Reliability and Validity of the Star Excursion Balance Test for Patients with Chronic Patellar Instability

The Star Excursion Balance Test (SEBT) is an eight-direction, maximal-reach balance test whose measurement properties are unknown in participants with chronic patellar instability. We designed an observational study with repeated measures to evaluate the test-retest reliability, cross-sectional and longitudinal construct validity, sensitivity to change and responsiveness of the SEBT in this population. Fifteen patients completed the SEBT and reported outcomes at baseline and two weeks and four patients completed testing three months later at the Fowler Kennedy Sports Medicine Clinic. Intra-class correlation coefficients (ICC) for the SEBT were fair to good, ranging from 0.66-0.84. The SEBT demonstrates good cross-sectional construct validity and we are unable to comment with certainty on longitudinal construct validity; correlations between SEBT reach distance and patient-reported outcomes showed agreement with our hypotheses in 93 of 126 (74%) and 46 of 108 (43%) directions. These are preliminary results of a larger continuing study; therefore definitive conclusions cannot be made

A +1 ribosomal frameshifting motif prevalent among plant amalgaviruses.

Sequence accessions attributable to novel plant amalgaviruses have been found in the Transcriptome Shotgun Assembly database. Sixteen accessions, derived from 12 different plant species, appear to encompass the complete protein-coding regions of the proposed amalgaviruses, which would substantially expand the size of genus Amalgavirus from 4 current species. Other findings include evidence for UUU_CGN as a +1 ribosomal frameshifting motif prevalent among plant amalgaviruses; for a variant version of this motif found thus far in only two amalgaviruses from solanaceous plants; for a region of α-helical coiled coil propensity conserved in a central region of the ORF1 translation product of plant amalgaviruses; and for conserved sequences in a C-terminal region of the ORF2 translation product (RNA-dependent RNA polymerase) of plant amalgaviruses, seemingly beyond the region of conserved polymerase motifs. These results additionally illustrate the value of mining the TSA database and others for novel viral sequences for comparative analyses.M.L.N. was supported in part by a subcontract from NIH grant 5R01GM033050-33. J.D.P. completed his work on this project during a lab rotation for the Ph.D. Training Program in Virology at Harvard University, Cambridge, MA, USA and was supported in part by NIH grant 2T32AI007245-31. A.E.F. was supported in part by the Wellcome Trust (grant 106207).This is the final version of the article. It first appeared from Elsevier via https://doi.org/10.1016/j.virol.2016.07.00

High-Resolution Analysis of Coronavirus Gene Expression by RNA Sequencing and Ribosome Profiling.

Members of the family Coronaviridae have the largest genomes of all RNA viruses, typically in the region of 30 kilobases. Several coronaviruses, such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and Middle East respiratory syndrome-related coronavirus (MERS-CoV), are of medical importance, with high mortality rates and, in the case of SARS-CoV, significant pandemic potential. Other coronaviruses, such as Porcine epidemic diarrhea virus and Avian coronavirus, are important livestock pathogens. Ribosome profiling is a technique which exploits the capacity of the translating ribosome to protect around 30 nucleotides of mRNA from ribonuclease digestion. Ribosome-protected mRNA fragments are purified, subjected to deep sequencing and mapped back to the transcriptome to give a global "snap-shot" of translation. Parallel RNA sequencing allows normalization by transcript abundance. Here we apply ribosome profiling to cells infected with Murine coronavirus, mouse hepatitis virus, strain A59 (MHV-A59), a model coronavirus in the same genus as SARS-CoV and MERS-CoV. The data obtained allowed us to study the kinetics of virus transcription and translation with exquisite precision. We studied the timecourse of positive and negative-sense genomic and subgenomic viral RNA production and the relative translation efficiencies of the different virus ORFs. Virus mRNAs were not found to be translated more efficiently than host mRNAs; rather, virus translation dominates host translation at later time points due to high levels of virus transcripts. Triplet phasing of the profiling data allowed precise determination of translated reading frames and revealed several translated short open reading frames upstream of, or embedded within, known virus protein-coding regions. Ribosome pause sites were identified in the virus replicase polyprotein pp1a ORF and investigated experimentally. Contrary to expectations, ribosomes were not found to pause at the ribosomal frameshift site. To our knowledge this is the first application of ribosome profiling to an RNA virus.NI was supported by a Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust, 092334/Z/10/Z). Work in the AEF lab was funded by grants from the Wellcome Trust (088789 and 106207), the U.K. Biotechnology and Biological Research Council (BBSRC) (BB/J007072/1 and BB/J015652/1), and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No [646891]). Work in the IB laboratory was supported by the Medical Research Council (MRC) (MR/M011747/1) and the Biotechnology and Biological Sciences Research Council (BBSRC) (BB/L000334/1).This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.ppat.100547

