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Purpose The currently used system to classify the lower limb alignment (neutral, varus, valgus) does not consider the orientation of the joint line or its relationship to the overall lower limb alignment. Similarly, current total knee arthroplasty (TKA) alignment concepts do not sufficiently consider the variability of the native coronal alignment. Therefore, the purpose of this study was (1) to introduce a new classification system for the lower limb alignment, based on phenotypes, and (2) to compare the alignment targets of different TKA alignment concepts with the native alignment of non-osteoarthritic patients. Methods Two recent articles phenotyped the lower limb, the femur and tibia of 308 non-osteoarthritic knees of 160 patients [male to female ratio = 102:58, mean age ± standard deviation 30 ± 7 years (16–44 years)]. The present study introduces functional knee phenotypes, which are a combination of all previously introduced phenotypes. The functional knee phenotypes therefore enable an evaluation of all parameters in relation to each other and thus a comprehensive analysis of the coronal alignment. The existing functional knee phenotypes in the female and male population were investigated. In addition, how many non-osteoarthritic knees had an alignment within the range of current TKA alignment targets (mechanical, anatomical and restricted kinematic alignment) was investigated. Therefore, it was defined which functional knee phenotypes represented a target of the TKA alignment concepts and which percentage of the population had such a phenotype. Results Out of 125 possible functional knee phenotypes, 43 were found (35 male, 26 and 18 mutual). The most common functional knee phenotype in males was NEU HKA 0° + NEU FMA 0° + NEU TMA 0° (19%), followed by VAR HKA 3° + NEU FMA 0° + VAR TMA 0° (8.2%). The most common functional knee phenotype in females was NEU HKA 0° + NEU FMA 0° + NEU TMA 0° (17.7%), closely followed by NEU HKA 0° + NEU FMA 0° + VAL TMA 0° (16.6%). The functional knee phenotype representing a mechanical alignment target was found in 5.6% of the males and 3.6% of the females. The phenotype representing an anatomical alignment target was found in 18% of the males and 17% in females. Five of the nine phenotypes representing a restricted kinematic alignment target were found in this population (male 5, female 4, mutual 4). They represented 31.3% of all males and 45.1% of all females. Conclusion A more individualized approach to TKA alignment is needed. The functional knee phenotypes enable a simple, but detailed assessment of a patient’s individual anatomy and thereby could be a helpful tool to individualize the approach to TKA. Level of clinical evidence III, retrospective cohort study.

Multiple sequence alignment (MSA) is a key modeling procedure when analyzing biological sequences. Homology and evolutionary modeling are the most common applications of MSAs. Both are known to be sensitive to the underlying MSA accuracy. In this work, we show how this problem can be partly overcome using the transitive consistency score (TCS), an extended version of the T-Coffee scoring scheme. Using this local evaluation function, we show that one can identify the most reliable portions of an MSA, as judged from BAliBASE and PREFAB structure-based reference alignments. We also show how this measure can be used to improve phylogenetic tree reconstruction using both an established simulated data set and a novel empirical yeast data set. For this purpose, we describe a novel lossless alternative to site filtering that involves overweighting the trustworthy columns. Our approach relies on the T-Coffee framework; it uses libraries of pairwise alignments to evaluate any third party MSA. Pairwise projections can be produced using fast or slow methods, thus allowing a trade-off between speed and accuracy. We compared TCS with Heads-or-Tails, GUIDANCE, Gblocks, and trimAl and found it to lead to significantly better estimates of structural accuracy and more accurate phylogenetic trees. The software is available from www.tcoffee.org/Projects/tcs.

Phylogenetic inference is generally performed on the basis of multiple sequence alignments (MSA). Because errors in an alignment can lead to errors in tree estimation, there is a strong interest in identifying and removing unreliable parts of the alignment. In recent years several automated filtering approaches have been proposed, but despite their popularity, a systematic and comprehensive comparison of different alignment filtering methods on real data has been lacking. Here, we extend and apply recently introduced phylogenetic tests of alignment accuracy on a large number of gene families and contrast the performance of unfiltered versus filtered alignments in the context of single-gene phylogeny reconstruction. Based on multiple genome-wide empirical and simulated data sets, we show that the trees obtained from filtered MSAs are on average worse than those obtained from unfiltered MSAs. Furthermore, alignment filtering often leads to an increase in the proportion of well-supported branches that are actually wrong. We confirm that our findings hold for a wide range of parameters and methods. Although our results suggest that light filtering (up to 20% of alignment positions) has little impact on tree accuracy and may save some computation time, contrary to widespread practice, we do not generally recommend the use of current alignment filtering methods for phylogenetic inference. By providing a way to rigorously and systematically measure the impact of filtering on alignments, the methodology set forth here will guide the development of better filtering algorithms,

