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1.
Appl Radiat Isot ; 182: 110139, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35180527

ABSTRACT

The specific activity of air in the large open room housing the 800-MeV proton synchrotron of the ISIS Spallation Neutron and Muon Source has been measured. Air from several positions within the ISIS synchrotron room was sucked through a long flexible tube, and run past a shielded HPGe gamma-ray detector outside the synchrotron room. In spite of an expectation that 13N should be the largest component of the overall activity in the air, the results of the measurements are consistent with the presence in the air of 11C and 41Ar only, and suggest that the activity in the air is mostly created not in the synchrotron room itself but in the massive shielding monoliths around the neutron-producing targets, monoliths through which ventilation air is drawn into the synchrotron room. Typical specific activities of 11C and 41Ar in the air in the synchrotron room are ∼0.10 and ∼0.03 Bq cm-3 respectively, the upper limit for 13N being at most ∼0.01 Bq cm-3.


Subject(s)
Air Pollutants, Radioactive/analysis , Nitrogen Radioisotopes/analysis , Synchrotrons , Argon/analysis , Carbon Isotopes/analysis , Protons
2.
Ann R Coll Surg Engl ; 104(3): 174-180, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34822303

ABSTRACT

INTRODUCTION: Men with gynaecomastia are routinely referred to breast clinics, yet most do not require breast surgical intervention. The aim of this study was to assess the impact of a novel point-of-care gynaecomastia decision infographic in primary care on the assessment, management and referral practices to tertiary breast surgical services. METHODS: A study was carried out of male patient referrals from primary care in Greater Manchester to a tertiary breast centre between January and March in 2018-2020. Referral patterns were compared before and after the infographic went live in general practices in Greater Manchester in January 2020. Data were collected for gynaecomastia referrals, including aetiology, investigation and management. RESULTS: In total, 394 men were referred to a tertiary breast centre from 163 general practices, of which 271 (68.8%) had a diagnosis of gynaecomastia. Use of the decision infographic by primary healthcare providers was associated with a decrease in male breast referrals with gynaecomastia (79.6% to 62.0%). Fewer gynaecomastia patients were referred with a benign physiological or drug-related cause after implementation of the infographic (52.2% vs 41.8%). Only 10 (3.7%) patients with gynaecomastia underwent breast surgery during the study period. CONCLUSION: Implementation of a gynaecomastia infographic in primary care in Manchester was associated with a reduction in gynaecomastia referrals to secondary care. We hypothesise that implementation of the infographic into primary care nationally may potentially translate to hundreds of patients receiving more specialty-appropriate referrals, improving overall management of gynaecomastia. Further study is warranted to test this hypothesis.


Subject(s)
Clinical Decision-Making , Data Visualization , Gynecomastia , Primary Health Care/methods , Referral and Consultation/statistics & numerical data , Adult , Aged , Gynecomastia/diagnosis , Gynecomastia/epidemiology , Gynecomastia/therapy , Humans , Male , Middle Aged , Practice Guidelines as Topic , United Kingdom
3.
Biochem Biophys Res Commun ; 588: 41-46, 2022 01 15.
Article in English | MEDLINE | ID: mdl-34942533

ABSTRACT

TRAAK (KCNK4, K2P4.1) is a mechanosensitive two-pore domain potassium (K2P) channel. Due to its expression within sensory neurons and genetic link to neuropathic pain it represents a promising potential target for novel analgesics. In common with many other channels in the wider K2P sub-family, there remains a paucity of small molecule pharmacological tools. Specifically, there is a lack of molecules selective for TRAAK over the other members of the TREK subfamily of K2P channels. We developed a thallium flux assay to allow high throughput screening of compounds and facilitate the identification of novel TRAAK activators. Using a library of ∼1200 drug like molecules we identified Aprepitant as a small molecule activator of TRAAK. Aprepitant is an NK-1 antagonist used to treat nausea and vomiting. Close structural analogues of Aprepitant and a range of NK-1 antagonists were also selected or designed for purchase or brief chemical synthesis and screened for their ability to activate TRAAK. Electrophysiology experiments confirmed that Aprepitant activates both the 'long' and 'short' transcript variants of TRAAK. We also demonstrated that Aprepitant is selective and does not activate other members of the K2P superfamily. This work describes the development of a high throughput assay to identify potential TRAAK activators and subsequent identification and confirmation of the novel TRAAK activator Aprepitant. This discovery identifies a useful tool compound which can be used to further probe the function of TRAAK K2P channels.


