterility of the final product. RESULTS: The data were reviewed and GMP compliance was confirmed by the German authorities (Paul-Ehrlich Institute). Forty-five BM cell preparations for clinical use were carried out following the validated methodology and standards. Additionally three selections of CD34+ BM cells for infusion were performed. All specification limits were met. Discussion In conclusion, preparation of BM cells for intracoronary application is feasible under GMP conditions. As the results of sterility testing may not be available at the time of intracoronary application, the highest possible standards to avoid bacterial and other contaminations have to be applied. The increased expense of the GMP-compliant process can be justified by higher safety for patients and better control of the final product.

Enriching Reverse Engineering with Annotations

Much of the knowledge about software systems is implicit, and therefore difficult to recover by purely automated techniques. Architectural layers and the externally visible features of software systems are two examples of information that can be difficult to detect from source code alone, and that would benefit from additional human knowledge. Typical approaches to reasoning about data involve encoding an explicit meta-model and expressing analyses at that level. Due to its informal nature, however, human knowledge can be difficult to characterize up-front and integrate into such a meta-model. We propose a generic, annotation-based approach to capture such knowledge during the reverse engineering process. Annotation types can be iteratively defined, refined and transformed, without requiring a fixed meta-model to be defined in advance. We show how our approach supports reverse engineering by implementing it in a tool called Metanool and by applying it to (i) analyzing architectural layering, (ii) tracking reengineering tasks, (iii) detecting design flaws, and (iv) analyzing features.

Ansätze zur Qualitätsbewertung von generativen Fertigungsverfahren durch die Einführung eines Kennzahlensystems

Generative Fertigungsverfahren haben sich in den letzten Jahren als effektive Werkzeuge für die schnelle Entwicklung von Produkten nahezu beliebiger Komplexität entwickelt. Gleichzeitig wird gefordert, die Reproduzierbarkeit der Bauteile und auch seriennahe bzw. seriengleiche Eigenschaften zu gewährleisten. Die Vielfalt und der Umfang der Anwendungen sowie die große Anzahl verschiedener generativer Fertigungsverfahren verlangen adäquate Qualitätsüberwachungs- und Qualitätskontrollsysteme. Ein Lösungsansatz für die Qualitätsbewertung von generativen Fertigungsverfahren besteht in der Einführung eines Kennzahlensystems. Hierzu müssen zunächst Anforderungsprofile und Qualitätsmerkmale für generativ hergestellte Bauteile definiert werden, welche durch Prüfkörpergeometrien abgebildet und mit Hilfe von Einzelkennzahlen klassifiziert werden. In Rahmen der durchgeführten Untersuchungen wurde die Qualitätsbewertung anhand von Prüfkörpergeometrien am Beispiel des Laser-Sinterprozesses qualifiziert. Durch Beeinflussung der Prozessparameter, d.h. der gezielten Einbringung von Störgrößen, welche einzeln oder in Kombination zu unzulässigen Qualitätsschwankungen führen können, ist es möglich, die Qualität des Produktes zu beurteilen. Die Definition von Einzelkennzahlen, die eine Steuerung und Kontrolle sowie eine Vorhersage potentieller Fehler ermöglicht, bietet hierbei essentielle Möglichkeiten zur Qualitätsbewertung. Eine Zusammenführung zu einem gesamtheitlichen Kennzahlensystem soll zum einen den Prozess auf Grundlage der definierten Anforderungsprofile bewerten und zum anderen einen direkten Zusammenhang der ausgewählten Störgrößen und Prozessgrößen herleiten, um vorab eine Aussage über die Bauteilqualität treffen zu können.

LGM Summer Climate on the Southern Margin of the Laurentide Ice Sheet: Wet Or Dry?

