Follicular dendritic-like cells derived from human monocytes

BACKGROUND: Follicular dendritic cells (FDCs) play a central role in controlling B-cell response maturation, isotype switching and the maintenance of B-cell memory. These functions are based on prolonged preservation of antigen and its presentation in its native form by FDCs. However, when entrapping entire pathogens, FDCs can turn into dangerous long-term reservoirs that may preserve viruses or prions in highly infectious form. Despite various efforts, the ontogeny of FDCs has remained elusive. They have been proposed to derive either from bone marrow stromal cells, myeloid cells or local mesenchymal precursors. Still, differentiating FDCs from their precursors in vitro may allow addressing many unsolved issues associated with the (patho-) biology of these important antigen-presenting cells. The aim of our study was to demonstrate that FDC-like cells can be deduced from monocytes, and to develop a protocol in order to quantitatively generate them in vitro. RESULTS: Employing highly purified human monocytes as a starter population, low concentrations of Il-4 (25 U/ml) and GM-CSF (3 U/ml) in combination with Dexamethasone (Dex) (0.5 μM) in serum-free medium trigger the differentiation into FDC-like cells. After transient de-novo membrane expression of alkaline phosphatase (AP), such cells highly up-regulate surface expression of complement receptor I (CD35). Co-expression of CD68 confirms the monocytic origin of both, AP(pos )and CD35(pos )cells. The common leukocyte antigen CD45 is strongly down-regulated. Successive stimulation with TNF-α up-regulates adhesion molecules ICAM-1 (CD54) and VCAM (CD106). Importantly, both, AP(pos )as well as AP(neg )FDC-like cells, heterotypically cluster with and emperipolese B cells and exhibit the FDC characteristic ability to entrap functionally preserved antigen for prolonged times. Identical characteristics are found in monocytes which were highly expanded in vitro by higher doses of GM-CSF (25 U/ml) in the absence of Dex and Il-4 before employing the above differentiation cocktail. CONCLUSION: In this work we provide evidence that FDC-like cells can be derived from monocytes in vitro. Monocyte-derived FDC-like cells quantitatively produced offer a broad utility covering basic research as well as clinical application

GMR at THz frequencies in coplanar waveguides

Tapered THz coplanar waveguides (CPWs) formed from Co/Cu multilayers with embedded low-temperature-grown gallium arsenide photoconductive switches were designed in order to observe giant magnetoresistance (GMR). Pulsed THz radiation was excited using the switches, and was transmitted through both straight and tapered CPWs. GMR-induced changes in the transmitted THz pulse amplitude were demonstrated

Focusing THz radiation in μm-scale waveguides

THz coplanar waveguides were fabricated on quartz wafers with integrated epitaxially transferred low temperature grown gallium arsenide photoconductive switches. THz radiation was excited on-chip and transmitted through a tapering of the coplanar waveguide structure where it was focused down to ~ 1.66μm. Theoretical modelling of the device confirms high E-field confinement and concentration

Gad65 is recognized by t-cells, but not by antibodies from nod-mice

Since the 64kDa-protein glutamic acid decarboxylase (GAD) is one of the major autoantigens in T-cell mediated Type 1 diabetes, its relevance as a T-cell antigen needs to be clarified. After isolation of splenic T-cells from non-obese diabetic (NOD) mice, a useful model for human Type 1 diabetes, we found that these T-cells proliferate spontaneously when incubated with human GAD65, but only marginally after incubation with GAD67, both recombinated in the baculovirus system. No effect was observed with non-diabetic NOD mice or with T-cells from H-2 identical NON-NOD-H-2g7 control mice. It has been published previously that NOD mice develop autoantibodies against a 64kDa protein detected with mouse beta cells. In immunoprecipitation experiments with sera from the same NOD mice and 33S-methionine-labelled GAD, no autoantibody binding could be detected. We conclude firstly that GAD65 is an important T-cell antigen which is relevant early in the development of Type 1 diabetes and secondly that there is an antigenic epitope in the human GAD65 molecule recognized by NOD T-cells, but not by NOD autoantibodies precipitating conformational epitopes. Our results therefore provide further evidence that GAD65 is a T-cell antigen in NOD mice, being possibly also involved in very early processes leading to the development of human Type 1 diabetes

