Phase I study evaluating the Fc-optimized FLT3 antibody FLYSYN in AML patients with measurable residual disease.

BACKGROUND: About half of AML patients achieving complete remission (CR) display measurable residual disease (MRD) and eventually relapse. FLYSYN is an Fc-optimized antibody for eradication of MRD directed to FLT3/CD135, which is abundantly expressed on AML cells. METHODS: This first-in-human, open-label, single-arm, multicenter trial included AML patients in CR with persisting or increasing MRD and evaluated safety/tolerability, pharmacokinetics and preliminary efficacy of FLYSYN at different dose levels administered intravenously (cohort 1-5: single dose of 0.5 mg/m2, 1.5 mg/m2, 5 mg/m2, 15 mg/m2, 45 mg/m2; cohort 6: 15 mg/m2 on day 1, 15 and 29). Three patients were treated per cohort except for cohorts 4 and 6, which were expanded to nine and ten patients, respectively. Primary objective was safety, and secondary efficacy objective was ≥ 1 log MRD reduction or negativity in bone marrow. RESULTS: Overall, 31 patients were treated, of whom seven patients (22.6%) experienced a transient decrease in neutrophil count (two grade 3, others ≤ grade 2). No infusion-related reaction or dose-limiting toxicity was observed. Adverse events (AEs) were mostly mild to moderate, with the most frequent AEs being hematologic events and laboratory abnormalities. Response per predefined criteria was documented in 35% of patients, and two patients maintained MRD negativity until end of study. Application of 45 mg/m2 FLYSYN as single or cumulative dose achieved objective responses in 46% of patients, whereas 28% responded at lower doses. CONCLUSIONS: FLYSYN monotherapy is safe and well-tolerated in AML patients with MRD. Early efficacy data are promising and warrant further evaluation in an up-coming phase II trial. Trial registration This clinical is registered on clinicaltrials.gov (NCT02789254).

Quantification of Conceptual Model Uncertainty in the Modeling of Wet Deposited Atmospheric Pollutants.

Conceptual model uncertainty and parameter uncertainty are dominant contributors to the total uncertainty of a radioecological model output. In the present study the focus is on conceptual model uncertainty, which is often not acknowledged. Conceptual model uncertainty is assessed by subtracting from the total uncertainty of the model output the propagated parameter uncertainty, obtained by means of Bayesian inference analysis. The conceptual model uncertainty is quantified for two process-based models, which describe the interception of wet deposited pollutants under equilibrium and kinetic conditions, respectively. The natural variability due the chemical valence of the elements considered is accounted for in both models. Quantitative evidence has been obtained that the conceptual model uncertainty can contribute to the total uncertainty budget of the models for interception of wet deposited pollutants at least as much as, if not more than, parameter uncertainty.

An updated strategic research agenda for the integration of radioecology in the european radiation protection research.

The ALLIANCE Strategic Research Agenda (SRA) for radioecology is a living document that defines a long-term vision (20 years) of the needs for, and implementation of, research in radioecology in Europe. The initial SRA, published in 2012, included consultation with a wide range of stakeholders (Hinton et al., 2013). This revised version is an update of the research strategy for identified research challenges, and includes a strategy to maintain and develop the associated required capacities for workforce (education and training) and research infrastructures and capabilities. Beyond radioecology, this SRA update constitutes a contribution to the implementation of a Joint Roadmap for radiation protection research in Europe (CONCERT, 2019a). This roadmap, established under the H2020 European Joint Programme CONCERT, provides a common and shared vision for radiation protection research, priority areas and strategic objectives for collaboration within a European radiation protection research programme to 2030 and beyond. Considering the advances made since the first SRA, this updated version presents research challenges and priorities including identified scientific issues that, when successfully resolved, have the potential to impact substantially and strengthen the system and/or practice of the overall radiation protection (game changers) in radioecology with regard to their integration into the global vision of European research in radiation protection. An additional aim of this paper is to encourage contribution from research communities, end users, decision makers and other stakeholders in the evaluation, further advancement and accomplishment of the identified priorities.

Crack Detection Zones: Computation and Validation.

