Passive transfer of IgG anti-GM1 antibodies impairs peripheral nerve repair.

Anti-GM1 antibodies are present in some patients with autoimmune neurological disorders. These antibodies are most frequently associated with acute immune neuropathy called Guillain-Barré syndrome (GBS). Some clinical studies associate the presence of these antibodies with poor recovery in GBS. The patients with incomplete recovery have failure of nerve repair, particularly axon regeneration. Our previous work indicates that monoclonal antibodies can inhibit axon regeneration by engaging cell surface gangliosides (Lehmann et al., 2007). We asked whether passive transfer of human anti-GM1 antibodies from patients with GBS modulate axon regeneration in an animal model. Human anti-GM1 antibodies were compared with other GM1 ligands, cholera toxin B subunit and a monoclonal anti-GM1 antibody. Our results show that patient derived anti-GM1 antibodies and cholera toxin beta subunit impair axon regeneration/repair after PNS injury in mice. Comparative studies indicated that the antibody/ligand-mediated inhibition of axon regeneration is dependent on antibody/ligand characteristics such as affinity-avidity and fine specificity. These data indicate that circulating immune effectors such as human autoantibodies, which are exogenous to the nervous system, can modulate axon regeneration/nerve repair in autoimmune neurological disorders such as GBS.

The Oxytricha trifallax macronuclear genome: a complex eukaryotic genome with 16,000 tiny chromosomes.

The macronuclear genome of the ciliate Oxytricha trifallax displays an extreme and unique eukaryotic genome architecture with extensive genomic variation. During sexual genome development, the expressed, somatic macronuclear genome is whittled down to the genic portion of a small fraction (∼5%) of its precursor "silent" germline micronuclear genome by a process of "unscrambling" and fragmentation. The tiny macronuclear "nanochromosomes" typically encode single, protein-coding genes (a small portion, 10%, encode 2-8 genes), have minimal noncoding regions, and are differentially amplified to an average of ∼2,000 copies. We report the high-quality genome assembly of ∼16,000 complete nanochromosomes (∼50 Mb haploid genome size) that vary from 469 bp to 66 kb long (mean ∼3.2 kb) and encode ∼18,500 genes. Alternative DNA fragmentation processes ∼10% of the nanochromosomes into multiple isoforms that usually encode complete genes. Nucleotide diversity in the macronucleus is very high (SNP heterozygosity is ∼4.0%), suggesting that Oxytricha trifallax may have one of the largest known effective population sizes of eukaryotes. Comparison to other ciliates with nonscrambled genomes and long macronuclear chromosomes (on the order of 100 kb) suggests several candidate proteins that could be involved in genome rearrangement, including domesticated MULE and IS1595-like DDE transposases. The assembly of the highly fragmented Oxytricha macronuclear genome is the first completed genome with such an unusual architecture. This genome sequence provides tantalizing glimpses into novel molecular biology and evolution. For example, Oxytricha maintains tens of millions of telomeres per cell and has also evolved an intriguing expansion of telomere end-binding proteins. In conjunction with the micronuclear genome in progress, the O. trifallax macronuclear genome will provide an invaluable resource for investigating programmed genome rearrangements, complementing studies of rearrangements arising during evolution and disease.

Reliability and quality of water isotope data collected with a lowbudget rain collector

RATIONALELow-budget rain collectors for water isotope analysis, such as the `ball-in-funnel type collector' (BiFC), are widely used in studies on stable water isotopes of rain. To date, however, an experimental quality assessment of such devices in relation to climatic factors does not exist. METHODSWe used Cavity Ring-Down Spectrometry (CRDS) to quantify the effects of evaporation on the O-18 values of reference water under controlled conditions as a function of the elapsed time between rainfall and collection for isotope analysis, the sample volume and the relative humidity (RH: 31% and 67%; 25 degrees C). The climate chamber conditions were chosen to reflect the warm and dry end of field conditions that favor evaporative enrichment (EE). We also tested the performance of the BiFC in the field, and compared our H-2/O-18 data obtained by isotope ratio mass spectrometry (IRMS) with those from the Swiss National Network for the Observation of Isotopes in the Water Cycle (ISOT). RESULTSThe EE increased with time, with a 1 increase in the O-18 values after 10days (RH: 25%; 25 degrees C; 35mL (corresponding to a 5mm rain event); p <0.001). The sample volume strongly affected the EE (max. value +1.5 parts per thousand for 7mL samples (i.e., 1mm rain events) after 72h at 31% and 67% RH; p <0.001), whereas the relative humidity had no significant effect. Using the BiFC in the field, we obtained very tight relationships of the H-2/O-18 values (r(2) 0.95) for three sites along an elevational gradient, not significantly different from that of the next ISOT station. CONCLUSIONSSince the chosen experimental conditions were extreme compared with the field conditions, it was concluded that the BiFC is a highly reliable and inexpensive collector of rainwater for isotope analysis. Copyright (c) 2014 John Wiley & Sons, Ltd.

