Naturally occurring antibodies/autoantibodies in polyclonal immunoglobulin concentrates

It was a long way from the use of hyperimmune animal sera for the treatment of toxin-producing infections to the production of polyclonal, polyspecific human immunoglobulin preparations and the use of NAbs as therapeutic tools for autoimmune and inflammatory diseases. Some highlights of the development of knowledge in blood fractionation techniques, basic science and clinical wisdom are reviewed in this chapter. Proudly we mention the outstanding contribution of Swiss scientists and clinicians in the development of IVIG as clinical tool for some otherwise untreatable diseases or taking advantage of its low adverse event profile in long-term treatment of other chronic autoimmune and inflammatory diseases. This chapter summarizes some of the characteristics and the effects in humans of NAbs which are present in IgG concentrates. We call attention to the fact that the human data remain, at least in part, incomplete, among others because even with the most efficient large-scale techniques available not more than approximately 50% of the total IgG in plasma can be fractionated into an immunoglobulin G concentrate.

Learning styles vary among general surgery residents: analysis of 12 years of data

PURPOSE: Understanding the learning styles of individuals may assist in the tailoring of an educational program to optimize learning. General surgery faculty and residents have been characterized previously as having a tendency toward particular learning styles. We seek to understand better the learning styles of general surgery residents and differences that may exist within the population. METHODS: The Kolb Learning Style Inventory was administered yearly to general surgery residents at the University of Cincinnati from 1994 to 2006. This tool allows characterization of learning styles into 4 groups: converging, accommodating, assimilating, and diverging. The converging learning style involves education by actively solving problems. The accommodating learning style uses emotion and interpersonal relationships. The assimilating learning style learns by abstract logic. The diverging learning style learns best by observation. Chi-square analysis and analysis of variance were performed to determine significance. RESULTS: Surveys from 1994 to 2006 (91 residents, 325 responses) were analyzed. The prevalent learning style was converging (185, 57%), followed by assimilating (58, 18%), accommodating (44, 14%), and diverging (38, 12%). At the PGY 1 and 2 levels, male and female residents differed in learning style, with the accommodating learning style being relatively more frequent in women and assimilating learning style more frequent in men (Table 1, p < or = 0.001, chi-square test). Interestingly, learning style did not seem to change with advancing PGY level within the program, which suggests that individual learning styles may be constant throughout residency training. If a resident's learning style changed, it tended to be to converging. In addition, no relation exists between learning style and participation in dedicated basic science training or performance on the ABSIT/SBSE. CONCLUSIONS: Our data suggests that learning style differs between male and female general surgery residents but not with PGY level or ABSIT/SBSE performance. A greater understanding of individual learning styles may allow more refinement and tailoring of surgical programs.

The Oklahoma Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome Registry: the Swiss connection

OBJECTIVES: Thrombotic thrombocytopenic purpura (TTP) was initially described as an uncommon and usually fatal disorder. With effective treatment it is more frequently diagnosed, the clinical presentations are more diverse, and long-term sequelae are becoming recognized. METHODS: Patient data are from The Oklahoma TTP-hemolytic uremic syndrome (HUS) Registry, an inception cohort of 348 consecutive patients with their first episode of clinically diagnosed TTP or HUS, 1989-2006. The Registry enrolls all patients in a defined region who are diagnosed with TTP or HUS and for whom plasma exchange treatment is requested. ADAMTS13 activity has been analyzed on 235 (93%) of 254 patients since 1995 at the University of Berne, Switzerland. Patients are described by clinical categories, related to their associated conditions and clinically apparent etiologies, and by the presence of severe ADAMTS13 deficiency. RESULTS AND CONCLUSIONS: The clinical spectrum of syndromes described as TTP is variable with multiple etiologies. Advances in clinical and laboratory investigation have provided better understanding of the pathogenesis of these syndromes, their clinical evaluation and management, and their long-term outcomes. In addition to new information about TTP, these studies provide a model for translational research to define the complete community spectrum of uncommon disorders.

