A prospective randomised control trial comparing functional with mechanical axis alignment in total knee arthroplasty: study protocol for an investigator initiated trial

Background A drive to improve functional outcomes for patients undergoing total knee arthroplasty (TKA) has led to alternative alignment being used. Functional alignment (FA) uses intraoperative soft tissue tension to determine the optimal position of the prosthesis within the patient’s soft tissue envelope. Angular limits for bone resections are followed to prevent long-term prosthesis failure. This study will use the aid of robotic assistance to plan and implement the final prosthesis position. This method has yet to be compared to the traditional mechanically aligned (MA) knee in a randomised trial. Methods A blinded randomised control trial with 100 patients will be undertaken via Perth Hip and Knee Clinic. Fifty patients will undergo a MA TKA and fifty will undergo a FA TKA. Both alignment techniques will be balanced via computer-assisted navigation to assess prosthetic gaps, being achieved via the initial bony resection and further soft tissue releases as required to achieve satisfactory balance. The primary outcome will be the Forgotten Joint Score (FJS) 2 years after surgery, with secondary outcomes being other patient-reported outcome measures, clinical functional assessment, radiographic position and complications. Other data that will be collected will be patient demography (sex, age, level of activity) and medical information (grade of knee injury, any other relevant medical information). The linear statistical model will be fitted to the response (FJS), including all the other variables as covariates. Discussion Many surgeons are utilising alternative alignment techniques with a goal of achieving better functional outcomes for their patients. Currently, MA TKA remains the gold standard with good outcomes and excellent longevity. There is no published RCTs comparing FA to MA yet and only two registered studies are planned or currently in progress. This study utilises a FA technique which differs from the two studies. This study will help determine if FA TKA has superior functional results for patients. Trial registration This trial has been registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) http://www.anzctr.org.au: U1111-1257-2291, registered 25th Jan 2021. It is also listed on www.clinicaltrials.gov: NCT04748510.

A Prospective Randomised Control Trial Comparing Functional with Mechanical Axis Alignment in Total Knee Arthroplasty: study protocol for an investigator initiated trial

Background: A drive to improve functional outcomes for patients undergoing total knee arthroplasty (TKA) has led to alternative alignment being used. Functional alignment (FA) uses intraoperative soft tissue tension to determine the optimal position of the prosthesis within the patients soft tissue envelope. Angular limits for bone resections are followed to prevent long term prosthesis failure. This study will use the aid of robotic assistance to plan and implement the final prosthesis position. This method has yet to be compared to the traditional mechanically aligned (MA) knee in a randomised trial. Methods: A blinded randomised control trial with 100 patients will be undertaken via Perth Hip and Knee clinic. Fifty patients will undergo a MA TKA and fifty will undergo a FA TKA. Both alignment techniques will be balanced via computer assisted navigation to assess prosthetic gaps, being achieved via the initial bony resection and further soft tissue releases as required to achieve satisfactory balance. The primary outcome will be the forgotten joint score (FJS) two years after surgery, with secondary outcomes being other patient reported outcome measures, clinical functional assessment, radiographic position and complications. Other data that will be collected will be patient demography (Sex, Age, level of activity) and medical information (grade of knee injury, any other relevant medical information). The linear statistical model will be fitted to the response (FJS), including all the other variables as covariates. Discussion: Many surgeons are utilising alternative alignment techniques with a goal of achieving better functional outcomes for their patients. Currently MA TKA remains the gold standard with good outcomes and excellent longevity. There is no published RCTs comparing FA to MA yet and only two registered studies are planned or currently in progress. This study utilizes a FA technique which differs from the two studies. This study will help determine if FA TKA has superior functional results for patients.Trial registration: This trial has been registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) http://www.anzctr.org.au: U1111-1257-2291, registered 25th Jan 2021. It is also listed on www.clinicaltrials.gov: NCT04748510

ClipKIT: A multiple sequence alignment trimming software for accurate phylogenomic inference

Highly divergent sites in multiple sequence alignments (MSAs), which can stem from erroneous inference of homology and saturation of substitutions, are thought to negatively impact phylogenetic inference. Thus, several different trimming strategies have been developed for identifying and removing these sites prior to phylogenetic inference. However, a recent study reported that doing so can worsen inference, underscoring the need for alternative alignment trimming strategies. Here, we introduce ClipKIT, an alignment trimming software that, rather than identifying and removing putatively phylogenetically uninformative sites, instead aims to identify and retain parsimony-informative sites, which are known to be phylogenetically informative. To test the efficacy of ClipKIT, we examined the accuracy and support of phylogenies inferred from 14 different alignment trimming strategies, including those implemented in ClipKIT, across nearly 140,000 alignments from a broad sampling of evolutionary histories. Phylogenies inferred from ClipKIT-trimmed alignments are accurate, robust, and time saving. Furthermore, ClipKIT consistently outperformed other trimming methods across diverse datasets, suggesting that strategies based on identifying and retaining parsimony-informative sites provide a robust framework for alignment trimming.

Sequence Comparison Alignment-Free Approach Based on Suffix Tree andL-WordsFrequency

The vast majority of methods available for sequence comparison rely on a first sequence alignment step, which requires a number of assumptions on evolutionary history and is sometimes very difficult or impossible to perform due to the abundance of gaps (insertions/deletions). In such cases, an alternative alignment-free method would prove valuable. Our method starts by a computation of a generalized suffix tree of all sequences, which is completed in linear time. Using this tree, the frequency of all possible words with a preset lengthL—L-words—in each sequence is rapidly calculated. Based on theL-wordsfrequency profile of each sequence, a pairwise standard Euclidean distance is then computed producing a symmetric genetic distance matrix, which can be used to generate a neighbor joining dendrogram or a multidimensional scaling graph. We present an improvement to word counting alignment-free approaches for sequence comparison, by determining a single optimal word length and combining suffix tree structures to the word counting tasks. Our approach is, thus, a fast and simple application that proved to be efficient and powerful when applied to mitochondrial genomes. The algorithm was implemented in Python language and is freely available on the web.

Fundamental Limits for 3D Wafer-to-Wafer Alignment Accuracy

Wafer-level three-dimensional (3D) integration as an emerging architecture for future chips offers high interconnect performance by reducing delays of global interconnects and high functionality with heterogeneous integration of materials, devices, and signals. Various 3D technology platforms have been investigated, with different combinations of alternative alignment, bonding, thinning and inter-wafer interconnection technologies. Precise alignment on the wafer level is one of the key challenges affecting the performance of the 3D interconnects. After a brief overview of the wafer-level 3D technology platforms, this paper focuses on waferto-wafer alignment fundamentals. Various alignment methods are reviewed. A higher emphasis lies on the analysis of the alignment accuracy. In addition to the alignment accuracy achieved prior to bonding, the impacts of wafer bonding and subsequent wafer thinning will be discussed.