Regional climate simulations are conducted using the Polar fifth-generation Pennsylvania State University (PSU)-NCAR Mesoscale Model (MM5) with a 60-km horizontal resolution domain over North America to explore the summer climate of the Last Glacial Maximum (LGM: 21 000 calendar years ago), when much of the continent was covered by the Laurentide Ice Sheet (LIS). Output from a tailored NCAR Community Climate Model version 3 (CCM3) simulation of the LGM climate is used to provide the initial and lateral boundary conditions for Polar MM5. LGM boundary conditions include continental ice sheets, appropriate orbital forcing, reduced CO2 concentration, paleovegetation, modified sea surface temperatures, and lowered sea level. The simulated LGM summer climate is characterized by a pronounced low-level thermal gradient along the southern margin of the LIS resulting from the juxtaposition of the cold ice sheet and adjacent warm ice-free land surface. This sharp thermal gradient anchors the midtropospheric jet stream and facilitates the development of synoptic cyclones that track over the ice sheet, some of which produce copious liquid precipitation along and south of the LIS terminus. Precipitation on the southern margin is orographically enhanced as moist southerly low-level flow (resembling a contemporary, Great Plains low-level jet configuration) in advance of the cyclone is drawn up the ice sheet slope. Composites of wet and dry periods on the LIS southern margin illustrate two distinctly different atmospheric flow regimes. Given the episodic nature of the summer rain events, it may be possible to reconcile the model depiction of wet conditions on the LIS southern margin during the LGM summer with the widely accepted interpretation of aridity across the Great Plains based on geological proxy evidence.

Migratory Urge and Gill Na(+),K(+)-ATPase Activity of Hatchery-Reared Atlantic Salmon Smolts from the Dennys and Penobscot River Stocks, Maine

Hatchery-reared Atlantic salmon Salmo salar smolts produced from captive-reared Dennys River and sea-run Penobscot River broodstock are released into their source rivers in Maine. The adult return rate of Dennys smolts is comparatively low, and disparity in smolt quality between stocks resulting from genetic or broodstock rearing effects is plausible. Smolt behavior and physiology were assessed during sequential 14-d trials conducted in seminatural annular tanks with circular flow. "Migratory urge'' (downstream movement) was monitored remotely using passive integrated transponder tags, and gill Na(+),K(+)-ATPase activity was measured at the beginning and end of the trials to provide an index of smolt development. The migratory urge of both stocks was low in early April, increased 20-fold through late May, and declined by the end of June. The frequency and seasonal distribution of downstream movement were independent of stock. In March and April, initial gill Na(+),K(+)-ATPase activities of Penobscot River smolts were lower than those of Dennys River smolts. For these trials, however, Penobscot River smolts increased enzyme activity after exposure to the tank, whereas Dennys River smolts did not, resulting in similar activities between stocks at the end of all trials. There was no clear relationship between migratory urge and gill Na(+),K(+)-ATPase activity. Gill Na(+),K(+)-ATPase activity of both stocks increased in advance of migratory urge and then declined while migratory urge was increasing. Maximum movement was observed from 2 h after sunset through 1 h after sunrise but varied seasonally. Dennys River smolts were slightly more nocturnal than Penobscot River smolts. These data suggest that Dennys and Penobscot River stocks are not markedly different in either physiological or behavioral expression of smolting.

An Early-Warning System for Hypo-/Hyperglycemic Events Based on Fusion of Adaptive Prediction Models

Introduction: Early warning of future hypoglycemic and hyperglycemic events can improve the safety of type 1 diabetes mellitus (T1DM) patients. The aim of this study is to design and evaluate a hypoglycemia / hyperglycemia early warning system (EWS) for T1DM patients under sensor-augmented pump (SAP) therapy. Methods: The EWS is based on the combination of data-driven online adaptive prediction models and a warning algorithm. Three modeling approaches have been investigated: (i) autoregressive (ARX) models, (ii) auto-regressive with an output correction module (cARX) models, and (iii) recurrent neural network (RNN) models. The warning algorithm performs postprocessing of the models′ outputs and issues alerts if upcoming hypoglycemic/hyperglycemic events are detected. Fusion of the cARX and RNN models, due to their complementary prediction performances, resulted in the hybrid autoregressive with an output correction module/recurrent neural network (cARN)-based EWS. Results: The EWS was evaluated on 23 T1DM patients under SAP therapy. The ARX-based system achieved hypoglycemic (hyperglycemic) event prediction with median values of accuracy of 100.0% (100.0%), detection time of 10.0 (8.0) min, and daily false alarms of 0.7 (0.5). The respective values for the cARX-based system were 100.0% (100.0%), 17.5 (14.8) min, and 1.5 (1.3) and, for the RNN-based system, were 100.0% (92.0%), 8.4 (7.0) min, and 0.1 (0.2). The hybrid cARN-based EWS presented outperforming results with 100.0% (100.0%) prediction accuracy, detection 16.7 (14.7) min in advance, and 0.8 (0.8) daily false alarms. Conclusion: Combined use of cARX and RNN models for the development of an EWS outperformed the single use of each model, achieving accurate and prompt event prediction with few false alarms, thus providing increased safety and comfort.

