Conventional versus highly cross-linked polyethylene in primary total knee replacement : a comparison of revision rates using data from the National Joint Registry for England, Wales, and Northern Ireland

There is evidence to support the use of highly cross-linked polyethylene (HXLPE) in patients undergoing total hip arthroplasty. However, the benefits for those undergoing total knee arthroplasty are uncertain, with conflicting reports based on previous cohort analyses. The purpose of the present study was to compare the revision rates following primary total knee arthroplasty with use of HXLPE as compared with conventional polyethylene (CPE) using data from the National Joint Registry (NJR) for England, Wales and Northern Ireland. We performed a retrospective analysis of primary total knee arthroplasties recorded in the NJR from 2003 to 2014. Cobalt-chromium (CoCr)-CPE and CoCr-HXLPE bearing surfaces were compared using all-cause revision, aseptic revision, and septic revision as end points. Survival analyses were conducted using rates per 100 years observed, Kaplan-Meier survival estimates, and Cox regression hazard ratios (HRs) adjusted for age, sex, American Society of Anesthesiologists (ASA) classification, body mass index (BMI), lead surgeon grade, and implant constraint. Secondary analyses compared the most commonly used HXLPEs (Zimmer Prolong, DePuy XLK, and Stryker X3) against CPE for the 3 most common total knee arthroplasty systems (NexGen, PFC Sigma, and Triathlon). In the present study of 550,658 total knee arthroplasties, the unadjusted aseptic revision rates were significantly lower following procedures performed with CPE (n = 513,744) as compared with those performed with HXLPE total knee replacements (n = 36,914) (0.29 [95% confidence interval (CI), 0.28 to 0.30] compared to 0.38 [95% CI, 0.35 to 0.42], p 35 kg/m, the "second-generation" Stryker X3 HXLPE demonstrated significantly better survival than its respective CPE, with CPE having an HR of 2.6 (95% CI, 1.2 to 5.9) (p = 0.02). Alternative bearings are marketed as having improved wear properties over traditional CoCr-CPE. This registry-based analysis demonstrated no overall survival benefit of HXLPE after a maximum duration of follow-up of 12 years. Because of their increased cost, the routine use of HXLPE bearings may not be justified. However, they may have a role in specific "higher demand" groups such as patients 35 kg/m. Therapeutic Level III. See Instructions for Authors for a complete list of levels of evidence

Optimizing Spectronaut Search Parameters to Improve Data Quality with Minimal Proteome Coverage Reductions in DIA Analyses of Heterogeneous Samples

Data-independent acquisition has seen breakthroughs that enable comprehensive proteome profiling using short gradients. As the proteome coverage continues to increase, the quality of the data generated becomes much more relevant. Using Spectronaut, we show that the default search parameters can be easily optimized to minimize the occurrence of false positives across different samples. Using an immunological infection model system to demonstrate the impact of adjusting search settings, we analyzed Mus musculus macrophages and compared their proteome to macrophages spiked withCandida albicans. This experimental system enabled the identification of “false positives” as Candida albicans peptides and proteins should not be present in the Mus musculus-only samples. We show that adjusting the search parameters reduced “false positive” identifications by 89% at the peptide and protein level, thereby considerably increasing the quality of the data. We also show that these optimized parameters incurred a moderate cost, only reducing the overall number of “true positive” identifications across each biological replicate by &lt;6.7% at both the peptide and protein level. We believe the value of our updated search parameters extends beyond a two-organism analysis and would be of great value to any DIA experiment analyzing heterogeneous populations of cell types or tissues.</p

Optimizing Spectronaut Search Parameters to Improve Data Quality with Minimal Proteome Coverage Reductions in DIA Analyses of Heterogeneous Samples

Data-independent acquisition has seen breakthroughs that enable comprehensive proteome profiling using short gradients. As the proteome coverage continues to increase, the quality of the data generated becomes much more relevant. Using Spectronaut, we show that the default search parameters can be easily optimized to minimize the occurrence of false positives across different samples. Using an immunological infection model system to demonstrate the impact of adjusting search settings, we analyzed Mus musculus macrophages and compared their proteome to macrophages spiked withCandida albicans. This experimental system enabled the identification of “false positives” as Candida albicans peptides and proteins should not be present in the Mus musculus-only samples. We show that adjusting the search parameters reduced “false positive” identifications by 89% at the peptide and protein level, thereby considerably increasing the quality of the data. We also show that these optimized parameters incurred a moderate cost, only reducing the overall number of “true positive” identifications across each biological replicate by &lt;6.7% at both the peptide and protein level. We believe the value of our updated search parameters extends beyond a two-organism analysis and would be of great value to any DIA experiment analyzing heterogeneous populations of cell types or tissues.</p

Reduction in host-finding behaviour in fungus-infected mosquitoes is correlated with reduction in olfactory receptor neuron responsiveness

