Online Interaction Turns the Congeniality Bias Into an Uncongeniality Bias.

Online phenomena like echo chambers and polarization are believed to be driven by humans' penchant to selectively expose themselves to attitudinally congenial content. However, if like-minded content were the only predictor of online behavior, heated debate and flaming on the Internet would hardly occur. Research has overlooked how online behavior changes when people are given an opportunity to reply to dissenters. Three experiments (total N = 320; convenience student samples from Germany) and an internal meta-analysis show that in a discussion-forum setting where participants can reply to earlier comments larger cognitive conflict between participant attitude and comment attitude predicts higher likelihood to respond (uncongeniality bias). When the discussion climate was friendly (vs. oppositional) to the views of participants, the uncongeniality bias was more pronounced and was also associated with attitude polarization. These results suggest that belief polarization on social media may not only be driven by congeniality but also by conflict.

Laser-induced molecular contamination de-risking activity for the Laser Interferometer Space Antenna.

The Laser Interferometer Space Antenna (LISA) will be the first space-based gravitational wave observatory. LISA uses continuous-wave, infrared laser beams propagating among three widely separated spacecrafts to measure their distances with picometer accuracy via time-delay interferometry. These measurements put very high demands on the laser wavefront and are thus very sensitive to any deposits on laser optics that could be induced by laser-induced molecular contamination (LIMC). In this work, we describe the results of an extensive experimental test campaign assessing LIMC related risks for LISA. We find that the LIMC concern for LISA, even considering the high demands on the laser wavefront, may be greatly reduced compared to that observed at shorter wavelengths or with pulsed laser radiation. This result is very promising for LISA as well as for other space missions using continuous-wave, infrared laser radiation, e.g., in free space laser communication or quantum key distribution.

Mycolactone-Dependent Depletion of Endothelial Cell Thrombomodulin Is Strongly Associated with Fibrin Deposition in Buruli Ulcer Lesions.

A well-known histopathological feature of diseased skin in Buruli ulcer (BU) is coagulative necrosis caused by the Mycobacterium ulcerans macrolide exotoxin mycolactone. Since the underlying mechanism is not known, we have investigated the effect of mycolactone on endothelial cells, focussing on the expression of surface anticoagulant molecules involved in the protein C anticoagulant pathway. Congenital deficiencies in this natural anticoagulant pathway are known to induce thrombotic complications such as purpura fulimans and spontaneous necrosis. Mycolactone profoundly decreased thrombomodulin (TM) expression on the surface of human dermal microvascular endothelial cells (HDMVEC) at doses as low as 2 ng/ml and as early as 8 hrs after exposure. TM activates protein C by altering thrombin's substrate specificity, and exposure of HDMVEC to mycolactone for 24 hours resulted in an almost complete loss of the cells' ability to produce activated protein C. Loss of TM was shown to be due to a previously described mechanism involving mycolactone-dependent blockade of Sec61 translocation that results in proteasome-dependent degradation of newly synthesised ER-transiting proteins. Indeed, depletion from cells determined by live-cell imaging of cells stably expressing a recombinant TM-GFP fusion protein occurred at the known turnover rate. In order to determine the relevance of these findings to BU disease, immunohistochemistry of punch biopsies from 40 BU lesions (31 ulcers, nine plaques) was performed. TM abundance was profoundly reduced in the subcutis of 78% of biopsies. Furthermore, it was confirmed that fibrin deposition is a common feature of BU lesions, particularly in the necrotic areas. These findings indicate that there is decreased ability to control thrombin generation in BU skin. Mycolactone's effects on normal endothelial cell function, including its ability to activate the protein C anticoagulant pathway are strongly associated with this. Fibrin-driven tissue ischemia could contribute to the development of the tissue necrosis seen in BU lesions.

Local Heat Application for the Treatment of Buruli Ulcer: Results of a Phase II Open Label Single Center Non Comparative Clinical Trial.

BACKGROUND: Buruli ulcer (BU) is a necrotizing skin disease most prevalent among West African children. The causative organism, Mycobacterium ulcerans, is sensitive to temperatures above 37°C. We investigated the safety and efficacy of a local heat application device based on phase change material. METHODS: In a phase II open label single center noncomparative clinical trial (ISRCTN 72102977) under GCP standards in Cameroon, laboratory confirmed BU patients received up to 8 weeks of heat treatment. We assessed efficacy based on the endpoints 'absence of clinical BU specific features' or 'wound closure' within 6 months ("primary cure"), and 'absence of clinical recurrence within 24 month' ("definite cure"). RESULTS: Of 53 patients 51 (96%) had ulcerative disease. 62% were classified as World Health Organization category II, 19% each as category I and III. The average lesion size was 45 cm(2). Within 6 months after completion of heat treatment 92.4% (49 of 53, 95% confidence interval [CI], 81.8% to 98.0%) achieved cure of their primary lesion. At 24 months follow-up 83.7% (41 of 49, 95% CI, 70.3% to 92.7%) of patients with primary cure remained free of recurrence. Heat treatment was well tolerated; adverse effects were occasional mild local skin reactions. CONCLUSIONS: Local thermotherapy is a highly effective, simple, cheap and safe treatment for M. ulcerans disease. It has in particular potential as home-based remedy for BU suspicious lesions at community level where laboratory confirmation is not available. CLINICAL TRIALS REGISTRATION: ISRCT 72102977.