During the development of aerospace structures, typically many fatigue tests are conducted. During these tests, much effort is put into inspections in order to detect the onset of failure before complete failure. Strain sensor data may be used to reduce inspection effort. For this, a sufficient number of sensors need to be positioned appropriately to collect the relevant data. In order to minimize cost and effort associated with sensor positioning, the method proposed here aims at minimizing the number of necessary strain sensors while positioning them such that fatigue-induced damage can still be detected before complete failure. A suitable detection criterion is established as the relative change of strain amplitudes under cyclic loading. Then, the space of all possible crack lengths is explored. The regions where the detection criterion is satisfied before complete failure occurs are assembled into so-called detection zones. One sensor in this zone is sufficient to detect criticality. The applicability of the approach is demonstrated on a representative airplane structure that resembles a lower wing section. The method shows that four fatigue critical spots can be monitored using only one strain sensor in a non-intuitive position. Furthermore, we discuss two different strain measures for crack detection. The results of this paper can be used for reliable structural health monitoring using a minimum number of sensors.

Skin vaccination via fractional infrared laser ablation - Optimization of laser-parameters and adjuvantation.

BACKGROUND: Methods to deliver an antigen into the skin in a painless, defined, and reproducible manner are essential for transcutaneous immunization (TCI). Here, we employed an ablative fractional infrared laser (P.L.E.A.S.E. Professional) to introduce clinically relevant vaccines into the skin. To elicit the highest possible antibody titers with this system, we optimized different laser parameters, such as fluence and pore number per area, and tested various adjuvants. METHODS: BALB/c mice were immunized with Hepatitis B surface antigen (HBsAg) by laser-microporation. Adjuvants used were alum, CRM197, monophosphoryl lipid A, heat-labile enterotoxin subunit B of E. coli (LT-B), and CpG ODN1826. The influence of different fluences (2.1 to 16.8J/cm2) and pore densities (5-15%) was investigated. Furthermore, immunogenicity of HBsAg and the commercially available conjugate vaccines ActHIB® and Menveo® applied via TCI was compared to standard i.m. injection. Antigen-specific antibody titers were assessed by luminometric ELISA. RESULTS: Antibody titers against HBsAg were dependent on pore depth and peaked at a fluence of 8.4J/cm2. Immunogenicity was independent of pore density. Adjuvantation with alum significantly reduced antibody titers after TCI, whereas other adjuvants only induced marginal changes in total IgG titers. LT-B and CpG shifted the polarization of the immune response as indicated by decreased IgG1/IgG2a ratios. HBsAg/LT-B applied via TCI induced similar antibody titers compared to i.m. injection of HBsAg/alum. In contrast to i.m. injection, we observed a dose response from 5 to 20µg after TCI. Both, ActHIB® and Menveo® induced high antibody titers after TCI, which were comparable to i.m. injection. CONCLUSIONS: Alum, the most commonly used adjuvant, is contraindicated for transcutaneous vaccination via laser-generated micropores. TCI with optimized laser parameters induces high antibody titers, which cannot be significantly increased by the tested adjuvants. Commercially available vaccines formulated without alum have the potential for successful TCI via laser-generated micropores, without the need for reformulation.

Wear, microleakage and plastic deformation of an implant-supported chair-side bar system.

PURPOSE: This in-vitro study was designed to evaluate retention forces, microleakage and plastic deformation of a prefabricated 2-implant bar attachment system (SFI-Bar, Cendres+Métaux, Switzerland). MATERIALS AND METHODS: Two SFI implant-adapters were torqued with 35 Ncm into two implant analogues. Before the tube bars were finally sealed, the inner cavity of the tube bar was filled with liquid red dye to evaluate microleakage. As tube bar sealing agents three different materials were used (AGC Cem (AGC, resin based), Cervitec Plus (CP; varnish) and Gapseal (GS; silicone based). Four groups with eight specimens each were tested (GS, GS+AGC, AGC, CP). For cyclic loading, the attachment system was assembled parallel to the female counterparts in a chewing simulator. The mean retention forces of the initial and final ten cycles were statistically evaluated (ANOVA, α≤.05). RESULTS: All groups showed a significant loss of retention forces. Their means differed between 30-39 N initially and 22-28 N after 50,000 loading cycles. No significant statistical differences could be found between the groups at the beginning (P=.224), at the end (P=.257) or between the loss of retention forces (P=.288). Microleakage occurred initially only in some groups but after 10,000 loading cycles all groups exhibited microleakage. CONCLUSION: Long-term retention forces of the SFI-Bar remained above 20 N which can be considered clinically sufficient. The sealing agents in this study are not suitable to prevent microleakage.

