OX2 (CD200) is a broadly expressed membrane glycoprotein, shown here to be important for regulation of the macrophage lineage. In mice lacking CD200, macrophage lineage cells, including brain ...microglia, exhibited an activated phenotype and were more numerous. Upon facial nerve transection, damaged CD200-deficient neurons elicited an accelerated microglial response. Lack of CD200 resulted in a more rapid onset of experimental autoimmune encephalomyelitis (EAE). Outside the brain, disruption of CD200-CD200 receptor interaction precipitated susceptibility to collagen-induced arthritis (CIA) in mice normally resistant to this disease. Thus, in diverse tissues OX2 delivers an inhibitory signal for the macrophage lineage.
Oral squamous cell carcinoma is the most common intraoral malignancy, for which we advocate radical primary resection with adjuvant treatment where indicated. The main aims of this paper are to ...identify the overall survival of a consecutive series of patients and to relate survival to clinical and pathological factors. Kaplan–Meier curves were produced for site, sex, TNM status, and use of postoperative radiotherapy. The data were analysed using IBM SPSS Statistics for Windows and probabilities of less than 0.05 were accepted as significant. A total of 921 patients were recorded in the database with a diagnosis of oral squamous cell carcinoma out of a total of 1958 with salivary gland conditions or other cancers of the head and neck (43.1%). The earliest date of diagnosis was 1973, and the data were censored at 31 March 2016. The database comprised 340 women (36.9%) and 581 men (63.1%). A total of 339 patients died (34.5%): 117 women (33.7%) and 222 men (65.5%). The mean (range) age at death was 73.4 (31.4–97.5) years for women and 68.7 (33.3–95.5) years for men (t (337)=3.28, p=0.001). Our overall survival was somewhat better than the 56% five-year survival reported for oral cancer in England in 2010, which may be a reflection of the treatment. This work supports the view that aggressive management may improve overall survival.
We describe and apply a simple prescription for defining connected structures in galaxy redshift surveys. The method is based upon two passes with a friends-of-friends group finder. The first pass ...uses a cylindrical linking volume to find galaxy groups and clusters in order to suppress the line-of-sight smearing introduced by the large random velocities of galaxies within these deep potential wells. The second pass, performed with a spherical linking volume, identifies the connected components. This algorithm has been applied to the Two-degree Field Galaxy Redshift Survey (2dFGRS), within which it picks out a total of 7603 systems containing at least two galaxies and having a mean redshift less than 0.12. Connected systems with many members appear filamentary in nature, and the algorithm recovers two particularly large filaments within the 2dFGRS. For comparison, the algorithm has also been applied to Λ cold dark matter (ΛCDM) mock galaxy surveys. While the model population of such systems is broadly similar to that in the 2dFGRS, it does not generally contain such extremely large structures.
There is an urgent global need for a safe macrofilaricide drug to accelerate elimination of the neglected tropical diseases onchocerciasis and lymphatic filariasis. From an anti-infective compound ...library, the macrolide veterinary antibiotic, tylosin A, was identified as a hit against
This bacterial endosymbiont is required for filarial worm viability and fertility and is a validated target for macrofilaricidal drugs. Medicinal chemistry was undertaken to develop tylosin A analogs with improved oral bioavailability. Two analogs, A-1535469 and A-1574083, were selected. Their efficacy was tested against the gold-standard second-generation tetracycline antibiotics, doxycycline and minocycline, in mouse and gerbil infection models of lymphatic filariasis (
and
) and onchocerciasis (
). A 1- or 2-week course of oral A-1535469 or A-1574083 provided >90%
depletion from nematodes in infected animals, resulting in a block in embryogenesis and depletion of microfilarial worm loads. The two analogs delivered comparative or superior efficacy compared to a 3- to 4-week course of doxycycline or minocycline. A-1574083 (now called ABBV-4083) was selected for further preclinical testing. Cardiovascular studies in dogs and toxicology studies in rats and dogs revealed no adverse effects at doses (50 mg/kg) that achieved plasma concentrations >10-fold above the efficacious concentration. A-1574083 (ABBV-4083) shows potential as an anti-
macrolide with an efficacy, pharmacology, and safety profile that is compatible with a short-term oral drug course for treating lymphatic filariasis and onchocerciasis.
Magnetic reconnection is the key process of plasma transport in the Earth's magnetotail. The ‘X‐line’ where magnetic field lines reconnect often moves away from the Earth. However, the precise cause ...of the X‐line motion remains unclear. Here we present data from five THEMIS probes positioned along the Sun‐Earth line and show that a tailward retreat motion of the X‐line (detected by the outermost probe P1) occurred when the dipolarized inner magnetosphere started to return to a more stretched, tail‐like configuration (observed by the inner probes P3, P4, and P5). At an intermediate location (P2), the total pressure was increasing. These observations are consistent with the idea that the pressure increase in the inner magnetosphere eventually causes the X‐line to retreat tailward.