Subject(s)
Aprepitant/pharmacology , Potassium Channels/metabolism , Cell Line , Humans , Ion Channel Gating/drug effects , Neurokinin-1 Receptor Antagonists/pharmacology , Patch-Clamp Techniques , Receptors, Neurokinin-1/metabolism , Structure-Activity Relationship , Thallium/metabolism
4.
Med Eng Phys ; 97: 47-55, 2021 11.
Article in English | MEDLINE | ID: mdl-34756338

ABSTRACT

Implants anchored by press-fit are predominantly implanted by impaction. This method allows sufficiently high forces to be generated easily by the surgeon. Suitable impaction should provide adequate implant seating without damaging the patient (tissues), the implant and implantation system, or the surgeon. However, issues have been documented for all of these factors. In this study a model to predict implant seating is developed, given an applied impaction impulse, the mass of the accelerated components and the push-in resistance force. The model was validated against experimental data for a contemporary femoral stem implanted in a polyurethane foam surrogate for bone, with the input parameters varied. The model tended to overestimate seating but represented seating patterns well. The model can be used to estimate implant seating using easily measured parameters and could be useful in the design of implantation systems, and in optimising impaction strategies.


Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Arthroplasty, Replacement, Hip/methods , Bone and Bones , Femur/surgery , Humans , Prosthesis Design
5.
Article in English | MEDLINE | ID: mdl-34089890

ABSTRACT

Evidence from mammals and aves alludes to a possibly conserved seasonal photoperiod induced neuroendocrine cascade which stimulates subsequent sexual maturation however our understanding of this mechanism in teleosts is lacking. Unlike all teleosts studied to date, the Atlantic cod (Gadus morhua) is a short day breeder with the reduction in day-length from the summer solstice stimulating gametogenesis. Cod specific orthologues of eya3, tshß and dio2 were identified and their expression was monitored in the brain and pituitary of cod held under either stimulated or inhibited photoperiod conditions. While no differential expression was apparent in brain dio2 & tshß and pituitary tshß, there was significant temporal variation in expression of pituitary eya3 under the SNP treatment, with expression level elevating in association with active gametogenesis. Under the LL treatment, sexual maturation was inhibited and there was a corresponding suppression of eya3 expression. In a second study the impact of size/energetic status on the initiation of sexual maturation was investigated. In the feed restricted population maturation was significantly suppressed (5% sexually mature) compared to the ab libitum fed stock (95% sexually mature) with there being a concomitant significant suppression in pituitary eya3 expression. Overall, these results suggest that pituitary eya3 has the potential to act as an integrator of both environmental and energetic regulation of sexual maturation of cod. Being the first account of eya3 induction in a short day breeding teleost, the conserved association with stimulation of reproduction and not seasonal state indicates that the upstream drivers which initiate the pathway differ among vertebrates according to their breeding strategies, but the pathway itself and its role in the reproductive cascade appears to be conserved across the vertebrate clade.


Subject(s)
Animal Nutritional Physiological Phenomena , Gadus morhua/physiology , Neurosecretory Systems , Photoperiod , Sexual Maturation , Animals , Circadian Rhythm/physiology , Female , Gene Expression Profiling , Gene Expression Regulation , Male , Phylogeny , Pituitary Gland/metabolism , Reproduction/physiology , Seasons , Time Factors , Vertebrates
6.
Biotechnol Biofuels ; 14(1): 121, 2021 May 22.
Article in English | MEDLINE | ID: mdl-34022944

