Active sites in heterogeneous ice nucleation-the example of K-rich feldspars

Ice formation on aerosol particles is a process of crucial importance to Earth's climate and the environmental sciences but it is not understood at the molecular level. This is so partly because the nature of active sites, local surface features where ice growth commences, is still unclear. Here we report direct electron-microscopic observations of deposition growth of aligned ice crystals on feldspar, an atmospherically important component of mineral dust. Our molecular-scale computer simulations indicate that this alignment arises from the preferential nucleation of prismatic crystal planes of ice on high-energy (100) surface planes of feldspar. The microscopic patches of (100) surface, exposed at surface defects such as steps, cracks, and cavities, are thought to be responsible for the high ice nucleation efficacy of K-feldspar particles

Ki-67 expression is superior to mitotic count and novel proliferation markers PHH3, MCM4 and mitosin as a prognostic factor in thick cutaneous melanoma

<p>Abstract</p> <p>Background</p> <p>Tumor cell proliferation is a predictor of survival in cutaneous melanoma. The aim of the present study was to evaluate the prognostic impact of mitotic count, Ki-67 expression and novel proliferation markers phosphohistone H3 (PHH3), minichromosome maintenance protein 4 (MCM4) and mitosin, and to compare the results with histopathological variables.</p> <p>Methods</p> <p>202 consecutive cases of nodular cutaneous melanoma were initially included. Mitotic count (mitosis per mm²) was assessed on H&E sections, and Ki-67 expression was estimated by immunohistochemistry on standard sections. PHH3, MCM4 and mitosin were examined by staining of tissue microarrays (TMA) sections.</p> <p>Results</p> <p>Increased mitotic count and elevated Ki-67 expression were strongly associated with increased tumor thickness, presence of ulceration and tumor necrosis. Furthermore, high mitotic count and elevated Ki-67 expression were also associated with Clark's level of invasion and presence of vascular invasion. High expression of PHH3 and MCM4 was correlated with high mitotic count, elevated Ki-67 expression and tumor ulceration, and increased PHH3 frequencies were associated with tumor thickness and presence of tumor necrosis. Univariate analyses showed a worse outcome in cases with elevated Ki-67 expression and high mitotic count, whereas PHH3, MCM4 and mitosin were not significant. Tumor cell proliferation by Ki-67 had significant prognostic impact by multivariate analysis.</p> <p>Conclusions</p> <p>Ki-67 was a stronger and more robust prognostic indicator than mitotic count in this series of nodular melanoma. PHH3, MCM4 and mitosin did not predict patient survival.</p

Displaced distal forearm fractures in children with an indication for reduction under general anesthesia should be percutaneously fixated

Surger

RAGE Reusable Game Software Components and Their Integration into Serious Game Engines

This paper presents and validates a methodology for integrating reusable software components in diverse game engines. While conforming to the RAGE com-ponent-based architecture described elsewhere, the paper explains how the interac-tions and data exchange processes between a reusable software component and a game engine should be implemented for procuring seamless integration. To this end, a RAGE-compliant C# software component providing a difficulty adaptation routine was integrated with an exemplary strategic tile-based game “TileZero”. Implementa-tions in MonoGame, Unity and Xamarin, respectively, have demonstrated successful portability of the adaptation component. Also, portability across various delivery platforms (Windows desktop, iOS, Android, Windows Phone) was established. Thereby this study has established the validity of the RAGE architecture and its un-derlying interaction processes for the cross-platform and cross-game engine reuse of software components. The RAGE architecture thereby accommodates the large scale development and application of reusable software components for serious gaming

Arthroscopy vs. MRI for a detailed assessment of cartilage disease in osteoarthritis: diagnostic value of MRI in clinical practice