Long-term efficacy and safety of biodegradable-polymer biolimus-eluting stents: main results of the Basel Stent Kosten-Effektivitäts Trial-PROspective Validation Examination II (BASKET-PROVE II), a randomized, controlled noninferiority 2-year outcome trial.

BACKGROUND: Biodegradable-polymer drug-eluting stents (BP-DES) were developed to be as effective as second-generation durable-polymer drug-eluting stents (DP-DES) and as safe >1 year as bare-metal stents (BMS). Thus, very late stent thrombosis (VLST) attributable to durable polymers should no longer appear. METHODS AND RESULTS: To address these early and late aspects, 2291 patients presenting with acute or stable coronary disease needing stents ≥3.0 mm in diameter between April 2010 and May 2012 were randomly assigned to biolimus-A9-eluting BP-DES, second-generation everolimus-eluting DP-DES, or thin-strut silicon-carbide-coated BMS in 8 European centers. All patients were treated with aspirin and risk-adjusted doses of prasugrel. The primary end point was combined cardiac death, myocardial infarction, and clinically indicated target-vessel revascularization within 2 years. The combined secondary safety end point was a composite of VLST, myocardial infarction, and cardiac death. The cumulative incidence of the primary end point was 7.6% with BP-DES, 6.8% with DP-DES, and 12.7% with BMS. By intention-to-treat BP-DES were noninferior (predefined margin, 3.80%) compared with DP-DES (absolute risk difference, 0.78%; -1.93% to 3.50%; P for noninferiority 0.042; per protocol P=0.09) and superior to BMS (absolute risk difference, -5.16; -8.32 to -2.01; P=0.0011). The 3 stent groups did not differ in the combined safety end point, with no decrease in events >1 year, particularly VLST with BP-DES. CONCLUSIONS: In large vessel stenting, BP-DES appeared barely noninferior compared with DP-DES and more effective than thin-strut BMS, but without evidence for better safety nor lower VLST rates >1 year. Findings challenge the concept that durable polymers are key in VLST formation. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01166685.

Mechanical resistance of screwless morse taper and screw-retained implant-abutment connections.

OBJECTIVE: The screwless morse taper (SMT) implant-abutment connection is an alternative to conventional external or internal screw-retained (ISR) connections. The aim of this in vitro study was to evaluate mechanical resistance of the SMT connection and to compare it with three different ISR connections. MATERIALS AND METHODS: Four implant systems were tested in this study: SMT system; Tasarimmed Octo (Istanbul, Turkey), ISR systems; Straumann Bone Level (Basel, Switzerland), Biohorizons Internal (Birmingham, AL, USA), and Dentsply Friadent Xive (Mannheim, Germany). Overall, 64 specimens with stylized single crowns were prepared: 32 for dynamic loading (DL) and 32 for static loading (SL). DL was carried out using a chewing simulator with 120 N at 1.75 Hz for 1.2 × 10(6) cycles, and SL was performed with a universal testing machine at a crosshead speed of 2 mm/min with an angulation of 30°. Cycles until failure from DL and fracture/bending loads at SL were recorded. Statistical analyses were made with Dunn's multiple comparison. RESULTS: Median cycles until failure in DL were as follows: Octo 86,354 (24,810-153,875), Straumann 1,200,000 (1,156,618-1,200,000), Biohorizons 539,719 (437,224-858,732), Xive 139,411 (139,411-139,411). Median fracture/bending loads in Newton at SL were as follows: Octo 429.6 (404.5-482.7), Straumann 574.6 (544.6-629.9), Biohorizons 548.7 (532.9-567.3), Xive 431.5 (412.5-520.5). There were significant differences between the implant systems under both loading conditions (P ≤ 0.05) revealing that the Octo implant system's SMT connection showed significantly lower cycles to failures and lower fracture/bending loads compared with the ISR connections of the Straumann and Biohorizons implant systems. However, there was no significant difference compared with the Xive implant system. CONCLUSION: The mechanical resistance of the screwless morse taper implant system is lower than that of the ISR implant systems that might result in more frequent clinical complications.

