Slosh Damping with Floating Magnetoactive Micro-Baffles

Liquid sloshing within propellant tanks of launch vehicles and other major vehicles has been a major concern. Various methods have been utilized for the damping of slosh through Propellant Management Devices (PMD) accomplishing a wide range of results. Exploratory research conducted at the Embry-Riddle Aeronautical University Fuel Slosh Test Facility in development of an innovative PMD is presented. Embedding floating micro-baffles with a magnetoactive material such that the baffle can be manipulated when exposed to a magnetic field preserves the benefits of both floating and static baffle designs. Activated micro-baffles form a rigid layer at the free surface and provide a restriction of the fluid motion. Proposed micro-baffle design and magnetic activation source method along with proof-of-concept experiments comparing the scope of this research to previous PMD methods are presented. A computational fluid dynamics approach is outlined to compliment these experimental results

Floating Active Baffles, System and Method of Slosh Damping Comprising the Same

This disclosure provides a system for damping slosh of a liquid within a tank, a baffle for use in the system, and a method of damping slosh using the system. The system includes a plurality of baffles. Each baffle has a body configured to substantially float upon the liquid. Each baffle also has an activation material received along at least a portion of the body. The activation material is magnetically reactive provided in a quantity sufficient to enable the body to be manipulated in the presence of a magnetic field (M). The system further includes an actuator configured to pro­vide the magnetic field (M)

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol

Background: Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival. Methods: We analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland. Eligible patients (no age restriction) had metastatic, histologically-confirmed prostate adenocarcinoma; a WHO performance status of 0–2; and adequate haematological, renal, and liver function. Patients were randomly assigned (1:1) using a computerised algorithm and a minimisation technique to either standard of care (androgen deprivation therapy; docetaxel 75 mg/m2 intravenously for six cycles with prednisolone 10 mg orally once per day allowed from Dec 17, 2015) or standard of care plus abiraterone acetate 1000 mg and prednisolone 5 mg (in the abiraterone trial) orally or abiraterone acetate and prednisolone plus enzalutamide 160 mg orally once a day (in the abiraterone and enzalutamide trial). Patients were stratified by centre, age, WHO performance status, type of androgen deprivation therapy, use of aspirin or non-steroidal anti-inflammatory drugs, pelvic nodal status, planned radiotherapy, and planned docetaxel use. The primary outcome was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who started treatment. A fixed-effects meta-analysis of individual patient data was used to compare differences in survival between the two trials. STAMPEDE is registered with ClinicalTrials.gov (NCT00268476) and ISRCTN (ISRCTN78818544). Findings: Between Nov 15, 2011, and Jan 17, 2014, 1003 patients were randomly assigned to standard of care (n=502) or standard of care plus abiraterone (n=501) in the abiraterone trial. Between July 29, 2014, and March 31, 2016, 916 patients were randomly assigned to standard of care (n=454) or standard of care plus abiraterone and enzalutamide (n=462) in the abiraterone and enzalutamide trial. Median follow-up was 96 months (IQR 86–107) in the abiraterone trial and 72 months (61–74) in the abiraterone and enzalutamide trial. In the abiraterone trial, median overall survival was 76·6 months (95% CI 67·8–86·9) in the abiraterone group versus 45·7 months (41·6–52·0) in the standard of care group (hazard ratio [HR] 0·62 [95% CI 0·53–0·73]; p<0·0001). In the abiraterone and enzalutamide trial, median overall survival was 73·1 months (61·9–81·3) in the abiraterone and enzalutamide group versus 51·8 months (45·3–59·0) in the standard of care group (HR 0·65 [0·55–0·77]; p<0·0001). We found no difference in the treatment effect between these two trials (interaction HR 1·05 [0·83–1·32]; pinteraction=0·71) or between-trial heterogeneity (I2 p=0·70). In the first 5 years of treatment, grade 3–5 toxic effects were higher when abiraterone was added to standard of care (271 [54%] of 498 vs 192 [38%] of 502 with standard of care) and the highest toxic effects were seen when abiraterone and enzalutamide were added to standard of care (302 [68%] of 445 vs 204 [45%] of 454 with standard of care). Cardiac causes were the most common cause of death due to adverse events (five [1%] with standard of care plus abiraterone and enzalutamide [two attributed to treatment] and one (<1%) with standard of care in the abiraterone trial). Interpretation: Enzalutamide and abiraterone should not be combined for patients with prostate cancer starting long-term androgen deprivation therapy. Clinically important improvements in survival from addition of abiraterone to androgen deprivation therapy are maintained for longer than 7 years. Funding: Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas

Orthognathic surgery in the immunosuppressed post-organ transplant individual

The use of immunosuppressive medication following organ transplant has become increasingly prevalent as both numbers of transplants being performed and long-term survival increase. As a result, there may be an increase in patients requiring oral and maxillofacial surgery, and in particular orthognathic surgery, whilst taking immunosuppressive medication. This report explores some of the considerations for orthognathic surgery in this cohort, and strategies to mitigate risks associated with surgical management

Not so silent sinus syndrome: A case report.