<p>Abstract</p> <p>Background</p> <p>In patients with osteoarthritis, a detailed assessment of degenerative cartilage disease is important to recommend adequate treatment. Using a representative sample of patients, this study investigated whether MRI is reliable for a detailed cartilage assessment in patients with osteoarthritis of the knee.</p> <p>Methods</p> <p>In a cross sectional-study as a part of a retrospective case-control study, 36 patients (mean age 53.1 years) with clinically relevant osteoarthritis received standardized MRI (sag. T1-TSE, cor. STIR-TSE, trans. fat-suppressed PD-TSE, sag. fat-suppressed PD-TSE, Siemens Magnetom Avanto syngo MR B 15) on a 1.5 Tesla unit. Within a maximum of three months later, arthroscopic grading of the articular surfaces was performed. MRI grading by two blinded observers was compared to arthroscopic findings. Diagnostic values as well as intra- and inter-observer values were assessed.</p> <p>Results</p> <p>Inter-observer agreement between readers 1 and 2 was good (kappa = 0.65) within all compartments. Intra-observer agreement comparing MRI grading to arthroscopic grading showed moderate to good values for readers 1 and 2 (kappa = 0.50 and 0.62, respectively), the poorest being within the patellofemoral joint (kappa = 0.32 and 0.52). Sensitivities were relatively low at all grades, particularly for grade 3 cartilage lesions. A tendency to underestimate cartilage disorders on MR images was not noticed.</p> <p>Conclusions</p> <p>According to our results, the use of MRI for precise grading of the cartilage in osteoarthritis is limited. Even if the practical benefit of MRI in pretreatment diagnostics is unequivocal, a diagnostic arthroscopy is of outstanding value when a grading of the cartilage is crucial for a definitive decision regarding therapeutic options in patients with osteoarthritis.</p

Targeting deficiencies in the TLR5 mediated vaginal response to treat female recurrent urinary tract infection

Abstract The identification of the host defence peptides as target effectors in the innate defence of the uro-genital tract creates new translational possibilities for immunomodulatory therapies, specifically vaginal therapies to treat women suffering from rUTI, particularly those carrying the TLR5_C1174T SNP. Urinary tract infections (UTIs) are a microbial disease reported worldwide. Women are particularly susceptible with many suffering debilitating recurrent (r) infections. Treatment is by antibiotics, but such therapy is linked to antibiotic resistance and re-infection. This study explored the innate protective mechanisms of the urogenital tract with the aim of boosting such defences therapeutically. Modelling UTIs in vitro, human vaginal and bladder epithelial cells were challenged with uropathogenic Escherichia coli (CFT073) and microbial PAMPs including flagellin, LPS and peptidoglycan. Flagellin functioning via the TLR5/NFκB pathway was identified as the key UPEC virulence factor causing a significant increase (P < 0.05) in the production of the host-defence peptide (HDP), BD2. BD2-depleted urine samples from bladder infected mice supported increased UPEC growth, strengthening the significance of the HDPs in protecting the urogenital tissues from infection. Clinically, vaginal-douche BD2 concentrations were reduced (p < 0.05) in women suffering rUTIs, compared to age-matched healthy controls with concentrations further decreased (p < 0.05) in a TLR5392Stop SNP rUTI subgroup. Topical vaginal estrogen treatment increased (p < 0.001) BD2 concentrations in all women, including those carrying the SNP. These data identify therapeutic and antibiotic sparing roles for vaginal immunomodulatory agents that specifically target HDP induction, facilitate bacterial killing and disrupt the UPEC infection cycle

Microneedle Array Design Determines the Induction of Protective Memory CD8+ T Cell Responses Induced by a Recombinant Live Malaria Vaccine in Mice

BACKGROUND: Vaccine delivery into the skin has received renewed interest due to ease of access to the immune system and microvasculature, however the stratum corneum (SC), must be breached for successful vaccination. This has been achieved by removing the SC by abrasion or scarification or by delivering the vaccine intradermally (ID) with traditional needle-and-syringes or with long microneedle devices. Microneedle patch-based transdermal vaccine studies have predominantly focused on antibody induction by inactivated or subunit vaccines. Here, our principal aim is to determine if the design of a microneedle patch affects the CD8(+) T cell responses to a malaria antigen induced by a live vaccine. METHODOLOGY AND FINDINGS: Recombinant modified vaccinia virus Ankara (MVA) expressing a malaria antigen was percutaneously administered to mice using a range of silicon microneedle patches, termed ImmuPatch, that differed in microneedle height, density, patch area and total pore volume. We demonstrate that microneedle arrays that have small total pore volumes induce a significantly greater proportion of central memory T cells that vigorously expand to secondary immunization. Microneedle-mediated vaccine priming induced significantly greater T cell immunity post-boost and equivalent protection against malaria challenge compared to ID vaccination. Notably, unlike ID administration, ImmuPatch-mediated vaccination did not induce inflammatory responses at the site of immunization or in draining lymph nodes. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that the design of microneedle patches significantly influences the magnitude and memory of vaccine-induced CD8(+) T cell responses and can be optimised for the induction of desired immune responses. Furthermore, ImmuPatch-mediated delivery may be of benefit to reducing unwanted vaccine reactogenicity. In addition to the advantages of low cost and lack of pain, the development of optimised microneedle array designs for the induction of T cell responses by live vaccines aids the development of solutions to current obstacles of immunization programmes