Modern judaism : or, a brief account of the opinions, traditions, rites and ceremonies of the Jews in modern times

by John Allen

Varia capita & dissertationes aliaque autoris supplementa

praemittitur Christoph. Matthaei Pfaffii

De legibus Hebraeorum ritualibus, et earum rationibus : libri tres

authore Joanne Spencero

De legibus hebraeorum ritualibus earumque rationibus

Johanni Spenceri

How Do Gastroenterologists Assess Overall Activity of Eosinophilic Esophagitis in Adult Patients?

OBJECTIVES:There is no "gold standard" for assessing disease activity in patients with eosinophilic esophagitis (EoE). We aimed to compare physicians' judgment of EoE activity with patients' judgment of symptom severity. We also aimed to examine the relative contribution of symptoms as well as endoscopic and histologic findings in shaping physicians' judgment of EoE activity.METHODS:Six gastroenterologists (all EoE experts) assessed EoE-associated symptoms in adult patients. Patients completed a symptom instrument and provided global assessment of EoE symptom severity (PatGA) (Likert scale: 0 (inactive) to 10 (most active)). Following esophagogastroduodenoscopy with biopsy sampling, gastroenterologists provided a global assessment of EoE activity (PhysGA) (Likert scale from 0 to 10) based on patient history and endoscopic and histologic findings. Linear regression and analysis of variance was used to quantify the extent to which variations in severity of EoE symptoms and endoscopic and histologic findings explain variations in PhysGA.RESULTS:A total of 149 EoE patients were prospectively included (71.8% male, median age at inclusion 38 years, 71.8% with concomitant allergies). A moderate positive correlation between PhysGA and PatGA (rho=0.442, P<0.001) was observed and the mean difference in the Bland-Altman plot was 1.77. Variations in severity of endoscopic findings, symptoms, and histologic findings alone explained 53%, 49%, and 30%, of the variability in PhysGA, respectively. Together, these findings explained 75% of variability in PhysGA.CONCLUSIONS:Gastroenterologists rate EoE activity mainly on the basis of endoscopic findings and symptoms and, to a lesser extent, on histologic findings.Am J Gastroenterol advance online publication, 3 March 2015; doi:10.1038/ajg.2015.32.

Multidisciplinary consensus on assessment of unruptured intracranial aneurysms: proposal of an international research group.

BACKGROUND AND PURPOSE To address the increasing need to counsel patients about treatment indications for unruptured intracranial aneurysms (UIA), we endeavored to develop a consensus on assessment of UIAs among a group of specialists from diverse fields involved in research and treatment of UIAs. METHODS After composition of the research group, a Delphi consensus was initiated to identify and rate all features, which may be relevant to assess UIAs and their treatment by using ranking scales and analysis of inter-rater agreement (IRA) for each factor. IRA was categorized as very high, high, moderate, or low. RESULTS Ultimately, 39 specialists from 4 specialties agreed (high or very high IRAs) on the following key factors for or against UIA treatment decisions: (1) patient age, life expectancy, and comorbid diseases; (2) previous subarachnoid hemorrhage from a different aneurysm, family history for UIA or subarachnoid hemorrhage, nicotine use; (3) UIA size, location, and lobulation; (4) UIA growth or de novo formation on serial imaging; (5) clinical symptoms (cranial nerve deficit, mass effect, and thromboembolic events from UIAs); and (6) risk factors for UIA treatment (patient age and life expectancy, UIA size, and estimated risk of treatment). However, IRAs for features rated with low relevance were also generally low, which underlined the existing controversy about the natural history of UIAs. CONCLUSIONS Our results highlight that neurovascular specialists currently consider many features as important when evaluating UIAs but also highlight that the appreciation of natural history of UIAs remains uncertain, even within a group of highly informed individuals.

Improving the dependability of research in personality and social psychology: Recommendations for research and educational practice

In this article, the Society for Personality and Social Psychology (SPSP) Task Force on Publication and Research Practices offers a brief statistical primer and recommendations for improving the dependability of research. Recommendations for research practice include (a) describing and addressing the choice of N (sample size) and consequent issues of statistical power, (b) reporting effect sizes and 95% confidence intervals (CIs), (c) avoiding “questionable research practices” that can inflate the probability of Type I error, (d) making available research materials necessary to replicate reported results, (e) adhering to SPSP’s data sharing policy, (f) encouraging publication of high-quality replication studies, and (g) maintaining flexibility and openness to alternative standards and methods. Recommendations for educational practice include (a) encouraging a culture of “getting it right,” (b) teaching and encouraging transparency of data reporting, (c) improving methodological instruction, and (d) modeling sound science and supporting junior researchers who seek to “get it right.”

