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Climate change potentially threatens the sustainable production of highly valued cold-water fish species in flow-through systems, such as salmonids. By analysing the relationship of water temperature to hydrological characteristics, air temperature, solar exposure, and precipitation, this study predicted temperature dynamics of five temperate cold-water aquaculture facilities under four projected climate change scenarios. Air temperature was found to be directly associated with facility site water temperature, and based on rational assumptions, two of the five facilities were predicted to face critical warming by mid-century. Extreme precipitation events induced acute short-term increases in water temperature of up to 5 °C. Significantly lower warming, roughly equal to the projected climate change-induced increase, was seen with artificial shading lowering temperature by 1 °C. Complementary niche modelling revealed that 37-77 % of current cold-water facilities will likely incur suboptimal climate conditions by the end of the century. Shading of raceways, more efficient water use, and disease management are proposed as key actions to preserve cold-water aquaculture., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Maximum likelihood estimation is among the most widely-used methods for inferring phylogenetic trees from sequence data. This paper solves the problem of computing solutions to the maximum likelihood problem for 3-leaf trees under the 2-state symmetric mutation model (CFN model). Our main result is a closed-form solution to the maximum likelihood problem for unrooted 3-leaf trees, given generic data; this result characterizes all of the ways that a maximum likelihood estimate can fail to exist for generic data and provides theoretical validation for predictions made in Parks and Goldman (Syst Biol 63(5):798-811, 2014). Our proof makes use of both classical tools for studying group-based phylogenetic models such as Hadamard conjugation and reparameterization in terms of Fourier coordinates, as well as more recent results concerning the semi-algebraic constraints of the CFN model. To be able to put these into practice, we also give a complete characterization to test genericity., (© 2024. The Author(s).)

The Aach cave loach (Barbatula barbatula), a recently discovered member of the Nemacheilidae family, offers a unique opportunity to understand the mechanisms underlying evolutionary change. In a common garden experiment, we reared groups of laboratory-bred cave, surface, and hybrid loach under different light conditions. Troglomorphic characters varied significantly among the fish, influenced to a different extent by parental origin and light conditions. Cavefish progeny consistently exhibited smaller eyes, lighter pigmentation, longer barbels, and larger olfactory epithelia than surface fish, while hybrids displayed intermediate characteristics. Surface and hybrid fish raised in complete darkness resembled the cavefish phenotype, while cavefish raised under a natural photoperiod approached the surface form. Characters associated with eye degeneration were found to be primarily heritable. Conversely, traits related to chemo- and mechano-reception were enhanced in the surface and hybrid groups reared in complete darkness, suggesting phenotypic plasticity. Our findings offer valuable insights into the interplay between genetic differentiation and phenotypic plasticity to troglomorphic adaption. This contributes to the broader understanding of the early stages of adaptation, where phenotypic plasticity, drift, and selection shape phenotypes. Relatively recently established cavefish, such as the Aach cave loach, are promising candidates for comparative research investigating evolutionary mechanisms., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Society for the Study of Evolution (SSE).)

We address the problem of rooting an unrooted species tree given a set of unrooted gene trees, under the assumption that gene trees evolve within the model species tree under the multispecies coalescent (MSC) model. Quintet Rooting (QR) is a polynomial time algorithm that was recently proposed for this problem, which is based on the theory developed by Allman, Degnan, and Rhodes that proves the identifiability of rooted 5-taxon trees from unrooted gene trees under the MSC. However, although QR had good accuracy in simulations, its statistical consistency was left as an open problem. We present QR-STAR, a variant of QR with an additional step and a different cost function, and prove that it is statistically consistent under the MSC. Moreover, we derive sample complexity bounds for QR-STAR and show that a particular variant of it based on "short quintets" has polynomial sample complexity. Finally, our simulation study under a variety of model conditions shows that QR-STAR matches or improves on the accuracy of QR. QR-STAR is available in open-source form on github.

In the welcome circumstance that species believed extinct are rediscovered, it is often the case that biological knowledge acquired before the presumed extinction is limited. Efforts to address these knowledge gaps, in particular to assess the taxonomic integrity and conservation status of such species, can be hampered by a lack of genetic data and scarcity of samples in museum collections. Here, we present a proof-of-concept case study based on a multidisciplinary data evaluation approach to tackle such problems. The approach was developed after the rediscovery, 40 years after its presumed extinction, of the enigmatic Lake Constance deep-water charr Salvelinus profundus. Targeted surveys led to the capture of further species and additional sympatric normal charr, Salvelinus cf. umbla. Since the lake had been subject to massive stocking in the past, an evaluation of the genetic integrity of both extant forms was called for in order to assess possible introgression. A two-step genomic approach was developed based on restriction site associated DNA (RAD). Diagnostic population genomic (single nucleotide polymorphism [SNP]) data were harvested from contemporary samples and used for RNA bait design to perform target capture in DNA libraries of archival scale material, enabling a comparison between extant and historic samples. Furthermore, life history traits and morphological data for both extant forms were gathered and compared with historical data from the past 60-120 years. While extant deep-water charr matched historical deep-water specimens in body shape, gill raker count, and growth rates, significant differences were discovered between historical and extant normal charr. These resulted were supported by genomic analyses of contemporary samples, revealing the two extant forms to be highly divergent. The results of population assignment tests suggest that the endemic deep-water charr persisted in Lake Constance during the eutrophic phase, but not one of the historical genomic samples could be assigned to the extant normal charr taxon. Stocking with non-endemic charr seems to be the most likely reason for these changes. This proof-of-concept study presents a multidisciplinary data evaluation approach that simultaneously tests population genomic integrity and addresses some of the conservation issues arising from rediscovery of a species characterized by limited data availability., (© 2022 The Authors. Ecological Applications published by Wiley Periodicals LLC on behalf of The Ecological Society of America.)

We consider species tree estimation from multiple loci subject to intralocus recombination. We focus on R ∗ , a summary coalescent-based method using rooted triplets, as well as a related quartet-based inference method. We demonstrate analytically that in both cases, intralocus recombination gives rise to an inconsistency zone, in which correct inference is not assured even in the limit of infinite amount of data. In addition, we validate and characterize this inconsistency zone through a simulation study, which suggests that differential rates of recombination between closely related taxa can amplify the effect of incomplete lineage sorting and contribute to inconsistency.