Purpose Restricted kinematic alignment (rKA) in total knee arthroplasty (TKA) aims to restore native soft tissue laxities while limiting alignment extremes that risk prosthetic failure. However, there is no consensus where restricted boundaries (RB) should be set. This study aims to determine the proportion of limbs in which constitutional alignment and joint line obliquity (JLO) would be restored with various RB scenarios, to inform decision making in rKA TKA. Methods The mechanical hip–knee–ankle (mHKA) angle, arithmetic hip–knee–ankle (aHKA) angle, lateral distal femoral angle (LDFA) and medial proximal tibial angle (MPTA) were measured on radiographs of 500 normal knees. Incrementally wider RBs were then applied. The proportion of limbs within each increment was determined when RBs were applied only to HKA, or to HKA, LDFA and MPTA together. In addition, the proportion of limbs within published adjusted mechanical alignment (aMA) and rKA protocols were determined, as well as those within one, two and three standard deviations of the means for HKA, LDFA and MPTA. Results When restrictions to mHKA alone were applied, 74.0% and 97.8% of knees were captured with boundaries of ± 3° and ± 6° respectively. However, when the same boundaries to HKA were also applied to MPTA and LDFA, 36.2% and 91.0% of knees were captured respectively, highlighting the limiting effect that JLO has on restoration of normal knee phenotypes. When comparing previously published boundaries, aMA of 0° ± 3° captured 36.2%; rKA of 0° ± 3 for HKA and 85° to 95° for LDFA/MPTA captured 67.8%; rKA of − 5° to 4° HKA and 86°–93° for LDFA/MPTA captured 63%; and rKA of − 6° to + 3° for HKA and 84°–93° for LDFA/MPTA captured 85.4%. Conclusion The greatest proportions of normal knee phenotypes were captured with boundaries that were centred around population means for HKA and JLO. Further, these findings demonstrate that restricting the JLO has a significant limiting influence on restoration of normal knee phenotypes beyond that of restricting HKA alone. Level of evidence III.

The electronic transfer and active surface area of carbon nanotubes (CNTs) have been increased by using a template for the growth of patterned vertically aligned carbon nanotubes (VACNTs). To get the novel template, spherical SiO sub(2) particles of 500 nm in diameter were synthesized by sol-gel method with high homogeneity in size and shape. The resulting particles were deposited as self-assembled monolayers over different substrates by Langmuir-Blodgett technique. The obtained monolayers were used as a sacrificial template for the growth of patterned VACNTs by plasma-enhanced chemical vapor deposition. Ni catalyst was deposited through the SiO sub(2) particles template by magnetron sputtering. Morphological and structural characterization of the substrate before and after the CNTs growth was carried out using different techniques. Raman spectroscopy was performed to analyze the quality and structure of the CNTs.

The continuous development of sequencing technologies has enabled researchers to obtain large amounts of biological sequence data, and this has resulted in increasing demands for software that can perform sequence alignment fast and accurately. A number of algorithms and tools for sequence alignment have been designed to meet the various needs of biologists. Here, the ideas that prevail in the research of sequence alignment and some quality estimation methods for multiple sequence alignment tools are summarized.

Purpose Total knee arthroplasty with functional alignment uses pre-resection balancing to determine component position within the soft tissue envelope to achieve balance and restoration of native joint obliquity. The purpose of this study was to assess the balance achievable with a mechanical axis alignment and kinematic axis alignment plan, and the subsequent balance achievable after adjustment of the component position to functional alignment. Methods A prospective cohort of 300 knees undergoing cruciate retaining total knee arthroplasty were included in this study. Of these, 130 were initially planned with mechanical alignment (MA) and 170 with kinematic alignment (KA). Maximal stressed virtual gaps were collected using an optical tracking software system. The gaps were measured medially and laterally in flexion and extension. Following assessment of balance, implant position was adjusted to balance the soft tissues in functional alignment (FA) and the maximal gaps reassessed. Gaps were considered to be balanced when within 2 mm of equality. Incidence of balance within each cohort was compared to independent samples proportions test. Results Functional alignment obtained significantly better balance in extension, medially and overall than both MA and KA alignment without soft tissue release ( p  < 0.001). Overall balance was observed in 97% of FA knees, 73% of KA knees and in 55% of MA knees. The difference between KA and MA was also significant ( p  = 0.002). Whilst there was no difference observed in balanced achieved or limb alignment when FA was planned with either MA or KA, the joint line obliquity was maintained with an initial KA plan. Conclusion Functional alignment more consistently achieves a balanced total knee arthroplasty than either mechanical alignment or kinematic alignment prior to undertaking soft tissue release. Utilising an individualised KA plan allows FA to best achieve the stated goals of maintaining joint line plane and obliquity. Level of evidence Level III: retrospective cohort study.