SMARTnet: First Experience of Setting Up a Telescope System to Survey the Geostationary Ring

Space debris in geostationary orbits may be detected with optical telescopes when the objects are illuminated by the Sun. The advantage compared to Radar can be found in the illumination: radar illuminates the objects and thus the detection sensitivity depletest proportional to the fourth power of the d istance. The German Space Operation Center, GSOC, together with the Astronomical Institute of the University of Bern, AIUB, are setting up a telescope system called SMARTnet to demonstrate the capability of performing geostationary surveillance. Such a telescope system will consist of two telescopes on one mount: a smaller telescope with an aperture of 20cm will serve for fast survey while the larger one, a telescope with an aperture of 50cm, will be used for follow-up observations. The telescopes will be operated by GSOC from Oberpfaffenhofen by the internal monitoring and control system called SMARTnetMAC. The observation plan will be generated by MARTnetPlanning seven days in advance by applying an optimized planning scheduler, taking into account fault time like cloudy nights, priority of objects etc. From each picture taken, stars will be identified and everything not being a star is treated as a possible object. If the same object can be identified on multiple pictures within a short time span, the trace is called a tracklet. In the next step, several tracklets will be correlated to identify individual objects, ephemeris data for these objects are generated and catalogued . This will allow for services like collision avoidance to ensure safe operations for GSOC’s satellites. The complete data processing chain is handled by BACARDI, the backbone catalogue of relational debris information and is presented as a poster.

Periodontal regeneration - furcation defects: a consensus report from the AAP Regeneration Workshop

BACKGROUND Treatment of furcation defects is a core component of periodontal therapy. The goal of this consensus report is to critically appraise the evidence and to subsequently present interpretive conclusions regarding the effectiveness of regenerative therapy for the treatment of furcation defects and recommendations for future research in this area. METHODS A systematic review was conducted before the consensus meeting. This review aims to evaluate and present the available evidence regarding the effectiveness of different regenerative approaches for the treatment of furcation defects in specific clinical scenarios compared with conventional surgical therapy. During the meeting, the outcomes of the systematic review, as well as other pertinent sources of evidence, were discussed by a committee of nine members. The consensus group members submitted additional material for consideration by the group in advance and at the time of the meeting. The group agreed on a comprehensive summary of the evidence and also formulated recommendations for the treatment of furcation defects via regenerative therapies and the conduction of future studies. RESULTS Histologic proof of periodontal regeneration after the application of a combined regenerative therapy for the treatment of maxillary facial, mesial, distal, and mandibular facial or lingual Class II furcation defects has been demonstrated in several studies. Evidence of histologic periodontal regeneration in mandibular Class III defects is limited to one case report. Favorable outcomes after regenerative therapy for maxillary Class III furcation defects are limited to clinical case reports. In Class I furcation defects, regenerative therapy may be beneficial in certain clinical scenarios, although generally Class I furcation defects may be treated predictably with non-regenerative therapies. There is a paucity of data regarding quantifiable patient-reported outcomes after surgical treatment of furcation defects. CONCLUSIONS Based on the available evidence, it was concluded that regenerative therapy is a viable option to achieve predictable outcomes for the treatment of furcation defects in certain clinical scenarios. Future research should test the efficacy of novel regenerative approaches that have the potential to enhance the effectiveness of therapy in clinical scenarios associated historically with less predictable outcomes. Additionally, future studies should place emphasis on histologic demonstration of periodontal regeneration in humans and also include validated patient-reported outcomes. CLINICAL RECOMMENDATIONS Based on the prevailing evidence, the following clinical recommendations could be offered. 1) Periodontal regeneration has been established as a viable therapeutic option for the treatment of various furcation defects, among which Class II defects represent a highly predictable scenario. Hence, regenerative periodontal therapy should be considered before resective therapy or extraction; 2) The application of a combined therapeutic approach (i.e., barrier, bone replacement graft with or without biologics) appears to offer an advantage over monotherapeutic algorithms; 3) To achieve predictable regenerative outcomes in the treatment of furcation defects, adverse systemic and local factors should be evaluated and controlled when possible; 4) Stringent postoperative care and subsequent supportive periodontal therapy are essential to achieve sustainable long-term regenerative outcomes.