Since 2012, a massive invasion of the three-spined stickleback (Gasterosteus aculeatus) has taken place into the pelagic area of Lake Constance. This species, which had previously been restricted to the littoral zone, is now the dominant pelagic fish and the previously dominant whitefish (Coregonus wartmanni) has suffered severe reductions in growth and recruitment. In this study, in total, 2871 sticklebacks were collected via monthly sessions over a 4-year period in pelagic and benthic areas of Lake Constance and examined for signs of infection with Schistocephalus solidus, a parasite known to be potentially fatal. The infection risk to sticklebacks increases throughout the course of the year and is size- and sex-dependent. Habitat has only a marginal impact. All parasite-induced harm is imparted after stickleback spawning and parental care is over. The results did not support the hypothesis that the invasion of the pelagic area might be driven by parasite-avoiding behaviour. Furthermore, the impact of the parasite is likely to be limited to post-reproductive adults, thereby ensuring stable reproduction of the hosts despite high rates of transmission and mortality. In consequence, stickleback stock development is independent of S. solidus infection, leading to secure coexistence of host and parasite even at extraordinary high host levels., (© 2022. The Author(s).)

Species tree estimation faces many significant hurdles. Chief among them is that the trees describing the ancestral lineages of each individual gene-the gene trees-often differ from the species tree. The multispecies coalescent is commonly used to model this gene tree discordance, at least when it is believed to arise from incomplete lineage sorting, a population-genetic effect. Another significant challenge in this area is that molecular sequences associated to each gene typically provide limited information about the gene trees themselves. While the modeling of sequence evolution by single-site substitutions is well-studied, few species tree reconstruction methods with theoretical guarantees actually address this latter issue. Instead, a standard-but unsatisfactory-assumption is that gene trees are perfectly reconstructed before being fed into a so-called summary method. Hence much remains to be done in the development of inference methodologies that rigorously account for gene tree estimation error-or completely avoid gene tree estimation in the first place. In previous work, a data requirement trade-off was derived between the number of loci m needed for an accurate reconstruction and the length of the locus sequences k. It was shown that to reconstruct an internal branch of length f, one needs m to be of the order of [Formula: see text]. That previous result was obtained under the restrictive assumption that mutation rates as well as population sizes are constant across the species phylogeny. Here we further generalize this result beyond this assumption. Our main contribution is a novel reduction to the molecular clock case under the multispecies coalescent, which we refer to as a stochastic Farris transform. As a corollary, we also obtain a new identifiability result of independent interest: for any species tree with [Formula: see text] species, the rooted topology of the species tree can be identified from the distribution of its unrooted weighted gene trees even in the absence of a molecular clock., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Phylogenomics-the estimation of species trees from multilocus data sets-is a common step in many biological studies. However, this estimation is challenged by the fact that genes can evolve under processes, including incomplete lineage sorting (ILS) and gene duplication and loss (GDL), that make their trees different from the species tree. In this article, we address the challenge of estimating the species tree under GDL. We show that species trees are identifiable under a standard stochastic model for GDL, and that the polynomial-time algorithm ASTRAL-multi, a recent development in the ASTRAL suite of methods, is statistically consistent under this GDL model. We also provide a simulation study evaluating ASTRAL-multi for species tree estimation under GDL.

Objective: To determine the influence of follow-up radiographic examination on recommendations made during routine clinical re-evaluation of dogs that had undergone uncomplicated tibial plateau leveling osteotomy (TPLO)., Study Design: Retrospective multi-institutional case series., Animals: Client-owned dogs (N = 1010) that underwent uncomplicated TPLO., Methods: Records from 11 institutions were searched for dogs that had been treated with unilateral TPLO and had no history of postoperative complications before their routine follow-up examination. The frequency of change in further clinical recommendations resulting from client- or clinician-voiced concerns or radiographic abnormalities was investigated., Results: Follow-up evaluation was performed at a median of 6 (range, 4-15) weeks after TPLO. Radiographic examination findings contributed to a change in recommendations in 4.15% (38/915) of dogs presented without client concerns and without abnormalities at orthopedic examination. Abnormal radiographic findings alone influenced the management of 3.76% (38/1010) of dogs. An association was detected between clinical features and radiological findings leading to a change in recommendations (P < .0001). Administration of analgesia at the time of follow-up was associated with radiographic abnormalities (P = .017) and change in postoperative plans (P = .0007)., Conclusion: Radiographic examination findings at follow-up did not influence the management of most dogs with uncomplicated TPLO., Clinical Significance: Radiographic examination findings are unlikely to influence the treatment of dogs that seem to be recovering uneventfully from an uncomplicated TPLO without concerns from clients, analgesia, or abnormal findings on thorough orthopedic examination by a surgical specialist, at the time of the planned clinical re-evaluation., (© 2020 American College of Veterinary Surgeons.)

We consider the problem of distance estimation under the TKF91 model of sequence evolution by insertions, deletions and substitutions on a phylogeny. In an asymptotic regime where the expected sequence lengths tend to infinity, we show that no consistent distance estimation is possible from sequence lengths alone. More formally, we establish that the distributions of pairs of sequence lengths at different distances cannot be distinguished with probability going to one.

