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An experimental investigation was conducted that consisted of 12 pairs of reinforced masonry specimens in which the two specimens were constructed with their longitudinal axes oriented parallel and perpendicular to the laboratory floor, respectively. This work was conducted to reassess the need for the χ-factor accounting for the direction of compressive stresses in masonry members in relation to the direction used to establish their masonry assemblage strength included in CSA S304-14 —Design of Masonry Structures. Parameters investigated included block size and reinforcement ratio. Test results suggest that the χ-factor can be eliminated from future editions of CSA S304 but should be considered with caution: a review of the literature and the current tests show that, in some cases, voids may develop between the exterior webs of adjacent blocks and so may be the source of the reduction in the magnitude of the equivalent rectangular compressive stress block.

Simultaneous bilateral total hip arthroplasty (SimBTHA) is often performed in younger, fitter patients with bilateral hip disease. If patients are deemed not suitable for SimBTHA due to concurrent comorbidity, it may be more appropriate to perform staged bilateral total hip arthroplasties (StBTHAs) 3-6 months apart to minimize complications and morbidity. Complication rates following hip arthroplasty are low and large national datasets are helpful for assessing these rare events. We aimed at comparing SimBTHA vs StBTHA in order to determine any differences in morbidity and mortality.Hospital Episode Statistics data for all patients who underwent bilateral THAs in the English National Health Service between April 2005 and July 2014 were obtained. Patients were grouped into SimBTHAs (same day) or staged, with the second THA occurring between 3 and 6 months after the first. Medical and surgical complications were compared and total length of stay was assessed.A total of 2507 underwent SimBTHAs and 9915 had StBTHAs. SimBTHA patients were significantly younger (60.6 vs 65.5 years, P.001) and more likely to be male, but had similar Charlson comorbidity scores. Compared to StBTHAs, patients undergoing SimBTHAs had a greater risk of pulmonary embolism, myocardial infarction, renal failure, chest infection, and inhospital death. Patients undergoing SimBTHAs had a significantly shorter overall hospital stay (8.9 vs 10.4 days). Patients undergoing SimBTHA at high-volume units had a lower average Charlson score and subsequent complication rate than low-volume units.These findings highlight the greater risks of SimBTHA in patients with Charlson score greater than 0 performed at lower-volume centers in England.

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 < 0.01). The 10-year HR associated with CPE was 0.4 (95% CI, 0.1 to 0.8, p = 0.03). There were no significant differences between the adjusted revision rates of HXPLE compared with CPE in individual analyses of the most common total knee arthroplasty systems. However, for the subset of patients who were both 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.

Background: More than 75,000 total hip replacements were performed in England and Wales in 2014, and this figure is predicted to increase. Trends in mortality and complications following total hip replacement from 2005 to 2014 were evaluated to quantify risk and to identify “at-risk” groups to better inform recommendations for patient care. Methods: Our primary analysis estimated 90-day inpatient mortality following total hip replacement using Hospital Episode Statistics data from 2005 to 2014. Secondary analyses explored 30-day rates of lower respiratory tract infection, renal failure, myocardial infarction, pulmonary embolism, deep-vein thrombosis, cerebrovascular accident, and Clostridium difficile. Hierarchical logistic regression was used to estimate population averages, adjusting for time and prognostic covariates. Results: From January 2005 to July 2014, a total of 540,623 total hip replacements were reported. The 90-day mortality rate dropped steadily, from 0.60% in 2005 to 0.15% in 2014. Reported postoperative complications (with the exception of lower respiratory tract infection and renal failure) reduced year-on-year, despite a steady rise in the average Charlson Comorbidity Index score. The 30-day rate of lower respiratory tract infection and renal failure increased from 0.54% to 0.84% and 0.21% to 1.09%, respectively. The risk of mortality was significantly higher for those who developed a lower respiratory tract infection (odds ratio [OR] = 42.3) or renal failure (OR = 36.5) than for those who developed pulmonary embolism (OR = 10.9) or deep-vein thrombosis (OR = 2.6). Conclusions: Despite a population with increasing levels of comorbidity, indicators of quality of care improved from 2005 to 2014, with the exception of the rates of lower respiratory tract infection and renal failure. Postoperative care should focus on reducing the risk of lower respiratory tract infection and renal failure, both of which increased and were strongly associated with mortality. Moreover, they appeared to occur in identifiable high-risk groups; modifications to routine care should be considered for these patients. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Global transcriptomic and proteomic analysis of T cells have been rich sources of unbiased data for understanding T cell activation. Lack of full concordance of these datasets illustrates that important facets of T cell activation are controlled at the level of translation. We undertook translatome analysis of CD8 T cell activation, combining polysome profiling and microarray analysis. We revealed that altering T cell receptor stimulation influenced recruitment of mRNAs to heavy polysomes and translation of subsets of genes. A major pathway that was compromised, when TCR signalling was suboptimal, was linked to ribosome biogenesis, a rate-limiting factor in both cell growth and proliferation. Defective TCR signalling affected transcription and processing of ribosomal RNA precursors, as well as the translation of specific ribosomal proteins and translation factors. Mechanistically, IL-2 production was compromised in weakly stimulated T cells affecting the abundance of Myc protein, a known regulator of ribosome biogenesis. Consequently, weakly activated T cells showed impaired production of ribosomes and a failure to maintain proliferative capacity following stimulation. We demonstrate that primary T cells respond to various environmental cues by regulating ribosome biogenesis and mRNA translation at multiple levels in order to sustain proliferation and differentiation.

Clinical data have demonstrated rapid and sustained antidepressant effects of ketamine, a noncompetitive NMDAR (N-methyl-daspartate receptor) antagonist. Recently, Zanos et al.2 claimed that the ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) is essential for the antidepressant effects of ketamine in mice in an NMDAR-independent manner, although no alternative mechanism was proposed, beyond unspecific activation of AMPAR (α -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor). Here we report that (2R,6R)-HNK blocks synaptic NMDARs in a similar manner to its parent compound, and we show that the effects of (2R,6R)-HNK on intracellular signalling are coupled to NMDAR inhibition. These data demonstrate that (2R,6R)-HNK inhibits synaptic NMDARs and subsequently elicits the same signal transduction pathway previously associated with NMDAR inhibition by ketamine.

The effects of a 12-h exposure to the lampricide 3-trifluoromethyl-4-nitrophenol (TFM) and a combination of TFM and 1% niclosamide (active ingredient in Bayluscide 70% wettable powder) on the short and long-term ( 10 mo post exposure) survival and behavior of two unionid freshwater mussel species Elliptio complanata and Pyganadon cataracta were measured. Growth of juvenile E. complanata mussels 10 months after exposure was also compared. Toxicity was determined after 12 h exposures at maximum concentrations from 2- to 2.5- fold higher than the LC99 for sea lamprey larvae. A logistic model was used to estimate the probability of survival among treatments, trials, species, and sizes. Mortality was minimal in all test concentrations of TFM alone and the TFM/1% niclosamide combination. Estimated survival decreased 6% for each unit increase in the relative toxicity of TFM. Survival was greater for E. complanata than for P. cataracta, and for adults relative to juveniles. Lampricide treatment caused narcotization of both mussels (defined as having gaped shells and an extended foot) in concentrations ≥ LC99 for sea lamprey larvae and narcotization ranged from 0–50% among treatments. Recovery from narcosis was apparent by 12 h post-exposure and complete by 36 h post-exposure. The rate of growth of E. complanata over the 10-month post-exposure period did not vary among treatments.