ABSTRACT

BACKGROUND: Chlamydomonas reinhardtii is a model green alga strain for molecular studies; its fully sequenced genome has enabled omic-based analyses that have been applied to better understand its metabolic responses to stress. Here, we characterised physiological and proteomic changes between a low-starch C. reinhardtii strain and the snow alga Chlamydomonas nivalis, to reveal insights into their contrasting responses to salinity stress. RESULTS: Each strain was grown in conditions tailored to their growth requirements to encourage maximal fatty acid (as a proxy measure of lipid) production, with internal controls to allow comparison points. In 0.2 M NaCl, C. nivalis accumulates carbohydrates up to 10.4% DCW at 80 h, and fatty acids up to 52.0% dry cell weight (DCW) over 12 days, however, C. reinhardtii does not show fatty acid accumulation over time, and shows limited carbohydrate accumulation up to 5.5% DCW. Analysis of the C. nivalis fatty acid profiles showed that salt stress improved the biofuel qualities over time. Photosynthesis and respiration rates are reduced in C. reinhardtii relative to C. nivalis in response to 0.2 M NaCl. De novo sequencing and homology matching was used in conjunction with iTRAQ-based quantitative analysis to identify and relatively quantify proteomic alterations in cells exposed to salt stress. There were abundance differences in proteins associated with stress, photosynthesis, carbohydrate and lipid metabolism proteins. In terms of lipid synthesis, salt stress induced an increase in dihydrolipoyl dehydrogenase in C. nivalis (1.1-fold change), whilst levels in C. reinhardtii remained unaffected; this enzyme is involved in acetyl CoA production and has been linked to TAG accumulation in microalgae. In salt-stressed C. nivalis there were decreases in the abundance of UDP-sulfoquinovose (- 1.77-fold change), which is involved in sulfoquinovosyl diacylglycerol metabolism, and in citrate synthase (- 2.7-fold change), also involved in the TCA cycle. Decreases in these enzymes have been shown to lead to increased TAG production as fatty acid biosynthesis is favoured. Data are available via ProteomeXchange with identifier PXD018148. CONCLUSIONS: These differences in protein abundance have given greater understanding of the mechanism by which salt stress promotes fatty acid accumulation in the un-sequenced microalga C. nivalis as it switches to a non-growth state, whereas C. reinhardtii does not have this response.

7.
Int Endod J ; 53(1): 122-134, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31483863

ABSTRACT

AIM: To identify chelators which when mixed with sodium hypochlorite (NaOCl) are stable, exhibiting minimal loss of free available chlorine (FAC) over 80 min and to further investigate potential mixtures by assessing FAC over 18 h and the capacity to remove smear layer. METHODOLOGY: 0.25 mol L-1 EDTA (10%), 0.25 mol L-1 EGTA (egtazic acid), 0.25 mol L-1 CDTA (cyclohexanediaminetetraacetic acid), 0.25 mol L-1 DTPA (pentetic acid), 0.5 mol L-1 ATMP (aminotri(methylene phosphonic acid)) and 1 mol L-1 HPAA, (hydroxyphosphonoacetic acid), all at alkaline pH, were mixed equally with 5% NaOCl. 0.5 mol L-1 alkaline clodronate and 0.5 mol L-1 Na4 etidronate (15%) were mixed equally with 10% NaOCl. For all mixtures, the pH and temperature were measured over 80 min and additionally for the clodronate mixture over 18 h. Iodometric titration was used to measure the FAC of all mixtures except for HPAA. The following were compared with respect to their ability to remove smear layer: 1 mol L-1 clodronate + 10% NaOCl, 0.5 mol L-1 clodronate + 10% NaOCl, 1 mol L-1 etidronate + 10% NaOCl, 0.5 mol L-1 clodronate + 10% NaOCl and the sequences 5% NaOCl/17% EDTA/5% NaOCl and 5% NaOCl/17% EDTA. The area fraction occupied by open dentinal tubules as a percentage of the total area (% AF) from scanning electron microscopy micrographs was calculated using Image J. The results were statistically analysed with alpha set at 0.05. RESULTS: Compared to its control, the mixture 0.5 mol L-1 clodronate + 10% NaOCl lost no FAC over 18 h (P > 0.05). The FAC of 0.25 mol L-1 CDTA mixed with 5% NaOCl fell to 96%, 92%, 75% and 4.9% at 20, 40, 60 and 80 min, respectively. Temperature rises were observed in all cases except in the etidronate and clodronate mixtures. Only in the clodronate mixture did the pH remain above pH 12 for the whole experiment. Although smear layer was removed, the % AF in 1 mol L-1 clodronate + 10% NaOCl, 0.5 mol L-1 clodronate + 10% NaOCl, 1 mol L-1 etidronate + 10% NaOCl was less than for 0.5 mol L-1 etidronate + 10% NaOCl and 5% NaOCl/17% EDTA/5% NaOCl and 5% NaOCl/17% EDTA. CONCLUSION: Alkaline 0.5 mol L-1 clodronate mixed equally with 10% NaOCl has potential for use in continuous chelation, based on this assessment of stability and smear layer removal. Further research is needed to establish its efficacy and safety.