Aim: Clinical photographs have been advocated in studies dealing with the quantity of root coverage. Changes in different angles of the camera when taking a photograph may lead to parallax errors resulting in inaccurate measurements. The aim of this study was to explore the distortion of the photographs according to the shooting angle., Methods: A dental simulation model with a recession defect on tooth 21 was used. Photographs were taken with a digital camera at 5° intervals between 0° to 35°, by shifting the position of the model. Recession depth and root surface area were calculated with ImageJ and implemented in a mathematical model. The relationship between the experimental measurements and the outcomes of the mathematical model was statistically evaluated. The model was confirmed by clinical data., Results: When the central axis of the lens of the camera focused on the experimental tooth is within a cone angle ≤36°, the maximum distortion of the recession area ranges from 0% to 14%, the maximum percentage occurring when the angle is coronal to the central axis., Conclusions: Photographs without an external device connected to the camera provide a valuable support for root coverage assessment when using ImageJ as a measuring tool., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Importance: The Patient Health Questionnaire depression module (PHQ-9) is a 9-item self-administered instrument used for detecting depression and assessing severity of depression. The Patient Health Questionnaire-2 (PHQ-2) consists of the first 2 items of the PHQ-9 (which assess the frequency of depressed mood and anhedonia) and can be used as a first step to identify patients for evaluation with the full PHQ-9., Objective: To estimate PHQ-2 accuracy alone and combined with the PHQ-9 for detecting major depression., Data Sources: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, PsycINFO, and Web of Science (January 2000-May 2018)., Study Selection: Eligible data sets compared PHQ-2 scores with major depression diagnoses from a validated diagnostic interview., Data Extraction and Synthesis: Individual participant data were synthesized with bivariate random-effects meta-analysis to estimate pooled sensitivity and specificity of the PHQ-2 alone among studies using semistructured, fully structured, or Mini International Neuropsychiatric Interview (MINI) diagnostic interviews separately and in combination with the PHQ-9 vs the PHQ-9 alone for studies that used semistructured interviews. The PHQ-2 score ranges from 0 to 6, and the PHQ-9 score ranges from 0 to 27., Results: Individual participant data were obtained from 100 of 136 eligible studies (44 318 participants; 4572 with major depression [10%]; mean [SD] age, 49 [17] years; 59% female). Among studies that used semistructured interviews, PHQ-2 sensitivity and specificity (95% CI) were 0.91 (0.88-0.94) and 0.67 (0.64-0.71) for cutoff scores of 2 or greater and 0.72 (0.67-0.77) and 0.85 (0.83-0.87) for cutoff scores of 3 or greater. Sensitivity was significantly greater for semistructured vs fully structured interviews. Specificity was not significantly different across the types of interviews. The area under the receiver operating characteristic curve was 0.88 (0.86-0.89) for semistructured interviews, 0.82 (0.81-0.84) for fully structured interviews, and 0.87 (0.85-0.88) for the MINI. There were no significant subgroup differences. For semistructured interviews, sensitivity for PHQ-2 scores of 2 or greater followed by PHQ-9 scores of 10 or greater (0.82 [0.76-0.86]) was not significantly different than PHQ-9 scores of 10 or greater alone (0.86 [0.80-0.90]); specificity for the combination was significantly but minimally higher (0.87 [0.84-0.89] vs 0.85 [0.82-0.87]). The area under the curve was 0.90 (0.89-0.91). The combination was estimated to reduce the number of participants needing to complete the full PHQ-9 by 57% (56%-58%)., Conclusions and Relevance: In an individual participant data meta-analysis of studies that compared PHQ scores with major depression diagnoses, the combination of PHQ-2 (with cutoff ≥2) followed by PHQ-9 (with cutoff ≥10) had similar sensitivity but higher specificity compared with PHQ-9 cutoff scores of 10 or greater alone. Further research is needed to understand the clinical and research value of this combined approach to screening.

Microplastics are frequently detected in the gastrointestinal tracts of aquatic organisms worldwide. A number of active and passive pathways have been suggested for fish, including the confusion of microplastic particles with prey, accidental uptake while foraging and transfer through the food chain, but a holistic understanding of influencing factors is still lacking. The aim of the study was to investigate frequently suggested theories and identify relevant biotic factors, as well as certain plastic properties, affecting microplastic intake in fish. Four species of freshwater fish, each representing a different combination of foraging style (visual/chemosensory) and domestic status (wild/farmed) were exposed to different realistic plastic concentrations and polymer types with and without the provision of genuine food. As most previous investigations of microplastic uptake routes consider only particles large enough to be perceptible to fish, the potential for accidental intake via drinking water has been somewhat neglected. This route is evaluated in the current study using a model approach. The results show that visually oriented fish forage actively on microplastic particles that optically resemble their usual food, while fish with a predominantly chemosensory foraging style are more able to discriminate inedible food items. Even so, the accidental uptake of microplastics while foraging is shown to be relevant pathway, occurring frequently in both visual and chemosensory foragers alike. Several factors were shown to increase plastic uptake, including microplastic concentration in the water, foraging behaviour promoted by availability of genuine food, and fish size. Although both wild and farmed fish ingested microplastic particles, cultured fish showed less discernment in terms of colour and were more likely to forage actively on microplastics when no food was available. Drinking has been identified as a possible source of microplastic intake specifically for large marine fish species. Particles smaller than <5 µm can pass the gastrointestinal tract wall and bioaccumulation could arise when uptake exceeds release or when particles are assimilated in tissues or organs. The effects of accumulation may be significant, especially in long-living species, with implications for food web transfer and fish as food items.

In evolutionary biology, the speciation history of living organisms is represented graphically by a phylogeny, that is, a rooted tree whose leaves correspond to current species and whose branchings indicate past speciation events. Phylogenetic analyses often rely on molecular sequences, such as DNA sequences, collected from the species of interest, and it is common in this context to employ statistical approaches based on stochastic models of sequence evolution on a tree. For tractability, such models necessarily make simplifying assumptions about the evolutionary mechanisms involved. In particular, commonly omitted are insertions and deletions of nucleotides-also known as indels. Properly accounting for indels in statistical phylogenetic analyses remains a major challenge in computational evolutionary biology. Here, we consider the problem of reconstructing ancestral sequences on a known phylogeny in a model of sequence evolution incorporating nucleotide substitutions, insertions and deletions, specifically the classical TKF91 process. We focus on the case of dense phylogenies of bounded height, which we refer to as the taxon-rich setting, where statistical consistency is achievable. We give the first explicit reconstruction algorithm with provable guarantees under constant rates of mutation. Our algorithm succeeds when the phylogeny satisfies the "big bang" condition, a necessary and sufficient condition for statistical consistency in this setting.