Long-range correlations and complex regulation of pacing in long-distance road racing.

PURPOSE: To analyze time-domain, spectral, and fractal properties of speed regulation during half-marathon racing. METHODS: In 21 male experienced runners, high-resolution data on speed (V), stride frequency (SF), and stride length (SL) were assessed during half-marathon competition (21,098 m). Performance times, time- and frequency-domain variability, spectral-scaling exponent (beta), and fractal dimension (FD) of V, SF, and SL were analyzed. RESULTS: V of 3.65 ± 0.41 m/s, SF of 1.41 ± 0.05 Hz, and SL of 2.58 ± 0.25 m occurred with higher (P < .05) individual variability in V and SL than in SF. Beta and FD were always 1.04-1.88 and 1.56-1.99, respectively. Beta and FD differed (P < .05) in SF and SL compared with V and were correlated in V and SL (r = .91, P < .05). Spectral peaks of V, SF, and SL occurred at wavelengths of 3-35 min, and those of V and SL were interrelated (r = .56, P < .05). Mean SF and mean SL were significantly correlated with performance (r = .59 and r = .95, P < .05). SL accounted for 84% ± 6% and SF for 16% ± 6% of speed variability. CONCLUSIONS: The observed nonrandom fluctuations in V, SF, and SL correspond to nonstationary fractional Brownian motion with inherent long-range correlations. This indicates a similar complex regulation process in experienced runners that is primarily mediated via SL.

Resin bonding to three types of polyaryletherketones (PAEKs)-durability and influence of surface conditioning.

OBJECTIVES: The purpose of this in vitro study was to evaluate the bond strength and durability of adhesive bonding systems to amorphous and crystalline PEKK and fiber-reinforced PEEK using five types of surface conditioning methods. METHODS: One hundred and fifty specimens of each material were conditioned mechanically and chemically, bonded with Multilink Automix to Plexiglas tubes, filled with Multicore Flow, and stored in water at 37°C for 3, 30 and 150 days. The long-term storage series were thermal cycled between 5 and 55°C for 10,000 times (30 days) or for 37,500 times (150 days) prior to tensile bond strength test (TBS). Statistical analysis was performed using Kruskal-Wallis and Wilcoxon tests with a Bonferroni-Holm correction for multiple testing (α=0.05). RESULTS: Fiber-reinforced PEEK exhibited higher bond strengths in all five conditioning groups and at all three storage times than crystalline and amorphous PEKK, which showed lowest TBS. Highest TBS was achieved after conditioning with silica coating and priming (Rocatec Soft, Monobond Plus, Luxatemp Glaze & Bond; TBS up to 23.6MPa). SIGNIFICANCE: The conditioning method has a significant influence to the bond strength of the bonding to the amorphous and crystalline PEKKs and fiber-reinforced PEEKs.

"What do you mean by spirituality? Please draw me a picture!" Complementary faith-based addiction treatment in Switzerland from the client's perspective.

This article reviews: (1) the relative importance of spirituality and religion in Switzerland and the United States, (2) the rationale for faith-based addiction intervention programs and the drawbacks of measurement approaches, and (3) results from a pilot study exploring the meaning of spirituality and religiosity from the consumer's perspective. Twenty-three patients entering the Swiss Südhang clinic in-patient alcohol user treatment program during the first five months in 2012 participated upon their admission in a video-taped drawing task, designed to provide their personal visualized definitions of the terms "spirituality" and "religiosity." Nine dimensions emerged pointing to a high complexity of the concepts.

Influence of cement film thickness on the retention of implant-retained crowns.

