Cemented total hip replacement in patients under 55 years:Good results in 104 hips followed up for ≥22 years

Background and purpose — About 86,000 total hip replacements (THR) have been registered in patients under 55 years in the National Joint Registry of England and Wales (NJR). The use of uncemented implants has increased, despite their outcomes not having been proven to be significantly better than cemented implants in this registry. We determined the implant survivorship and functional outcomes of cemented THR in patients under 55 years at a minimum follow-up of 22 years. Patients and methods — 104 hips in 100 patients were included in this prospective study. Functional outcome was assessed using the Harris Hip Score and radiographs were assessed for implant failure and “at risk” of failure. Kaplan–Meier survivorship analysis was performed. Results — 89% of hips showed good to excellent results at final follow-up with a mean Harris Hip Score of 88 at a mean follow-up of 25 years. Revision was performed in 3/104 hips. 14 acetabular components and 4 femoral components were “at risk” of failure. The survivorship at minimum 22 years with revision for any reason as the end-point was 97% (95% CI 95–98). Interpretation — Cemented hip replacements perform well in young patients with good long-term functional and radiographic outcomes

Troubling identities: teacher education students` constructions of class and ethnicity

Working with diverse student populations productively depends on teachers and teacher educators recognizing and valuing difference. Too often, in teacher education programs, when markers of identity such as gender, ethnicity, \u27race\u27, or social class are examined, the focus is on developing student teachers\u27 understandings of how these discourses shape learner identities and rarely on how these also shape teachers\u27 identities. This article reports on a research project that explored how student teachers understand ethnicity and socio-economic status. In a preliminary stage of the research, we asked eight Year 3 teacher education students who had attended mainly Anglo-Australian, middle class schools as students and as student teachers, to explore their own ethnic and classed identities. The complexities of identity are foregrounded in both the assumptions we made in selecting particular students for the project and in the ways they constructed their own identities around ethnicity and social class. In this article we draw on these findings to interrogate how categories of identity are fluid, shifting and ongoing processes of negotiation, troubling and complex. We also consider the implications for teacher education.<br /

The lived experience of discrimination by white women in committed interracial relationships with black men

Abstract: This study explores the experiences of discrimination by white women in committed interracial relationships with black men within the South African context from a descriptive phenomenological perspective. Three white females in committed interracial relationships with black males were recruited and interviewed. Open-ended interviews were conducted in order to elicit rich and in-depth first-person descriptions of the participants’ lived experiences of discrimination as a result of being in committed interracial relationships. The data analysis entailed a descriptive phenomenological content analysis and description. The results of this study suggest that white women in committed interracial relationships with black men experienced discrimination in various contexts where discrimination manifests as either a negative or a positive encounter; in addition, discrimination evokes various emotional responses and is coped with in either maladaptive or adaptive ways. Finally the experience of discrimination, although personal, necessarily impacts on the interracial relationship. Discrimination experienced by white women in committed interracial relationships with black men is thus multi-layered and both an intra-personal and inter-personal phenomenon

New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections

Toxoplasma gondii, the most common parasitic infection of human brain and eye, persists across lifetimes, can progressively damage sight, and is currently incurable. New, curative medicines are needed urgently. Herein, we develop novel models to facilitate drug development: EGS strain T. gondii forms cysts in vitro that induce oocysts in cats, the gold standard criterion for cysts. These cysts highly express cytochrome b. Using these models, we envisioned, and then created, novel 4-(1H)-quinolone scaffolds that target the cytochrome bc1 complex Qi site, of which, a substituted 5,6,7,8-tetrahydroquinolin-4-one inhibits active infection (IC50, 30 nM) and cysts (IC50, 4 μM) in vitro, and in vivo (25 mg/kg), and drug resistant Plasmodium falciparum (IC50, <30 nM), with clinically relevant synergy. Mutant yeast and co-crystallographic studies demonstrate binding to the bc1 complex Qi site. Our results have direct impact on improving outcomes for those with toxoplasmosis, malaria, and ~2 billion persons chronically infected with encysted bradyzoites

Gravitationally Lensed Quasar SDSS J1442+4055: Redshifts of Lensing Galaxies, Time Delay, Microlensing Variability, and Intervening Metal System at z ∼2

We present r-band photometric monitoring of the two images, A and B, of the gravitationally lensed quasar SDSS J1442+4055 using the Liverpool Telescope (LT). From the LT light curves between 2015 December and 2018 August, we derive at once a time delay of 25.0 ± 1.5 days (1σ confidence interval; A is leading) and microlensing magnification gradients below 10-4 mag day-1. The delay interval is not expected to be affected by an appreciable microlensing-induced bias, so it can be used to estimate cosmological parameters. This paper also focuses on new Gran Telescopio Canarias (GTC) and LT spectroscopic observations of the lens system. We determine the redshift of two bright galaxies around the doubly imaged quasar using LT spectroscopy, while GTC data lead to low-noise individual spectra of A, B, and the main lensing galaxy, G1. The G1 spectral shape is accurately matched to an early-type galaxy template at z = 0.284, and it has potential for further relevant studies. Additionally, the quasar spectra show absorption by metal-rich gas at z ~ 2. This dusty absorber is responsible for an extinction bump at a rest-frame wavelength of 2209 ± 2 Å, which has strengths of ~0.47 and 0.76 mag μm−1 for A and B, respectively. In such an intervening system, the dust-to-gas ratio, gas-phase metallicity indicator [Zn/H], and dust depletion level [Fe/Zn] are relatively hig.We are grateful to the SDSS collaboration for doing that public database. This research as been conducted in the framework of the Gravitational LENses and DArk MAtter (GLENDAMA) project, which was /is supported by Spanish Department of Research, Development and Innovation grant AYA2013-47744-C3-2-P; MINECO/AEI/FEDER-UE grant AYA2017-89815-P; the complementary action “Lentes Gravitatorias y Materia Oscura” financed by the SOciedad para el DEsarrollo Regional de CANtabria (SODERCAN S.A.); the Operational Programme of FEDER-UE; and the University of Cantabri

