Optimal Wavelet Selection for Signal Denoising.

Wavelet denoising plays a key role in removing noise from signals and is widely used in many applications. In denoising, selection of the mother wavelet is desirable for maximizing the separation of noise and signal coefficients in the wavelet domain for effective noise thresholding. At present, wavelet selection is carried out in a heuristic manner or using a trial-and-error that is time consuming and prone to error, including human bias. This paper introduces a universal method to select optimal wavelets based on the sparsity of Detail components in the wavelet domain, an empirical approach. A mean of sparsity change ( µ s c ) parameter is defined that captures the mean variation of noisy Detail components. The efficacy of the presented method is tested on simulated and experimental signals from Electron Spin Resonance spectroscopy at various SNRs. The results reveal that the µ s c values of signal vary abruptly between wavelets, whereas for noise it displays similar values for all wavelets. For low Signal-to-Noise Ratio (SNR) data, the change in µ s c between highest and second highest value is ≈ 8 - 10% and for high SNR data it is around 5%. The mean of sparsity change increases with the SNR of the signal, which implies that multiple wavelets can be used for denoising a signal, whereas, the signal with low SNR can only be efficiently denoised with a few wavelets. Either a single wavelet or a collection of optimal wavelets (i.e., top five wavelets) should be selected from the highest µ s c values. The code is available on GitHub and the signalsciencelab.com website.

Sparse Group Penalties for bi-level variable selection.

Many data sets exhibit a natural group structure due to contextual similarities or high correlations of variables, such as lipid markers that are interrelated based on biochemical principles. Knowledge of such groupings can be used through bi-level selection methods to identify relevant feature groups and highlight their predictive members. One of the best known approaches of this kind combines the classical Least Absolute Shrinkage and Selection Operator (LASSO) with the Group LASSO, resulting in the Sparse Group LASSO. We propose the Sparse Group Penalty (SGP) framework, which allows for a flexible combination of different SGL-style shrinkage conditions. Analogous to SGL, we investigated the combination of the Smoothly Clipped Absolute Deviation (SCAD), the Minimax Concave Penalty (MCP) and the Exponential Penalty (EP) with their group versions, resulting in the Sparse Group SCAD, the Sparse Group MCP, and the novel Sparse Group EP (SGE). Those shrinkage operators provide refined control of the effect of group formation on the selection process through a tuning parameter. In simulation studies, SGPs were compared with other bi-level selection methods (Group Bridge, composite MCP, and Group Exponential LASSO) for variable and group selection evaluated with the Matthews correlation coefficient. We demonstrated the advantages of the new SGE in identifying parsimonious models, but also identified scenarios that highlight the limitations of the approach. The performance of the techniques was further investigated in a real-world use case for the selection of regulated lipids in a randomized clinical trial.

Interpretability of bi-level variable selection methods.

Variable selection is usually performed to increase interpretability, as sparser models are easier to understand than full models. However, a focus on sparsity is not always suitable, for example, when features are related due to contextual similarities or high correlations. Here, it may be more appropriate to identify groups and their predictive members, a task that can be accomplished with bi-level selection procedures. To investigate whether such techniques lead to increased interpretability, group exponential LASSO (GEL), sparse group LASSO (SGL), composite minimax concave penalty (cMCP), and least absolute shrinkage, and selection operator (LASSO) as reference methods were used to select predictors in time-to-event, regression, and classification tasks in bootstrap samples from a cohort of 1001 patients. Different groupings based on prior knowledge, correlation structure, and random assignment were compared in terms of selection relevance, group consistency, and collinearity tolerance. The results show that bi-level selection methods are superior to LASSO in all criteria. The cMCP demonstrated superiority in selection relevance, while SGL was convincing in group consistency. An all-round capacity was achieved by GEL: the approach jointly selected correlated and content-related predictors while maintaining high selection relevance. This method seems recommendable when variables are grouped, and interpretation is of primary interest.

Co-evolution of gene transfer agents and their alphaproteobacterial hosts.