<p>Abstract</p> <p>Background</p> <p>Chemical insecticides against mosquitoes are a major component of malaria control worldwide. Fungal entomopathogens formulated as biopesticides and applied as insecticide residual sprays could augment current control strategies and mitigate the evolution of resistance to chemical-based insecticides.</p> <p>Methods</p> <p><it>Anopheles stephensi </it>mosquitoes were exposed to <it>Beauveria bassiana </it>or <it>Metarhizium acridum </it>fungal spores and sub-lethal effects of exposure to fungal infection were studied, especially the potential for reductions in feeding and host location behaviours related to olfaction. Electrophysiological techniques, such as electroantennogram, electropalpogram and single sensillum recording techniques were then employed to investigate how fungal exposure affected the olfactory responses in mosquitoes.</p> <p>Results</p> <p>Exposure to <it>B. bassiana </it>caused significant mortality and reduced the propensity of mosquitoes to respond and fly to a feeding stimulus. Exposure to <it>M. acridum </it>spores induced a similar decline in feeding propensity, albeit more slowly than <it>B. bassiana </it>exposure. Reduced host-seeking responses following fungal exposure corresponded to reduced olfactory neuron responsiveness in both antennal electroantennogram and maxillary palp electropalpogram recordings. Single cell recordings from neurons on the palps confirmed that fungal-exposed behavioural non-responders exhibited significantly impaired responsiveness of neurons tuned specifically to 1-octen-3-ol and to a lesser degree, to CO₂.</p> <p>Conclusions</p> <p>Fungal infection reduces the responsiveness of mosquitoes to host odour cues, both behaviourally and neuronally. These pre-lethal effects are likely to synergize with fungal-induced mortality to further reduce the capacity of mosquito populations exposed to fungal biopesticides to transmit malaria.</p

The Human Tissue-Biomaterial Interface : A Role for PPARγ-Dependent Glucocorticoid Receptor Activation in Regulating the CD163(+) M2 Macrophage Phenotype

In vivo studies of implanted acellular biological scaffolds in experimental animals have shown constructive remodeling mediated by anti-inflammatory macrophages. Little is known about the human macrophage response to such biomaterials, or the nature of the signaling mechanisms that govern the macrophage phenotype in this environment. The cellular events at the interface of a tissue and implanted decellularized biomaterial were examined by establishing a novel ex vivo tissue culture model in which surgically excised human urinary tract tissue was combined with porcine acellular bladder matrix (PABM). Evaluation of the tissue-biomaterial interface showed a time-dependent infiltration of the biomaterial by CD68(+) CD80(-) macrophages. The migration of CD68(+) cells from the tissue to the interface was accompanied by maturation to a CD163(hi) phenotype, suggesting that factor(s) associated with the biomaterial or the wound edge was/were responsible for the active recruitment and polarization of local macrophages. Glucocorticoid receptor (GR) and peroxisome proliferator activated receptor gamma (PPARγ) signaling was investigated as candidate pathways for integrating inflammatory responses; both showed intense nuclear labeling in interface macrophages. GR and PPARγ activation polarized peripheral blood-derived macrophages from a default M1 (CD80(+)) toward an M2 (CD163(+)) phenotype, but PPARγ signaling predominated, as its antagonism blocked any GR-mediated effect. Seeding on PABM was effective at polarizing peripheral blood-derived macrophages from a default CD80(+) phenotype on glass to a CD80(-) phenotype, with intense nuclear localization of PPARγ. These results endorse in vivo observations that the infiltration of decellularized biological scaffolds, exemplified here by PABM, is pioneered by macrophages. Thus, it appears that natural factors present in PABM are involved in the active recruitment and polarization of macrophages to a CD163(+) phenotype, with activation of PPARγ identified as the candidate pathway. The harnessing of these natural matrix-associated factors may be useful in enhancing the integration of synthetic and other natural biomaterials by polarizing macrophage activation toward an M2 regulatory phenotype

Resummation of Nonalternating Divergent Perturbative Expansions

A method for the resummation of nonalternating divergent perturbation series is described. The procedure constitutes a generalization of the Borel-Pad\'{e} method. Of crucial importance is a special integration contour in the complex plane. Nonperturbative imaginary contributions can be inferred from the purely real perturbative coefficients. A connection is drawn from the quantum field theoretic problem of resummation to divergent perturbative expansions in other areas of physics.Comment: 5 pages, LaTeX, 2 tables, 1 figure; discussion of the Carleman criterion added; version to appear in Phys. Rev.