Author Correction: New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections

Correction to: Scientific Reports https://doi.org/10.1038/srep29179, published online 14 July 201

Resistance of Bovine Spongiform Encephalopathy (BSE) Prions to Inactivation

Distinct prion strains often exhibit different incubation periods and patterns of neuropathological lesions. Strain characteristics are generally retained upon intraspecies transmission, but may change on transmission to another species. We investigated the inactivation of two related prions strains: BSE prions from cattle and mouse-passaged BSE prions, termed 301V. Inactivation was manipulated by exposure to sodium dodecyl sulfate (SDS), variations in pH, and different temperatures. Infectivity was measured using transgenic mouse lines that are highly susceptible to either BSE or 301V prions. Bioassays demonstrated that BSE prions are up to 1,000-fold more resistant to inactivation than 301V prions while Western immunoblotting showed that short acidic SDS treatments reduced protease-resistant PrPSc from BSE prions and 301V prions at similar rates. Our findings argue that despite being derived from BSE prions, mouse 301V prions are not necessarily a reliable model for cattle BSE prions. Extending these comparisons to human sporadic Creutzfeldt-Jakob disease and hamster Sc237 prions, we found that BSE prions were 10- and 106-fold more resistant to inactivation, respectively. Our studies contend that any prion inactivation procedures must be validated by bioassay against the prion strain for which they are intended to be used

Phase I study of pegylated liposomal doxorubicin and the multidrug-resistance modulator, valspodar

Valspodar, a P-glycoprotein modulator, affects pharmacokinetics of doxorubicin when administered in combination, resulting in doxorubicin dose reduction. In animal models, valspodar has minimal interaction with pegylated liposomal doxorubicin (PEG-LD). To determine any pharmacokinetic interaction in humans, we designed a study to determine maximum tolerated dose, dose-limiting toxicity (DLT), and pharmacokinetics of total doxorubicin, in PEG-LD and valspodar combination therapy in patients with advanced malignancies. Patients received PEG-LD 20–25 mg m−2 intravenously over 1 h for cycle one. In subsequent 2-week cycles, valspodar was administered as 72 h continuous intravenous infusion with PEG-LD beginning at 8 mg m−2 and escalated in an accelerated titration design to 25 mg m−2. Pharmacokinetic data were collected with and without valspodar. A total of 14 patients completed at least two cycles of therapy. No DLTs were observed in six patients treated at the highest level of PEG-LD 25 mg m−2. The most common toxicities were fatigue, nausea, vomiting, mucositis, palmar plantar erythrodysesthesia, diarrhoea, and ataxia. Partial responses were observed in patients with breast and ovarian carcinoma. The mean (range) total doxorubicin clearance decreased from 27 (10–73) ml h−1 m−2 in cycle 1 to 18 (3–37) ml h−1 m−2 with the addition of valspodar in cycle 2 (P=0.009). Treatment with PEG-LD 25 mg m−2 in combination with valspodar results in a moderate prolongation of total doxorubicin clearance and half-life but did not increase the toxicity of this agent

TESS Delivers Five New Hot Giant Planets Orbiting Bright Stars From The Full-Frame Images

We present the discovery and characterization of five hot and warm Jupiters—TOI-628 b (TIC 281408474; HD 288842), TOI-640 b (TIC 147977348), TOI-1333 b (TIC 395171208, BD+47 3521A), TOI-1478 b (TIC 409794137), and TOI-1601 b (TIC 139375960)—based on data from NASA\u27s Transiting Exoplanet Survey Satellite (TESS). The five planets were identified from the full-frame images and were confirmed through a series of photometric and spectroscopic follow-up observations by the TESS Follow-up Observing Program Working Group. The planets are all Jovian size (RP = 1.01–1.77 RJ) and have masses that range from 0.85 to 6.33 MJ. The host stars of these systems have F and G spectral types (5595 ≤ Teff ≤ 6460 K) and are all relatively bright (9.5 \u3c V \u3c 10.8, 8.2 \u3c K \u3c 9.3), making them well suited for future detailed characterization efforts. Three of the systems in our sample (TOI-640 b, TOI-1333 b, and TOI-1601 b) orbit subgiant host stars ($\mathrm{log}$ g \u3c 4.1). TOI-640 b is one of only three known hot Jupiters to have a highly inflated radius (RP \u3e 1.7 RJ, possibly a result of its host star\u27s evolution) and resides on an orbit with a period longer than 5 days. TOI-628 b is the most massive, hot Jupiter discovered to date by TESS with a measured mass of ${6.31}_{-0.30}^{+0.28}$MJ and a statistically significant, nonzero orbital eccentricity of e = ${0.074}_{-0.022}^{+0.021}$. This planet would not have had enough time to circularize through tidal forces from our analysis, suggesting that it might be remnant eccentricity from its migration. The longest-period planet in this sample, TOI-1478 b (P = 10.18 days), is a warm Jupiter in a circular orbit around a near-solar analog. NASA\u27s TESS mission is continuing to increase the sample of well-characterized hot and warm Jupiters, complementing its primary mission goals