Key Points
An X‐line retreated tailward in association with dipolarization
The total pressure enhanced just earthward of the X‐line
We propose that the large scale pressure variation led to the retreat motion
Elimination of filariasis requires a macrofilaricide treatment that can be delivered within a 7-day period. Here we have identified a synergy between the anthelmintic albendazole (ABZ) and drugs ...depleting the filarial endosymbiont Wolbachia, a proven macrofilaricide target, which reduces treatment from several weeks to 7 days in preclinical models. ABZ had negligible effects on Wolbachia but synergized with minocycline or rifampicin (RIF) to deplete symbionts, block embryogenesis, and stop microfilariae production. Greater than 99% Wolbachia depletion following 7-day combination of RIF+ABZ also led to accelerated macrofilaricidal activity. Thus, we provide preclinical proof-of-concept of treatment shortening using antibiotic+ABZ combinations to deliver anti-Wolbachia sterilizing and macrofilaricidal effects. Our data are of immediate public health importance as RIF+ABZ are registered drugs and thus immediately implementable to deliver a 1-wk macrofilaricide. They also suggest that novel, more potent anti-Wolbachia drugs under development may be capable of delivering further treatment shortening, to days rather than weeks, if combined with benzimidazoles.
We present a new cluster-detection algorithm designed for the Panoramic Survey Telescope and Rapid Response System (Pan-STARRS) survey but with generic application to any multiband data. The method ...makes no prior assumptions about the properties of clusters other than (i) the similarity in colour of cluster galaxies (the 'red sequence'); and (ii) an enhanced projected surface density. The detector has three main steps: (i) it identifies cluster members by photometrically filtering the input catalogue to isolate galaxies in colour-magnitude space; (ii) a Voronoi diagram identifies regions of high surface density; and (iii) galaxies are grouped into clusters with a Friends-of-Friends technique. Where multiple colours are available, we require systems to exhibit sequences in two colours. In this paper, we present the algorithm and demonstrate it on two data sets. The first is a 7-deg2 sample of the deep Sloan Digital Sky Survey (SDSS) equatorial stripe (Stripe 82), from which we detect 97 clusters with z≤ 0.6. Benefitting from deeper data, we are 100 per cent complete in the maxBCG optically selected cluster catalogue (based on shallower single-epoch SDSS data) and find an additional 78 previously unidentified clusters. The second data set is a mock Medium Deep Survey Pan-STARRS catalogue, based on the Λ cold dark matter (ΛCDM) model and a semi-analytic galaxy formation recipe. Knowledge of galaxy-halo memberships in the mock catalogue allows for the quantification of algorithm performance. We detect 305 mock clusters in haloes with mass >1013 h
−1 M⊙ at z≲ 0.6 and determine a spurious detection rate of <1 per cent, consistent with tests on the Stripe 82 catalogue. The detector performs well in the recovery of model ΛCDM clusters. At the median redshift of the catalogue, the algorithm achieves >75 per cent completeness down to halo masses of 1013.4 h
−1 M⊙ and recovers >75 per cent of the total stellar mass of clusters in haloes down to 1013.8 h
−1 M⊙. A companion paper presents the complete cluster catalogue over the full 270-deg2 Stripe 82 catalogue.
Summary
The American Orthopaedic Association initiated the
Own the Bone
(OTB) quality improvement program in 2009. Herein we show that the data collected through this program is similar to that ...collected in other large studies. Thus, the OTB registry functions as an externally valid cohort for studying fragility fracture patients.
Introduction
The American Orthopedic Association initiated the
Own the Bone
(OTB) quality improvement program in 2009 to improve secondary prevention of fragility fractures. In this study, we present a summary of the data collected by the OTB program and compare it to data from other large fragility fracture registries with an aim to externally validate the OTB registry.
Methods
The OTB registry contained 35,038 unique cases of fragility fracture as of September, 2016. We report the demographics, presenting fracture characteristics, past fracture history, and bone mineral density (BMD) data and compare these to data from large fragility fracture studies across the world.
Results
Seventy-three percent of the patients in the OTB registry were female, Caucasian, and post-menopausal. In 54.4% of cases, patients had a hip fracture; spine fractures were the second most common fracture type occurring in 11.1% of patients. Thirty-four percent of the patients had a past history of fragility fracture, and the most common sites were the spine and hip. The average femoral neck T-score was − 2.06. When compared to other studies, the OTB database showed similar findings with regard to patient age, gender, race, BMI, BMD profile, prior fracture history, and family history of fragility fractures.
Conclusion
OTB is the first and largest multi-center voluntary fragility fracture registry in the USA. The data collected through the OTB program is comparable to that collected in international studies. Thus, the OTB registry functions as an externally valid cohort for further studies assessing the clinical characteristics, interventions, and outcomes achieved in patients who present with a fragility fracture in the USA.
Once developed, end-stage renal disease cannot be reversed by any current therapy. Bone morphogenetic protein-7 (BMP-7), however, is a possible treatment for reversing end-stage renal disease. ...Previously, we showed that the BMP antagonist uterine sensitization-associated gene-1 (USAG-1, also known as ectodin and sclerostin domain-containing 1) negatively regulates the renoprotective action of BMP-7. Here, we show that the ratio between USAG-1 and BMP-7 expression increased dramatically in the later stage of kidney development, with USAG-1 expression overlapping BMP-7 only in differentiated distal tubules. Examination of USAG-1 expression in developing kidney indicated that a mosaic of proximal and distal tubule marker-positive cells reside side by side in the immature nephron. This suggests that each cell controls its own fate for becoming a proximal or distal tubule cell. In kidney injury models, the ratio of USAG-1 to BMP-7 expression decreased with kidney damage but increased after subsequent kidney regeneration. Our study suggests that USAG-1 expression in a kidney biopsy could be useful in predicting outcome.
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