Summary Background Total hip replacement (THR) is extremely common. Some prostheses fail, particularly in younger patients, and need to be revised, most commonly for loosening secondary to wear or ...dislocation. Surgeons have tried to address these problems by implanting large diameter metal-on-metal bearing surfaces. Our aim was to assess if metal-on-metal bearing surfaces lead to increased implant survival compared with other bearing surfaces in stemmed THR and, additionally, if larger head sizes result in improved implant survival. Methods We analysed the National Joint Registry of England and Wales for primary hip replacements (402 051, of which 31 171 were stemmed metal-on-metal) undertaken between 2003 and 2011. Our analysis was with a multivariable flexible parametric survival model to estimate the covariate-adjusted cumulative incidence of revision adjusting for the competing risk of death. Findings Metal-on-metal THR failed at high rates. Failure was related to head size, with larger heads failing earlier (3·2% cumulative incidence of revision 95% CI 2·5–4·1 for 28 mm and 5·1% 4·2–6·2 for 52 mm head at 5 years in men aged 60 years). 5 year revision rates in younger women were 6·1% (5·2–7·2) for 46 mm metal-on-metal compared with 1·6% (1·3–2·1) for 28 mm metal-on-polyethylene. By contrast, for ceramic-on-ceramic articulations larger head sizes were associated with improved survival (5 year revision rate of 3·3% 2·6–4·1 with 28 mm and 2·0% 1·5–2·7 with 40 mm for men aged 60 years). Interpretation Metal-on-metal stemmed articulations give poor implant survival compared with other options and should not be implanted. All patients with these bearings should be carefully monitored, particularly young women implanted with large diameter heads. Since large diameter ceramic-on-ceramic bearings seem to do well we support their continued use. Funding National Joint Registry of England and Wales.
Leptin is an adipocyte‐derived hormone that acts on the hypothalamus to influence feeding, metabolism and reproduction, but the cellular and molecular targets for the action of leptin in the brain ...have yet to be fully elucidated. Kisspeptins are encoded by the Kiss1 gene, which is expressed in the hypothalamus and has been implicated in the neuroendocrine regulation of gonadotrophin‐releasing hormone secretion. We tested the hypothesis that kisspeptin‐expressing neurones are targets for leptin. First, we examined whether leptin regulates the expression of Kiss1 by comparing levels of KiSS‐1 mRNA in the arcuate nucleus among groups of mice having different circulating levels of leptin: (i) wild‐type (WT); (ii) leptin‐deficient ob/ob; and (iii) ob/ob mice treated with leptin. All mice were castrated to control for endogenous concentrations of gonadal steroids. KiSS‐1 mRNA was significantly reduced in ob/ob compared to WT mice and levels of KiSS‐1 mRNA in ob/ob mice treated with leptin were increased, but not fully restored to that found in WT animals. Second, we performed double‐label in situ hybridisation for KiSS‐1 mRNA and the leptin receptor (Ob‐Rb) mRNA and found that almost one‐half (approximately 40%) of KiSS‐1 mRNA‐expressing cells in the arcuate nucleus expressed Ob‐Rb mRNA. These results demonstrate that KiSS‐1 neurones are direct targets for regulation by leptin and suggest that the reproductive deficits associated with leptin‐deficient states may be attributable, in part, to diminished expression of Kiss1.
Effects of H2O on the activity and deactivation of Pd catalysts used for the oxidation of unburned CH4 present in the exhaust gas of natural-gas vehicles (NGVs) are reviewed. CH4 oxidation in a ...catalytic converter is limited by low exhaust gas temperatures (500–550 °C) and low concentrations of CH4 (400–1500 ppmv) that must be reacted in the presence of large quantities of H2O (10–15%) and CO2 (15%), under transient exhaust gas flows, temperatures, and compositions. Although Pd catalysts have the highest known activity for CH4 oxidation, water-induced sintering and reaction inhibition by H2O deactivate these catalysts. Recent studies have shown the reversible inhibition by H2O adsorption causes a significant drop in catalyst activity at lower reaction temperatures (below 450 °C), but its effect decreases (water adsorption becomes more reversible) with increasing reaction temperature. Thus above 500 °C H2O inhibition is negligible, while Pd sintering and occlusion by support species become more important. H2O inhibition is postulated to occur by either formation of relatively stable Pd(OH)2 and/or partial blocking by OH groups of the O exchange between the support and Pd active sites thereby suppressing catalytic activity. Evidence from FTIR and isotopic labeling favors the latter route. Pd catalyst design, including incorporation of a second noble metal (Rh or Pt) and supports high O mobility (e.g., CeO2) are known to improve catalyst activity and stability. Kinetic studies of CH4 oxidation at conditions relevant to natural gas vehicles have quantified the thermodynamics and kinetics of competitive H2O adsorption and Pd(OH)2 formation, but none have addressed effects of H2O on O mobility.
