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

A matched study of surgically treated stage IB adenosquamous carcinoma and adenocarcinoma of the uterine cervix

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72055/1/j.1525-1438.1993.03040245.x.pd

Structural Requirements for Dihydrobenzoxazepinone Anthelmintics: Actions against Medically Important and Model Parasites: Trichuris muris, Brugia malayi, Heligmosomoides polygyrus, and Schistosoma mansoni

Nine hundred million people are infected with the soil-transmitted helminths Ascaris lumbricoides (roundworm), hookworm, and Trichuris trichiura (whipworm). However, low single-dose cure rates of the benzimidazole drugs, the mainstay of preventative chemotherapy for whipworm, together with parasite drug resistance, mean that current approaches may not be able to eliminate morbidity from trichuriasis. We are seeking to develop new anthelmintic drugs specifically with activity against whipworm as a priority and previously identified a hit series of dihydrobenzoxazepinone (DHB) compounds that block motility of ex vivo Trichuris muris. Here, we report a systematic investigation of the structure–activity relationship of the anthelmintic activity of DHB compounds. We synthesized 47 analogues, which allowed us to define features of the molecules essential for anthelmintic action as well as broadening the chemotype by identification of dihydrobenzoquinolinones (DBQs) with anthelmintic activity. We investigated the activity of these compounds against other parasitic nematodes, identifying DHB compounds with activity against Brugia malayi and Heligmosomoides polygyrus. We also demonstrated activity of DHB compounds against the trematode Schistosoma mansoni, a parasite that causes schistosomiasis. These results demonstrate the potential of DHB and DBQ compounds for further development as broad-spectrum anthelmintics

Lifespan extension and the doctrine of double effect

Recent developments in biogerontology—the study of the biology of ageing—suggest that it may eventually be possible to intervene in the human ageing process. This, in turn, offers the prospect of significantly postponing the onset of age-related diseases. The biogerontological project, however, has met with strong resistance, especially by deontologists. They consider the act of intervening in the ageing process impermissible on the grounds that it would (most probably) bring about an extended maximum lifespan—a state of affairs that they deem intrinsically bad. In a bid to convince their deontological opponents of the permissibility of this act, proponents of biogerontology invoke an argument which is grounded in the doctrine of double effect. Surprisingly, their argument, which we refer to as the ‘double effect argument’, has gone unnoticed. This article exposes and critically evaluates this ‘double effect argument’. To this end, we first review a series of excerpts from the ethical debate on biogerontology in order to substantiate the presence of double effect reasoning. Next, we attempt to determine the role that the ‘double effect argument’ is meant to fulfil within this debate. Finally, we assess whether the act of intervening in ageing actually can be justified using double effect reasoning

Structural Requirements for Dihydrobenzoxazepinone Anthelmintics: Actions against Medically Important and Model Parasites: Trichuris muris, Brugia malayi, Heligmosomoides polygyrus, and Schistosoma mansoni.

Nine hundred million people are infected with the soil-transmitted helminths Ascaris lumbricoides (roundworm), hookworm, and Trichuris trichiura (whipworm). However, low single-dose cure rates of the benzimidazole drugs, the mainstay of preventative chemotherapy for whipworm, together with parasite drug resistance, mean that current approaches may not be able to eliminate morbidity from trichuriasis. We are seeking to develop new anthelmintic drugs specifically with activity against whipworm as a priority and previously identified a hit series of dihydrobenzoxazepinone (DHB) compounds that block motility of ex vivo Trichuris muris. Here, we report a systematic investigation of the structure-activity relationship of the anthelmintic activity of DHB compounds. We synthesized 47 analogues, which allowed us to define features of the molecules essential for anthelmintic action as well as broadening the chemotype by identification of dihydrobenzoquinolinones (DBQs) with anthelmintic activity. We investigated the activity of these compounds against other parasitic nematodes, identifying DHB compounds with activity against Brugia malayi and Heligmosomoides polygyrus. We also demonstrated activity of DHB compounds against the trematode Schistosoma mansoni, a parasite that causes schistosomiasis. These results demonstrate the potential of DHB and DBQ compounds for further development as broad-spectrum anthelmintics

