Microhabitat selection in the common lizard: implications of biotic interactions, age, sex, local processes, and model transferability among populations.

Modeling species' habitat requirements are crucial to assess impacts of global change, for conservation efforts and to test mechanisms driving species presence. While the influence of abiotic factors has been widely examined, the importance of biotic factors and biotic interactions, and the potential implications of local processes are not well understood. Testing their importance requires additional knowledge and analyses at local habitat scale. Here, we recorded the locations of species presence at the microhabitat scale and measured abiotic and biotic parameters in three different common lizard (Zootoca vivipara) populations using a standardized sampling protocol. Thereafter, space use models and cross-evaluations among populations were run to infer local processes and estimate the importance of biotic parameters, biotic interactions, sex, and age. Biotic parameters explained more variation than abiotic parameters, and intraspecific interactions significantly predicted the spatial distribution. Significant differences among populations in the relationship between abiotic parameters and lizard distribution, and the greater model transferability within populations than between populations are in line with effects predicted by local adaptation and/or phenotypic plasticity. These results underline the importance of including biotic parameters and biotic interactions in space use models at the population level. There were significant differences in space use between sexes, and between adults and yearlings, the latter showing no association with the measured parameters. Consequently, predictive habitat models at the population level taking into account different sexes and age classes are required to understand a specie's ecological requirements and to allow for precise conservation strategies. Our study therefore stresses that future predictive habitat models at the population level and their transferability should take these parameters into account

Complementing Prostate SBRT VMAT With a Two-Beam Non-Coplanar IMRT Class Solution to Enhance Rectum and Bladder Sparing With Minimum Increase in Treatment Time

Purpose Enhance rectum and bladder sparing in prostate SBRT with minimum increase in treatment time by complementing dual-arc coplanar VMAT with a two-beam non-coplanar IMRT class solution (CS). Methods For twenty patients, an optimizer for automated multi-criterial planning with integrated beam angle optimization (BAO) was used to generate dual-arc VMAT plans, supplemented with five non-coplanar IMRT beams with individually optimized orientations (VMAT+5). In all plan generations, reduction of high rectum dose had the highest priority after obtaining adequate PTV coverage. A CS with two most preferred directions in VMAT+5 and largest rectum dose reductions compared to dual-arc VMAT was then selected to define VMAT+CS. VMAT+CS was compared with automatically generated i) dual-arc coplanar VMAT plans (VMAT), ii) VMAT+5 plans, and iii) IMRT plans with 30 patient-specific non-coplanar beam orientations (30-NCP). Plans were generated for a 4 x 9.5 Gy fractionation scheme. Differences in PTV doses, healthy tissue sparing, and computation and treatment delivery times were quantified. Results For equal PTV coverage, VMAT+CS, consisting of dual-arc VMAT supplemented with two fixed, non-coplanar IMRT beams with fixed Gantry/Couch angles of 65 degrees/30 degrees and 295 degrees/-30 degrees, significantly reduced OAR doses and the dose bath, compared to dual-arc VMAT. Mean relative differences in rectum D-mean, D-1cc, V-40GyEq and V-60GyEq were 19.4 +/- 10.6%, 4.2 +/- 2.7%, 34.9 +/- 20.3%, and 39.7 +/- 23.2%, respectively (all p Conclusions The proposed two-beam non-coplanar class solution to complement coplanar dual-arc VMAT resulted in substantial plan quality improvements for OARs (especially rectum) and reduced irradiated patient volumes with minor increases in treatment delivery times

IgG light chain-independent secretion of heavy chain dimers: consequence for therapeutic antibody production and design

Rodent monoclonal antibodies with specificity towards important biological targets are developed for therapeutic use by a process of humanisation. This process involves the creation of molecules, which retain the specificity of the rodent antibody but contain predominantly human coding sequence. Here we show that some humanised heavy chains can fold, form dimers and be secreted even in the absence of light chain. Quality control of recombinant antibody assembly in vivo is thought to rely upon folding of the heavy chain CH1 domain. This domain acts as a switch for secretion, only folding upon interaction with the light chain CL domain. We show that the secreted heavy-chain dimers contain folded CH1 domains and contribute to the heterogeneity of antibody species secreted during the expression of therapeutic antibodies. This subversion of the normal quality control process is dependent upon the heavy chain variable domain, is prevalent with engineered antibodies and can occur when only the Fab fragments are expressed. This discovery will impact on the efficient production of both humanised antibodies as well as the design of novel antibody formats

Tsetse fly inspired steerable bone drill—a proof of concept

The fixation strength of pedicle screws could be increased by fixating along the much stronger cortical bone layer, which is not possible with the current rigid and straight bone drills. Inspired by the tsetse fly, a single-plane steerable bone drill was developed. The drill has a flexible transmission using two stacked leaf springs such that the drill is flexible in one plane and can drill along the cortical bone layer utilizing wall guidance. A proof-of-principle experiment was performed which showed that the Tsetse Drill was able to successfully drill through 5, 10 and 15 PCF cancellous bone phantom which has similar mechanical properties to severe osteoporotic, osteoporotic and healthy cancellous bone. Furthermore, the Tsetse Drill was able to successfully steer and drill along the cortical wall utilizing wall guidance for an insertion angle of 5°, 10° and 15°. The experiments conclude that the tsetse fly-inspired drilling method is successful and even allows the drilling along the cortical bone layer. The Tsetse Drill can create curved tunnels utilizing wall guidance which could increase the fixation strength of bone anchors and limit the risk of cortical breach and damage to surrounding anatomy

Clinical, Radiologic, and Functional Outcomes Following Methotrexate Withdrawal in Etanercept-Treated Patients with Active Early Rheumatoid Arthritis: A Subanalysis of COMET Year 2 by Week 52 DAS28 Status

Introduction: This post-hoc analysis explored Methotrexate (MTX) withdrawal on clinical, radiographic, and functional outcomes in patients with early rheumatoid arthritis who previously received 52 weeks of Etanercept (ETN) + MTX treatment in the COMET study. Methods: Response at week 104 was analyzed based on the attainment of remission (28-joint disease activity score [DAS28] <2.6; Boolean); low disease activity (LDA; 2.6 ≤DAS28 ≤3.2); normal Health Assessment Questionnaire-Disability Index (HAQ-DI) score (≤0.5); or radiographic non-progression (change in modified Total Sharp Score ≤0.5). Results: Of 208 patients with baseline DAS28 scores at week 52, 105 received ETN + MTX and 103 received ETN over weeks 52-104 (Period 2). At week 104, rates of LDA (70% vs 67%), remission (59% vs 52%), and normal HAQ-DI (63% vs 61%) were similar in both arms; week 52 responders also had a higher response rate at week 104 irrespective of treatment during Period 2. Overall rates of radiographic non-progression were higher for ETN + MTX (90%) vs ETN (74%) at week 104; week 52 non-responders in the Period 2 ETN + MTX arm had a 21-27% higher rate vs ETN, while the treatment difference was 11-12% for week 52 responders. Conclusion: The data suggest that for responders to ETN + MTX at week 52, MTX may be safely withdrawn. For non-responders where de-escalation would not be considered, the continuation of the combination is advisable. Radiological outcome was numerically worse, but of uncertain clinical significance