Strongly étale difference algebras and Babbitt’s decomposition

We introduce a class of strongly etale difference algebras, whose role in the study of difference equations is analogous to the role of etale algebras in the study of algebraic equations. We deduce an improved version of Babbitt’s decomposition theorem and we present applications to difference algebraic groups and the compatibility problem

WHY LESS IS MORE: AN EYE TRACKING STUDY ON IDEA PRESENTATION AND ATTRIBUTE ATTENDANCE IN IDEA SELECTION

Innovation contests often result in several hundred ideas generated. Raters have to process this huge amount of ideas that consist of attributes like idea descriptions and various types of feedback infor-mation with limited cognitive resources in order to separate good from bad ideas. It is not clear to what extent raters attend the available information during idea selection. In order to improve our un-derstanding of how to best support raters in idea selection, this study investigated the influence of vari-ations of the presentation mode (two versus four ideas per screen) on the attention paid to information on idea attributes using eye-tracking. We investigated attributes that refer to idea descriptions, feed-back about the content of ideas (creativity score, tags) and about the community comprising the idea-tors and the crowd (historical success of the ideator, likes). The results of our study show that with fewer alternatives per screen, feedback attributes received more attendance, while we found no signifi-cant difference for the processing of idea descriptions. These findings provide first insights into the information-processing behaviour of raters and can inform the design of selection platforms and theory building on the effects of feedback in idea selection

Aortomonoiliac Endografting after Failed Endovascular Aneurysm Repair: Indications and Long-term Results

AbstractObjectivesTo present long-term results of endoleak/endograft migration treatment by aortomonoiliac (AMI) endografting after failed endovascular aneurysm repair (EVAR) of infrarenal abdominal aortic aneurysms.DesignPost hoc analysis of a prospectively gathered database at a tertiary care university hospital.Materials and methodsFrom March 1995 to November 2010, 23 patients were identified who underwent modification into AMI configuration after failed elective EVAR. Major causes for modification were type I (with/without endograft migration) or type III endoleaks with aneurysm expansion. An average increase in aneurysm size of 1.6 cm (range: −1.5 to 10.5 cm) since initial aneurysm treatment was observed. Interventional outcomes and long-term results were recorded for analysis.ResultsTechnical success rate of AMI endografting was 95.65% (n = 22). All except two endoleaks could be successfully sealed with this manoeuvre (94.44%). Median time to modification was 5.3 years (interquartile range Q1–Q3: 1.3–9.3 years). No intra-operative conversion to open surgery was necessary and mortality was 0%. Median follow-up was 44 months (interquartile range Q1–Q3: 17–69 months).ConclusionsTreatment of graft-related endoleaks/endograft migration by AMI endografting after failed EVAR represents a safe and feasible procedure. This approach broadens the minimal invasive opportunities of aneurysm treatment, and open surgical conversion may be avoided except in selected patients

Isolated IgG4-related interstitial lung disease: unusual histological and radiological features of a pathologically proven case

IgG4-related lung disease is commonly associated with autoimmune pancreatitis. Recently, isolated IgG4-related interstitial lung disease (ILD) without other organ involvement has newly been reported in two cases with clinical features of nonspecific interstitial pneumonitis (NSIP). We report the first case of an isolated IgG4-related ILD in a 78-year-old man with dry cough and dyspnea, whose clinical findings proved to be different from NSIP. Serum IgG4 levels were increased. Chest CT scan revealed bilateral consolidations especially in the lower lobes, enlarged mediastinal and hilar lymph nodes and pleural effusions. Video-assisted thoracoscopic (VATS) lung biopsy revealed a pattern similar to usual interstitial pneumonia (UIP) and an abundant IgG4-positive plasma cell infiltration. He was effectively treated by steroid therapy. Increasing recognition of IgG4 related diseases has led to a growing number of new entities. The novel concept of isolated IgG4-related ILD as a pulmonary manifestation of a systemic IgG4-related disorder should be taken into account as a possible differential diagnosis of ILD and mass-forming lesions, even when no other organ manifestation is clinically apparent at the time of diagnosis. Lung specific diagnostic criteria and algorithms are required to enhance diagnostic accuracy in cases of possible IgG4-related ILD

Cryoprobe biopsy increases the diagnostic yield in endobronchial tumor lesions

ObjectiveForceps biopsy is the standard method to obtain specimens in endoscopically visible lesions. It is common to combine forceps biopsy with cytology methods to increase the diagnostic yield. Although the flexible cryoprobe has been established for bronchoscopic interventions in malignant stenosis, the obtained biopsies, called “cryobiopsies,” have not been investigated in a large cohort of patients. The aim of this feasibility study was to prospectively evaluate the diagnostic yield and safety of cryobiopsy and forceps biopsy.MethodsDuring a 6-year period, 296 patients with visible endoluminal tumor lesions were included in the study at the bronchoscopy unit of a university hospital. In the first consecutively conducted 55 cases, both techniques, forceps biopsy and cryobiopsy, were applied simultaneously. Pathologic and quantitative image analyses were performed to evaluate the size and quality of the obtained specimens. We evaluated the safety and diagnostic yield to describe the feasibility of cryobiopsy.ResultsComparative analysis of the first conducted and randomly assigned 55 cases revealed a significantly higher diagnostic yield for cryobiopsy compared with forceps biopsy (89.1% vs 65.5%, P < .05). In this cohort, quantitative image analysis showed significantly larger biopsies regarding size and artifact-free tissue sections for cryobiopsy compared with forceps biopsy (P < .0001). The overall diagnostic yield of cryobiopsy was 89.5%. Mild bleeding occurred in 11 cases (3.7%), moderate bleeding occurred in 3 cases (1.0%), and severe bleeding occurred in 1 case (0.3%).ConclusionCryobiopsy is safe and increases the diagnostic yield in endobronchial tumor lesions. The method also is feasible under routine conditions