Cell replacement therapy for intracerebral hemorrhage

Intracerebral hemorrhage (ICH), for which no effective treatment strategy is currently available, constitutes one of the most devastating forms of stroke. As a result, developing therapeutic options for ICH is of great interest to the medical community. The 3 potential therapies that have the most promise are cell replacement therapy, enhancing endogenous repair mechanisms, and utilizing various neuroprotective drugs. Replacement of damaged cells and restoration of function can be accomplished by transplantation of cells derived from different sources, such as embryonic or somatic stem cells, umbilical cord blood, and genetically modified cell lines. Early experimental data showing the benefits of cell transplantation on functional recovery after ICH have been promising. Nevertheless, several studies have focused on another therapeutic avenue, investigating novel ways to activate and direct endogenous repair mechanisms in the central nervous system, through exposure to specific neuronal growth factors or by inactivating inhibitory molecules. Lastly, neuroprotective drugs may offer an additional tool for improving neuronal survival in the perihematomal area. However, a number of scientific issues must be addressed before these experimental techniques can be translated into clinical therapy. In this review, the authors outline the recent advances in the basic science of treatment strategies for ICH.

Neer Award 2007: Reversion of structural muscle changes caused by chronic rotator cuff tears using continuous musculotendinous traction. An experimental study in sheep

HYPOTHESIS: Chronic rotator cuff tears are associated with irreversible architectural muscle changes and a high rate of repair failure. The changes observed in man and their irreversibility with a single stage repair can be reproduced in sheep. It was the purpose of this experiment to test the hypothesis that slow, continuous elongation of a retracted musculotendinous unit allows reversal of the currently irreversible structural muscle changes. MATERIALS AND METHODS: The infraspinatus tendon of 12 sheep was released using a greater tuberosity osteotomy and allowed to retract for 4 months. Then, a new device was mounted on the scapular spine and used to extend the infraspinatus muscuculotendinous unit transcutaneously by 1 mm per day. Thereafter, the tendon was repaired back to the greater tuberosity. We assessed the muscular architecture using magnetic resonance imaging, macroscopic dissection, histology, and electron microscopy. Fatty infiltration (in Hounsfield units 1/4 HU) and muscular cross-sectional area (in % of the control side) were monitored with computed tomography at tendon release, initiation of elongation, repair, and at sacrifice. RESULTS: Sixteen weeks after tendon release, the mean tendon retraction was 29 +/- 6 mm (14% of original length, P = .008). In 8 sheep, elongation was achieved as planned (group I), but in 4, the elongation failed technically (group II). The mean traction time was 24 +/- 6 days with a mean traction distance of 19 +/- 4 mm. At sacrifice, the mean pennation angle in the infraspinatus of group I was not different from the control side (29.8 degrees +/-7.5 degrees vs. 30 degrees +/-6 degrees , P = .575). In group II, the pennation angle had increased from 30 degrees +/-6 degrees to 55 degrees +/-14 degrees (P = .035). There was no fatty infiltration at the time of tendon release. After retraction, there was a significant increase in fatty infiltration of the infraspinatus muscle and a decrease of its cross-sectional area to 57% of the contralateral side (P = .0001). During traction, the degree of fatty infiltration remained unchanged (36 HU to 38 HU, P = .381), and atrophy improved to a muscle square area of 78% of the contralateral side (P = .0001) in group I. In group II, an increase of fatty infiltration was measured from 36 HU to 28 HU; however, this increase was not significant (P = .144). Atrophy did not change in group II (57-55%, P = .946). At sacrifice, the remaining muscle mass was 64% in group I and 46% in group II (P = .019). DISCUSSION: Our preliminary results document, that continuous elongation of a retracted, fatty infiltrated and atrophied musculotendinous unit is technically feasible. CONCLUSION: In the sheep, continuous elongation can lead to restoration of normal muscle architecture, to partial reversal of muscle atrophy, and to arrest of the progression of fatty infiltration. LEVEL OF EVIDENCE: Basic science level 2; Prospective comparative therapeutic study.