Objective: The ESCAPE multicentre survey was designed to (a) compare the agreement of three relevant aesthetic scoring systems among different centres, and (b) evaluate the reproducibility of each question of the questionnaires., Materials and Methods: EFP centres (n = 14) were involved in an e-survey. Forty-two participants (28 teachers, 14 postgraduate students) were asked to score the one-year aesthetic outcomes of photographs using the Before-After Scoring System (BASS), the Pink Esthetic Score (PES) and the Root coverage Esthetic Score (RES). Mean values of kappa statistics performed on each question were provided to resume global agreement of each method., Results: Between teachers, a difference of kappa ≥ 0.41 (p = .01) was found for BASS (75%) and PES (57%). Similarly, RES (84%) and PES (57%) were different (p < .001). No difference was found between BASS (75%) and RES (84%). No difference was found between students, whatever the scoring system. Questions of each scoring system showed differences in their reproducibility., Conclusions: The outcomes of this study indicate that BASS and RES scoring systems are reproducible tools to evaluate aesthetic after root coverage therapies between different centres. Among the various variables, lack of scar, degree of root coverage, colour match and gingival margin that follows the CEJ show the best reliability., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In a comprehensive study of microplastic contamination in southern Germany, 1167 individual fish of 22 different species were sampled from 11 rivers and 6 lakes across the state. The microplastic burden of investigated fish was analyzed on the basis of habitat type, location, and a number of abiotic and biotic factors. A particle size distribution analysis of the detected microplastics was carried out. The results showed a relatively low plastic prevalence of 18.8%, with significant differences between rivers (20.6%) and lakes (16.5%). The number of ingested plastic particles ranged between 1 and 4 particles per fish. The majority of abiotic and biotic factors seem to play little or no role in the ingestion of microplastics, suggesting that in most cases uptake is passive or accidental. It is notable that piscivorous fish appeared significantly less burdened, suggesting a low transfer rate and no accumulation in the food web. However, size distribution analysis identified a power law growth fit in particle numbers at the smallest end of the distribution. This carries a worrying implication, that >95% of particles are likely to be smaller than 40 μm and thereby beyond the detection range of this and most other microplastic surveys conducted so far. When the frequency development of small particles is taken into account, the likely microplastic prevalence in the present study increases to 100%, with an average intensity of around 23 predominantly small particles per fish. A striking 70% of those particles would be smaller than 5 μm and therefore eligible for translocation into tissues, with critical implications for fish health and consumer exposure. This raises a question as to whether current estimates of microplastic burden in fishes generally might be overlooking a majority of potential contamination within the critical smaller particle size classes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

With advances in sequencing technologies, there are now massive amounts of genomic data from across all life, leading to the possibility that a robust Tree of Life can be constructed. However, "gene tree heterogeneity", which is when different genomic regions can evolve differently, is a common phenomenon in multi-locus data sets, and reduces the accuracy of standard methods for species tree estimation that do not take this heterogeneity into account. New methods have been developed for species tree estimation that specifically address gene tree heterogeneity, and that have been proven to converge to the true species tree when the number of loci and number of sites per locus both increase (i.e., the methods are said to be "statistically consistent"). Yet, little is known about the biologically realistic condition where the number of sites per locus is bounded. We show that when the sequence length of each locus is bounded (by any arbitrarily chosen value), the most common approaches to species tree estimation that take heterogeneity into account (i.e., traditional fully partitioned concatenated maximum likelihood and newer approaches, called summary methods, that estimate the species tree by combining estimated gene trees) are not statistically consistent, even when the heterogeneity is extremely constrained. The main challenge is the presence of conditions such as long branch attraction that create biased tree estimation when the number of sites is restricted. Hence, our study uncovers a fundamental challenge to species tree estimation using both traditional and new methods.

Background: This study investigated the long-term effects (12 months post-rehabilitation) of a standard inpatient multidisciplinary rehabilitation program for patients with chronic low back pain (CLBP), in which a control group (CG) received pain competence training and an intervention group (IG) received combined pain competence and depression prevention training., Methods: In this prospective control group study with cluster-block randomization, a total of n = 583 patients were included into per protocol analyses. To examine the effects of rehabilitation on depressive symptoms, pain self-efficacy, and work ability, patients were stratified in repeated-measures analyses of variance by treatment condition (IG vs. CG), level of depressive symptoms (low vs. high), and time of assessment (pre, post, 6, and 12 months after rehabilitation). The impact of each treatment on pain-related days of sick leave (DSL; dichotomized into ≤ vs. > 2 weeks) was determined separately by conducting non-parametric analyses. Multiple imputations (n = 1225) confirmed the results. Effects were interpreted if clinical significance was given., Results: Only patients with high levels of depressive symptoms showed long-term improvements in depressive symptoms and self-efficacy. Long-term improvements in work ability index and mental work ability item were restricted to the IG. Furthermore, long-term effects on pain-related DSL were ascertained by per protocol and multiple imputation analyses only for the IG., Conclusions: Patients with high levels of depressive symptoms showed improvements in depressive symptoms and self-efficacy, supporting the psychological effectiveness of both interventions. However, the beneficial long-term effects of rehabilitation on work ability and pain-related DSL among the IG support implementation of combined pain competence and depression prevention training., Trial Registration: DRKS00015465 (German Clinical Trial Register DRKS); date of registration: 03.09.2018.

To sample marginalized and/or hard-to-reach populations, respondent-driven sampling (RDS) and similar techniques reach their participants via peer referral. Under a Markov model for RDS, previous research has shown that if the typical participant refers too many contacts, then the variance of common estimators does not decay like [Formula: see text], where n is the sample size. This implies that confidence intervals will be far wider than under a typical sampling design. Here we show that generalized least squares (GLS) can effectively reduce the variance of RDS estimates. In particular, a theoretical analysis indicates that the variance of the GLS estimator is [Formula: see text] We then derive two classes of feasible GLS estimators. The first class is based upon a Degree Corrected Stochastic Blockmodel for the underlying social network. The second class is based upon a rank-two model. It might be of independent interest that in both model classes, the theoretical results show that it is possible to estimate the spectral properties of the population network from a random walk sample of the nodes. These theoretical results point the way to entirely different classes of estimators that account for the network structure beyond node degree. Diagnostic plots help to identify situations where feasible GLS estimators are more appropriate. The computational experiments show the potential benefits and also indicate that there is room to further develop these estimators in practical settings., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