Subject(s)
Chelating Agents , Smear Layer , Clodronic Acid , Dental Pulp Cavity , Edetic Acid , Humans , Microscopy, Electron, Scanning , Root Canal Irrigants , Root Canal Preparation , Sodium Hypochlorite
8.
Sci Rep ; 9(1): 15179, 2019 10 23.
Article in English | MEDLINE | ID: mdl-31645599

ABSTRACT

Understanding how temperature affects the relative phenology of predators and prey is necessary to predict climate change impacts and recruitment variation. This study examines the role of temperature in the phenology of a key forage fish, the lesser sandeel (Ammodytes marinus, Raitt) and its copepod prey. Using time-series of temperature, fish larval and copepod abundance from a Scottish coastal monitoring site, the study quantifies how thermal relationships affect the match between hatching in sandeel and egg production of its copepod prey. While sandeel hatch time was found to be related to the rate of seasonal temperature decline during the autumn and winter through effects on gonad and egg development, variation in copepod timing mostly responded to February temperature. These two temperature relationships defined the degree of trophic mismatch which in turn explained variation in local sandeel recruitment. Projected warming scenarios indicated an increasing probability of phenological decoupling and concomitant decline in sandeel recruitment. This study sheds light on the mechanisms by which future warming could increase the trophic mismatch between predator and prey, and demonstrates the need to identify the temperature-sensitive stages in predator-prey phenology for predicting future responses to climate change.

10.
Radiography (Lond) ; 24(4): 283-288, 2018 11.
Article in English | MEDLINE | ID: mdl-30292495

ABSTRACT

INTRODUCTION: To measure the range of T1 values of synovitis using three Tesla (3 T) magnetic resonance imaging (MRI) in patients with osteoarthritis to assess the potential of T1 mapping for identifying synovitis from other features in the knee on unenhanced magnetic resonance scans. METHODS: After receiving institutional ethical approval, 83 patients who met the American College of Rheumatology criteria for diagnosis of osteoarthritis of the knee were scanned using a 3 T Magnetic Resonance Imaging scanner. T1 maps were calculated from spoiled gradient echo images acquired with five different flip angles of 5°-25°. Mean values for the T1 measurements were calculated and compared to existing data from the published literature for anatomical and pathological structures of the knee. RESULTS: T1 values recorded in patients suffering from osteoarthritis demonstrated that T1 values for synovitis (confirmed on gadolinium enhanced images) fall in a narrow range (849-1277 ms, mean 1005 ms SD 91) delineating this from other structures of the knee such as muscle (T1 value range 1305-2638 ms, mean 1785 ms SD 304) and synovial fluid (T1 value range 3867-4129 ms, mean 3915 SD 899) at 3 T. CONCLUSION: T1 values measured in synovitis in patients with osteoarthritis of the knee demonstrated a range of values distinct to those measured in muscle and synovial fluid at 3 T. This offers potential for the use of T1 maps to delineate or quantify synovitis in patients who are unwilling or unable to receive injectable contrast agents.