INTRODUCTION: Silent sinus syndrome (SSS) is a rare disorder with protean manifestations. An absence of familiarity with ambiguous and atypical presentations may complicate diagnosis and delay management. CASE PRESENTATION: A 28year old female patient presented with a chronic history of headache, post-nasal discharge and recurrent facial pain refractory to analgesics. Enophthalmos and hypoglobus progressed over a period of 2 months, and a diagnosis of SSS was confirmed via imaging. Definitive treatment was withheld given the patient's postpartum state and improvement of symptoms. DISCUSSION: SSS typically manifests with painless and progressive, unilateral, enophthalmos and hypoglobus. Since presentation is dominated by ophthalmologic complaints, the ordinary route by which SSS is diagnosed is through ophthalmology review. The predominant complaint in our patient was chronic headaches with facial pain, and mild enophthalmos and hypoglobus were only noted 2 months later at follow-up. This represents an atypical presentation of SSS, and exemplifies the subtle and often ambiguous presenting features of this disorder. CONCLUSION: The protean manifestations of SSS mean that patients may initially present to specialities other than ophthalmology. To ensure rapid diagnosis and appropriate management, it is important that clinicians, particularly in ophthalmology, maxillofacial surgery, and ears, nose and throat (ENT), are familiar with this obscure condition.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.ijscr.2016.04.00

Fatal thalamic abscess secondary to dental infection.

We present the case of poor neurological recovery and subsequent death secondary to a thalamic abscess in a 53-year-old man. This patient initially presented with sudden dysarthria and left hemiparesis while driving. Neuroimaging showed a multilobular abscess involving the right thalamus with oedema extending to the basal ganglionic region and brainstem. The source of the abscess was initially unknown and it required draining multiple times while the different causes were being explored. The patient's neurological state along with intubation made for a difficult and inconclusive oral examination. It was only after neuroimaging included tooth-bearing areas that it became evident that this patient had extensive periodontal disease with multiple areas of periapical radiolucencies. The patient underwent complete dental clearance alongside repeated drainage of the abscess. Despite initial postoperative improvement, the patient never recovered from the neurological damage and died 3 weeks later

Activation of protein kinase B/Akt and endothelial nitric oxide synthase mediates agmatine-induced endothelium-dependent relaxation

The ability of agmatine, formed from L-arginine by the enzyme arginine decarboxylase (ADC), to modulate vasomotor function in rat aorta was investigated in the present study. Agmatine-mediated modulation of vasomotor tone was studied in organ chambers, protein expression quantified by Western blot analysis and cyclic guanosine 5'-monophosphate (cGMP) levels measured by radioimmunoassay. Agmatine (10-10 to 10-3 M) produced concentration-dependent relaxations (82 ± 5%) in phenylephrine-contracted endothelium intact rat aorta. Relaxations to agmatine were diminished on denudation of endothelium and nitric oxide synthase (NOS) inhibition by L-Nω-nitro arginine or soluble guanylate cyclase inhibition by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (P < 0.001) abolished agmatine-mediated relaxations, while relaxations were insensitive to inducible NOS inhibition by 1400W. Agmatine-treated aorta demonstrated increased protein expression of phosphorylated S473-Akt and phosphorylated S1177-endothelial nitric oxide synthase (eNOS), and elevated the levels of cyclic GMP (P < 0.01). Agmatine-mediated potentiation of relaxations and elevation of cGMP levels was sensitive to phosphatidylinositol 3'-kinase inhibitor, wortmannin. Relaxations to agmatine were also affected by pre-treatment with tetraethylammonium (P < 0.01) or apamin (P < 0.05), and were not affected by charybdotoxin. Relaxations to agmatine were partially affected by pre-treatment of aortic rings with barium chloride (P < 0.05), and glybenclamide (P < 0.05). Results obtained suggest that agmatine activates protein kinase B/Akt to phosphorylate eNOS and elevate cyclic GMP levels to produce vasodilatation of aorta. Agmatine-mediated relaxations in rat aorta seems to be mediated mainly by endothelial NO-mediated activation of small conductance Ca2+-activated K+ channels, and partly by ATP-sensitive and inward rectifying K+ channels