Probing the function of ionotropic and G protein-coupled receptors in surface-confined membranes

This article reports on recent electrical and optical techniques for investigating cellular signaling reactions in artificial and native membranes immobilized on solid supports. The first part describes the formation of planar artificial lipid bilayers on gold electrodes, which reveal giga-ohm electrical resistance and the insertion and characterization of ionotropic receptors therein. These membranes are suited to record a few or even single ion channels by impedance spectroscopy. Such tethered membranes on planar arrays of microelectrodes offer mechanically robust, long-lasting measuring devices to probe the influence of different chemistries on biologically important ionotropic receptors and therefore will have a future impact to probe the function of channel proteins in basic science and in biosensor applications. In a second part, we present complementary approaches to form inside-out native membrane sheets that are immobilized on micrometer-sized beads or across submicrometer-sized holes machined in a planar support. Because the native membrane sheets are plasma membranes detached from live cells, these approaches offer a unique possibility to investigate cellular signaling processes, such as those mediated by ionotropic or G protein-coupled receptors, with original composition of lipids and proteins.

A Critical Response to Kevin Stenson’s Governing the Local: Sovereignty, Social Governance and Community Safety

In his compelling case study of local governance and community safety in the UK Thames Valley, Kevin Stenson makes several important contributions to the field of governmentality studies. While the paper’s merits are far-reaching, to this reader’s assessment they can be summarized in the following key areas: 1) Empirically, the article enhances our knowledge of the political economic transformation of a region otherwise overlooked in social science research ; 2) Conceptually, Stenson offers several theoretical and analytical refrains that, while becoming increasingly commonplace, are nonetheless still germane and rightly oriented to offer push back against otherwise totalizing, reified accounts of roll back/roll out neoliberalism. A welcomed new approach is offered as a corrective, The Realist Governmentality perspective, which emphasizes the interrelated and co-constitutive nature of politics, local culture, and habitus in processes related to the restructuring of social governance; 3) Methodologically, the paper makes a pitch for the ways in which finely grained, nuanced, mixed-method/ethnographic analyses have the potential to further problematize and recast a field of governmentality studies far too often dominated by discursive and textual approaches.

Autorenwerkzeuge für digitale, multimediale und interaktive Lernbausteine im Web 2.0

Die vorliegende Forschungsarbeit siedelt sich im Dreieck der Erziehungswissenschaften, der Informatik und der Schulpraxis an und besitzt somit einen starken interdisziplinären Charakter. Aus Sicht der Erziehungswissenschaften handelt es sich um ein Forschungsprojekt aus den Bereichen E-Learning und Multimedia Learning und der Fragestellung nach geeigneten Informatiksystemen für die Herstellung und den Austausch von digitalen, multimedialen und interaktiven Lernbausteinen. Dazu wurden zunächst methodisch-didaktische Vorteile digitaler Lerninhalte gegenüber klassischen Medien wie Buch und Papier zusammengetragen und mögliche Potentiale im Zusammenhang mit neuen Web 2.0-Technologien aufgezeigt. Darauf aufbauend wurde für existierende Autorenwerkzeuge zur Herstellung digitaler Lernbausteine und bestehende Austauschplattformen analysiert, inwieweit diese bereits Web 2.0-Technologien unterstützen und nutzen. Aus Sicht der Informatik ergab sich aus der Analyse bestehender Systeme ein Anforderungsprofil für ein neues Autorenwerkzeug und eine neue Austauschplattform für digitale Lernbausteine. Das neue System wurde nach dem Ansatz des Design Science Research in einem iterativen Entwicklungsprozess in Form der Webapplikation LearningApps.org realisiert und stetig mit Lehrpersonen aus der Schulpraxis evaluiert. Bei der Entwicklung kamen aktuelle Web-Technologien zur Anwendung. Das Ergebnis der Forschungsarbeit ist ein produktives Informatiksystem, welches bereits von tausenden Nutzern in verschiedenen Ländern sowohl in Schulen als auch in der Wirtschaft eingesetzt wird. In einer empirischen Studie konnte das mit der Systementwicklung angestrebte Ziel, die Herstellung und den Austausch von digitalen Lernbausteinen zu vereinfachen, bestätigt werden. Aus Sicht der Schulpraxis liefert LearningApps.org einen Beitrag zur Methodenvielfalt und zur Nutzung von ICT im Unterricht. Die Ausrichtung des Werkzeugs auf mobile Endgeräte und 1:1-Computing entspricht dem allgemeinen Trend im Bildungswesen. Durch die Verknüpfung des Werkzeugs mit aktuellen Software-Entwicklungen zur Herstellung von digitalen Schulbüchern werden auch Lehrmittelverlage als Zielgruppe angesprochen.

