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

Global warming and geothermal profiles: the surface rock-temperature response in South Africa

Southern hemisphere and South African regional air temperature anomalies for the period 1860–1996 are compared to borehole‐derived surface rock‐temperature anomalies to assess the extent to which surface rock temperatures reflect possible global warming in South Africa. The warming of the southern hemisphere since the mid‐nineteenth century is evident in the regional air temperatures for South Africa. Following a temperature increase to a maximum in the 1920s, the climate cooled until strong warming recommenced in the mid 1970s. Highest temperatures have been experienced in the 1990s. Borehole‐derived surface rock temperatures followed a similar pattern, but with a lag of a few decades in the case of the 1920s maximum. The overall warming trend is clearly evident in the rock temperatures. Despite uncertainties in the different data sets, an encouraging degree of agreement exists between the increase in rock temperatures during the twentieth century, the corresponding regional South African air temperature increase and the southern hemisphere counterpart

Introduction

Humanity recognised millennia ago the importance of climate variability to the sustenance of life, whether that variability was expressed in the form of droughts, floods, heat, cold, or wind. Coping strategies, developed to handle the consequences of climate variability, helped ensure mankind’s survival, although the historic record indicates that not all societies successfully overcame past challenges imposed by long-term droughts, extensive flooding, and the like. Early coping strategies included migration, invasion, appropriation and storage. In addition many, probably most, perhaps all, societies developed indigenous knowledge or belief systems that they felt enabled them to foresee or control those elements of the climate that are so critical for maintaining water and food supplies

Water, health and early warnings

Water management is the focus in the first section, in which a number of projects are described whereby historical and forecast information is used directly in planning specific actions; in this case the forecaster-user chain is short and manageable at a personal level. Next is a detailed account of the steps required to establish climate services in the health area. Finally, Early Warning Systems are described. Early Warning Systems have not tended to use predictions until recently, traditionally having been built around historical observations. In that context Early Warning Systems provide an example of an application mainly designed for humanitarian benefit built solely using climate data alongside other information, but with growing use of predictions. A worked example is included establishing the impact of climate variability on disease incidence, the results of which provide a basis for incorporating seasonal climate forecasts into a Malaria Early Warning System in southern Africa

Signed weighted gene co-expression network analysis of transcriptional regulation in murine embryonic stem cells

<p>Abstract</p> <p>Background</p> <p>Recent work has revealed that a core group of transcription factors (TFs) regulates the key characteristics of embryonic stem (ES) cells: pluripotency and self-renewal. Current efforts focus on identifying genes that play important roles in maintaining pluripotency and self-renewal in ES cells and aim to understand the interactions among these genes. To that end, we investigated the use of unsigned and signed network analysis to identify pluripotency and differentiation related genes.</p> <p>Results</p> <p>We show that signed networks provide a better systems level understanding of the regulatory mechanisms of ES cells than unsigned networks, using two independent murine ES cell expression data sets. Specifically, using signed weighted gene co-expression network analysis (WGCNA), we found a pluripotency module and a differentiation module, which are not identified in unsigned networks. We confirmed the importance of these modules by incorporating genome-wide TF binding data for key ES cell regulators. Interestingly, we find that the pluripotency module is enriched with genes related to DNA damage repair and mitochondrial function in addition to transcriptional regulation. Using a connectivity measure of module membership, we not only identify known regulators of ES cells but also show that Mrpl15, Msh6, Nrf1, Nup133, Ppif, Rbpj, Sh3gl2, and Zfp39, among other genes, have important roles in maintaining ES cell pluripotency and self-renewal. We also report highly significant relationships between module membership and epigenetic modifications (histone modifications and promoter CpG methylation status), which are known to play a role in controlling gene expression during ES cell self-renewal and differentiation.</p> <p>Conclusion</p> <p>Our systems biologic re-analysis of gene expression, transcription factor binding, epigenetic and gene ontology data provides a novel integrative view of ES cell biology.</p

A way forward for seasonal climate services

The enthusiasm for engaging the challenges of Seasonal to Interannual Prediction, both within the disciplines of physical and social sciences and at their interface, was well demonstrated through the energetic engagement of all during the May to June 2005 NATO ASI course, upon which this book is based. Several panel sessions were held during the course, which permitted everyone to offer views within an informal setting; some, not reflected in the main body of the book, are incorporated in this chapter. Little stays stationary in such a fast-developing field, and so, to provide the most advanced position at publication, this summarising chapter has included some of the latest development to supplement the material drawn from the course presentations and the panel discussions. Additionally, a view to the future is offered so as to provide further stimulation to those interested in the fascinating field of Seasonal to Interannual Climat

The transcription factor Foxg1 regulates telencephalic progenitor proliferation cell autonomously, in part by controlling Pax6 expression levels

<p>Abstract</p> <p>Background</p> <p>The transcription factor Foxg1 is an important regulator of telencephalic cell cycles. Its inactivation causes premature lengthening of telencephalic progenitor cell cycles and increased neurogenic divisions, leading to severe hypoplasia of the telencephalon. These proliferation defects could be a secondary consequence of the loss of Foxg1 caused by the abnormal expression of several morphogens (Fibroblast growth factor 8, bone morphogenetic proteins) in the telencephalon of <it>Foxg1 </it>null mutants. Here we investigated whether Foxg1 has a cell autonomous role in the regulation of telencephalic progenitor proliferation. We analysed <it>Foxg1^+/+</it>↔<it>Foxg1^-/-</it>chimeras, in which mutant telencephalic cells have the potential to interact with, and to have any cell non-autonomous defects rescued by, normal wild-type cells.</p> <p>Results</p> <p>Our analysis showed that the <it>Foxg1^-/-</it>cells are under-represented in the chimeric telencephalon and the proportion of them in S-phase is significantly smaller than that of their wild-type neighbours, indicating that their under-representation is caused by a cell autonomous reduction in their proliferation. We then analysed the expression of the cell-cycle regulator Pax6 and found that it is cell-autonomously downregulated in <it>Foxg1^-/-</it>dorsal telencephalic cells. We went on to show that the introduction into <it>Foxg1^-/-</it>embryos of a transgene designed to reverse Pax6 expression defects resulted in a partial rescue of the telencephalic progenitor proliferation defects.</p> <p>Conclusions</p> <p>We conclude that Foxg1 exerts control over telencephalic progenitor proliferation by cell autonomous mechanisms that include the regulation of Pax6, which itself is known to regulate proliferation cell autonomously in a regional manner.</p

The short term debt vs. long term debt puzzle: a model for the optimal mix

This paper argues that the existing finance literature is inadequate with respect to its coverage of capital structure of small and medium sized enterprises (SMEs). In particular it is argued that the cost of equity (being both conceptually ill defined and empirically non quantifiable) is not applicable to the capital structure decisions for a large proportion of SMEs and the optimal capital structure depends only on the mix of short and long term debt. The paper then presents a model, developed by practitioners for optimising the debt mix and demonstrates its practical application using an Italian firm's debt structure as a case study