Carbonyl sulfide (COS) has recently emerged as an atmospheric tracer of gross primary production. All modeling studies of COS air‐monitoring data rely on a climatological anthropogenic inventory that ...does not reflect present conditions or support interpretation of ice core and firn trends. Here we develop a global anthropogenic inventory for the years 1850 to 2013 based on new emission measurements and material‐specific data. By applying methods from a recent regional inventory to global data, we find that the anthropogenic source is similar in magnitude to the plant sink, confounding carbon cycle applications. However, a material‐specific approach results in a current anthropogenic source that is only one third of plant uptake and is concentrated in Asia, supporting carbon cycle applications of global air‐monitoring data. Furthermore, changes in the anthropogenic source alone cannot explain the century‐scale mixing ratio growth, which suggests that ice and firn data may provide the first global history of gross primary production.
Key Points
First temporally explicit inventory of COS anthropogenic sources
Current source is much smaller than suggested by previous methods
Ice core data may contain the first global history of gross primary production
With Canada's growing opioid crisis, many communities are attempting to monitor cases in real-time. Paramedic Naloxone Administration (PNA) has become a common metric for monitoring overdoses. We ...evaluate whether the use of naloxone administration counts represents an effective monitoring tool for community opioid overdoses.
The electronic ambulance call report database of Peterborough Paramedics (Ontario, Canada) was examined. De-identified records from 2016-2019 with problem codes of "Opioid Overdose", along with all patients documented as receiving naloxone were extracted. Chi-square and Bonferroni-adjusted post hoc proportion tests were used for comparison of counts.
558 opioid overdoses were identified, 124 (22%) of which had PNA documented, 181(32%) had naloxone prior to arrival documented and 264 (47%) received no naloxone. Over the three years, the annual number of overdose cases increased, while the proportion of patients receiving PNA decreased significantly each year. PNA was also associated with calls in a residence. Naloxone was administered by a non-paramedic in 262 cases, with 181 of these identified as opioid overdoses and was more common in later years and in cases occurring in public places.
PNA calls did not account for a significant percentage of opioid overdoses attended to by paramedics. The strong association between PNA and call location being a residence, along with increasing use of community naloxone kits, may cause certain populations to be under-represent if PNA is used as a standalone metric. The decreasing association with time may also lead to a falsely improving metric further reducing its effectiveness. Thus, PNA when used alone may no longer be a suitable metric for opioid overdose tracking.
We present a study of the filamentary structure in the emission from the neutral atomic hydrogen (H
I
) at 21 cm across velocity channels in the 40′′ and 1.5-km s
−1
resolution ...position-position-velocity cube, resulting from the combination of the single-dish and interferometric observations in The H
I
/OH/recombination-line survey of the inner Milky Way. Using the Hessian matrix method in combination with tools from circular statistics, we find that the majority of the filamentary structures in the H
I
emission are aligned with the Galactic plane. Part of this trend can be assigned to long filamentary structures that are coherent across several velocity channels. However, we also find ranges of Galactic longitude and radial velocity where the H
I
filamentary structures are preferentially oriented perpendicular to the Galactic plane. These are located (i) around the tangent point of the Scutum spiral arm and the terminal velocities of the Molecular Ring, around
l
≈ 28° and
v
LSR
≈ 100 km s
−1
, (ii) toward
l
≈ 45° and
v
LSR
≈ 50 km s
−1
, (iii) around the Riegel-Crutcher cloud, and (iv) toward the positive and negative terminal velocities. A comparison with numerical simulations indicates that the prevalence of horizontal filamentary structures is most likely the result of large-scale Galactic dynamics and that vertical structures identified in (i) and (ii) may arise from the combined effect of supernova (SN) feedback and strong magnetic fields. The vertical filamentary structures in (iv) can be related to the presence of clouds from extra-planar H
I
gas falling back into the Galactic plane after being expelled by SNe. Our results indicate that a systematic characterization of the emission morphology toward the Galactic plane provides an unexplored link between the observations and the dynamical behavior of the interstellar medium, from the effect of large-scale Galactic dynamics to the Galactic fountains driven by SNe.
