Reliability of maximal isometric knee strength testing with modified hand-held dynamometry in patients awaiting total knee arthroplasty: useful in research and individual patient settings? A reliability study

<p>Abstract</p> <p><b>Background</b></p> <p>Patients undergoing total knee arthroplasty (TKA) often experience strength deficits both pre- and post-operatively. As these deficits may have a direct impact on functional recovery, strength assessment should be performed in this patient population. For these assessments, reliable measurements should be used. This study aimed to determine the inter- and intrarater reliability of hand-held dynamometry (HHD) in measuring isometric knee strength in patients awaiting TKA.</p> <p><b>Methods</b></p> <p>To determine interrater reliability, 32 patients (81.3% female) were assessed by two examiners. Patients were assessed consecutively by both examiners on the same individual test dates. To determine intrarater reliability, a subgroup (n = 13) was again assessed by the examiners within four weeks of the initial testing procedure. Maximal isometric knee flexor and extensor strength were tested using a modified Citec hand-held dynamometer. Both the affected and unaffected knee were tested. Reliability was assessed using the Intraclass Correlation Coefficient (ICC). In addition, the Standard Error of Measurement (SEM) and the Smallest Detectable Difference (SDD) were used to determine reliability.</p> <p><b>Results</b></p> <p>In both the affected and unaffected knee, the inter- and intrarater reliability were good for knee flexors (ICC range 0.76-0.94) and excellent for knee extensors (ICC range 0.92-0.97). However, measurement error was high, displaying SDD ranges between 21.7% and 36.2% for interrater reliability and between 19.0% and 57.5% for intrarater reliability. Overall, measurement error was higher for the knee flexors than for the knee extensors.</p> <p><b>Conclusions</b></p> <p>Modified HHD appears to be a reliable strength measure, producing good to excellent ICC values for both inter- and intrarater reliability in a group of TKA patients. High SEM and SDD values, however, indicate high measurement error for individual measures. This study demonstrates that a modified HHD is appropriate to evaluate knee strength changes in TKA patient groups. However, it also demonstrates that modified HHD is not suitable to measure individual strength changes. The use of modified HHD is, therefore, not advised for use in a clinical setting.</p

Importance of Human Leukocyte Antigen (HLA) Class I and II Alleles on the Risk of Multiple Sclerosis

Multiple sclerosis (MS) is a complex disease of the central nervous system of unknown etiology. The human leukocyte antigen (HLA) locus on chromosome 6 confers a considerable part of the susceptibility to MS, and the most important factor is the class II allele HLA-DRB1*15:01. In addition, we and others have previously established a protective effect of HLA-A*02. Here, we genotyped 1,784 patients and 1,660 healthy controls from Scandinavia for the HLA-A, HLA-B, HLA-C and HLA-DRB1 genes and investigated their effects on MS risk by logistic regression. Several allele groups were found to exert effects independently of DRB1*15 and A*02, in particular DRB1*01 (OR = 0.82, p = 0.034) and B*12 (including B*44/45, OR = 0.76, p = 0.0028), confirming previous reports. Furthermore, we observed interaction between allele groups: DRB1*15 and DRB1*01 (multiplicative: OR = 0.54, p = 0.0041; additive: AP = 0.47, p = 4×10−06), DRB1*15 and C*12 (multiplicative: OR = 0.37, p = 0.00035; additive: AP = 0.58, p = 2.6×10−05), indicating that the effect size of these allele groups varies when taking DRB1*15 into account. Analysis of inferred haplotypes showed that almost all DRB1*15 bearing haplotypes were risk haplotypes, and that all A*02 bearing haplotypes were protective as long as they did not carry DRB1*15. In contrast, we found one class I haplotype, carrying A*02-C*05-B*12, which abolished the risk of DRB1*15. In conclusion, these results confirms a complex role of HLA class I and II genes that goes beyond DRB1*15 and A*02, in particular by including all three classical HLA class I genes as well as functional interactions between DRB1*15 and several alleles of DRB1 and class I genes