Intensive care unit utilization among patients with cancer at the end of life

Over the last 2 decades, survival rates in critically ill cancer patients have improved. Despite the increase in survival, the intensive care unit (ICU) continues to be a location where end-of-life care takes place. More than 20% of deaths in the United States occur after admission to an ICU, and as baby boomers reach the seventh and eighth decades of their lives, the volume of patients in the ICU is predicted to rise. The aim of this study was to evaluate intensive care unit utilization among patients with cancer who were at the end of life. End of life was defined using decedent and high-risk cohort study designs. The decedent study evaluated characteristics and ICU utilization during the terminal hospital stay among patients who died at The University of Texas MD Anderson Cancer Center during 2003-2007. The high-risk cohort study evaluated characteristics and ICU utilization during the index hospital stay among patients admitted to MD Anderson during 2003-2007 with a high risk of in-hospital mortality. Factors associated with higher ICU utilization in the decedent study included non-local residence, hematologic and non-metastatic solid tumor malignancies, malignancy diagnosed within 2 months, and elective admission to surgical or pediatric services. Having a palliative care consultation on admission was associated with dying in the hospital without ICU services. In the cohort of patients with high risk of in-hospital mortality, patients who went to the ICU were more likely to be younger, male, with newly diagnosed non-metastatic solid tumor or hematologic malignancy, and admitted from the emergency center to one of the surgical services. A palliative care consultation on admission was associated with a decreased likelihood of having an ICU stay. There were no differences in ethnicity, marital status, comorbidities, or insurance status between patients who did and did not utilize ICU services. Inpatient mortality probability models developed for the general population are inadequate in predicting in-hospital mortality for patients with cancer. The following characteristics that differed between the decedent study and high-risk cohort study can be considered in future research to predict risk of in-hospital mortality for patients with cancer: ethnicity, type and stage of malignancy, time since diagnosis, and having advance directives. Identifying those at risk can precipitate discussions in advance to ensure care remains appropriate and in accordance with the wishes of the patient and family.^

La expansión urbana y procesos sociales en Yerba Buena (Gran San Miguel de Tucumán, Tucumán) : countries y barrios privados

En Argentina el auge de las urbanizaciones cerradas se produjo a fines de los ochenta y principios de los noventa y ocurrió en las principales ciudades del país: Buenos Aires (Janoschka 2003; Svampa 2003), Rosario (Bragos et al 2003), Mendoza (Roitman 2003) y Tucumán (Malizia y Paolasso 2007). El fenómeno de las urbanizaciones cerradas también se reproduce, en menor escala, en ciudades intermedias como el Gran San Miguel de Tucumán -GSMT- (Mertins 1995). Este trabajo hace análisis de la distribución espacial de las urbanizaciones cerradas, cambios que se producen en la estructura urbana y procesos sociales resultantes de la interacción entre “los de adentro" y “los de afuera". El mismo se focaliza en el municipio de Yerba Buena, ubicado al oeste del GSMT, dado que concentra la mayor cantidad de urbanizaciones cerradas del aglomerado; en el 2005 ya se habían construido 45 emprendimientos de este tipo. En la actualidad en esta zona se conjugan la vivienda social, la ocupación ilegal de terrenos, los asentamientos precarios y los emprendimientos residenciales destinados a la clase media alta y alta (Müller 2000/01; Mertins 1995). Estos últimos impulsan la conformación de un CBD en rápida expansión y la construcción de centros comerciales, entretenimientos y otros en sus fronteras de avance. Esta expansión produce, a su vez, la fragmentación de la ciudad que se manifiesta en una marcada tendencia hacia una “ciudad de islas", tal como lo expresa Janoschka (2002) en su nuevo modelo de análisis de las metrópolis latinoamericanas.

