Oral versus intravenous antibiotics for bone and joint infection

BACKGROUND The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. METHODS We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. RESULTS Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of −1.4 percentage points (90% confidence interval [CI], −4.9 to 2.2; 95% CI, −5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). CONCLUSIONS Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927. opens in new tab.

A quantitative reassessment of morphology-based taxonomic schemes for Turkish tortoises (Testudo graeca)

In the last decade, Asian populations of Testudo graeca were split into as many as 10 species based on morphology and morphometry and then subsequently synonymized based on genetic evidence. We generate new morphometric data for six of these disputed species from Turkey, a major center of morphological and genetic diversity for Asian T. graeca. We test the concordance of our data with previous morphological assignments. Our morphometric data and analyses do not support all of the results of previous morphometric studies. Instead we find that putatively named taxa from the Mediterranean coast ("antakyensis" , "anamurensis", and "terrestris") are not morphometrically distinct. On the other hand, some inland populations from eastern Turkey ("armeniaca" and "perses") are morphometrically distinct as previously claimed. Tortoise populations from northern and southern Turkey, which may correspond to the ibera and terrestris mt clades, also appear to be morphometrically distinct. In this respect, the morphometric data reflects the emerging genetic pattern, although the picture is complicated by a lack of genetic sampling within Turkey and morphometric studies outside of Turkey. © Koninklijke Brill NV, Leiden, 2010.Alfred P. Sloan Foundation 102T104, TBAG-2206 John D. and Catherine T. MacArthur FoundationAcknowledgements. This study is financially supported by the Scientific and Technological Research Council of Turkey (TUBITAK) with a project number TBAG-2206 (102T104). The authors would like to thank Jim Buskirk (Oakland, USA) for their help during some of the fieldwork. JFP is supported by the John D. and Catherine T. MacArthur Foundation, the Alfred P. Sloan Foundation and would like to thank Sarah Rieboldt (U.C. Berkeley) for her support. This is UCMP contribution #1978. -

The phylogeny of Mediterranean tortoises and their close relatives based on complete mitochondrial genome sequences from museum specimens

As part of an ongoing project to generate a mitochondrial database for terrestrial tortoises based on museum specimens, the complete mitochondrial genome sequences of 10 species and a ∼14 kb sequence from an eleventh species are reported. The sampling of the present study emphasizes Mediterranean tortoises (genus Testudo and their close relatives). Our new sequences are aligned, along with those of two testudinoid turtles from GenBank, Chrysemys picta and Mauremys reevesii, yielding an alignment of 14,858 positions, of which 3238 are parsimony informative. We develop a phylogenetic taxonomy for Testudo and related species based on well-supported, diagnosable clades. Several well-supported nodes are recovered, including the monophyly of a restricted Testudo, T. kleinmanni + T. marginata (the Chersus clade), and the placement of the enigmatic African pancake tortoise (Malacochersus tornieri) within the predominantly Palearctic greater Testudo group (Testudona tax. nov.). Despite the large amount of sequence reported, there is low statistical support for some nodes within Testudona and so we do not propose names for those groups. A preliminary and conservative estimation of divergence times implies a late Miocene diversification for the testudonan clade (6-10 million years ago), matching their first appearance in the fossil record. The multi-continental distribution of testudonan turtles can be explained by the establishment of permanent connections between Europe, Africa, and Asia at this time. The arrival of testudonan turtles to Africa occurred after one or more initial tortoise invasions gave rise to the diverse (>25 species) 'Geochelone complex.' Two unusual genomic features are reported for the mtDNA of one tortoise, M. tornieri: (1) nad4 has a shift of reading frame that we suggest is resolved by translational frameshifting of the mRNA on the ribosome during protein synthesis and (2) there are two copies of the control region and trnF, with the latter having experienced multiple-nucleotide substitutions in a pattern suggesting that each is being maintained by selection. © 2005 Elsevier Inc. All rights reserved

Optimization of experimental designs by incorporating NIF facility impacts

For experimental campaigns on the National Ignition Facility (NIF) to be successful, they must obtain useful data without causing unacceptable impact on the facility. Of particular concern is excessive damage to optics and diagnostic components. There are 192 fused silica main debris shields (MDS) exposed to the potentially hostile target chamber environment on each shot. Damage in these optics results either from the interaction of laser light with contamination and pre-existing imperfections on the optic surface or from the impact of shrapnel fragments. Mitigation of this second damage source is possible by identifying shrapnel sources and shielding optics from them. It was recently demonstrated that the addition of 1.1-mm thick borosilicate disposable debris shields (DDS) blocks the majority of debris and shrapnel fragments from reaching the relatively expensive MDS's. However, DDS's cannot stop large, fast moving fragments. We have experimentally demonstrated one shrapnel mitigation technique showing that it is possible to direct fast moving fragments by changing the source orientation, in this case a Ta pinhole array. Another mitigation method is to change the source material to one that produces smaller fragments. Simulations and validating experiments are necessary to determine which fragments can penetrate or break 1-3 mm thick DDS's. Three-dimensional modeling of complex target-diagnostic configurations is necessary to predict the size, velocity, and spatial distribution of shrapnel fragments. The tools we are developing will be used to assure that all NIF experimental campaigns meet the requirements on allowed level of debris and shrapnel generation