Evidence for a novel coding sequence overlapping the 5'-terminal ~90 codons of the Gill-associated and Yellow head okavirus envelope glycoprotein gene

The genus Okavirus (order Nidovirales) includes a number of viruses that infect crustaceans, causing major losses in the shrimp industry. These viruses have a linear positive-sense ssRNA genome of ~26-27 kb, encoding a large replicase polyprotein that is expressed from the genomic RNA, and several additional proteins that are expressed from a nested set of 3'-coterminal subgenomic RNAs. In this brief report, we describe the bioinformatic discovery of a new, apparently coding, ORF that overlaps the 5' end of the envelope glycoprotein encoding sequence, ORF3, in the +2 reading frame. The new ORF has a strong coding signature and, in fact, is more conserved at the amino acid level than the overlapping region of ORF3. We propose that translation of the new ORF initiates at a conserved AUG codon separated by just 2 nt from the ORF3 AUG initiation codon, resulting in a novel 86 amino acid protein

The use of duplex-specific nuclease in ribosome profiling and a user-friendly software package for Ribo-seq data analysis.

Ribosome profiling is a technique that permits genome-wide, quantitative analysis of translation and has found broad application in recent years. Here we describe a modified profiling protocol and software package designed to benefit more broadly the translation community in terms of simplicity and utility. The protocol, applicable to diverse organisms, including organelles, is based largely on previously published profiling methodologies, but uses duplex-specific nuclease (DSN) as a convenient, species-independent way to reduce rRNA contamination. We show that DSN-based depletion compares favorably with other commonly used rRNA depletion strategies and introduces little bias. The profiling protocol typically produces high levels of triplet periodicity, facilitating the detection of coding sequences, including upstream, downstream, and overlapping open reading frames (ORFs) and an alternative ribosome conformation evident during termination of protein synthesis. In addition, we provide a software package that presents a set of methods for parsing ribosomal profiling data from multiple samples, aligning reads to coding sequences, inferring alternative ORFs, and plotting average and transcript-specific aspects of the data. Methods are also provided for extracting the data in a form suitable for differential analysis of translation and translational efficiency.This work was supported by an EMBL long-term postdoctoral fellowship to B.Y.C., Sir Henry Wellcome Fellowships to B.Y.C. and N.I., a Wellcome Trust PhD scholarship to J.D.J., a Wellcome Trust Fellowship to A.E.F. (088789), and UK Biotechnology and Biological Sciences Research Council grants to I.B. (BB/L000334/ 1) and A.E.F. (BB/J007072/1). Work in the Baulcombe laboratory is supported by The Gatsby Charitable Foundation and the European Research Council Advanced Investigator grant TRIBE. D.C.B. is the Royal Society Edward Penley Abraham Research Professor. We wish to thank Professor Stuart G. Siddell, University of Bristol, for providing the murine 17 clone 1 cellsThis is the final version of the article. It was first available from Cold Springs Harbor Press via http://dx.doi.org/10.1261/rna.052548.11

Closing-Wedge Posterior Tibial Slope-Reducing Osteotomy in Complex Revision ACL Reconstruction