Territorialidades, espacios vividos y sentidos de lugar en tiempos de avance de la frontera productiva

En pleno proceso de corrimiento de la frontera productiva y emergente disputa por el uso y apropiación de los recursos, la intervención de distintos sujetos sociales en el oeste de La Pampa está redefiniendo las prácticas productivas-reproductivas de los crianceros campesinos y, en consecuencia, la construcción social del espacio. Desde la finalización de las campañas militares contra las sociedades indígenas diferentes agentes, mediante el ejercicio de poder, construyeron determinadas representaciones territoriales y pusieron en acción prácticas tendientes a articular el oeste pampeano con la economía nacional. Sin embargo la escasa valorización de este espacio posibilitó el desarrollo de cierta autonomía en las formas de organización socio-productivas y simbólicas. Ante la expansión de la frontera ganadera, el impuso hidrocarburífero en la región y creciente presencia de nuevas lógicas territoriales crecen las confrontaciones por el desigual acceso a los recursos naturales, por la apropiación del espacio y la construcción de territorialidades. En este marco, el artículo focaliza la mirada en la organización interna de los asentamientos rurales y en los usos sociales de los espacios a través del tiempo, en dos áreas del "extremo" oeste: La Humada y Chos Malal. De este modo se pretende establecer cómo se organizaron diacrónicamente los espacios doméstico, peridoméstico y monte y qué sentidos expresan los sujetos en torno a los espacios de vida y lugares en tiempos de expansión de la frontera productiva. El nuevo campo social generado producto del avance del capitalismo sobre las unidades campesinas se expresa, no sólo en las modificaciones en las formas de manejo del ganado, organización de la producción y construcción social del espacio, sino también en las formas de sociabilidad y estrategias de resistencia colectivas. Este proceso, que se está gestando en la región, tiene un desarrollo similar en otros espacios donde el avance productivo se ha generado con anterioridad o a un ritmo más acelerado. Para la realización de la investigación se articulan diferentes estrategias de metodología cualitativa que combinan el estudio de caso con historias de vida, entrevistas en profundidad y análisis de fuentes documentales.

Territorialidades, espacios vividos y sentidos de lugar en tiempos de avance de la frontera productiva

En pleno proceso de corrimiento de la frontera productiva y emergente disputa por el uso y apropiación de los recursos, la intervención de distintos sujetos sociales en el oeste de La Pampa está redefiniendo las prácticas productivas-reproductivas de los crianceros campesinos y, en consecuencia, la construcción social del espacio. Desde la finalización de las campañas militares contra las sociedades indígenas diferentes agentes, mediante el ejercicio de poder, construyeron determinadas representaciones territoriales y pusieron en acción prácticas tendientes a articular el oeste pampeano con la economía nacional. Sin embargo la escasa valorización de este espacio posibilitó el desarrollo de cierta autonomía en las formas de organización socio-productivas y simbólicas. Ante la expansión de la frontera ganadera, el impuso hidrocarburífero en la región y creciente presencia de nuevas lógicas territoriales crecen las confrontaciones por el desigual acceso a los recursos naturales, por la apropiación del espacio y la construcción de territorialidades. En este marco, el artículo focaliza la mirada en la organización interna de los asentamientos rurales y en los usos sociales de los espacios a través del tiempo, en dos áreas del "extremo" oeste: La Humada y Chos Malal. De este modo se pretende establecer cómo se organizaron diacrónicamente los espacios doméstico, peridoméstico y monte y qué sentidos expresan los sujetos en torno a los espacios de vida y lugares en tiempos de expansión de la frontera productiva. El nuevo campo social generado producto del avance del capitalismo sobre las unidades campesinas se expresa, no sólo en las modificaciones en las formas de manejo del ganado, organización de la producción y construcción social del espacio, sino también en las formas de sociabilidad y estrategias de resistencia colectivas. Este proceso, que se está gestando en la región, tiene un desarrollo similar en otros espacios donde el avance productivo se ha generado con anterioridad o a un ritmo más acelerado. Para la realización de la investigación se articulan diferentes estrategias de metodología cualitativa que combinan el estudio de caso con historias de vida, entrevistas en profundidad y análisis de fuentes documentales.