Subject(s)
Magnetic Resonance Imaging , Osteoarthritis, Knee/diagnostic imaging , Synovitis/diagnostic imaging , Female , Humans , Image Processing, Computer-Assisted , Knee Joint/diagnostic imaging , Magnetic Resonance Imaging/methods , Male , Middle Aged , Prospective Studies
11.
J Exp Biol ; 221(Pt 8)2018 04 13.
Article in English | MEDLINE | ID: mdl-29511069

ABSTRACT

Fishes acclimated to hypoxic environments often increase gill surface area to improve O2 uptake. In some species, surface area is increased via reduction of an interlamellar cell mass (ILCM) that fills water channels between gill lamellae. Amphibious fishes, however, may not increase gill surface area in hypoxic water because these species can, instead, leave water and breathe air. To differentiate between these possibilities, we compared wild amphibious mangrove rivulus Kryptolebias marmoratus from two habitats that varied in O2 availability - a hypoxic freshwater pool versus nearly anoxic crab burrows. Fish captured from crab burrows had less gill surface area (as ILCMs were enlarged by ∼32%), increased rates of normoxic O2 consumption and increased critical O2 tension compared with fish from the freshwater pool. Thus, wild mangrove rivulus do not respond to near-anoxic water by decreasing metabolism or increasing O2 extraction. Instead, fish from the crab burrow habitat spent three times longer out of water, which probably caused the observed changes in gill morphology and respiratory phenotype. We also tested whether critical O2 tension is influenced by genetic heterozygosity, as K. marmoratus is one of only two hermaphroditic vertebrate species that can produce both self-fertilized (inbred) or out-crossed (more heterozygous) offspring. We found no evidence for inbreeding depression, suggesting that self-fertilization does not impair respiratory function. Overall, our results demonstrate that amphibious fishes that inhabit hypoxic aquatic habitats can use a fundamentally different strategy from that used by fully aquatic water-breathing fishes, relying on escape behaviour rather than metabolic depression or increased O2 extraction ability.


Subject(s)
Cyprinodontiformes/anatomy & histology , Cyprinodontiformes/physiology , Gills/anatomy & histology , Gills/physiology , Oxygen/analysis , Animals , Cyprinodontiformes/genetics , Ecosystem , Fresh Water/chemistry , Hermaphroditic Organisms , Inbreeding Depression , Oxygen Consumption
12.
Clin Otolaryngol ; 43(3): 846-853, 2018 06.
Article in English | MEDLINE | ID: mdl-29341454

ABSTRACT

OBJECTIVES: The aim of this longitudinal study was to examine the distribution of head and neck cancer (HANC) disease burden across the region comparing it to national trends. DESIGN: We undertook a retrospective study of routine data combining it with indicators of deprivation and lifestyle at small geographical areas within the 9 Local Authorities (LAs) of Merseyside and Cheshire Network (MCCN) for head and neck cancers. Data from the North West of England and England were used as comparator regions. SETTING: This research was undertaken by the Cheshire and Merseyside Public Health Collaborative, UK. PARTICIPANTS: The Merseyside and Cheshire region serves a population of 2.2 million. Routine data allowed us to identify HANC patients diagnosed with cancers coded ICD C00-C14 and C30-C32 within 3 cohorts 1998-2000, 2008-2010 and 2009-2011 for our analysis. MAIN OUTCOME MEASURES: Directly age-standardised incidence rates and directly age-standardised mortality rates in the LAs and comparator regions were measured. Lifestyle and deprivation indicators were plotted against them and measured by Pearson's correlation coefficients. RESULTS: The incidence of head and neck cancer has increased across the region from 1998-2000 to 2008-2010 with a peak incidence for Liverpool males at 35/100 000 population. Certain Middle Super Output Areas contribute disproportionately to the significant effect of incidence and mortality within LAs. Income deprivation had the strongest correlation with incidence (r = .59) and mortality (r = .53) of head and neck cancer. CONCLUSION: Our study emphasises notable geographical variations within the region which need to be addressed through public health measures.