Gene transfer agents (GTAs) are enigmatic elements that resemble small viruses and are known to be produced during nutritional stress by some bacteria and archaea. The production of GTAs is regulated by quorum sensing, under which a small fraction of the population acts as GTA producers, while the rest becomes GTA recipients. In contrast to canonical viruses, GTAs cannot propagate themselves because they package pieces of the producing cell's genome. In alphaproteobacteria, GTAs are mostly vertically inherited and reside in their hosts' genomes for hundreds of millions of years. While GTAs' ability to transfer genetic material within a population and their long-term preservation suggest an increased fitness of GTA-producing microbes, the associated benefits and type of selection that maintains GTAs are poorly understood. By comparing rates of evolutionary change in GTA genes to the rates in gene families abundantly present across 293 alphaproteobacterial genomes, we detected 59 gene families that likely co-evolve with GTA genes. These gene families are predominantly involved in stress response, DNA repair, and biofilm formation. We hypothesize that biofilm formation enables the physical proximity of GTA-producing cells, limiting GTA-derived benefits only to a group of closely related cells. We further conjecture that the population structure of biofilm-forming sub-populations ensures that the trait of GTA production is maintained despite the inevitable rise of "cheating" genotypes. Because release of GTA particles kills the producing cell, maintenance of GTAs is an exciting example of social evolution in a microbial population.IMPORTANCEGene transfer agents (GTAs) are viruses domesticated by some archaea and bacteria as vehicles for carrying pieces of the host genome. Produced under certain environmental conditions, GTA particles can deliver DNA to neighboring, closely related cells. The function of GTAs remains uncertain. While making GTAs is suicidal for a cell, GTA-encoding genes are widespread in genomes of alphaproteobacteria. Such GTA persistence implies functional benefits but raises questions about how selection maintains this lethal trait. By showing that GTA genes co-evolve with genes involved in stress response, DNA repair, and biofilm formation, we provide support for the hypothesis that GTAs facilitate DNA exchange during the stress conditions and present a model for how GTAs persist in biofilm-forming bacterial populations despite being lethal.

Selection of Fusion Levels in Adolescent Idiopathic Scoliosis.

PURPOSE OF REVIEW: Posterior spinal fusion (PSF) is the preferred treatment for adolescent idiopathic scoliosis (AIS) patients with surgical range curves. Selection of the proper upper and lower instrumented vertebrae (UIV and LIV) is essential in curve correction and achieving a successful outcome, while preventing short and long-term complications. RECENT FINDINGS: The literature lacks high-level evidence, especially on outcomes of modern surgical techniques. However, evidence seems to show that a great majority of AIS patients have excellent clinical and functional long-term outcomes after PSF. We have reviewed the evidence and provided our level selection recommendations, which should be weighed against the body of evidence on the topic when selecting fusion levels in AIS.

Selection of Optimal Lower Instrumented Vertebra for Adolescent Idiopathic Scoliosis Surgery.

Adolescent idiopathic scoliosis (AIS) affects approximately 2% of adolescents across all ethnicities. The objectives of surgery for AIS are to halt curve progression, correct the deformity in 3 dimensions, and preserve as many mobile spinal segments as possible, avoiding junctional complications. Despite ongoing development in algorithms and classification systems for the surgical treatment of AIS, there is still considerable debate about selecting the appropriate fusion level. In this study, we review the literature on fusion selection and present current concepts regarding the lower instrumented vertebra in the selection of the fusion level for AIS surgery.

Carcinogenicity testing in drug development: Getting it right.

For a pharmaceutical drug, carcinogenicity testing occurs in rodents to identify its tumorigenic potential to allow assessment of the risk from its use in humans. Testing takes the form of 2-year studies in mice and rats and/or more recently, a 6-month study in transgenic mice. This paper examines the process of regulatory interaction regarding carcinogenicity testing, notably through the United States (US) Food and Drug Administration (FDA) Special Protocol Assessment (SPA) process to seek Executive Carcinogenicity Assessment Committee (ECAC) approval. The content of 37 submissions to CAC were examined. The paper also examines the outcome from such agency engagement, notably around study dose level selection as well as looking at the design of proposed carcinogenicity study protocols used in submissions (including numbers of animals, control group aspects and toxicokinetic [TK] evaluation). Overall, it was shown that the current process of regulatory interaction allows for studies acceptable to support eventual drug approval and marketing. However, it was established that areas exist to improve the content of submission documents and study design aspects.

Replaying the evolution of multicellularity.

The first organisms on Earth were presumably unicellular. At one point, evolution shaped these individual cells into multicellular organisms, which was a significant transition in the history of life on Earth. To investigate how this change happened, Bozdag et al. re-ran evolution in the lab and observed how single-celled yeast forms large multicellular aggregates.

Bi-level structured functional analysis for genome-wide association studies.