Background: A posterior tibial slope (PTS) >12° has been shown to correlate with failure of anterior cruciate ligament (ACL) reconstruction (ACLR). PTS-reducing osteotomy has been described to correct the PTS in patients with a deficient ACL, mostly after failure of primary ACLR. Purpose: To report radiologic indices, clinical outcomes, and postoperative complications after PTS-reducing osteotomy performed concurrently with revision ACLR (R-ACLR). Study design: Case series; Level of evidence, 4. Methods: A review of medical records at 3 institutions was performed of patients who had undergone PTS-reducing osteotomy concurrently with R-ACLR between August 2010 and October 2020. Radiologic parameters recorded included the PTS, patellar height according to the Caton-Deschamps Index (CDI), and anterior tibial translation (ATT). Patient-reported outcomes (International Knee Documentation Committee [IKDC] and Knee injury and Osteoarthritis Outcome Score [KOOS]), reoperations, and complications were evaluated. Results: Included were 23 patients with a mean follow-up of 26.7 months (range, 6-84 months; median, 22.5 months). Statistically significant differences from preoperative to postoperative values were found in PTS (median [range], 14.0° [12°-18°] vs 4.0° [0°-15°], respectively; P < .001), CDI (median, 1.00 vs 1.10, respectively; P = .04) and ATT (median, 8.5 vs 3.6 mm, respectively; P = .001). At the final follow-up, the IKDC score was 52.4 ± 19.2 and the KOOS subscale scores were 81.5 ± 9.5 (Pain), 74 ± 21.6 (Symptoms), 88.5 ± 8 (Activities of Daily Living); 52.5 ± 21.6 (Sport and Recreation), and 48.8 ± 15.8 (Quality of Life). A traumatic ACL graft failure occurred in 2 patients (8.7%). Reoperations were necessary for 6 patients (26.1%) because of symptomatic hardware, and atraumatic recurrent knee instability was diagnosed in 1 patient (4.3%). Conclusion: Tibial slope-reducing osteotomy resulted in a significant decrease of ATT and can be considered in patients with a preoperative PTS ≥12° and ≥1 ACLR failure. In highly complex patients with multiple prior surgeries, the authors found a reasonably low graft failure rate (8.7%) when utilizing PTS-reducing osteotomy. Surgeons must be aware of potential complications in patients with multiple previous failed ACLRs

Candidates in Astroviruses, Seadornaviruses, Cytorhabdoviruses and Coronaviruses for +1 frame overlapping genes accessed by leaky scanning

<p>Abstract</p> <p>Background</p> <p>Overlapping genes are common in RNA viruses where they serve as a mechanism to optimize the coding potential of compact genomes. However, annotation of overlapping genes can be difficult using conventional gene-finding software. Recently we have been using a number of complementary approaches to systematically identify previously undetected overlapping genes in RNA virus genomes. In this article we gather together a number of promising candidate new overlapping genes that may be of interest to the community.</p> <p>Results</p> <p>Overlapping gene predictions are presented for the astroviruses, seadornaviruses, cytorhabdoviruses and coronaviruses (families <it>Astroviridae</it>, <it>Reoviridae</it>, <it>Rhabdoviridae </it>and <it>Coronaviridae</it>, respectively).</p

Optical and Near-Infrared Observations of the Peculiar Type Ia Supernova 1999ac

We present 39 nights of optical photometry, 34 nights of infrared photometry, and 4 nights of optical spectroscopy of the Type Ia SN 1999ac. This supernova was discovered two weeks before maximum light, and observations were begun shortly thereafter. At early times its spectra resembled the unusual SN 1999aa and were characterized by very high velocities in the Ca II H and K lines, but very low velocities in the Si II 6355 A line. The optical photometry showed a slow rise to peak brightness but, quite peculiarly, was followed by a more rapid decline from maximum. Thus, the B- and V-band light curves cannot be characterized by a single stretch factor. We argue that the best measure of the nature of this object is not the decline rate parameter Delta m_15 (B). The B-V colors were unusual from 30 to 90 days after maximum light in that they evolved to bluer values at a much slower rate than normal Type Ia supernovae. The spectra and bolometric light curve indicate that this event was similar to the spectroscopically peculiar slow decliner SN 1999aa.Comment: 42 pages, 14 figures, accepted for publication in the Astronomical Journal (January 28, 2006

The First New Zealanders? An Alternative Interpretation of Stable Isotope Data from Wairau Bar, New Zealand.