Subject(s)
Cost of Illness , Head and Neck Neoplasms/epidemiology , Health Status Disparities , Socioeconomic Factors , Adult , Age Distribution , Aged , Aged, 80 and over , England/epidemiology , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Sex Distribution , Survival Rate
13.
Cytopathology ; 29(1): 71-79, 2018 02.
Article in English | MEDLINE | ID: mdl-29193477

ABSTRACT

OBJECTIVE: To compare endoscopic ultrasound (EUS)-FNAC diagnosis of pancreatic lesions with patient outcome based upon the Papanicolaou Society of Cytopathology pancreaticobiliary terminology classification scheme diagnostic categories: Panc 1 (non-diagnostic); Panc 2 (negative for malignancy/neoplasia); Panc 3 (atypical); Panc 4B (neoplastic, benign); Panc 4O (neoplastic, other); Panc 5 (suspicious of malignancy); and Panc 6 (positive/malignant). METHODS: All EUS-FNA pancreas specimens taken at Manchester Royal Infirmary in 2015 were prospectively classified according to the above scheme at the time of cytology reporting and data recorded prospectively. Subsequently, outcomes based on clinical follow-up or histopathology diagnosis were compared with the cytology diagnosis. RESULTS: 120 EUS-FNA pancreas specimens from 111 patients were received, of which 112 (93.3%) specimens had follow-up data. There were 79 and 41 EUS-FNA pancreas specimens from solid and cystic lesions, respectively. Based on the cytology diagnosis the specimens were classified as Panc 1 (7.5%), Panc 2 (33.3%), Panc 3 (2.5%), Panc 4B (2.5%), Panc 4O (15.0%), Panc 5 (3.3%) and Panc 6 (35.9%). The performance indicators for diagnosis of malignancy or neoplasia with malignant potential, included sensitivity (95.4%), specificity (100%), positive predictive value (100%), negative predictive value (92.3%), false positive rate (0%) and false negative rate (4.6%). CONCLUSIONS: The Papanicolaou Society of Cytopathology pancreaticobiliary terminology classification scheme is a logical system that can easily be introduced in a diagnostic cytopathology service. This classification scheme acts as an aid to diagnostic reporting, clear communication of significant results including risk of neoplasia/malignancy to clinicians, clinical audit and comparison of results with other centres.


Subject(s)
Cytodiagnosis/methods , Pancreatic Neoplasms/classification , Pancreatic Neoplasms/diagnostic imaging , Adult , Aged , Aged, 80 and over , Biopsy, Fine-Needle/methods , Biopsy, Fine-Needle/standards , Cytodiagnosis/standards , Female , Humans , Male , Middle Aged , Pancreatic Neoplasms/pathology , Papanicolaou Test/methods , Papanicolaou Test/standards , Ultrasonography, Interventional/methods , Ultrasonography, Interventional/standards , Young Adult
14.
J Physiol Pharmacol ; 68(4): 547-553, 2017 Aug.
Article in English | MEDLINE | ID: mdl-29151071

ABSTRACT

This study sought to compare postpartum blood loss and maternal outcomes after 3IU and 5IU oxytocin at elective caesarean delivery. In a prospective observational study, 73 women undergoing elective caesarean delivery under spinal anaesthetic received a slow I.V. injection of either 3IU (n = 35) or 5IU (n = 38) oxytocin after delivery. The main outcome was gravimetrically measured 24-hour postpartum blood loss with a non-inferiority margin of 300 mL. Uterine tone, phenylephrine dose, emesis and hypotension after oxytocin administration were secondary outcomes. Gravimetric postpartum blood loss was lower in the 3IU group (-58.8 mL [95% CI: -212.1, 94.3]) after adjusting for BMI, pre-delivery vasopressor dose, parity, and risk of uterine atony, with the upper confidence limit below the 300 mL margin in support of non-inferiority. Patients receiving 3IU had a higher (non-significant) rate of having post-delivery phenylephrine to treat hypotension (RR = 1.59 [95% CI: 0.97, 2.63]), but of those treated, the 3IU group required significantly less (-427 mcg [95% CI: -740, -114]). The 3IU group had a lower prevalence of vomiting compared to those receiving 5IU (6% versus 24%; P = 0.047). Administration of 3IU oxytocin was non-inferior compared to standard 5IU with respect to blood loss in women undergoing elective caesarean delivery.