Thermodynamic Measurements in a Strongly Interacting Fermi Gas

We conduct a series of measurements on the thermodynamic properties of an optically-trapped strongly interacting Fermi gas, including the energy $E$, entropy $S$, and sound velocity $c$. Our model-independent measurements of $E$ and $S$ enable a precision study of the finite temperature thermodynamics. The $E(S)$ data are directly compared to several recent predictions. The temperature in both the superfluid and normal fluid regime is obtained from the fundamental thermodynamic relation $T=\partial E/\partial S$ by parameterizing the $E(S)$ data. Our $E(S)$ data are also used to experimentally calibrate the endpoint temperatures obtained for adiabatic sweeps of the magnetic field between the ideal and strongly interacting regimes. This enables the first experimental calibration of the temperature scale used in experiments on fermionic pair condensation. Our calibration shows that the ideal gas temperature measured for the onset of pair condensation corresponds closely to the critical temperature estimated in the strongly interacting regime from the fits to our $E(S)$ data. The results are in very good agreement with recent predictions. Finally, using universal thermodynamic relations, we estimate the chemical potential and heat capacity of the trapped gas from the $E(S)$ data.Comment: 29 pages, 12 figures. To appear in JLTP online, and in the January, 2009 volum

Population-Based Resequencing of Experimentally Evolved Populations Reveals the Genetic Basis of Body Size Variation in Drosophila melanogaster

Body size is a classic quantitative trait with evolutionarily significant variation within many species. Locating the alleles responsible for this variation would help understand the maintenance of variation in body size in particular, as well as quantitative traits in general. However, successful genome-wide association of genotype and phenotype may require very large sample sizes if alleles have low population frequencies or modest effects. As a complementary approach, we propose that population-based resequencing of experimentally evolved populations allows for considerable power to map functional variation. Here, we use this technique to investigate the genetic basis of natural variation in body size in Drosophila melanogaster. Significant differentiation of hundreds of loci in replicate selection populations supports the hypothesis that the genetic basis of body size variation is very polygenic in D. melanogaster. Significantly differentiated variants are limited to single genes at some loci, allowing precise hypotheses to be formed regarding causal polymorphisms, while other significant regions are large and contain many genes. By using significantly associated polymorphisms as a priori candidates in follow-up studies, these data are expected to provide considerable power to determine the genetic basis of natural variation in body size

Diffusionâ weighted imaging outside the brain: Consensus statement from an ISMRMâ sponsored workshop

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134160/1/jmri25196_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134160/2/jmri25196.pd

Complementary therapy use by patients and parents of children with asthma and the implications for NHS care: a qualitative study

BACKGROUND: Patients are increasingly using complementary therapies, often for chronic conditions. Asthma is the most common chronic condition in the UK. Previous research indicates that some asthma patients experience gaps in their NHS care. However, little attention has been given to how and why patients and parents of children with asthma use complementary therapies and the implications for NHS care. METHODS: Qualitative study, comprising 50 semi-structured interviews with a purposeful sample of 22 adults and 28 children with asthma (plus a parent), recruited from a range of NHS and non-NHS settings in Bristol, England. Data analysis was thematic, drawing on the principles of constant comparison. RESULTS: A range of complementary therapies were being used for asthma, most commonly Buteyko breathing and homeopathy. Most use took place outside of the NHS, comprising either self-treatment or consultation with private complementary therapists. Complementary therapies were usually used alongside not instead of conventional asthma treatment. A spectrum of complementary therapy users emerged, including "committed", "pragmatic" and "last resort" users. Motivating factors for complementary therapy use included concerns about conventional NHS care ("push factors") and attractive aspects of complementary therapies ("pull factors"). While participants were often uncertain whether therapies had directly helped their asthma, breathing techniques such as the Buteyko Method were most notably reported to enhance symptom control and enable reduction in medication. Across the range of therapies, the process of seeking and using complementary therapies seemed to help patients in two broad ways: it empowered them to take greater personal control over their condition rather than feel dependant on medication, and enabled exploration of a broader range of possible causes of their asthma than commonly discussed within NHS settings. CONCLUSION: Complementary therapy use reflects patients' and parents' underlying desire for greater self-care and need of opportunities to address some of their concerns regarding NHS asthma care. Self-management of chronic conditions is increasingly promoted within the NHS but with little attention to complementary therapy use as one strategy being used by patients and parents. With their desire for self-help, complementary therapy users are in many ways adopting the healthcare personas that current policies aim to encourage

Differential Production Cross Section of Z Bosons as a Function of Transverse Momentum at sqrt{s}=1.8 TeV

We present a measurement of the transverse momentum distribution of Z bosons produced in ppbar collisions at sqrt{s}=1.8 TeV using data collected by the D0 experiment at the Fermilab Tevatron Collider during 1994--1996. We find good agreement between our data and a current resummation calculation. We also use our data to extract values of the non-perturbative parameters for a particular version of the resummation formalism, obtaining significantly more precise values than previous determinations.Comment: 10 pages, 2 figures, submitted to Phys. Rev. Letters v2 has margin error correcte