Effect of temporary cements on the shear bond strength of luting cements

OBJECTIVE: The purpose of this study was to evaluate, by shear bond strength (SBS) testing, the influence of different types of temporary cements on the final cementation using conventional and self-etching resin-based luting cements. Material and Methods: Forty human teeth divided in two halves were assigned to 8 groups (n=10): I and V (no temporary cementation); II and VI: Ca(OH)2-based cement; III and VII: zinc oxide (ZO)-based cement; IV and VIII: ZO-eugenol (ZOE)-based cement. Final cementation was done with RelyX ARC cement (groups I to IV) and RelyX Unicem cement (groups V to VIII). Data were analyzed statistically by ANOVA and Tukey's test at 5% significance level. RESULTS: Means were (MPa): I - 3.80 (&plusmn;1.481); II - 5.24 (&plusmn;2.297); III - 6.98 (&plusmn;1.885); IV - 6.54 (&plusmn;1.459); V - 5.22 (&plusmn;2.465); VI - 4.48 (&plusmn;1.705); VII - 6.29 (&plusmn;2.280); VIII - 2.47 (&plusmn;2.076). Comparison of the groups that had the same temporary cementation (Groups II and VI; III and VII; IV and VIII) showed statistically significant difference (p<0.001) only between Groups IV and VIII, in which ZOE-based cements were used. The use of either Ca(OH)2-based (Groups II and VI) or ZO-based (Groups III and VII) cements showed no statistically significant difference (p>0.05) for the different luting cements (RelyX TM ARC and RelyX TM Unicem). The groups that had no temporary cementation (Groups I and V) did not differ significantly from each other either (p>0.05). CONCLUSION: When temporary cementation was done with ZO- or ZOE-based cements and final cementation was done with RelyX ARC, there was an increase in the SBS compared to the control. In the groups cemented with RelyX Unicem, however, the use of a ZOE-based temporary cement affected negatively the SBS of the luting agent used for final cementation

Adverse Events in a Cohort of HIV Infected Pregnant and Non-Pregnant Women Treated with Nevirapine versus Non-Nevirapine Antiretroviral Medication

BACKGROUND: Predictors of adverse events (AE) associated with nevirapine use are needed to better understand reports of severe rash or liver enzyme elevation (LEE) in HIV+ women. METHODOLOGY: AE rates following ART initiation were retrospectively assessed in a multi-site cohort of 612 women. Predictors of onset of rash or LEE were determined using univariate and multivariate analyses. PRINCIPAL FINDINGS: Of 612 subjects, 152 (24.8%) initiated NVP-based regimens with 86 (56.6%) pregnant; 460 (75.2%) initiated non-NVP regimens with 67 (14.6%) pregnant. LEE: No significant difference was found between regimens in the development of new grade ≥2 LEE (p  =  0.885). Multivariate logistic regression demonstrated an increased likelihood of LEE with HCV co-infection (OR 2.502, 95% CI: 1.04 to 6, p =  0.040); pregnancy, NVP-based regimen, and baseline CD4 >250 cells/mm(3) were not associated with this toxicity. RASH: NVP initiation was associated with rash after controlling for CD4 and pregnancy (OR 2.78; 95%CI: 1.14-6.76), as was baseline CD4 >250 cells/mm(3) when controlling for pregnancy and type of regimen (OR 2.68; 95% CI: 1.19-6.02 p  =  0.017). CONCLUSIONS: CD4 at initiation of therapy was a predictor of rash but not LEE with NVP use in HIV+ women. Pregnancy was not an independent risk factor for the development of AEs assessed. The findings from this study have significant implications for women of child-bearing age initiating NVP-based ART particularly in resource limited settings. This study sheds more confidence on the lack of LEE risk and the need to monitor rash with the use of this medication