Subject(s)
Oxytocin/administration & dosage , Postpartum Hemorrhage/drug therapy , Adult , Cesarean Section/methods , Female , Humans , Hypotension/chemically induced , Injections, Intravenous/methods , Oxytocin/adverse effects , Phenylephrine/administration & dosage , Pregnancy , Prospective Studies , Uterus/drug effects , Vasoconstrictor Agents/administration & dosage , Vasoconstrictor Agents/adverse effects
15.
JRSM Cardiovasc Dis ; 6: 2048004017734431, 2017.
Article in English | MEDLINE | ID: mdl-29051816

ABSTRACT

INTRODUCTION: Glycoprotein IIb/IIIa inhibitors are recommended by guidelines in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. There are few studies directly comparing these agents. The aim of this study was to assess whether eptifibatide is a safe and cost-effective alternative to abciximab in the treatment of primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. METHODS: This was an observational cohort study of 3863 patients who received a GPIIb/IIIa inhibitor whilst undergoing primary percutaneous coronary intervention from 2007 to 2014. Patients who did not receive a GPIIb/IIIa inhibitor were excluded. Time to first major adverse cardiac event defined as death, non-fatal myocardial infarction, stroke or target vessel revascularization, and total hospital costs were compared between the groups. RESULTS: In all, 1741 patients received abciximab with 2122 receiving eptifibatide. Patients who received eptifibatide had higher rates of previous MI/percutaneous coronary intervention and were more likely to undergo a procedure from the radial route. Unadjusted Kaplan-Meier analysis revealed no significant difference in the 1-year event rates between patients given eptifibatide versus abciximab (p = 0.201). Age-adjusted Cox analysis demonstrated no difference in 1-year outcome between abciximab and eptifibatide (hazard ratio: 0.83; 95% confidence interval: 0.73-1.39), which persisted after multivariate adjustment (hazard ratio: 0.92; 95% confidence interval: 0.79-1.56) including the incorporation of a propensity score (hazard ratio: 0.88; 95% confidence interval: 0.71-1.44). Eptifbatide was associated with significant cost savings being 87% cheaper overall compared to abciximab (on average £650 cheaper per patient and saving approximately £950,000). CONCLUSION: This observational data suggest that eptifibatide is associated with similar outcomes and significant cost savings compared to abciximab when used in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

16.
J Fish Biol ; 91(1): 362-367, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28691400

ABSTRACT

Ovarian development was examined in relation to size and temperature in late pre-spawning Ammodytes marinus over 5 years. Oocyte diameter was positively related to length indicating that larger females spawned earlier. Age and temperature, whilst accounting for the effect of length, were not found to affect oocyte development, although the thermal range examined was only 1·3° C.


Subject(s)
Body Size/physiology , Fishes/anatomy & histology , Fishes/physiology , Reproduction/physiology , Animals , Female , Likelihood Functions , Linear Models , North Sea , Oocytes/growth & development , Oocytes/ultrastructure , Oogenesis/physiology , Scotland , Statistics, Nonparametric , Temperature , Time Factors
17.
Article in English | MEDLINE | ID: mdl-28382745

ABSTRACT

Prostate cancer (PCa) can negatively impact on men's sexual, urinary and emotional functioning, affecting quality of life. Most men with PCa are older (≥65 years), married and heterosexual and little is known about the impact on men who are younger, unpartnered or gay. We aimed to synthesise existing qualitative research on these three groups of men. A systematic metasynthesis was undertaken that included data on the unique impacts of PCa on younger (<65 years) (n = 7 papers), unpartnered (n = 17 papers) or gay or bisexual men (n = 11 papers) using a modified meta-ethnographic approach. The three overarching constructs illustrated the magnified disruption to men's biographies, that included: marginalisation, isolation and stigma-relating to men's sense of being "out of sync"; the burden of emotional and embodied vulnerabilities and the assault on identity-illustrating the multiple threats to men's work, sexual and social identities; shifting into different communities of practice-such as the shift from being part of a sexually active community to celibacy. These findings suggest that PCa can have a particular impact on the quality of life of younger, unpartnered and gay men. This has implications for the provision of tailored support and information to these potentially marginalised groups.


