Tumor budding score based on 10 high-power fields is a promising basis for a standardized prognostic scoring system in stage II colorectal cancer

Tumor budding is recognized by the World Health Organization as an additional prognostic factor in colorectal cancer but remains unreported in diagnostic work due to the absence of a standardized scoring method. This study aims to assess the most prognostic and reproducible scoring systems for tumor budding in colorectal cancer. Tumor budding on pancytokeratin-stained whole tissue sections from 105 well-characterized stage II patients was scored by 3 observers using 7 methods: Hase, Nakamura, Ueno, Wang (conventional and rapid method), densest high-power field, and 10 densest high-power fields. The predictive value for clinicopathologic features, the prognostic significance, and interobserver variability of each scoring method was analyzed. Pancytokeratin staining allowed accurate evaluation of tumor buds. Interobserver agreement for 3 observers was excellent for densest high-power field (intraclass correlation coefficient, 0.83) and 10 densest high-power fields (intraclass correlation coefficient, 0.91). Agreement was moderate to substantial for the conventional Wang method (κ = 0.46-0.62) and moderate for the rapid method (κ = 0.46-0.58). For Nakamura, moderate agreement (κ = 0.41-0.52) was reached, whereas concordance was fair to moderate for Ueno (κ = 0.39-0.56) and Hase (κ = 0.29-0.51). The Hase, Ueno, densest high-power field, and 10 densest high-power field methods identified a significant association of tumor budding with tumor border configuration. In multivariate analysis, only tumor budding as evaluated in densest high-power field and 10 densest high-power fields had significant prognostic effects on patient survival (P < .01), with high prognostic accuracy over the full 10-year follow-up. Scoring tumor buds in 10 densest high-power fields is a promising method to identify stage II patients at high risk for recurrence in daily diagnostics; it is highly reproducible, accounts for heterogeneity, and has a strong predictive value for adverse outcome.

Training-related modulations of the autonomic nervous system in endurance athletes: is female gender cardioprotective?

The risk of sudden death is increased in athletes with a male predominance. Regular physical activity increases vagal tone, and may protect against exercise-induced ventricular arrhythmias. We investigated training-related modulations of the autonomic nervous system in female and male endurance athletes. Runners of a 10-mile race were invited. Of 873 applicants, 68 female and 70 male athletes were randomly selected and stratified according to their average weekly training hours in a low (≤4 h) and high (>4 h) volume training group. Analysis of heart rate variability was performed over 24 h. Spectral components (high frequency [HF] and low frequency [LF] power in normalized units) were analyzed for hourly 5 min segments and averaged for day- and nighttime. One hundred and fourteen athletes (50 % female, mean age 42 ± 7 years) were included. No significant gender difference was observed for training volume and 10-mile race time. Over the 24-h period, female athletes exhibited a higher HF and lower LF power for each hourly time-point. Female gender and endurance training hours were independent predictors of a higher HF and lower LF power. In female athletes, higher training hours were associated with a higher HF and lower LF power during nighttime. In male athletes, the same was true during daytime. In conclusion, female and male athletes showed a different circadian pattern of the training-related increase in markers of vagal tone. For a comparable amount of training volume, female athletes maintained their higher markers of vagal tone, possibly indicating a superior protection against exercise-induced ventricular arrhythmias.

Avant-garde or supplement? Advisory bodies of transnational associations as alternatives to the League’s Minority Protection System, 1919-1939

This exegesis focuses on the work of minority committees of transnational associations in the interwar period. Most of their members considered the League system to be inefficient and supported the establishment of non-state alternatives, which included private investigations on the spot, publicity for specific problems of minorities, and attempts to reconcile representatives of ethnic minorities with those of the majority. Members of non-involved states were pre-destined especially to act as neutral moderators. Only those in close contact with League officials avoided being misused by political forces that did not seek reconciliation but border revision. They learnt that the League rules looked inadequate from the outside but turned out to be useful in coming to applicable solutions once they started their own alternative methods. Their publications and investigative journeys turned out to deepen the problems, whilst their reconciliation work became an appreciated supplement of the League system.

Novel emboli protection system during cardiac surgery: a multi-center, randomized, clinical trial.