The sample frequency spectrum (SFS), which describes the distribution of mutant alleles in a sample of DNA sequences, is a widely used summary statistic in population genetics. The expected SFS has a strong dependence on the historical population demography and this property is exploited by popular statistical methods to infer complex demographic histories from DNA sequence data. Most, if not all, of these inference methods exhibit pathological behavior, however. Specifically, they often display runaway behavior in optimization, where the inferred population sizes and epoch durations can degenerate to zero or diverge to infinity, and show undesirable sensitivity to perturbations in the data. The goal of this article is to provide theoretical insights into why such problems arise. To this end, we characterize the geometry of the expected SFS for piecewise-constant demographies and use our results to show that the aforementioned pathological behavior of popular inference methods is intrinsic to the geometry of the expected SFS. We provide explicit descriptions and visualizations for a toy model, and generalize our intuition to arbitrary sample sizes using tools from convex and algebraic geometry. We also develop a universal characterization result which shows that the expected SFS of a sample of size n under an arbitrary population history can be recapitulated by a piecewise-constant demography with only [Formula: see text] epochs, where [Formula: see text] is between [Formula: see text] and [Formula: see text] The set of expected SFS for piecewise-constant demographies with fewer than [Formula: see text] epochs is open and nonconvex, which causes the above phenomena for inference from data., (Copyright © 2018 by the Genetics Society of America.)

Species tree reconstruction from genomic data is increasingly performed using methods that account for sources of gene tree discordance such as incomplete lineage sorting. One popular method for reconstructing species trees from unrooted gene tree topologies is ASTRAL. In this paper, we derive theoretical sample complexity results for the number of genes required by ASTRAL to guarantee reconstruction of the correct species tree with high probability. We also validate those theoretical bounds in a simulation study. Our results indicate that ASTRAL requires gene trees to reconstruct the species tree correctly with high probability where is the number of species and is the length of the shortest branch in the species tree. Our simulations, some under the anomaly zone, show trends consistent with the theoretical bounds and also provide some practical insights on the conditions where ASTRAL works well.

Background Because of high rates of comorbid mental disorders among patients with chronic low back pain, an intervention for pain competence and depression prevention for multidisciplinary inpatient rehabilitation was newly developed and evaluated concerning depressive symptoms, anxiety and pain related parameters. Methods Per protocol regression analyses with data of n=723 patients were conducted to evaluate the intervention. Intraindividual changes were quantified by Cohen's d based on repeated measures analyses of variance. The results of the regression analyses were validated by n=1306 multiple imputed data. Results Patients benefited in all analyzed parameters in the short- and mid-term (6 months after intervention) from the rehabilitation with as well as without supplemental depression prevention training. Depressive symptoms in the beginning of the rehabilitation were a significant predictor for all analyzed parameters. Additionally, the depression prevention training reduced the lowest pain intensity in the short-term independent from depressive symptoms. The results were confirmed by analyses with multiple imputations. However, improvements declined especially in depressive symptoms and anxiety in the months after rehabilitation. Discussion The results support the influence of depressive symptoms on psychological and pain related parameters, which emphasizes the relevance of an early treatment of depressive symptoms. Though, the supplemental depression prevention training had no additional effect in the inpatient rehabilitation setting, which could be explained by the high effect sizes of the sole pain competence training. Moreover, beneficial effects should be supported by aftercare, because effects declined during the 6 months after rehabilitation., Competing Interests: Interessenkonflikt: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To report diaphyseal fractures of the proximal tibia following tibial tuberosity advancement without plate stabilisation for the management of cranial cruciate ligament rupture in dogs., Methods: Members of the British Veterinary Orthopaedic Association's online discussion forum were invited to submit revision cases of tibial diaphyseal fracture following tibial tuberosity advancement without plate fixation. Data collected included signalment, surgical revision technique, pre- and postoperative revision radiographic findings, complications and veterinary assessment. Owners were invited to complete the Liverpool Osteoarthritis in Dogs questionnaire., Results: A total of 17 dogs were included in the study. Eleven dogs had OrthoFoam-wedge modified Maquet procedures and six had the tibial tuberosity advancement rapid procedure. Tibial tuberosity advancement was maintained in 14/17 cases. Postrevision surgery complications occurred in eight cases: minor complications in 3/17 dogs; major in 5/17 and no catastrophic complications. Surgical site infection was the most common complication (4/8). Final clinical outcome found 8/17 of dogs to have excellent, 8/17 satisfactory and 1/17 poor clinical outcome. The median Liverpool Osteoarthritis in Dogs score was 12/52 (range 2 to 28). Final outcome was 6/13 owners that were very satisfied, 2/13 owners indifferent and 5/13 owners very disappointed., Clinical Significance: This is the first case series reporting tibial diaphyseal fractures following tibial tuberosity advancement without plate stabilisation. The authors report here a wide spectrum of potential fixation strategies should one of these fractures occur., (© 2017 British Small Animal Veterinary Association.)

The rising evidence of microplastic pollution impacts on aquatic organisms in both marine and freshwater ecosystems highlights a pressing need for adequate and comparable detection methods. Available tissue digestion protocols are time-consuming (>10 h) and/or require several procedural steps, during which materials can be lost and contaminants introduced. This novel approach comprises an accelerated digestion step using sodium hydroxide and nitric acid in combination to digest all organic material within 1 h plus an additional separation step using sodium iodide which can be used to reduce mineral residues in samples where necessary. This method yielded a microplastic recovery rate of ≥95%, and all tested polymer types were recovered with only minor changes in weight, size, and color with the exception of polyamide. The method was also shown to be effective on field samples from two benthic freshwater fish species, revealing a microplastic burden comparable to that indicated in the literature. As a consequence, the present method saves time, minimizes the loss of material and the risk of contamination, and facilitates the identification of plastic particles and fibers, thus providing an efficient method to detect and quantify microplastics in the gastrointestinal tract of fishes.

Background: Chronic low back pain is often accompanied by fear-avoidance cognitions, increased depressive symptoms and decreased quality of life., Objective: Is the relationship between fear-avoidance cognitions and quality of life mediated by depressive symptoms?, Methods: Mediation analyses were conducted to predict the long-term quality of life with depressive symptoms as mediator using longitudinal data from 131 patients., Results: Fear-avoidance cognitions prior to rehabilitation predicted the physical quality of life 24 months after rehabilitation, which was mediated by the degree of depressive symptoms 6 months after rehabilitation. The other assumed models could not be tested due to non-significant correlations between the model variables., Conclusion: To improve the physical quality of life, depressive symptoms should be included into the treatment of chronic low back pain.