Animal Ecosystem Engineers Modulate the Diversity-Invasibility Relationship

Invasions of natural communities by non-indigenous species are currently rated as one of the most important global-scale threats to biodiversity. Biodiversity itself is known to reduce invasions and increase stability. Disturbances by ecosystem engineers affect the distribution, establishment, and abundance of species but this has been ignored in studies on diversity-invasibility relationships.We determined natural plant invasion into 46 plots varying in the number of plant species (1, 4, and 16) and plant functional groups (1, 2, 3, and 4) for three years beginning two years after the establishment of the Jena Experiment. We sampled subplots where earthworms were artificially added and others where earthworm abundance was reduced. We also performed a seed-dummy experiment to investigate the role of earthworms as secondary seed dispersers along a plant diversity gradient. Horizontal dispersal and burial of seed dummies were significantly reduced in subplots where earthworms were reduced in abundance. Seed dispersal by earthworms decreased with increasing plant species richness and presence of grasses but increased in presence of small herbs. These results suggest that dense vegetation inhibits the surface activity of earthworms. Further, there was a positive relationship between the number of earthworms and the number and diversity of invasive plants. Hence, earthworms decreased the stability of grassland communities against plant invasion.Invasibility decreased and stability increased with increasing plant diversity and, most remarkably, earthworms modulated the diversity-invasibility relationship. While the impacts of earthworms were unimportant in low diverse (low earthworm densities) and high diverse (high floral structural complexity) plant communities, earthworms decreased the stability of intermediate diverse plant communities against plant invasion. Overall, the results document that fundamental processes in plant communities like plant seed burial and invader establishment are modulated by soil fauna calling for closer cooperation between soil animal and plant ecologists

Development of a Management Algorithm for Post-operative Pain (MAPP) after total knee and total hip replacement: study rationale and design.

BACKGROUND: Evidence from clinical practice and the extant literature suggests that post-operative pain assessment and treatment is often suboptimal. Poor pain management is likely to persist until pain management practices become consistent with guidelines developed from the best available scientific evidence. This work will address the priority in healthcare of improving the quality of pain management by standardising evidence-based care processes through the incorporation of an algorithm derived from best evidence into clinical practice. In this paper, the methodology for the creation and implementation of such an algorithm that will focus, in the first instance, on patients who have undergone total hip or knee replacement is described. METHODS: In partnership with clinicians, and based on best available evidence, the aim of the Management Algorithm for Post-operative Pain (MAPP) project is to develop, implement, and evaluate an algorithm designed to support pain management decision-making for patients after orthopaedic surgery. The algorithm will provide guidance for the prescription and administration of multimodal analgesics in the post-operative period, and the treatment of breakthrough pain. The MAPP project is a multisite study with one coordinating hospital and two supporting (rollout) hospitals. The design of this project is a pre-implementation-post-implementation evaluation and will be conducted over three phases. The Promoting Action on Research Implementation in Health Services (PARiHS) framework will be used to guide implementation. Outcome measurements will be taken 10 weeks post-implementation of the MAPP. The primary outcomes are: proportion of patients prescribed multimodal analgesics in accordance with the MAPP; and proportion of patients with moderate to severe pain intensity at rest. These data will be compared to the pre-implementation analgesic prescribing practices and pain outcome measures. A secondary outcome, the efficacy of the MAPP, will be measured by comparing pain intensity scores of patients where the MAPP guidelines were or were not followed. DISCUSSION: The outcomes of this study have relevance for nursing and medical professionals as well as informing health service evaluation. In establishing a framework for the sustainable implementation and evaluation of a standardised approach to post-operative pain management, the findings have implications for clinicians and patients within multiple surgical contexts

The CCR4-NOT Complex Physically and Functionally Interacts with TRAMP and the Nuclear Exosome