Epigenetic diversity increases the productivity and stability of plant populations

Biological diversity within species can be an important driver of population and ecosystem functioning. Until now, such within-species diversity effects have been attributed to underlying variation in DNA sequence. However, within-species differences, and thus potentially functional biodiversity, can also be created by epigenetic variation. Here, we show that epigenetic diversity increases the productivity and stability of plant populations. Epigenetically diverse populations of Arabidopsis thaliana produce up to 40% more biomass than epigenetically uniform populations. The positive epigenetic diversity effects are strongest when populations are grown together with competitors and infected with pathogens, and they seem to be partly driven by complementarity among epigenotypes. Our study has two implications: first, we may need to re-evaluate previous within-species diversity studies where some effects could reflect epigenetic diversity; second, we need to incorporate epigenetics into basic ecological research, by quantifying natural epigenetic diversity and testing for its ecological consequences across many different species.

Tenocytes of chronic rotator cuff tendon tears can be stimulated by platelet-released growth factors

BACKGROUND Bone-to-tendon healing after rotator cuff repairs is mainly impaired by poor tissue quality. The tenocytes of chronic rotator cuff tendon tears are not able to synthesize normal fibrocartilaginous extracellular matrix (ECM). We hypothesized that in the presence of platelet-released growth factors (PRGF), tenocytes from chronically retracted rotator cuff tendons proliferate and synthesize the appropriate ECM proteins. MATERIALS AND METHODS Tenocytes from 8 patients with chronic rotator cuff tears were cultured for 4 weeks in 2 different media: standard medium (Iscove's Modified Dulbecco's Media + 10% fetal calf serum + 1% nonessential amino acids + 0.5 μg/mL ascorbic acid) and media with an additional 10% PRGF. Cell proliferation was assessed at 7, 14, 21, and 28 days. Messenger (m)RNA levels of collagens I, II, and X, decorin, biglycan, and aggrecan were analyzed using real time reverse-transcription polymerase chain reaction. Immunocytochemistry was also performed. RESULTS The proliferation rate of tenocytes was significantly higher at all time points when cultured with PRGF. At 21 days, the mRNA levels for collagens I, II, and X, decorin, aggrecan, and biglycan were significantly higher in the PRGF group. The mRNA data were confirmed at protein level by immunocytochemistry. CONCLUSIONS PRGFs enhance tenocyte proliferation in vitro and promote synthesis of ECM to levels similar to those found with insertion of the normal human rotator cuffs. CLINICAL RELEVANCE Biologic augmentation of repaired rotator cuffs with PRGF may enhance the properties of the repair tissue. However, further studies are needed to determine if application of PRGF remains safe and effective in long-term clinical studies. LEVEL OF EVIDENCE Basic Science Study, Cell Biology.

Political Depolarization in German Public Opinion, 1980–2010

Little is known about political polarization in German public opinion. This article offers an issue-based perspective and explores trends of opinion polarization in Germany. Public opinion polarization is conceptualized and measured as alignment of attitudes. Data from the German General Social Survey (1980 to 2010) comprise attitudes towards manifold issues, which are classified into several dimensions. This study estimates multilevel models that reveal general and issue- as well as dimension-specific levels and trends in attitude alignment for both the whole German population and sub-groups. It finds that public opinion polarization has decreased over the last three decades in Germany. In particular, highly educated and more politically interested people have become less polarized over time. However, polarization seems to have increased in attitudes regarding gender issues. These findings provide interesting contrasts to existing research on the American public.

How large are actor and partner effects of personality on relationship satisfaction? The importance of controlling for shared method variance

Previous research suggests that the personality of a relationship partner predicts not only the individual’s own satisfaction with the relationship but also the partner’s satisfaction. Based on the actor–partner interdependence model, the present research tested whether actor and partner effects of personality are biased when the same method (e.g., self-report) is used for the assessment of personality and relationship satisfaction and, consequently, shared method variance is not controlled for. Data came from 186 couples, of whom both partners provided self- and partner reports on the Big Five personality traits. Depending on the research design, actor effects were larger than partner effects (when using only self-reports), smaller than partner effects (when using only partner reports), or of about the same size as partner effects (when using self- and partner reports). The findings attest to the importance of controlling for shared method variance in dyadic data analysis.