Diffusion processes on trees are commonly used in evolutionary biology to model the joint distribution of continuous traits, such as body mass, across species. Estimating the parameters of such processes from tip values presents challenges because of the intrinsic correlation between the observations produced by the shared evolutionary history, thus violating the standard independence assumption of large-sample theory. For instance (Ho and Ané, Ann Stat 41:957-981, 2013) recently proved that the mean (also known in this context as selection optimum) of an Ornstein-Uhlenbeck process on a tree cannot be estimated consistently from an increasing number of tip observations if the tree height is bounded. Here, using a fruitful connection to the so-called reconstruction problem in probability theory, we study the convergence rate of parameter estimation in the unbounded height case. For the mean of the process, we provide a necessary and sufficient condition for the consistency of the maximum likelihood estimator (MLE) and establish a phase transition on its convergence rate in terms of the growth of the tree. In particular we show that a loss of [Formula: see text]-consistency (i.e., the variance of the MLE becomes [Formula: see text], where n is the number of tips) occurs when the tree growth is larger than a threshold related to the phase transition of the reconstruction problem. For the covariance parameters, we give a novel, efficient estimation method which achieves [Formula: see text]-consistency under natural assumptions on the tree. Our theoretical results provide practical suggestions for the design of comparative data collection.

On mineral, gas or oil extraction sites, medical care is often provided in uncommon conditions by doctors or paramedical staff. Caregivers must fulfil certain requirements, but must also possess the necessary human, technical, physical and psychological qualities to be able to provide high quality care throughout their mission on a remote site., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Bei chronischen, nicht spezifischen Rückenschmerzen haben psychische Komorbiditäten deutlich zugenommen, sodass im Rahmen einer multimodalen Behandlung zunehmend auch psychotherapeutische Behandlungsansätze implementiert werden. Ziel dieses Reviews war es, die aktuelle Forschung zu psychologischen Aspekten bei der Behandlung von chronischen Rückenschmerzen zu thematisieren. Dazu wurde eine selektive Literaturrecherche durchgeführt, um Studien aus Deutschland zu identifizieren, die in den letzten 5 Jahren veröffentlicht wurden. Dabei wurden 12 Artikel von 5 Forschergruppen gefunden, die unterschiedliche Aspekte der stationären, teilstationären und ambulanten Rehabilitation sowie der Nachsorge thematisierten. Die Evidenz für die Effektivität von psychologischer Behandlung bei chronischen Rückenschmerzen ist in den letzten Jahren gestiegen, gerade im Bereich der Nachsorge ist jedoch weitere Forschung für eine erfolgreiche Implementierung notwendig., (© Georg Thieme Verlag KG Stuttgart · New York.)

The estimation of species trees using multiple loci has become increasingly common. Because different loci can have different phylogenetic histories (reflected in different gene tree topologies) for multiple biological causes, new approaches to species tree estimation have been developed that take gene tree heterogeneity into account. Among these multiple causes, incomplete lineage sorting (ILS), modeled by the multi-species coalescent, is potentially the most common cause of gene tree heterogeneity, and much of the focus of the recent literature has been on how to estimate species trees in the presence of ILS. Despite progress in developing statistically consistent techniques for estimating species trees when gene trees can differ due to ILS, there is substantial controversy in the systematics community as to whether to use the new coalescent-based methods or the traditional concatenation methods. One of the key issues that has been raised is understanding the impact of gene tree estimation error on coalescent-based methods that operate by combining gene trees. Here we explore the mathematical guarantees of coalescent-based methods when analyzing estimated rather than true gene trees. Our results provide some insight into the differences between promise of coalescent-based methods in theory and their performance in practice., (© The Author(s) 2015. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

We consider the problem of estimating the evolutionary history of a set of species (phylogeny or species tree) from several genes. It is known that the evolutionary history of individual genes (gene trees) might be topologically distinct from each other and from the underlying species tree, possibly confounding phylogenetic analysis. A further complication in practice is that one has to estimate gene trees from molecular sequences of finite length. We provide the first full data-requirement analysis of a species tree reconstruction method that takes into account estimation errors at the gene level. Under that criterion, we also devise a novel reconstruction algorithm that provably improves over all previous methods in a regime of interest.

The reconstruction of a species tree from genomic data faces a double hurdle. First, the (gene) tree describing the evolution of each gene may differ from the species tree, for instance, due to incomplete lineage sorting. Second, the aligned genetic sequences at the leaves of each gene tree provide merely an imperfect estimate of the topology of the gene tree. In this note, we demonstrate formally that a basic statistical problem arises if one tries to avoid accounting for these two processes and analyses the genetic data directly via a concatenation approach. More precisely, we show that, under the multispecies coalescent with a standard site substitution model, maximum likelihood estimation on sequence data that has been concatenated across genes and performed under the incorrect assumption that all sites have evolved independently and identically on a fixed tree is a statistically inconsistent estimator of the species tree. Our results provide a formal justification of simulation results described of Kubatko and Degnan (2007) and others, and complements recent theoretical results by DeGIorgio and Degnan (2010) and Chifman and Kubtako (2014)., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The unusual yellow-finned morph of European perch Perca fluviatilis found in Lake Constance suffers more severely from macroparasite infections, including the tapeworm Triaenophorus nodulosus and the gill worm Ancyrocephalus percae, than conspecifics elsewhere. Microsatellite analysis of yellow-finned P. fluviatilis and red-finned variant recently discovered in Lake Constance revealed significant genetic differentiation. Red-finned P. fluviatilis and fish with mixed fin colour, suggested backcrosses between red and yellow-finned colour morphs, exhibit better resilience to parasite infection, suggesting that the inability of the yellow-finned morph to reject macroparasites may have a genetic basis., (© 2015 The Fisheries Society of the British Isles.)