Subject(s)
Prostatic Neoplasms/psychology , Quality of Life , Sexual and Gender Minorities/psychology , Single Person/psychology , Age Factors , Cost of Illness , Homosexuality, Male , Humans , Male , Middle Aged , Prostatic Neoplasms/therapy , Qualitative Research
18.
Leukemia ; 31(3): 720-727, 2017 03.
Article in English | MEDLINE | ID: mdl-27604819

ABSTRACT

Heterozygous somatic mutations affecting the spliceosome gene SF3B1 drive age-related clonal hematopoiesis, myelodysplastic syndromes (MDS) and other neoplasms. To study their role in such disorders, we generated knock-in mice with hematopoietic-specific expression of Sf3b1-K700E, the commonest type of SF3B1 mutation in MDS. Sf3b1K700E/+ animals had impaired erythropoiesis and progressive anemia without ringed sideroblasts, as well as reduced hematopoietic stem cell numbers and host-repopulating fitness. To understand the molecular basis of these observations, we analyzed global RNA splicing in Sf3b1K700E/+ hematopoietic cells. Aberrant splicing was associated with the usage of cryptic 3' splice and branchpoint sites, as described for human SF3B1 mutants. However, we found a little overlap between aberrantly spliced mRNAs in mouse versus human, suggesting that anemia may be a consequence of globally disrupted splicing. Furthermore, the murine orthologues of genes associated with ring sideroblasts in human MDS, including Abcb7 and Tmem14c, were not aberrantly spliced in Sf3b1K700E/+ mice. Our findings demonstrate that, despite significant differences in affected transcripts, there is overlap in the phenotypes associated with SF3B1-K700E between human and mouse. Future studies should focus on understanding the basis of these similarities and differences as a means of deciphering the consequences of spliceosome gene mutations in MDS.


Subject(s)
Anemia, Sideroblastic/etiology , Anemia, Sideroblastic/pathology , Hematopoiesis/genetics , Myelodysplastic Syndromes/complications , Myelodysplastic Syndromes/genetics , Phosphoproteins/genetics , RNA Splicing Factors/genetics , RNA Splicing , Anemia, Sideroblastic/mortality , Animals , Disease Models, Animal , Gene Targeting , Humans , Mice , Mice, Transgenic , Mutation , Phenotype , RNA Splicing Factors/metabolism
19.
Faraday Discuss ; 192: 181-195, 2016 10 20.
Article in English | MEDLINE | ID: mdl-27476480

ABSTRACT

The zero length column (ZLC) technique is used to investigate the stability of Mg- and Ni-CPO-27 metal-organic framework (MOF) crystals in the presence of water and humid flue gas. The design of the ZLC enables the stability test to be conducted over a considerably shorter time period and with lower gas consumption than other conventional techniques. A key advantage over other experimental methods for testing the stability of adsorbents is the fact that the ZLC allows us to quantify the amount adsorbed of every component present in the gas mixture. The developed protocol is based on a two-stage stability test. The samples were first exposed to a humid carbon dioxide and helium mixture in order to study the effect of water on the carbon dioxide adsorption capacity of the samples. In the second stage the samples were exposed to a flue gas mixture containing water. From the preliminary water stability test, the Ni-sample exhibited the highest tolerance to the presence of water, retaining approximately 85% of its pristine CO2 capacity. The Mg-MOFs deactivated rapidly in the presence of water. The Ni-CPO-27 was then selected for the second stage of the protocol in which the material was exposed to the wet flue gas. The sample showed an initial drop in CO2 capacity after the first exposure to the wet flue gas, followed by a stabilisation of the performance over several cycles.

20.
Mol Biosyst ; 12(7): 2064-8, 2016 06 21.
Article in English | MEDLINE | ID: mdl-27170554

ABSTRACT

Fourier transform infrared (FTIR) microspectroscopy and confocal imaging have been used to demonstrate that the neutral rhenium(i) tricarbonyl 1,10-phenanthroline complex bound to 4-cyanophenyltetrazolate as the ancillary ligand is able to localise in regions with high concentrations of polar lipids such as phosphatidylethanolamine (PE), sphingomyelin, sphingosphine and lysophosphatidic acid (LPA) in mammalian adipocytes.


Subject(s)
Adipocytes/metabolism , Lipid Metabolism , Lipids , Luminescent Agents , Rhenium , Spectroscopy, Fourier Transform Infrared , 3T3-L1 Cells , Animals , Lipids/chemistry , Mice
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