PURPOSE: The main goal of this study was to establish a new, high precision procedure to evaluate the influence of cement film thickness on the retention of cemented implant-retained crowns. MATERIALS AND METHODS: Ninety-six tapered titanium abutments (6° taper, 4.3 mm diameter, Camlog) were shortened to 4 mm. Computer-aided design was used to design the crowns, and selective laser sintering, using a cobalt-chromium alloy, was used to produce the crowns. This method used a focused high-energy laser beam to fuse a localized region of metal powder to build up the crowns gradually. Before cementing, preset cement film thicknesses of 15, 50, 80, or 110 µm were established. Glass ionomer, polycarboxylate, or resin cements were used for cementation. After 3 days storage in demineralized water, the retention of the crowns was measured in tension using a universal testing machine. RESULTS: The cement film thicknesses could be achieved with a high level of precision. Interactions between the factors cement and cement film thickness could be found (p ≤ 0.001). For all cements, crown retention decreased significantly between a cement film thickness of 15 and 50 µm (p ≤ 0.001). At 15 µm cement film thickness, the resin cement was the most retentive cement, followed by the polycarboxylate and then the glass ionomer cement (p ≤ 0.05). CONCLUSIONS: The results suggest that cement film thickness has an influence on the retentive strength of cemented implant-retained crowns.

Long-Range Correlations and Complex Regulation of Pacing in Long-Distance Road Racing.

Purpose: To analyse time domain, spectral and fractal properties of speed regulation during half-marathon racing. Methods: In twenty-one male experienced runners high-resolution data on speed (V), stride frequency (SF) and stride length (SL) were assessed during half-marathon competition (21098 m). Performance times, time and frequency domain variability, spectral scaling exponent (beta) and fractal dimension (FD) of V, SF and SL were analysed. Results: V of 3.65±0.41 m·s-1, SF of 1.41±0.05 Hz and SL of 2.58±0.25 m occurred with higher (p<0.05) individual variability in V and SL compared to SF. Beta and FD were always in between 1.04 and 1.88 and 1.56 to 1.99, respectively. Beta and FD differed (p<0.05) in SF and SL compared to V and were correlated in V and SL (r=0.91, p<0.05). Spectral peaks of V, SF and SL occurred at wavelengths in between 3 to 35 min, and those of V and SL were interrelated (r=0.56, p<0.05). Mean SF and mean SL were significantly correlated with performance (r=0.59 and r=0.95, p<0.05). SL accounted for 84±6 % and SF for 16±6 % of speed variability, respectively. Conclusions: The observed non-random fluctuations in V, SF and SL correspond to non-stationary fractional Brownian motion with inherent long-range correlations. This indicates a similar complex regulation process in experienced runners that is primarily mediated via SL.

Forces affecting orbital floor reconstruction materials--a cadaver study.

INTRODUCTION: The objectives of this study were: (i) to evaluate the applied force and the displacement of the orbital contents after orbital floor reconstruction using artificially aged reconstruction materials in fresh frozen human heads and (ii) to analyze the puncture strength of the materials. MATERIAL AND METHODS: Six fresh frozen human heads were used, and orbital floor defects in the right and left orbit were created by 3.0 J direct impacts on the globe and infraorbital rim. The orbital floor defect sizes and displacements were evaluated after a Le-Fort-I osteotomy. RESULTS: The orbital floor defect sizes were 208.3(SD, 33.4) mm(2) for the globe impacts and 221.8(SD, 53.1) mm(2) for the infraorbital impacts. The forces on the incorporated materials were approximately 0.003 N and 0.03 N for the PDS-foil and collagen membrane, respectively. The displacements of the materials were +0.9 mm and +0.7 mm for the PDS-foil and collagen membrane, respectively. The puncture strengths of the PDS-foil and collagen membrane decreased from approximately 70 N and 12 N at week 1 to approximately 5 N and 1.5 N at week 8 of artificial aging. CONCLUSION: The force applied to the orbital content is minimal, and the puncture strengths of the artificially aged materials are more than sufficient for the measured forces.

Multidisciplinary Assessment to Personalize Length of Stay in Acute Decompensated Heart Failure (OPTIMA II ADHF).