Staatsverfassung der Israeliten

von Karl Dietrich Hüllmann

Neural correlates of wishful thinking.

Wishful thinking (WT) implies the overestimation of the likelihood of desirable events. It occurs for outcomes of personal interest, but also for events of interest to others we like. We investigated whether WT is grounded on low-level selective attention or on higher level cognitive processes including differential weighting of evidence or response formation. Participants in our MRI study predicted the likelihood that their favorite or least favorite team would win a football game. Consistent with expectations, favorite team trials were characterized by higher winning odds. Our data demonstrated activity in a cluster comprising parts of the left inferior occipital and fusiform gyri to distinguish between favorite and least favorite team trials. More importantly, functional connectivities of this cluster with the human reward system were specifically involved in the type of WT investigated in our study, thus supporting the idea of an attention bias generating WT. Prefrontal cortex activity also distinguished between the two teams. However, activity in this region and its functional connectivities with the human reward system were altogether unrelated to the degree of WT reflected in the participants' behavior and may rather be related to social identification, ensuring the affective context necessary for WT to arise.

Symptoms Have Modest Accuracy in Detecting Endoscopic and Histologic Remission in Adults With Eosinophilic Esophagitis.

BACKGROUND & AIMS It is not clear whether symptoms alone can be used to estimate the biologic activity of eosinophilic esophagitis (EoE). We aimed to evaluate whether symptoms can be used to identify patients with endoscopic and histologic features of remission. METHODS Between April 2011 and June 2014, we performed a prospective, observational study and recruited 269 consecutive adults with EoE (67% male; median age, 39 years old) in Switzerland and the United States. Patients first completed the validated symptom-based EoE activity index patient-reported outcome instrument and then underwent esophagogastroduodenoscopy with esophageal biopsy collection. Endoscopic and histologic findings were evaluated with a validated grading system and standardized instrument, respectively. Clinical remission was defined as symptom score <20 (range, 0-100); histologic remission was defined as a peak count of <20 eosinophils/mm(2) in a high-power field (corresponds to approximately <5 eosinophils/median high-power field); and endoscopic remission as absence of white exudates, moderate or severe rings, strictures, or combination of furrows and edema. We used receiver operating characteristic analysis to determine the best symptom score cutoff values for detection of remission. RESULTS Of the study subjects, 111 were in clinical remission (41.3%), 79 were in endoscopic remission (29.7%), and 75 were in histologic remission (27.9%). When the symptom score was used as a continuous variable, patients in endoscopic, histologic, and combined (endoscopic and histologic remission) remission were detected with area under the curve values of 0.67, 0.60, and 0.67, respectively. A symptom score of 20 identified patients in endoscopic remission with 65.1% accuracy and histologic remission with 62.1% accuracy; a symptom score of 15 identified patients with both types of remission with 67.7% accuracy. CONCLUSIONS In patients with EoE, endoscopic or histologic remission can be identified with only modest accuracy based on symptoms alone. At any given time, physicians cannot rely on lack of symptoms to make assumptions about lack of biologic disease activity in adults with EoE. ClinicalTrials.gov, Number: NCT00939263.

Poly-N-acetyl glucosamine nanofibers for negative-pressure wound therapies

The wound healing promoting effect of negative wound pressure therapies (NPWT) takes place at the wound interface. The use of bioactive substances at this site represents a major research area for the development of future NPWT therapies. To assess wound healing kinetics in pressure ulcers treated by NPWT with or without the use of a thin interface membrane consisting of poly-N-acetyl glucosamine nanofibers (sNAG) a prospective randomized clinical trial was performed. The safety of the combination of NPWT and sNAG was also assessed in patients treated with antiplatelet drugs. In the performed study, the combination of NPWT and sNAG in 10 patients compared to NPWT alone in 10 patients promoted wound healing due to an improved contraction of the wound margins (p = 0.05) without a change in wound epithelization. In 6 patients treated with antiplatelet drugs no increased wound bleeding was observed in patients treated by NPWT and sNAG. In conclusion, the application of thin membranes of sNAG nanofibers at the wound interface using NPWT was safe and augmented the action of NPWT leading to improved wound healing due to a stimulation of wound contraction.