BACKGROUND Stroke is a major cause of morbidity and mortality during open-heart surgery. Up to 60% of intraoperative cerebral events are emboli induced. This randomized, controlled, multicenter trial is the first human study evaluating the safety and efficacy of a novel aortic cannula producing simultaneous forward flow and backward suction for extracting solid and gaseous emboli from the ascending aorta and aortic arch upon their intraoperative release. METHODS Sixty-six patients (25 females; 68±10 years) undergoing elective aortic valve replacement surgery, with or without coronary artery bypass graft surgery, were randomized to the use of the CardioGard (CardioGard Medical, Or-Yehuda, Israel) Emboli Protection cannula ("treatment") or a standard ("control") aortic cannula. The primary endpoint was the volume of new brain lesions measured by diffusion-weighted magnetic resonance imaging (DW-MRI), performed preoperatively and postoperatively. Device safety was investigated by comparisons of complications rate, namely neurologic events, stroke, renal insufficiency and death. RESULTS Of 66 patients (34 in the treatment group), 51 completed the presurgery and postsurgery MRI (27 in the treatment group). The volume of new brain lesion for the treatment group was (mean±standard error of the mean) 44.00±64.00 versus 126.56±28.74 mm3 in the control group (p=0.004). Of the treatment group, 41% demonstrated new postoperative lesions versus 66% in the control group (p=0.03). The complication rate was comparable in both groups. CONCLUSIONS The CardioGard cannula is safe and efficient in use during open-heart surgery. Efficacy was demonstrated by the removal of a substantial amount of emboli, a significant reduction in the volume of new brain lesions, and the percentage of patients experiencing new brain lesions.

A Passive WiFi Source Localization System based on Fine-grained Power-based Trilateration

Indoor localization systems become more interesting for researchers because of the attractiveness of business cases in various application fields. A WiFi-based passive localization system can provide user location information to third-party providers of positioning services. However, indoor localization techniques are prone to multipath and Non-Line Of Sight (NLOS) propagation, which lead to significant performance degradation. To overcome these problems, we provide a passive localization system for WiFi targets with several improved algorithms for localization. Through Software Defined Radio (SDR) techniques, we extract Channel Impulse Response (CIR) information at the physical layer. CIR is later adopted to mitigate the multipath fading problem. We propose to use a Nonlinear Regression (NLR) method to relate the filtered power information to propagation distances, which significantly improves the ranging accuracy compared to the commonly used log-distance path loss model. To mitigate the influence of ranging errors, a new trilateration algorithm is designed as well by combining Weighted Centroid and Constrained Weighted Least Square (WC-CWLS) algorithms. Experiment results show that our algorithm is robust against ranging errors and outperforms the linear least square algorithm and weighted centroid algorithm.

Yellow laser light generation by frequency doubling of the output from a master oscillator fiber power amplifier system

We present a power-scalable approach for yellow laser-light generation based on standard Ytterbium (Yb) doped fibers. To force the cavity to lase at 1154 nm, far above the gain-maximum, measures must be taken to fulfill lasing condition and to suppress competing amplified spontaneous emission (ASE) in the high-gain region. To prove the principle we built a fiber-laser cavity and a fiber-amplifier both at 1154 nm. In between cavity and amplifier we suppressed the ASE by 70 dB using a fiber Bragg grating (FBG) based filter. Finally we demonstrated efficient single pass frequency doubling to 577 nm with a periodically poled lithium niobate crystal (PPLN). With our linearly polarized 1154 nm master oscillator power fiber amplifier (MOFA) system we achieved slope efficiencies of more than 15 % inside the cavity and 24 % with the fiber-amplifier. The frequency doubling followed the predicted optimal efficiency achievable with a PPLN crystal. So far we generated 1.5 W at 1154nm and 90 mW at 577 nm. Our MOFA approach for generation of 1154 nm laser radiation is power-scalable by using multi-stage amplifiers and large mode-area fibers and is therefore very promising for building a high power yellow laser-light source of several tens of Watt.

Complete protection against P. berghei malaria upon heterologous prime/boost immunization against circumsporozoite protein employing Salmonella type III secretion system and Bordetella adenylate cyclase toxoid

Sterile immunity against malaria can be achieved by the induction of IFNgamma-producing CD8(+) T cells that target infected hepatocytes presenting epitopes of the circumsporozoite protein (CSP). In the present study we evaluate the protective efficacy of a heterologous prime/boost immunization protocol based on the delivery of the CD8(+) epitope of Plasmodium berghei CSP into the MHC class I presentation pathway, by either a type III secretion system of live recombinant Salmonella and/or by direct translocation of a recombinant Bordetella adenylate cyclase toxoid fusion (ACT-CSP) into the cytosol of professional antigen-presenting cells (APCs). A single intraperitoneal application of the recombinant ACT-CSP toxoid, as well as a single oral immunization with the Salmonella vaccine, induced a specific CD8(+) T cell response, which however conferred only a partial protection on mice against a subsequent sporozoite challenge. In contrast, a heterologous prime/boost vaccination with the live Salmonella followed by ACT-CSP led to a significant enhancement of the CSP-specific T cell response and induced complete protection in all vaccinated mice.