Genome-wide association studies (GWAS) have led to great successes in identifying genotype-phenotype associations for complex human diseases. In such studies, the high dimensionality of single nucleotide polymorphisms (SNPs) often makes analysis difficult. Functional analysis, which interprets SNPs densely distributed in a chromosomal region as a continuous process rather than discrete observations, has emerged as a promising avenue for overcoming the high dimensionality challenges. However, the majority of the existing functional studies continue to be individual SNP based and are unable to sufficiently account for the intricate underpinning structures of SNP data. SNPs are often found in groups (e.g., genes or pathways) and have a natural group structure. Additionally, these SNP groups can be highly correlated with coordinated biological functions and interact in a network. Motivated by these unique characteristics of SNP data, we develop a novel bi-level structured functional analysis method and investigate disease-associated genetic variants at the SNP level and SNP group level simultaneously. The penalization technique is adopted for bi-level selection and also to accommodate the group-level network structure. Both the estimation and selection consistency properties are rigorously established. The superiority of the proposed method over alternatives is shown through extensive simulation studies. A type 2 diabetes SNP data application yields some biologically intriguing results.

Two-level Bayesian interaction analysis for survival data incorporating pathway information.

Genetic interactions play an important role in the progression of complex diseases, providing explanation of variations in disease phenotype missed by main genetic effects. Comparatively, there are fewer studies on survival time, given its challenging characteristics such as censoring. In recent biomedical research, two-level analysis of both genes and their involved pathways has received much attention and been demonstrated as more effective than single-level analysis. However, such analysis is usually limited to main effects. Pathways are not isolated, and their interactions have also been suggested to have important contributions to the prognosis of complex diseases. In this paper, we develop a novel two-level Bayesian interaction analysis approach for survival data. This approach is the first to conduct the analysis of lower-level gene-gene interactions and higher-level pathway-pathway interactions simultaneously. Significantly advancing from the existing Bayesian studies based on the Markov Chain Monte Carlo (MCMC) technique, we propose a variational inference framework based on the accelerated failure time model with effective priors to accommodate two-level selection as well as censoring. Its computational efficiency is much desirable for high-dimensional interaction analysis. We examine performance of the proposed approach using extensive simulation. The application to TCGA melanoma and lung adenocarcinoma data leads to biologically sensible findings with satisfactory prediction accuracy and selection stability.

Risk factors for proximal junctional kyphosis after pediatric spinal deformity surgery with halo gravity traction.

PURPOSE: To determine risk factors for proximal junctional kyphosis (PJK) in pediatric patients with scoliosis undergoing halo gravity traction (HGT) prior to posterior spinal fusion (PSF). METHODS: Data from consecutive patients who underwent PSF after HGT with 2-year follow-up were retrospectively collected from a single center. Patients were divided into two groups: PJK vs. no PJK. RESULTS: Twenty-five patients (age 13.6 ± 3.1 years) underwent HGT for a mean of 42 ± 37 days. Eight patients (32%) developed radiographic PJK and 1 (4%) developed proximal junctional failure. PJK patients had greater loss of cervical lordosis (-17.4 ± 23.2 vs. 2.7 ± 16.2°, p < 0.05), greater increase in lumbar lordosis (9.3 ± 19.5 vs. -2.8 ± 12.8°; p = 0.034) during traction, and smaller overall major coronal curve angle correction (-16.8 ± 30.6 vs. -36.6 ± 16.4°; p = 0.026). From postoperative to last follow-up, PJK patients had a greater increase in upper end vertebrae (UEV) slope (3.3 ± 7.8 vs. -4.0 ± 7.7°; p = 0.004). Selection of UIV based on which vertebra was most level either pre-traction or in-traction was not associated with PJK development (p > 0.05). CONCLUSION: In-traction radiographic changes of decreased cervical lordosis, decreased major coronal curve, increased lumbar lordosis, and disruption of cervical sagittal balance at last follow-up may have implications for level selection and risk of PJK.

Leaders of war: modelling the evolution of conflict among heterogeneous groups.