BACKGROUND: Ccr4-Not is a highly conserved multi-protein complex consisting in yeast of 9 subunits, including Not5 and the major yeast deadenylase Ccr4. It has been connected functionally in the nucleus to transcription by RNA polymerase II and in the cytoplasm to mRNA degradation. However, there has been no evidence so far that this complex is important for RNA degradation in the nucleus. METHODOLOGY/PRINCIPAL FINDINGS: In this work we point to a new role for the Ccr4-Not complex in nuclear RNA metabolism. We determine the importance of the Ccr4-Not complex for the levels of non-coding nuclear RNAs, such as mis-processed and polyadenylated snoRNAs, whose turnover depends upon the nuclear exosome and TRAMP. Consistently, mutation of both the Ccr4-Not complex and the nuclear exosome results in synthetic slow growth phenotypes. We demonstrate physical interactions between the Ccr4-Not complex and the exosome. First, Not5 co-purifies with the exosome. Second, several exosome subunits co-purify with the Ccr4-Not complex. Third, the Ccr4-Not complex is important for the integrity of large exosome-containing complexes. Finally, we reveal a connection between the Ccr4-Not complex and TRAMP through the association of the Mtr4 helicase with the Ccr4-Not complex and the importance of specific subunits of Ccr4-Not for the association of Mtr4 with the nuclear exosome subunit Rrp6. CONCLUSIONS/SIGNIFICANCE: We propose a model in which the Ccr4-Not complex may provide a platform contributing to dynamic interactions between the nuclear exosome and its co-factor TRAMP. Our findings connect for the first time the different players involved in nuclear and cytoplasmic RNA degradation

Density-Independent Mortality and Increasing Plant Diversity Are Associated with Differentiation of Taraxacum officinale into r- and K-Strategists

Background: Differential selection between clones of apomictic species may result in ecological differentiation without mutation and recombination, thus offering a simple system to study adaptation and life-history evolution in plants. Methodology/Principal Findings: We caused density-independent mortality by weeding to colonizer populations of the largely apomictic Taraxacum officinale (Asteraceae) over a 5-year period in a grassland biodiversity experiment (Jena Experiment). We compared the offspring of colonizer populations with resident populations deliberately sown into similar communities. Plants raised from cuttings and seeds of colonizer and resident populations were grown under uniform conditions. Offspring from colonizer populations had higher reproductive output, which was in general agreement with predictions of r-selection theory. Offspring from resident populations had higher root and leaf biomass, fewer flower heads and higher individual seed mass as predicted under K-selection. Plants grown from cuttings and seeds differed to some degree in the strength, but not in the direction, of their response to the r- vs. K-selection regime. More diverse communities appeared to exert stronger K-selection on resident populations in plants grown from cuttings, while we did not find significant effects of increasing species richness on plants grown from seeds. Conclusions/Significance: Differentiation into r- and K-strategists suggests that clones with characteristics of r-strategists were selected in regularly weeded plots through rapid colonization, while increasing plant diversity favoured the selection of clones with characteristics of K-strategists in resident populations. Our results show that different selection pressures may result in a rapid genetic differentiation within a largely apomictic species. Even under the assumption that colonizer and resident populations, respectively, happened to be r- vs. K-selected already at the start of the experiment, our results still indicate that the association of these strategies with the corresponding selection regimes was maintained during the 5-year experimental period

Critical evaluation of key evidence on the human health hazards of exposure to bisphenol A