Cross modal perception of body size in domestic dogs (Canis familiaris)

While the perception of size-related acoustic variation in animal vocalisations is well documented, little attention has been given to how this information might be integrated with corresponding visual information. Using a cross-modal design, we tested the ability of domestic dogs to match growls resynthesised to be typical of either a large or a small dog to size- matched models. Subjects looked at the size-matched model significantly more often and for a significantly longer duration than at the incorrect model, showing that they have the ability to relate information about body size from the acoustic domain to the appropriate visual category. Our study suggests that the perceptual and cognitive mechanisms at the basis of size assessment in mammals have a multisensory nature, and calls for further investigations of the multimodal processing of size information across animal species

Endoscopic and surgical treatment outcomes of colitis-associated advanced colorectal neoplasia:a multicenter cohort study

BACKGROUND: Inflammatory bowel disease (IBD) patients are at increased risk of advanced neoplasia (high-grade dysplasia or colorectal cancer). The authors aimed to (1) assess synchronous and metachronous neoplasia following (sub)total or proctocolectomy, partial colectomy or endoscopic resection for advanced neoplasia in IBD, and (2) identify factors associated with treatment choice. MATERIAL AND METHODS: In this retrospective multicenter cohort study, the authors used the Dutch nationwide pathology databank (PALGA) to identify patients diagnosed with IBD and colonic advanced neoplasia (AN) between 1991 and 2020 in seven hospitals in the Netherlands. Logistic and Fine &amp; Gray's subdistribution hazard models were used to assess adjusted subdistribution hazard ratios for metachronous neoplasia and associations with treatment choice. RESULTS: The authors included 189 patients (high-grade dysplasia n =81; colorectal cancer n =108). Patients were treated with proctocolectomy ( n =33), (sub)total colectomy ( n =45), partial colectomy ( n =56) and endoscopic resection ( n =38). Partial colectomy was more frequently performed in patients with limited disease and older age, with similar patient characteristics between Crohn's disease and ulcerative colitis. Synchronous neoplasia was found in 43 patients (25.0%; (sub)total or proctocolectomy n =22, partial colectomy n =8, endoscopic resection n =13). The authors found a metachronous neoplasia rate of 6.1, 11.5 and 13.7 per 100 patient-years after (sub)total colectomy, partial colectomy and endoscopic resection, respectively. Endoscopic resection, but not partial colectomy, was associated with an increased metachronous neoplasia risk (adjusted subdistribution hazard ratios 4.16, 95% CI 1.64-10.54, P &lt;0.01) compared with (sub)total colectomy. CONCLUSION: After confounder adjustment, partial colectomy yielded a similar metachronous neoplasia risk compared to (sub)total colectomy. High metachronous neoplasia rates after endoscopic resection underline the importance of strict subsequent endoscopic surveillance.</p

Endoscopic and surgical treatment outcomes of colitis-associated advanced colorectal neoplasia:a multicenter cohort study

BACKGROUND: Inflammatory bowel disease (IBD) patients are at increased risk of advanced neoplasia (high-grade dysplasia or colorectal cancer). The authors aimed to (1) assess synchronous and metachronous neoplasia following (sub)total or proctocolectomy, partial colectomy or endoscopic resection for advanced neoplasia in IBD, and (2) identify factors associated with treatment choice.MATERIAL AND METHODS: In this retrospective multicenter cohort study, the authors used the Dutch nationwide pathology databank (PALGA) to identify patients diagnosed with IBD and colonic advanced neoplasia (AN) between 1991 and 2020 in seven hospitals in the Netherlands. Logistic and Fine &amp; Gray's subdistribution hazard models were used to assess adjusted subdistribution hazard ratios for metachronous neoplasia and associations with treatment choice.RESULTS: The authors included 189 patients (high-grade dysplasia n =81; colorectal cancer n =108). Patients were treated with proctocolectomy ( n =33), (sub)total colectomy ( n =45), partial colectomy ( n =56) and endoscopic resection ( n =38). Partial colectomy was more frequently performed in patients with limited disease and older age, with similar patient characteristics between Crohn's disease and ulcerative colitis. Synchronous neoplasia was found in 43 patients (25.0%; (sub)total or proctocolectomy n =22, partial colectomy n =8, endoscopic resection n =13). The authors found a metachronous neoplasia rate of 6.1, 11.5 and 13.7 per 100 patient-years after (sub)total colectomy, partial colectomy and endoscopic resection, respectively. Endoscopic resection, but not partial colectomy, was associated with an increased metachronous neoplasia risk (adjusted subdistribution hazard ratios 4.16, 95% CI 1.64-10.54, P &lt;0.01) compared with (sub)total colectomy.CONCLUSION: After confounder adjustment, partial colectomy yielded a similar metachronous neoplasia risk compared to (sub)total colectomy. High metachronous neoplasia rates after endoscopic resection underline the importance of strict subsequent endoscopic surveillance.</p