War, in human and animal societies, can be extremely costly but can also offer significant benefits to the victorious group. We might expect groups to go into battle when the potential benefits of victory (V) outweigh the costs of escalated conflict (C); however, V and C are unlikely to be distributed evenly in heterogeneous groups. For example, some leaders who make the decision to go to war may monopolize the benefits at little cost to themselves ('exploitative' leaders). By contrast, other leaders may willingly pay increased costs, above and beyond their share of V ('heroic' leaders). We investigated conflict initiation and conflict participation in an ecological model where single-leader-multiple-follower groups came into conflict over natural resources. We found that small group size, low migration rate and frequent interaction between groups increased intergroup competition and the evolution of 'exploitative' leadership, while converse patterns favoured increased intragroup competition and the emergence of 'heroic' leaders. We also found evidence of an alternative leader/follower 'shared effort' outcome. Parameters that favoured high contributing 'heroic' leaders, and low contributing followers, facilitated transitions to more peaceful outcomes. We outline and discuss the key testable predictions of our model for empiricists studying intergroup conflict in humans and animals. This article is part of the theme issue 'Intergroup conflict across taxa'.

The complicated legacy of E. O. Wilson with respect to genetics and human behavior.

Over the arc of his career, E. O. Wilson first embraced, then popularized, and finally rejected an extreme genetical hereditarian view of human nature. The controversy that ensued during the period of popularization (largely in the 1970s and 1980s) obscured the fact that empirical and theoretical research during this time undercut the assumptions necessary for this view. By the end of his career, Wilson accepted the fact that individual/kin selection models were insufficient to explain human behavior and society, and he began conducting research based upon multilevel (group) selection, an idea he had previously scorned.

How to Select the Lower Instrumented Vertebra in Traditional Growing Rods Index Surgery.

BACKGROUND: There are still no consensus criteria on how to select the lower instrumented vertebra (LIV) for traditional growing rods (TGRs) at index surgery. The aim was to evaluate whether the criteria used for adolescent idiopathic scoliosis fusion adapts to early onset scoliosis (EOS). METHODS: Retrospective analysis of prospectively longitudinal collected data in a consecutive cohort of patients with EOS treated with TGR, expanding from index surgery to 2 years after graduation. The LIV was analyzed regarding its relation to the stable vertebra (SV), substantially touched vertebra (STV), and not STV (NSTV). Failure of LIV selection was considered when revision surgery with distal extension was needed during follow up, due to adding on (ΔLIV tilt > 10°). RESULTS: A total of 25 patients met inclusion criteria. Mean age was 8.6 ± 3 (at index surgery), 15.1 ± 1.8 (at graduation), and 17.8 ± 1.6 (at final follow up). The most frequent LIV at index surgery was L3 (13/25); in 13 cases, STV was selected as LIV; in 7, it was NSTV; and in 5, SV on the standard postero-anterior radiographs. During follow up, a significant increase in the mean LIV tilt (P = .049) and distal junctional angle (P = .017) was found. Nine of the 25 patients (36%) developed adding on: 20% (1/5) of those with LIV at SV, 38.5% (5/13) at STV, and 42.8% (3/7) at NSTV. Of those 9 cases of adding on, only four needed distal extension (mean LIV tilt = 17.6°): 2 STV patients (15.4%), and 2 NSTV patients (28.6%). None of the patients with the LIV chosen at SV needed distal extension due to adding on. CONCLUSIONS: The more cranial the selection of the LIV above the SV, the higher the risk of adding on and of revision surgery with distal extension during follow up. Saving motion segments could be justified by choosing STV as LIV because the need for distal extension is not high, and it can be scheduled during lengthening procedures or at graduation surgery. LEVEL OF EVIDENCE: 4. CLINICAL RELEVANCE: Choosing the correct LIV in TGR index surgery is crucial to have a secure distal foundation, control and correct the deformity during growth, and save distal segments to allow growth and mobility.

Within-ejaculate sperm competition.

Sperm competition was defined by Geoff Parker 50 years ago as the competition between sperm from two or more males over the fertilization of a set of eggs. Since the publication of his seminal paper, sperm competition has developed into a large field of research, and many aspects are still being discovered. One of the relatively poorly understood aspects is the importance of selection and competition among sperm within the ejaculate of a male. The sheer number of sperm present in a male's ejaculate suggests that the competition among sibling sperm produced by the same male may be intense. In this review, we summarize Parker's theoretical models generating predictions about the evolution of sperm traits under the control of the haploid gamete as opposed to the diploid male. We review the existing evidence of within-ejaculate competition from a wide range of fields and taxa. We also discuss the conceptual and practical hurdles we have been facing to study within-ejaculate sperm competition, and how novel technologies may help in addressing some of the currently open questions. This article is part of the theme issue 'Fifty years of sperm competition'.

Clinical psychology is an applied evolutionary science.