Millions of species are currently being sequenced, and their genomes are being compared. Many of them have more complex genomes than model systems and raise novel challenges for genome alignment. Widely used local alignment strategies often produce limited or incongruous results when applied to genomes with dispersed repeats, long indels, and highly diverse sequences. Moreover, alignment using many-to-many or reciprocal best hit approaches conflicts with well-studied patterns between species with different rounds of whole-genome duplication. Here, we introduce Anchored Wavefront alignment (AnchorWave), which performs whole-genome duplication–informed collinear anchor identification between genomes and performs base pair–resolved global alignment for collinear blocks using a two-piece affine gap cost strategy. This strategy enables AnchorWave to precisely identify multikilobase indels generated by transposable element (TE) presence/absence variants (PAVs). When aligning two maize genomes, AnchorWave successfully recalled 87% of previously reported TE PAVs. By contrast, other genome alignment tools showed low power for TE PAV recall. AnchorWave precisely aligns up to three times more of the genome as position matches or indels than the closest competitive approach when comparing diverse genomes. Moreover, AnchorWave recalls transcription factor–binding sites at a rate of 1.05- to 74.85-fold higher than other tools with significantly lower false-positive alignments. AnchorWave complements available genome alignment tools by showing obvious improvement when applied to genomes with dispersed repeats, active TEs, high sequence diversity, and wholegenome duplication variation.

Purpose Recommendations for resecting distal femur and proximal tibia in mechanical and anatomical alignment techniques are standardized. Kinematic alignment propagates individualizing resection planes. Whether significant variation exists, to warrant departure from standardized resection planes, has not been shown thus far in a large cohort of knees and with a wide range of varus deformity. The null hypothesis of this study was that there was no phenotypic variation in varus osteoarthritic knees. The aim of this paper was to determine whether distinct phenotypes could be identified, based on variations in coronal femoral and tibial morphology, which could aid in surgical planning and categorizing varus knees for future studies. Methods 2129 full-leg weightbearing radiographs were analyzed (1704 preoperative; 425 of contralateral arthritic knee). Measurements made were of HKA (hip-knee-ankle angle), VCA (valgus correction angle), mLDFA (lateral mechanical distal femoral angle), aLDFA (lateral anatomical distal femoral angle), MPTA (medial proximal tibial angle), MNSA (medial neck shaft angle), TAMA (angle between tibial mechanical and anatomical axes), and TPDR (percentage length of tibia proximal to extra-articular deformity). Results Seven distinct types were identified covering 2021 knees, reducible to 4 broad phenotypes: 11% were Type 1 ‘Neutral’ knees showing values close to reported normal knees (mean VCA 5.5°, mLDFA 87°, aLDFA 81°). 38% were Type 2 ‘Intra-articular varus’ with medial intra-articular bone loss (mean mLDFA 90.9°, MPTA 85.4°, VCA of 5.7°). 41% were Type 3 ‘Extra-articular varus’ with extra-articular deformity (EAD). Type 3a had proximal tibial EAD; Type 3b had tibial diaphyseal EAD; Type 3c had femoral EAD (mean VCA 8.7°, HKA 166°), and severe medial bone loss (mean mLDFA 92°, MPTA 83°). 9% were Type 4 ‘Valgoid type’ with features of valgus knees: Type 4a had medial femoral bowing (mean VCA 2.9°); Type 4b had significant distal femoral valgus (mean mLDFA 85.3°, aLDFA 78.6°). Conclusions The null hypothesis that there was no phenotypic variation in varus osteoarthritic knees was rejected as considerable variation was found in coronal morphology of femur and tibia. Four broad phenotypic groups could be identified. Plane of the knee joint articular surface was quite variable. This has relevance to planning and performance of corrective osteotomies, unicompartmental and total knee arthroplasty. Level of Evidence III, retrospective cohort study.