Mutation rate variation across loci is well known to cause difficulties, notably identifiability issues, in the reconstruction of evolutionary trees from molecular sequences. Here we introduce a new approach for estimating general rates-across-sites models. Our results imply, in particular, that large phylogenies are typically identifiable under rate variation. We also derive sequence-length requirements for high-probability reconstruction. Our main contribution is a novel algorithm that clusters sites according to their mutation rate. Following this site clustering step, standard reconstruction techniques can be used to recover the phylogeny. Our results rely on a basic insight: that, for large trees, certain site statistics experience concentration-of-measure phenomena.

Lateral gene transfer (LGT) is a common mechanism of nonvertical evolution, during which genetic material is transferred between two more or less distantly related organisms. It is particularly common in bacteria where it contributes to adaptive evolution with important medical implications. In evolutionary studies, LGT has been shown to create widespread discordance between gene trees as genomes become mosaics of gene histories. In particular, the Tree of Life has been questioned as an appropriate representation of bacterial evolutionary history. Nevertheless a common hypothesis is that prokaryotic evolution is primarily treelike, but that the underlying trend is obscured by LGT. Extensive empirical work has sought to extract a common treelike signal from conflicting gene trees. Here we give a probabilistic perspective on the problem of recovering the treelike trend despite LGT. Under a model of randomly distributed LGT, we show that the species phylogeny can be reconstructed even in the presence of surprisingly many (almost linear number of) LGT events per gene tree. Our results, which are optimal up to logarithmic factors, are based on the analysis of a robust, computationally efficient reconstruction method and provides insight into the design of such methods. Finally, we show that our results have implications for the discovery of highways of gene sharing.

Incomplete lineage sorting (ILS) is a common source of gene tree incongruence in multilocus analyses. Numerous approaches have been developed to infer species trees in the presence of ILS. Here we provide a mathematical analysis of several coalescent-based methods. The analysis is performed on a three-taxon species tree and assumes that the gene trees are correctly reconstructed along with their branch lengths. It suggests that maximum likelihood (and some equivalents) can be significantly more accurate in this setting than other methods, especially as ILS gets more pronounced.

Objective: To evaluate the use of hybrid total hip replacement (THR), using a cementless acetabular component and a cemented femoral component., Study Design: Prospective case series., Sample Population: Client-owned dogs (n = 71)., Materials and Methods: Consecutive clinical cases that had hybrid THR were studied. Radiographic features, pain scores, and lameness scores were recorded pre- and postoperatively. Longer term outcome was assessed by owner questionnaire., Results: Hybrid THRs (n = 78) were performed in 71 dogs. Four cases (5%) had major postoperative complications; 3 were resolved after revision surgery, and 1 owner requested an explantation. No other major complications were identified on follow-up radiographs (67 THR) at 12 weeks. On clinical follow up (77 THR) at 4 weeks, lameness had improved in 68, was unchanged in 8, and was worse in 1. Pain had decreased in 72, was unchanged in 4, and was worse in 1. At 12 weeks (69 THR) compared with preoperative status, lameness had improved in 67 and was unchanged in 2. Pain had improved in 68 and was unchanged in 1. Longer term follow-up (mean, 16 months) was available for all hips. No further complications were reported. Owner satisfaction was good for 76 THRs and reasonable for 2., Conclusions: Hybrid THR can be performed successfully with a low complication rate and represents an alternative to either entirely cemented or cementless implantation., (© Copyright 2011 by The American College of Veterinary Surgeons.)

The accurate reconstruction of phylogenies from short molecular sequences is an important problem in computational biology. Recent work has highlighted deep connections between sequence-length requirements for high-probability phylogeny reconstruction and the related problem of the estimation of ancestral sequences. In Daskalakis et al. (in Probab. Theory Relat. Fields 2010), building on the work of Mossel (Trans. Am. Math. Soc. 356(6):2379-2404, 2004), a tight sequence-length requirement was obtained for the simple CFN model of substitution, that is, the case of a two-state symmetric rate matrix Q. In particular the required sequence length for high-probability reconstruction was shown to undergo a sharp transition (from O(log n) to poly(n), where n is the number of leaves) at the "critical" branch length g (ML)(Q) (if it exists) of the ancestral reconstruction problem defined roughly as follows: below g (ML)(Q) the sequence at the root can be accurately estimated from sequences at the leaves on deep trees, whereas above g (ML)(Q) information decays exponentially quickly down the tree.Here, we consider a more general evolutionary model, the GTR model, where the q×q rate matrix Q is reversible with q≥2. For this model, recent results of Roch (Preprint, 2009) show that the tree can be accurately reconstructed with sequences of length O(log (n)) when the branch lengths are below g (Lin)(Q), known as the Kesten-Stigum (KS) bound, up to which ancestral sequences can be accurately estimated using simple linear estimators. Although for the CFN model g (ML)(Q)=g (Lin)(Q) (in other words, linear ancestral estimators are in some sense best possible), it is known that for the more general GTR models one has g (ML)(Q)≥g (Lin)(Q) with a strict inequality in many cases. Here, we show that this phenomenon also holds for phylogenetic reconstruction by exhibiting a family of symmetric models Q and a phylogenetic reconstruction algorithm which recovers the tree from O(log n)-length sequences for some branch lengths in the range (g (Lin)(Q),g (ML)(Q)). Second, we prove that phylogenetic reconstruction under GTR models requires a polynomial sequence-length for branch lengths above g (ML)(Q).

The matrix of evolutionary distances is a model-based statistic, derived from molecular sequences, summarizing the pairwise phylogenetic relations between a collection of species. Phylogenetic tree reconstruction methods relying on this matrix are relatively fast and thus widely used in molecular systematics. However, because of their intrinsic reliance on summary statistics, distance-matrix methods are assumed to be less accurate than likelihood-based approaches. In this paper, pairwise sequence comparisons are shown to be more powerful than previously hypothesized. A statistical analysis of certain distance-based techniques indicates that their data requirement for large evolutionary trees essentially matches the conjectured performance of maximum likelihood methods--challenging the idea that summary statistics lead to suboptimal analyses. On the basis of a connection between ancestral state reconstruction and distance averaging, the critical role played by the covariances of the distance matrix is identified.