Single-layer resonant-waveguide grating for polarization and wavelength selection in Yb:YAG thin-disk lasers.

A single-layer resonant-waveguide grating consisting of a sub-wavelength grating coupler etched into a waveguide is proposed in order to achieve high polarization and high spectral selectivity inside an Yb:YAG thin-disk laser resonator. The designed structure was fabricated with the help of a Lloyd's-mirror interference lithography setup followed by reactive ion beam etching down to the desired grating groove depth. The wavelength and polarization dependent reflectivity is measured and compared to the design results. The behaviour of the device at higher temperatures is also investigated in the present work. The device is introduced as the end mirror of an Yb:YAG thin-disk laser cavity. Output powers of up to 123 W with a spectral bandwidth of about 0.5 nm (FWHM) is demonstrated in a multimode configuration (M2~6). In fundamental-mode operation (TEM00 with M2~1.1) 70 W of power with a spectral bandwidth of about 20 pm have been obtained. Moreover, the degree of linear polarization was measured to be higher than 99% for both multimode and fundamental mode operation.

High-power radially polarized Yb:YAG thin-disk laser with high efficiency.

Radially polarized beams with an output power of 275 W, M2=2.3 and an efficiency of about 52.5% were generated from an Yb:YAG thin-disk laser. An intra-cavity circular resonant waveguide grating was used as a polarization selective mirror inside the laser cavity. We report on the design and the fabrication using a scanning beam interference lithography system and discuss the calculated and measured performances of the presented polarizing grating mirrors.

Very-large-mode-area, single-mode multicore fiber.

A single-mode evanescently coupled multicore fiber consisting of 19 hexagonally arranged cores is investigated. Theoretical and experimental results are presented and compared to an equivalent hypothetical step-index fiber. A fundamental mode with an effective area of 465 microm(2) and a beam propagation factor M(2) of 1.02 was measured, showing the high potential of the developed fiber.

Spatial Distribution of Mycobacterium ulcerans in Buruli Ulcer Lesions: Implications for Laboratory Diagnosis.

BACKGROUND: Current laboratory diagnosis of Buruli ulcer (BU) is based on microscopic detection of acid fast bacilli, quantitative real-time PCR (qPCR), histopathology or cultivation. Insertion sequence (IS) 2404 qPCR, the most sensitive method, is usually only available at reference laboratories. The only currently available point-of-care test, microscopic detection of acid fast bacilli (AFB), has limited sensitivity and specificity. METHODOLOGY/ PRINCIPAL FINDINGS: Here we analyzed AFB positive tissue samples (n = 83) for the presence, distribution and amount of AFB. AFB were nearly exclusively present in the subcutis with large extracellular clusters being most frequently (67%) found in plaque lesions. In ulcerative lesions small clusters and dispersed AFB were more common. Beside this, 151 swab samples from 37 BU patients were analyzed by IS2404 qPCR and ZN staining in parallel. The amount of M. ulcerans DNA in extracts from swabs correlated well with the probability of finding AFB in direct smear microscopy, with 56.1% of the samples being positive in both methods and 43.9% being positive only in qPCR. By analyzing three swabs per patient instead of one, the probability to have at least one positive swab increased from 80.2% to 97.1% for qPCR and from 45% to 66.1% for AFB smear examination. CONCLUSION / SIGNIFICANCE: Our data show that M. ulcerans bacteria are primarily located in the subcutis of BU lesions, making the retrieval of the deep subcutis mandatory for examination of tissue samples for AFB. When laboratory diagnosis is based on the recommended less invasive collection of swab samples, analysis of three swabs from different areas of ulcerative lesions instead of one increases the sensitivity of both qPCR and of smear microscopy substantially.

Locally Confined Clonal Complexes of Mycobacterium ulcerans in Two Buruli Ulcer Endemic Regions of Cameroon.