Territorialidades, espacios vividos y sentidos de lugar en tiempos de avance de la frontera productiva

En pleno proceso de corrimiento de la frontera productiva y emergente disputa por el uso y apropiación de los recursos, la intervención de distintos sujetos sociales en el oeste de La Pampa está redefiniendo las prácticas productivas-reproductivas de los crianceros campesinos y, en consecuencia, la construcción social del espacio. Desde la finalización de las campañas militares contra las sociedades indígenas diferentes agentes, mediante el ejercicio de poder, construyeron determinadas representaciones territoriales y pusieron en acción prácticas tendientes a articular el oeste pampeano con la economía nacional. Sin embargo la escasa valorización de este espacio posibilitó el desarrollo de cierta autonomía en las formas de organización socio-productivas y simbólicas. Ante la expansión de la frontera ganadera, el impuso hidrocarburífero en la región y creciente presencia de nuevas lógicas territoriales crecen las confrontaciones por el desigual acceso a los recursos naturales, por la apropiación del espacio y la construcción de territorialidades. En este marco, el artículo focaliza la mirada en la organización interna de los asentamientos rurales y en los usos sociales de los espacios a través del tiempo, en dos áreas del "extremo" oeste: La Humada y Chos Malal. De este modo se pretende establecer cómo se organizaron diacrónicamente los espacios doméstico, peridoméstico y monte y qué sentidos expresan los sujetos en torno a los espacios de vida y lugares en tiempos de expansión de la frontera productiva. El nuevo campo social generado producto del avance del capitalismo sobre las unidades campesinas se expresa, no sólo en las modificaciones en las formas de manejo del ganado, organización de la producción y construcción social del espacio, sino también en las formas de sociabilidad y estrategias de resistencia colectivas. Este proceso, que se está gestando en la región, tiene un desarrollo similar en otros espacios donde el avance productivo se ha generado con anterioridad o a un ritmo más acelerado. Para la realización de la investigación se articulan diferentes estrategias de metodología cualitativa que combinan el estudio de caso con historias de vida, entrevistas en profundidad y análisis de fuentes documentales.

Holocene sea-surface reconstructions for the Californian margin

Time series of alkenone unsaturation indices gathered along the California margin reveal large (4° to 8°C) glacial-interglacial changes in sea surface temperature (SST) over the past 550,000 years. Interglacial times with SSTs equal to or exceeding that of the Holocene contain peak abundances in the pollen of redwood, the distinctive component of the temperate rainforest of the northwest coast of California. In the region now dominated by the California Current, SSTs warmed 10,000 to 15,000 years in advance of deglaciation at each of the past five glacial maxima. SSTs did not rise in advance of deglaciation south of the modern California Current front. Glacial warming along the California margin therefore is a regional signal of the weakening of the California Current during times when large ice sheets reorganized wind systems over the North Pacific. Both the timing and magnitude of the SST estimates suggest that the Devils Hole (Nevada) calcite record represents regional but not global paleotemperatures, and hence does not pose a fundamental challenge to the orbital ("Milankovitch") theory of the Ice Ages.