BACKGROUND: Acute decompensated heart failure (ADHF) causes a substantial burden for health care systems. Data to rationally define the need for hospitalization or the appropriate length of stay (LOS) is limited. Our aim was to personalize length of stay in patients admitted to hospital for acute decompensated heart failure. METHODS: Consecutive patients with ADHF presenting to our emergency department were prospectively followed. We daily conducted a multidisciplinary risk assessment and compared proposed with actually observed triage decisions. RESULTS: At presentation, all patients required hospitalization. Median LOS was 11 days including 1 day after reaching medical stability. In 42.7% of patients, hospitalization was prolonged after medical stability mainly for nursing and organizational reasons. Within 30 days of enrollment, 7 (9.3%) patients were rehospitalized, 3 of them for persisting or relapsing heart failure. CONCLUSIONS: There appears to be potential to shorten inhospital stay in patients with ADHF mainly by providing post discharge ambulatory nursing care in order to improve resource utilization and to diminish "hospitalization-associated disability".

Influence of abutment height and thermocycling on retrievability of cemented implant-supported crowns.

PURPOSE: To evaluate the influence of abutment height and thermocycling on the retrievability of cemented implant crowns. MATERIALS AND METHODS: Ninety tapered titanium abutments (6 degree taper, 4.3 mm diameter, 8.5 mm height) were shortened to 2, 3, or 4 mm, respectively. Ninety crowns were designed and manufactured using CAD/CAM techniques and laser sintering a CoCr alloy. The crowns were cemented either with a glass-ionomer, a polycarboxylate, or a composite resin cement followed by 3-day storage in demineralized water without thermocycling or 150-day storage with 37,500 thermal cycles. The force (in N) and the number of attempts needed to remove the crowns using a universal testing machine (UTM) or a clinically used removal device (Coronaflex) were recorded. Statistical analysis at a level of significance of P ≤ .05 was conducted using the Kruskal-Wallis and Mann-Whitney U tests (Coronaflex) and three-way and two-way ANOVA, Tukey's HSD post hoc tests, and t tests (UTM). RESULTS: Regardless of whether the crowns were retrieved with Coronaflex or UTM, the crowns cemented with the glass-ionomer cement were significantly easier to retrieve followed by the polycarboxylate and the resin cement, both of which differed significantly from each other (P ≤ .001). With both retrieval methods, the cement, abutment height, and thermocycling were significantly influential (P ≤ .0001). Significant interactions could be found for retrieval with UTM between the abutment height and thermocycling, between the cement and thermocycling, and between all three factors (P ≤ .05). CONCLUSIONS: Glass-ionomer cement may be used for retrievable cementation of implant restorations, whereas polycarboxylate cement and especially composite resin cement should be used for a nonretrievable permanent cementation.

Maximum forces applied to the orbital floor after fractures.

The objective of this study was to measure the force on and displacement of completely detached intraorbital tissue from the bony orbit, as a worst-case scenario after orbital trauma, to preserve the maximum load and predict the necessary strength of reconstruction materials. Six fresh-frozen human heads were used, and orbital floor defects in the right and left orbits were created by the direct impact of 3.0 J onto the globe and infraorbital rim. The orbital floor defect sizes and displacements were evaluated after performing a Le Fort I osteotomy. In addition, after the repositioning of the completely detached intraorbital tissue, the forces and displacements were measured. The mean orbital floor defect sizes were 208.3 (SD, 33.4) mm2 for globe impacts and 221.8 (SD, 53.1) mm2 for infraorbital impacts. The mean intraorbital tissue displacement after the impact and before repositioning was 5.6 (SD, 1.0) mm for globe impacts and 2.8 (SD, 0.7) mm for infraorbital impacts. After repositioning, the displacements were 0.8 (SD, 0.5) mm and 1.1 (SD, 0.7) mm, respectively. The measured forces were 0.10519 (SD, 0.00958) N without the incorporation and approximately 0.11128 (SD, 0.003599) N with the incorporation of reconstruction materials. The maximum forces on the completely detached orbital tissue were minimal (∼0.11 N) and suggest the use of collagen membranes as reconstruction materials for orbital floor defects, at least in medium-sized fractures.

Forces charging the orbital floor after orbital trauma.