Exploiting proteomic data for genome annotation and gene model validation in Aspergillus niger

<p>Abstract</p> <p>Background</p> <p>Proteomic data is a potentially rich, but arguably unexploited, data source for genome annotation. Peptide identifications from tandem mass spectrometry provide <it>prima facie </it>evidence for gene predictions and can discriminate over a set of candidate gene models. Here we apply this to the recently sequenced <it>Aspergillus niger </it>fungal genome from the Joint Genome Institutes (JGI) and another predicted protein set from another <it>A.niger </it>sequence. Tandem mass spectra (MS/MS) were acquired from 1d gel electrophoresis bands and searched against all available gene models using Average Peptide Scoring (APS) and reverse database searching to produce confident identifications at an acceptable false discovery rate (FDR).</p> <p>Results</p> <p>405 identified peptide sequences were mapped to 214 different <it>A.niger </it>genomic <it>loci </it>to which 4093 predicted gene models clustered, 2872 of which contained the mapped peptides. Interestingly, 13 (6%) of these <it>loci </it>either had no preferred predicted gene model or the genome annotators' chosen "best" model for that genomic locus was not found to be the most parsimonious match to the identified peptides. The peptides identified also boosted confidence in predicted gene structures spanning 54 introns from different gene models.</p> <p>Conclusion</p> <p>This work highlights the potential of integrating experimental proteomics data into genomic annotation pipelines much as expressed sequence tag (EST) data has been. A comparison of the published genome from another strain of <it>A.niger </it>sequenced by DSM showed that a number of the gene models or proteins with proteomics evidence did not occur in both genomes, further highlighting the utility of the method.</p

Discussion of a spin-cluster model for the low temperature phase of NaV_2O_5

We discuss magnetic excitations of a spin-cluster model which has been suggested to describe the low temperature phase of alpha'-NaV_2O_5. This model fulfills all symmetry criteria proposed by recent x-ray investigations. We find that this model is not able to describe the occurence of two well separated magnon lines perpendicular to the ladder direction as observed in INS experiments. We suggest further experimental analysis to generally distinguish between models with double reflection or inversion symmetry.Comment: 4 pages, 4 figures, added a calculation of level repulsio

Statement on the dossier for a derogation request for the US authorities concerning cold-treated strawberry plants intended for planting.

Following a request from the European Commission, the EFSA Panel on Plant Health examined the report “Evaluation of Strawberry Nursery Plant Cold Treatments on Survival of the Whitefly, Bemisia tabaci”, submitted to the European Commission by the United States Department of Agriculture (USDA). The report serves as technical justification for a derogation from requirements listed in Annex IV, Part A, Section 1, point 46 of the Council Directive 2000/29/EC. The Panel concluded that due to shortcomings in the report itself and in the experimental design of the study, this report does not demonstrate the effectiveness of the cold treatment proposed for the elimination of B. tabaci from strawberry plant consignments prepared for shipment to the EU. In addition, the Panel conducted a preliminary review of the available literature on viruses of strawberry and concluded that no B. tabaci‐transmitted viruses are currently known to infect strawberry and that no viruses of Fragaria listed in European Council Directive 2000/29/EC are known to be transmitted by B. tabaci. However, adult whiteflies of B. tabaci on strawberry consignments can carry plant viruses irrespective of whether strawberry is a host plant for these viruses and thus represent a pathway for the introduction of non‐European viruses. There is also some uncertainty concerning the extent to which known or unknown B. tabaci‐transmitted viruses could infect strawberry. Irrespective of the presence of B. tabaci, strawberry transplants from the US may represent a pathway for the introduction of any non‐European virus (and other potentially harmful organisms) of Fragaria

Scientific Opinion on the assessment of the risk of solanaceous pospiviroids for the EU territory and the identification and evaluation of risk management options.

Following a request from the EU Commission, the EFSA PLH Panel conducted a risk assessment for the EU territory of pospiviroids affecting solanaceous crops, identified and evaluated risk reduction options and evaluated the EU provisional emergency measures targeting Potato spindle tuber viroid (PSTVd). The risk assessment included PSTVd, Citrus exocortis viroid, Columnea latent viroid, Mexican papita viroid, Tomato apical stunt viroid, Tomato chlorotic dwarf viroid, Tomato planta macho viroid, Chrysanthemum stunt viroid and Pepper chat fruit viroid. Four entry pathways were identified, three involving plant propagation material, with moderate probability of entry, and one involving plant products for human consumption, with low probability of entry. The probability of establishment was considered very high. Spread was considered likely within a crop and moderately likely between crop species, with exception of spread to potato, rated as unlikely. The probability of long distance spread within vegetatively propagated crops was estimated as likely/very likely. The direct consequences were expected to be major in potato and tomato, moderate in pepper, minimal/minor in other vegetables and minimal in ornamentals. Main risk assessment uncertainties derive from limited knowledge on pospiviroids other than PSTVd, although all pospiviroids are expected to have similar biological properties. Management options to reduce risk of entry, spread and consequences were identified and evaluated. No management options can prevent establishment. Examples of successful PSTVd eradication are linked to timely and strict implementation of measures. Uncertainty exists on the effectiveness of risk reduction strategies targeting only one pathway. The EU provisional emergency measures appeared to have significantly reduced PSTVd incidence in Solanum jasminoides and Brugmansia sp., even though eradication from the EU is so far incomplete. The low PSTVd incidence in food crops did not permit to conclude whether the reduction in PSTVd prevalence in ornamentals led to a reduction in outbreaks in food crops