BACKGROUND: Mycobacterium ulcerans is the causative agent of the necrotizing skin disease Buruli ulcer (BU), which has been reported from over 30 countries worldwide. The majority of notified patients come from West African countries, such as Côte d'Ivoire, Ghana, Benin and Cameroon. All clinical isolates of M. ulcerans from these countries are closely related and their genomes differ only in a limited number of single nucleotide polymorphisms (SNPs). METHODOLOGY/PRINCIPAL FINDINGS: We performed a molecular epidemiological study with clinical isolates from patients from two distinct BU endemic regions of Cameroon, the Nyong and the Mapé river basins. Whole genome sequencing of the M. ulcerans strains from these two BU endemic areas revealed the presence of two phylogenetically distinct clonal complexes. The strains from the Nyong river basin were genetically more diverse and less closely related to the M. ulcerans strain circulating in Ghana and Benin than the strains causing BU in the Mapé river basin. CONCLUSIONS: Our comparative genomic analysis revealed that M. ulcerans clones diversify locally by the accumulation of SNPs. Case isolates coming from more recently emerging BU endemic areas, such as the Mapé river basin, may be less diverse than populations from longer standing disease foci, such as the Nyong river basin. Exchange of strains between distinct endemic areas seems to be rare and local clonal complexes can be easily distinguished by whole genome sequencing.

Phase change material for thermotherapy of Buruli ulcer: a prospective observational single centre proof-of-principle trial.

BACKGROUND: Buruli ulcer (BU) is an infection of the subcutaneous tissue leading to chronic necrotizing skin ulcers. The causative pathogen, Mycobacterium ulcerans, grows best at 30 degrees C-33 degrees C and not above 37 degrees C. We explored the safety, tolerability and efficacy of phase change material (PCM), a novel heat application system for thermotherapy of BU. METHODOLOGY/PRINCIPAL FINDINGS: In a prospective observational single centre proof-of-principle trial in Ayos/Cameroon, six laboratory reconfirmed patients with ulcerative Buruli lesions received 28-31 (ulcers < or = 2 cm) or 50-55 (ulcers > 2 cm) days of thermotherapy with the PCM sodium acetate trihydrate as heat application system. This PCM is widely used in commercial pocket heat pads, it is easy to apply, rechargeable in hot water, non-toxic and non-hazardous to the environment. All patients enrolled in the trial completed treatment. Being completely mobile during the well-tolerated heat application, acceptability of the PCM bandages was very high. In patients with smaller ulcers, wounds healed completely without further intervention. Patients with large defects had skin grafting after successful heat treatment. Heat treatment was not associated with marked increases in local inflammation or the development of ectopic lymphoid tissue. One and a half years after completion of treatment, all patients are relapse-free. CONCLUSIONS/SIGNIFICANCE: Our reusable PCM-based heat application device appears perfectly suited to treat BU in endemic countries with limited resources and infrastructure. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN88392614.

Multilayer polarizing grating mirror used for the generation of radial polarization in Yb:YAG thin-disk lasers.

The design, fabrication and characterization of a multilayer polarizing grating mirror developed for an Yb:YAG thin-disk laser resonator are reported. The potential of the proposed solution is discussed together with the first demonstration of a radially polarized Yb:YAG thin-disk laser.

Altered expression of type II sodium/phosphate cotransporter in polycystic kidney disease.

Renal phosphate (Pi) absorption is mediated via the type II sodium/Pi cotransporter (NaPi-2) in the brush border membrane (BBM) of proximal tubules. Simultaneous detection of NaPi-2 mRNA by in situ hybridization and of NaPi-2 immunoreactivity by immunohistochemistry was performed to investigate the distribution of the cotransporter in healthy control rats and during progression of autosomal dominant polycystic kidney disease (ADPKD). The purpose of the study was to disclose a relation between proximal tubular cell differentiation and NaPi-2 expression. In controls, NaPi-2 expression was present in the entire proximal tubule. In the Han:SPRD (cy/+) model for ADPKD, the proximal nephron is primarily affected by the cystic changes. Epithelial proliferation and impaired epithelial-matrix interaction result in a loss of cell differentiation that eventually leads to cystic enlargement of the nephron. Normal expression of NaPi-2 in this model was found only in tubules with intact BBM. Loss of BBM and cellular interdigitation were paralleled by the loss of NaPi-2 in situ hybridization and immunoreactive signals. These changes were moderate and focal in 2-mo-old rats and generalized all over the cortex after 8 mo. Advanced renal damage in the older PKD group was associated with mild phosphaturia, which suggests functional insufficiency of tubular NaPi-2 reabsorption. These data show how proliferative changes and loss of tubular epithelial differentiation in ADPKD may prevent functional expression of the NaPi-2 system in the proximal tubule in a rapidly progressive manner. NaPi-2 in proximal tubule BBM is suggested to play an important role in impaired tubular absorption of Pi in renal disease.