PLOS ONE Volume 8 includes an article “The First New Zealanders: Patterns of Diet and Mobility Revealed through Isotope Analysis”. The paper proposes that burial groups within the settlement phase site of Wairau Bar differ in terms of dietary stable isotopes and 87Sr/86Sr. The authors argue this difference is probably due to one group being a founding population while the other burials are later. Here we review the work of Kinaston et al. and present an alternative analysis and interpretation of the isotopic data. Treating the isotope data independently from cultural and biological factors we find that sex best explains dietary variation. Our reassessment of 87Sr/86Sr confirms the authors original finding of high mobility of early New Zealanders but suggests a larger range of individuals should be considered ‘non-local’ on current evidence

Effect of sirolimus on malignancy and survival after kidney transplantation: systematic review and meta-analysis of individual patient data

Objective To examine risk of malignancy and death in patients with kidney transplant who receive the immunosuppressive drug sirolimus.Design Systematic review and meta-analysis of individual patient data.Data sources Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to March 2013.Eligibility Randomized controlled trials comparing immunosuppressive regimens with and without sirolimus in recipients of kidney or combined pancreatic and renal transplant for which the author was willing to provide individual patient level data. Two reviewers independently screened titles/abstracts and full text reports of potentially eligible trials to identify studies for inclusion. All eligible trials reported data on malignancy or survival.Results the search yielded 2365 unique citations. Patient level data were available from 5876 patients from 21 randomized trials. Sirolimus was associated with a 40% reduction in the risk of malignancy (adjusted hazard ratio 0.60, 95% confidence interval 0.39 to 0.93) and a 56% reduction in the risk of non-melanoma skin cancer (0.44, 0.30 to 0.63) compared with controls. the most pronounced effect was seen in patients who converted to sirolimus from an established immunosuppressive regimen, resulting in a reduction in risk of malignancy (0.34, 0.28 to 0.41), non-melanoma skin cancer (0.32, 0.24 to 0.42), and other cancers (0.52, 0.38 to 0.69). Sirolimus was associated with an increased risk of death (1.43, 1.21 to 1.71) compared with controls.Conclusions Sirolimus was associated with a reduction in the risk of malignancy and non-melanoma skin cancer in transplant recipients. the benefit was most pronounced in patients who converted from an established immunosuppressive regimen to sirolimus. Given the risk of mortality, however, the use of this drug does not seem warranted for most patients with kidney transplant. Further research is needed to determine if different populations, such as those at high risk of cancer, might benefit from sirolimus.PfizerOttawa Hosp, Res Inst, Ottawa, ON K1H 7W9, CanadaUniv Ottawa, Ottawa, ON, CanadaCairo Univ, Cairo Kidney Ctr, Cairo, EgyptLimites Med Res, Vacallo, SwitzerlandUniv Manitoba, Dept Pediat & Childs Hlth, Winnipeg, MB, CanadaLund Univ, Dept Nephrol & Transplantat, Malmo, SwedenUniversidade Federal de São Paulo, Hosp Rim & Hipertensao, São Paulo, BrazilAddenbrookes Hosp, Dept Renal Med, Cambridge, EnglandNorthwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USAMaastricht Univ, Med Ctr, Maastricht, NetherlandsSt Louis Hosp, Dept Nephrol, Paris, FranceHosp JW Goethe, Div Nephrol, Frankfurt, GermanyUniv Munich, Dept Surg, Munich, GermanyGoethe Univ Frankfurt, JW Goethe Clin, Clin Dermatol Venerol & Allergol, Frankfurt, GermanyInst Klin Expt Med, Dept Nephrol, Prague, Czech RepublicUniv Cambridge, Addenbrookes Hosp, Dept Surg, NIHR Cambridge Biomed Res Ctr, Cambridge CB2 2QQ, EnglandUniversidade Federal de São Paulo, Hosp Rim & Hipertensao, São Paulo, BrazilWeb of Scienc