We introduce a simple computationally efficient algorithm for reconstructing phylogenies from multiple gene trees in the presence of incomplete lineage sorting, that is, when the topology of the gene trees may differ from that of the species tree. We show that our technique is statistically consistent under standard stochastic assumptions, that is, it returns the correct tree given sufficiently many unlinked loci. We also show that it can tolerate moderate estimation errors.

Five cats were treated for a fracture of the medial malleolus, 10 for a fracture of the lateral malleolus and 15 for fractures of both malleoli. Open reduction and internal fixation with Kirschner wires (K-wires) with or without a tension band wire was applied to 26 of the fractures. Unilateral-uniplanar or bilateral-uniplanar transarticular external skeletal fixators were applied to provide coaptation in 19 cases and appeared to be well tolerated. In 24 cases fracture healing was assessed radiographically between four and eight weeks after treatment. In seven cases fracture healing was good, in 12 cases it was reasonable, in four cases it was poor and in one case with two fractures healing was poor in one and reasonable in the other. The 12 fractures treated by open reduction and internal fixation with K-wires and a tension band wire all showed evidence of good or reasonable healing. The nine fractures treated by open reduction and internal fixation with K-wires without a tension band wire showed evidence of good or reasonable healing in six cases and poor healing in three cases. Complications occurred in nine of the cats and included persistent talocrural instability, soft tissue necrosis, implant migration and external fixator pin breakage. Twenty-one of the cats were followed up by telephone questionnaire for between 5.5 and 84 months; the owner satisfaction was excellent in 17 cases, good in two cases, moderate in one case and poor in one case.

Ancestral maximum likelihood (AML) is a method that simultaneously reconstructs a phylogenetic tree and ancestral sequences from extant data (sequences at the leaves). The tree and ancestral sequences maximize the probability of observing the given data under a Markov model of sequence evolution, in which branch lengths are also optimized but constrained to take the same value on any edge across all sequence sites. AML differs from the more usual form of maximum likelihood (ML) in phylogenetics because ML averages over all possible ancestral sequences. ML has long been know to be statistically consistent--that is, it converges on the correct tree with probability approaching 1 as the sequence length grows. However, the statistical consistency of AML has not been formally determined, despite informal remarks in a literature that dates back 20 years. In this short note we prove a general result that implies that AML is statistically inconsistent. In particular we show that AML can 'shrink' short edges in a tree, resulting in a tree that has no internal resolution as the sequence length grows. Our results apply to any number of taxa.

This case report describes the treatment of recurrent medial patellar luxation associated with varus deformity of the distal femur by distal femoral ostectomy stabilised using a distal femoral plate. Four dogs (five affected limbs) were included in the study. All cases had received previous surgery for medial patellar luxation but remained significantly lame. All were treated by femoral ostectomy to correct distal femoral varus deformity with application of a distal femoral bone plate. All cases improved following surgery. An excellent outcome was recorded in four of five cases. Lameness persisted in one case despite satisfactory patellar stability as a result of concurrent cranial cruciate ligament deficiency. One case suffered implant failure. Femoral ostectomy is an effective treatment for medial patellar luxation associated with femoral varus deformity. The distal femoral plate provides a convenient method by which to stabilise the ostectomy. Care should be exercised when the 2 mm distal femoral plate is applied.

Objectives: To report the complications encountered following tarsal arthrodesis surgery with bone plate fixation and describe the previously unreported complication of plantar necrosis., Methods: Medical records of 40 dogs that had been treated by tarsal arthrodesis with bone plate fixation were reviewed to determine the major and minor complications and the associated risk factors., Results: The major complication rate was 32.5 per cent and the minor complication rate was 42.5 per cent. Pantarsal arthrodeses had a higher major complication rate than partial tarsal arthrodeses. Plantar necrosis was the most common major complication and occurred in 15 per cent of cases. Plantar necrosis occurred more frequently when a bone plate was applied to the medial aspect of the hock, and only occurred in cases where tarsometatarsal joint arthrodesis was performed., Clinical Significance: Plantar necrosis is a catastrophic complication that may be associated with injury to the dorsal pedal artery or perforating metatarsal artery. Application of a bone plate to the medial aspect of the hock should be performed with care during tarsal arthrodesis, particularly where the tarsometatarsal joint is debrided of cartilage. Strict attention to surgical technique and proper postoperative coaptation is critical to reduce the potential for complications with tarsal arthrodesis.

If someone is nice to you, you feel good and may be inclined to be nice to somebody else. This every day experience is borne out by experimental games: the recipients of an act of kindness are more likely to help in turn, even if the person who benefits from their generosity is somebody else. This behaviour, which has been called 'upstream reciprocity', appears to be a misdirected act of gratitude: you help somebody because somebody else has helped you. Does this make any sense from an evolutionary or a game theoretic perspective? In this paper, we show that upstream reciprocity alone does not lead to the evolution of cooperation, but it can evolve and increase the level of cooperation if it is linked to either direct or spatial reciprocity. We calculate the random walks of altruistic acts that are induced by upstream reciprocity. Our analysis shows that gratitude and other positive emotions, which increase the willingness to help others, can evolve in the competitive world of natural selection.

Maximum likelihood is one of the most widely used techniques to infer evolutionary histories. Although it is thought to be intractable, a proof of its hardness has been lacking. Here, we give a short proof that computing the maximum likelihood tree is NP-hard by exploiting a connection between likelihood and parsimony observed by Tuffley and Steel.

Stimulation of human monocyte-derived-macrophages (MDM) with interferon gamma induces the L-tryptophan degrading enzyme indoleamine 2,3-dioxygenase (IDO). It has been well documented that the growth of some intra-cellular parasites such as Chlamydia and Toxoplasma in human fibroblasts and glioblastoma cells is inhibited by IDO mediated L-tryptophan depletion. We have recently shown that IDO induction in cord blood MDM is also responsible for the growth inhibition of extra-cellular group B streptococci and thus for the first time shown an anti-bacterial effect of IDO activation. In view of this immunological function we sought to investigate the regulation, and in particular the downregulation of IDO by the immune system. We describe here the effect of cytokines on IDO activation and in particular the inhibitory function of IL-10, TGF beta and IL-4.