Serum sclerostin levels in renal cell carcinoma patients with bone metastases

Sclerostin has been proposed as a potent inhibitor of bone formation. Sclerostin antibodies are under clinical development to treat osteoporosis and metastatic bone disease. Serum sclerostin level is elevated in multiple myeloma, an osteolytic malignancy, where it might serve as predictive marker for the use of sclerostin-directed antibodies. As renal cell carcinoma (RCC) patients often present with osteolytic metastases, we aimed to investigate serum sclerostin levels in RCC patients. Our study included 53 RCC patients (19 with bone metastases, 25 with visceral metastases and 9 with localized disease) and 53 age- and gender-matched non-osteoporotic controls. Frozen serum samples were subjected to sclerostin quantitative sandwich ELISA. The mean serum sclerostin levels of RCC patients and controls were 45.8 pmol/l and 45.1 pmol/l, respectively (p = 0.86). Analysis of variance showed no difference between the subgroups of RCC patients with regard to visceral or bone metastases or localized disease (p = 0.22). There was no significant association between eGFR (estimated glomerular filtration rate) and serum sclerostin levels in RCC patients (r = 0.05; p = 0.74) and controls (r = 0.06; p = 0.68). Our results indicate that serum sclerostin levels appear not to be a valuable biomarker to assess the occurrence of bone metastases in RCC patients

Chemical Functionalization and Characterization of Graphene-based Materials

Graphene-based materials (GBMs), with graphene, their most known member, at the head, constitute a large family of materials which has aroused the interest of scientists working in different research fields such as chemistry, physics, or materials science, to mention a few, arguably as no other material before. In this review, we offer a general overview on the most relevant synthetic approaches for the covalent and non-covalent functionalization and characterization of GBMs. Moreover, some representative examples of the incorporation into GBMs of electroactive units such as porphyrins, phthalocyanines, or ferrocene, among others, affording electron donor–acceptor (D–A) hybrids are presented. For the latter systems, the photophysical characterization of their ground- and excited-state features has also been included, paying particular attention to elucidate the fundamental dynamics of the energy transfer and charge separation processes of these hybrids. For some of the presented architectures, their application in solar energy conversion schemes and energy production has been also discussed

Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape

A comprehensive understanding of the regions on HIV-1 envelope trimers targeted by broadly neutralizing antibodies may contribute to rational design of an HIV-1 vaccine. We previously identified a participant in the CAPRISA cohort, CAP248, who developed trimer-specific antibodies capable of neutralizing 60% of heterologous viruses at three years post-infection. Here, we report the isolation by B cell culture of monoclonal antibody CAP248-2B, which targets a novel membrane proximal epitope including elements of gp120 and gp41. Despite low maximum inhibition plateaus, often below 50% inhibitory concentrations, the breadth of CAP248-2B significantly correlated with donor plasma. Site-directed mutagenesis, X-ray crystallography, and negative-stain electron microscopy 3D reconstructions revealed how CAP248-2B recognizes a cleavage-dependent epitope that includes the gp120 C terminus. While this epitope is distinct, it overlapped in parts of gp41 with the epitopes of broadly neutralizing antibodies PGT151, VRC34, 35O22, 3BC315, and 10E8. CAP248-2B has a conformationally variable paratope with an unusually long 19 amino acid light chain third complementarity determining region. Two phenylalanines at the loop apex were predicted by docking and mutagenesis data to interact with the viral membrane. Neutralization by CAP248-2B is not dependent on any single glycan proximal to its epitope, and low neutralization plateaus could not be completely explained by N- or O-linked glycosylation pathway inhibitors, furin co-transfection, or pre-incubation with soluble CD4. Viral escape from CAP248-2B involved a cluster of rare mutations in the gp120-gp41 cleavage sites. Simultaneous introduction of these mutations into heterologous viruses abrogated neutralization by CAP248-2B, but enhanced neutralization sensitivity to 35O22, 4E10, and 10E8 by 10-100-fold. Altogether, this study expands the region of the HIV-1 gp120-gp41 quaternary interface that is a target for broadly neutralizing antibodies and identifies a set of mutations in the gp120 C terminus that exposes the membrane-proximal external region of gp41, with potential utility in HIV vaccine design

Identification of broadly neutralizing antibody epitopes in the HIV-1 envelope glycoprotein using evolutionary models

Background: Identification of the epitopes targeted by antibodies that can neutralize diverse HIV-1 strains can provide important clues for the design of a preventative vaccine. Methods: We have developed a computational approach that can identify key amino acids within the HIV-1 envelope glycoprotein that influence sensitivity to broadly cross-neutralizing antibodies. Given a sequence alignment and neutralization titers for a panel of viruses, the method works by fitting a phylogenetic model that allows the amino acid frequencies at each site to depend on neutralization sensitivities. Sites at which viral evolution influences neutralization sensitivity were identified using Bayes factors (BFs) to compare the fit of this model to that of a null model in which sequences evolved independently of antibody sensitivity. Conformational epitopes were identified with a Metropolis algorithm that searched for a cluster of sites with large Bayes factors on the tertiary structure of the viral envelope. Results: We applied our method to ID50 neutralization data generated from seven HIV-1 subtype C serum samples with neutralization breadth that had been tested against a multi-clade panel of 225 pseudoviruses for which envelope sequences were also available. For each sample, between two and four sites were identified that were strongly associated with neutralization sensitivity (2ln(BF) > 6), a subset of which were experimentally confirmed using site-directed mutagenesis. Conclusions: Our results provide strong support for the use of evolutionary models applied to cross-sectional viral neutralization data to identify the epitopes of serum antibodies that confer neutralization breadth