Objectives
The aim of the study was to assess the impact of the gain in body mass index (BMI) observed immediately after antiretroviral therapy (ART) initiation on the subsequent risk of ...cardiovascular disease (CVD) and diabetes.
Methods
We analysed data from the Data Collection on Adverse Events of Anti‐HIV Drugs (D:A:D) cohort study. Outcomes were development of (i) CVD (composite of myocardial infarction/stroke/coronary procedure) and (ii) diabetes. The main exposure variable was change in BMI from ART initiation (pre‐ART) to 1 year after initiation (continuous variable) in treatment‐naïve individuals initiating ART with no history of CVD or diabetes (for respective outcomes). BMI weight (kg)/(height (m))2 was categorized as underweight (< 18.5), normal (18.5–25), overweight (25–30) and obese (> 30). Poisson regression models were fitted stratified for each pre‐ART BMI category to allow for category‐specific estimates of incidence rate ratio (IRR). Models were adjusted for pre‐ART BMI and CD4 count, key known risk factors (time‐updated where possible) and calendar year.
Results
A total of 97 CVD events occurred in 43 982 person‐years (n = 9321) and 125 diabetes events in 43 278 person‐years (n = 9193). In fully adjusted analyses for CVD, the IRR/unit gain in BMI (95% confidence interval) in the first year of ART, by pre‐ART BMI category, was: underweight, 0.90 (0.60–1.37); normal, 1.18 (1.05–1.33); overweight, 0.87 (0.70–1.10), and obese, 0.95 (0.71–1.28) (P for interaction = 0.04). For diabetes, the IRR/unit gain in BMI was 1.11 (95% confidence interval 1.03 to 1.21), regardless of pre‐ART BMI (P for interaction > 0.05).
Conclusions
Short‐term gain in BMI following ART initiation appeared to increase the longer term risk of CVD, but only in those with pre‐ART BMI in the normal range. It was also associated with increased risk of diabetes regardless of pre‐ART BMI.
Abstract
We present search results of 22 high-latitude (∣
b
∣ > 25°) sightlines for OH 18 cm emission using the 305 m radio telescope at the Arecibo Observatory. These sightlines appear in neutral ...hydrogen emission at intermediate velocities −90 ≤
V
LSR
≤ −20 km s
−1
and are predicted to have a sufficient molecular composition so as to be detectable in molecular emission. Such objects, known as intermediate-velocity molecular clouds (IVMCs), have historically been detected through
12
CO emission. Recent studies indicate that IVMCs may be widespread in the galaxy and have important implications for models of the interstellar medium and star formation. However, we report nondetections of OH emission toward the 22 sightlines and provide stringent upper limits on the OH column density. Using available H
i
and
A
v
data in combination with existing state-of-the-art PDR models, we estimate H
2
column densities and find that they are more than an order of magnitude lower than the predicted values. We also find that the hydrogen volume density of these clouds is ≲25 cm
−3
. In addition, we discuss the known IVMCs with previous
12
CO detections in the context of the PDR models. Our analysis of these clouds indicates that the structure of molecular material in IVMCs is morphologically clumpy. These results motivate the need for future sensitive, on-the-fly searches (rather than targeted searches) for CO emission from IVMCs with resolutions on the order of ∼1′. High angular resolution (∼1′) H
i
and
A
v
data will also be helpful to better constrain the structure and composition of IVMCs.
Atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G) are associated with dysregulation and overactivation of the complement alternative pathway. Typically, gene analysis for aHUS and ...C3G is undertaken in small patient numbers, yet it is unclear which genes most frequently predispose to aHUS or C3G. Accordingly, we performed a six-center analysis of 610 rare genetic variants in 13 mostly complement genes (
,
,
,
,
,
,
,
,
,
,
,
, and
) from >3500 patients with aHUS and C3G. We report 371 novel rare variants (RVs) for aHUS and 82 for C3G. Our new interactive Database of Complement Gene Variants was used to extract allele frequency data for these 13 genes using the Exome Aggregation Consortium server as the reference genome. For aHUS, significantly more protein-altering rare variation was found in five genes
,
,
,
, and
than in the Exome Aggregation Consortium (allele frequency < 0.01%), thus correlating these with aHUS. For C3G, an association was only found for RVs in
and the N-terminal C3b-binding or C-terminal nonsurface-associated regions of
In conclusion, the RV analyses showed nonrandom distributions over the affected proteins, and different distributions were observed between aHUS and C3G that clarify their phenotypes.
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