Assessment of regression-based methods to adjust for publication bias through a comprehensive simulation study

<p>Abstract</p> <p>Background</p> <p>In meta-analysis, the presence of funnel plot asymmetry is attributed to publication or other small-study effects, which causes larger effects to be observed in the smaller studies. This issue potentially mean inappropriate conclusions are drawn from a meta-analysis. If meta-analysis is to be used to inform decision-making, a reliable way to adjust pooled estimates for potential funnel plot asymmetry is required.</p> <p>Methods</p> <p>A comprehensive simulation study is presented to assess the performance of different adjustment methods including the novel application of several regression-based methods (which are commonly applied to detect publication bias rather than adjust for it) and the popular Trim & Fill algorithm. Meta-analyses with binary outcomes, analysed on the log odds ratio scale, were simulated by considering scenarios with and without i) publication bias and; ii) heterogeneity. Publication bias was induced through two underlying mechanisms assuming the probability of publication depends on i) the study effect size; or ii) the p-value.</p> <p>Results</p> <p>The performance of all methods tended to worsen as unexplained heterogeneity increased and the number of studies in the meta-analysis decreased. Applying the methods conditional on an initial test for the presence of funnel plot asymmetry generally provided poorer performance than the unconditional use of the adjustment method. Several of the regression based methods consistently outperformed the Trim & Fill estimators.</p> <p>Conclusion</p> <p>Regression-based adjustments for publication bias and other small study effects are easy to conduct and outperformed more established methods over a wide range of simulation scenarios.</p

Moral hazard in marriage: the use of domestic labor as an incentive device

This paper argues that some women in developing countries use domestic labor as a tool to incentivize husbands. A theoretical model is derived based on the traditions of rural Malawi, where men often supplement farm income with wage labor. As wage labor is not observed by the wife, this creates moral hazard: husbands may not make enough effort to bring home wages. The model predicts that women overcome this by using domestic labor as an incentive device: they increase their domestic labor and reduce their leisure in response to good consumption outcomes, but only if they cannot rely on divorce threat as an alternative source of incentives. This prediction is confirmed using survey data from Malawi. Identification is based on the fact that Malawi's kinship traditions exogenously determine women's accessibility to divorce. Where divorce is not an option, women make inefficient labor choices in order to provide incentives

The acute mania of King George III: A computational linguistic analysis.

We used a computational linguistic approach, exploiting machine learning techniques, to examine the letters written by King George III during mentally healthy and apparently mentally ill periods of his life. The aims of the study were: first, to establish the existence of alterations in the King's written language at the onset of his first manic episode; and secondly to identify salient sources of variation contributing to the changes. Effects on language were sought in two control conditions (politically stressful vs. politically tranquil periods and seasonal variation). We found clear differences in the letter corpus, across a range of different features, in association with the onset of mental derangement, which were driven by a combination of linguistic and information theory features that appeared to be specific to the contrast between acute mania and mental stability. The paucity of existing data relevant to changes in written language in the presence of acute mania suggests that lexical, syntactic and stylometric descriptions of written discourse produced by a cohort of patients with a diagnosis of acute mania will be necessary to support the diagnosis independently and to look for other periods of mental illness of the course of the King's life, and in other historically significant figures with similarly large archives of handwritten documents