The objectives of this study were (i) to evaluate different fracture mechanisms for orbital floor fractures and (ii) to measure forces and displacement of intraorbital tissue after orbital traumata to predict the necessity of strength for reconstruction materials. Six fresh frozen human heads were used, and orbital floor defects in the right and left orbit were created by a direct impact of 3.0 J onto the globe and infraorbital rim, respectively. Orbital floor defect sizes and displacement were evaluated after a Le Fort I osteotomy. In addition, after reposition of the intraorbital tissue, forces and displacement were measured. The orbital floor defect sizes were 208.3 (SD, 33.4) mm(2) for globe impact and 221.8 (SD, 53.1) mm(2) for infraorbital impact. The intraorbital tissue displacement after the impact and before reposition was 5.6 (SD, 1.0) mm for globe impact and 2.8 (SD, 0.7) mm for infraorbital impact. After reposition, the displacement was 0.8 (SD, 0.5) mm and 1.1 (SD, 0.7) mm, respectively. The measured applied forces were 0.061 (SD, 0.014) N for globe impact and 0.066 (SD, 0.022) N for infraorbital impact. Different fracture-inductive mechanisms are not reflected by the pattern of the fracture. The forces needed after reposition are minimal (~0.07 N), which may explain the success of PDS foils [poly-(p-dioxanone)] and collagen membranes as reconstruction materials.

A scientific nutrition strategy improves time trial performance by ≈6% when compared with a self-chosen nutrition strategy in trained cyclists: a randomized cross-over study.

We investigated whether an athlete's self-chosen nutrition strategy (A), compared with a scientifically determined one (S), led to an improved endurance performance in a laboratory time trial after an endurance exercise. S consisted of about 1000 mL·h(-1) fluid, in portions of 250 mL every 15 min, 0.5 g sodium·L(-1), 60 g glucose·h(-1), 30 g fructose·h(-1), and 5 mg caffeine·kg body mass(-1). Eighteen endurance-trained cyclists (16 male; 2 female) were tested using a randomized crossover-design at intervals of 2 weeks, following either A or S. After a warm-up, a maximal oxygen uptake test was performed. Following a 30-min break, a 2.5-h endurance exercise on a bicycle ergometer was carried out at 70% maximal oxygen uptake. After 5 min of rest, a time trial of 64.37 km (40 miles) was completed. The ingested nutrition was recorded every 15 min. In S, the athletes completed the time trial faster (128 vs. 136 min; p ≤ 0.001) and with a significantly higher power output (212 vs. 184 W; p ≤ 0.001). The intake of fluid, energy (carbohydrate-, mono-, and disaccharide), and sodium was significantly higher in S compared with A (p ≤ 0.001) during the endurance exercise. In the time trial, only sodium intake was significantly higher in S (p ≤ 0.001). We concluded that a time trial performance after a 2.5-h endurance exercise in a laboratory setting was significantly improved following a scientific nutrition strategy.

Intralymphatic immunotherapy for cat allergy induces tolerance after only 3 injections.

BACKGROUND: Subcutaneous allergen-specific immunotherapy frequently causes allergic side effects and requires 30 to 80 injections over 3 to 5 years. OBJECTIVE: We sought to improve immunotherapy by using intralymphatic allergen administration (intralymphatic immunotherapy [ILIT]) and by targeting allergen to the MHC class II pathway. METHODS: Recombinant major cat dander allergen Fel d 1 was fused to a translocation sequence (TAT) and to part of the human invariant chain, generating a modular antigen transporter (MAT) vaccine (MAT-Fel d 1). In a randomized double-blind trial ILIT with MAT-Fel d 1 in alum was compared with ILIT with placebo (saline in alum) in allergic patients (ClinicalTrials.govNCT00718679). RESULTS: ILIT with MAT-Fel d 1 elicited no adverse events. After 3 placebo injections within 2 months, nasal tolerance increased less than 3-fold, whereas 3 intralymphatic injections with MAT-Fel d 1 increased nasal tolerance 74-fold (P < .001 vs placebo). ILIT with MAT-Fel d 1 stimulated regulatory T-cell responses (P = .026 vs placebo) and increased cat dander-specific IgG(4) levels by 5.66-fold (P = .003). The IgG(4) response positively correlated with IL-10 production (P < .001). CONCLUSION: In a first-in-human clinical study ILIT with MAT-Fel d 1 was safe and induced allergen tolerance after 3 injections.