Despite the fact that more than 5000 safety-related studies have been published on bisphenol A (BPA), there seems to be no resolution of the apparently deadlocked controversy as to whether exposure of the general population to BPA causes adverse effects due to its estrogenicity. Therefore, the Advisory Committee of the German Society of Toxicology reviewed the background and cutting-edge topics of this BPA controversy. The current tolerable daily intake value (TDI) of 0.05 mg/kg body weight [bw]/day, derived by the European Food Safety Authority (EFSA), is mainly based on body weight changes in two- and three-generation studies in mice and rats. Recently, these studies and the derivation of the TDI have been criticized. After having carefully considered all arguments, the Committee had to conclude that the criticism was scientifically not justified; moreover, recently published additional data further support the reliability of the two-and three-generation studies demonstrating a lack of estrogen-dependent effects at and below doses on which the current TDI is based. A frequently discussed topic is whether doses below 5 mg/ kg bw/day may cause adverse health effects in laboratory animals. Meanwhile, it has become clear that positive results from some explorative studies have not been confirmed in subsequent studies with higher numbers of animals or a priori defined hypotheses. Particularly relevant are some recent studies with negative outcomes that addressed effects of BPA on the brain, behavior, and the prostate in rodents for extrapolation to the human situation. The Committee came to the conclusion that rodent data can well be used as a basis for human risk evaluation. Currently published conjectures that rats are insensitive to estrogens compared to humans can be refuted. Data from toxicokinetics studies show that the half-life of BPA in adult human subjects is less than 2 hours and BPA is completely recovered in urine as BPA-conjugates. Tissue deconjugation of BPA-glucuronide and -sulfate may occur. Because of the extremely low quantities, it is only of minor relevance for BPA toxicity. Biomonitoring studies have been used to estimate human BPA exposure and show that the daily intake of BPA is far below the TDI for the general population. Further topics addressed in this article include reasons why some studies on BPA are not reproducible; the relevance of oral versus non-oral exposure routes; the degree to which newborns are at higher systemic BPA exposure; increased BPA exposure by infusions in intensive care units; mechanisms of action other than estrogen receptor activation; and the current regulatory status in Europe, as well as in the USA, Canada, Japan, New Zealand, and Australia. Overall, the Committee concluded that the current TDI for BPA is adequately justified and that the available evidence indicates that BPA exposure represents no noteworthy risk to the health of the human population, including newborns and babies

Transcriptome-wide analysis of alternative routes for RNA substrates into the exosome complex

<div><p>The RNA exosome complex functions in both the accurate processing and rapid degradation of many classes of RNA. Functional and structural analyses indicate that RNA can either be threaded through the central channel of the exosome or more directly access the active sites of the ribonucleases Rrp44 and Rrp6, but it was unclear how many substrates follow each pathway <i>in vivo</i>. We used CRAC (UV crosslinking and analysis of cDNA) in growing cells to identify transcriptome-wide interactions of RNAs with the major nuclear exosome-cofactor Mtr4 and with individual exosome subunits (Rrp6, Csl4, Rrp41 and Rrp44) along the threaded RNA path. We compared exosome complexes lacking Rrp44 exonuclease activity, carrying a mutation in the Rrp44 S1 RNA-binding domain predicted to disfavor direct access, or with multiple mutations in Rrp41 reported to impede RNA access to the central channel <i>in vitro</i>. Preferential use of channel-threading was seen for mRNAs, 5S rRNA, scR1 (SRP) and aborted tRNAs transcripts. Conversely, pre-tRNAs preferentially accessed Rrp44 directly. Both routes participated in degradation and maturation of RNAPI transcripts, with hand-over during processing. Rrp41 mutations blocked substrate passage through the channel to Rrp44 only for cytoplasmic mRNAs, supporting the predicted widening of the lumen in the Rrp6-associated, nuclear complex. Many exosome substrates exhibited clear preferences for a specific path to Rrp44. Other targets showed redundancy, possibly allowing the efficient handling of highly diverse RNA-protein complexes and RNA structures. Both threading and direct access routes involve the RNA helicase Mtr4. mRNAs that are predominately nuclear or cytoplasmic exosome substrates can be distinguished <i>in vivo</i>.</p></div

Supersymmetric QCD corrections to e+e−→tbˉH−e^+e^-\to t\bar{b}H^- and the Bernstein-Tkachov method of loop integration

The discovery of charged Higgs bosons is of particular importance, since their existence is predicted by supersymmetry and they are absent in the Standard Model (SM). If the charged Higgs bosons are too heavy to be produced in pairs at future linear colliders, single production associated with a top and a bottom quark is enhanced in parts of the parameter space. We present the next-to-leading-order calculation in supersymmetric QCD within the minimal supersymmetric SM (MSSM), completing a previous calculation of the SM-QCD corrections. In addition to the usual approach to perform the loop integration analytically, we apply a numerical approach based on the Bernstein-Tkachov theorem. In this framework, we avoid some of the generic problems connected with the analytical method.Comment: 14 pages, 6 figures, accepted for publication in Phys. Rev.