Historically there has been only a limited relationship between clinical psychology and evolutionary science. This article considers the status of that relationship in light of a modern multi-dimensional and multi-level extended evolutionary approach. Evolution can be purposive and even conscious, and evolutionary principles can give guidance and provide consilience to clinical psychology, especially as it focuses more on processes of change. The time seems ripe to view clinical psychology as an applied evolutionary science.

Eco-evolutionary dynamics of nested Darwinian populations and the emergence of community-level heredity.

Interactions among microbial cells can generate new chemistries and functions, but exploitation requires establishment of communities that reliably recapitulate community-level phenotypes. Using mechanistic mathematical models, we show how simple manipulations to population structure can exogenously impose Darwinian-like properties on communities. Such scaffolding causes communities to participate directly in the process of evolution by natural selection and drives the evolution of cell-level interactions to the point where, despite underlying stochasticity, derived communities give rise to offspring communities that faithfully re-establish parental phenotype. The mechanism is akin to a developmental process (developmental correction) that arises from density-dependent interactions among cells. Knowledge of ecological factors affecting evolution of developmental correction has implications for understanding the evolutionary origin of major egalitarian transitions, symbioses, and for top-down engineering of microbial communities.

Honeybee colonies provide foragers with costly fuel to promote pollen collection.

Honeybee pollen foragers departing the hive carry concentrated nectar to use as fuel for flight and glue for forming pollen loads. Since nectar is concentrated by in-hive bees at the cost of time and energy, using concentrated nectar increases the cost of foraging at the colony level. This experimental study explored the potential benefit to honeybees of using concentrated nectar for pollen collection by diluting nectar carried by pollen foragers from the hive. Mass feeding with 30% sugar solution successfully reduced the crop-load-sugar concentration in putative pollen foragers departing the hive, but while those bees tended to increase the crop-load volume, such increase did not fully compensate for the decreased amount of dissolved sugars in the crop load. Feeding 30% sugar solution reduced the pollen load dry weight by approx. 10-20% compared to the unfed control and to another test group fed 60% sugar solution. In addition, the pollen load size and sugar concentration of crop load remaining in returning pollen foragers was positively correlated. These results clearly show the advantage to honeybees of using concentrated nectar for pollen foraging.

Despotic aggression in pre-moulting painted buntings.

Aggression in territorial social systems is easy to interpret because the benefits of territorial defence mostly accrue to the territorial holder. However, in non-territorial systems, high aggression seems puzzling and raises intriguing evolutionary questions. We describe extreme rates of despotism between age classes in a passerine bird, the painted bunting (Passerina ciris), during the pre-moulting period. Aggressive encounters were not associated with aggressors gaining immediate access to resources. Instead, conspecifics, and even other species, were pursued as though being harassed; this aggression generated an ideal despotic habitat distribution such that densities of adult males were higher in high-quality sites. Aggression was not a by-product of elevated testosterone carried over from the breeding season but, rather, appeared associated with dehydroepiandrosterone, a hormone that changes rates of aggression in non-breeding birds without generating the detrimental effects of high testosterone titres that control aggression in the breeding season. This extraordinary pre-moult aggression seems puzzling because individual buntings do not hold defined territories during their moult. We speculate that this high aggression evolved as a means of regulating the number of conspecifics that moulted in what were historically small habitat patches with limited food for supporting the extremely rapid moults of painted buntings.

Group and individual selection during evolutionary transitions in individuality: meanings and partitions.

The Price equation embodies the 'conditions approach' to evolution in which the Darwinian conditions of heritable variation in fitness are represented in equation form. The equation can be applied recursively, leading to a partition of selection at the group and individual levels. After reviewing the well-known issues with the Price partition, as well as issues with a partition based on contextual analysis, we summarize a partition of group and individual selection based on counterfactual fitness, the fitness that grouped cells would have were they solitary. To understand 'group selection' in multi-level selection models, we assume that only group selection can make cells suboptimal when they are removed from the group. Our analyses suggest that there are at least three kinds of selection that can be occurring at the same time: group-specific selection along with two kinds of individual selection, within-group selection and global individual selection. Analyses based on counterfactual fitness allow us to specify how close a group is to being a pseudo-group, and this can be a basis for quantifying progression through an evolutionary transition in individuality (ETI). During an ETI, fitnesses at the two levels, group and individual, become decoupled, in the sense that fitness in a group may be quite high, even as counterfactual fitness goes to zero. This article is part of the theme issue 'Fifty years of the Price equation'.