Geomorphological control on boulder transport and coastal erosion before, during and after an extreme extra-tropical cyclone

This is the final version of the article. Available from Wiley via the DOI in this record.Extreme wave events in coastal zones are principal drivers of geomorphic change. Evidence of boulder entrainment and erosional impact during storms is increasing. However, there is currently poor time coupling between pre- and post-storm measurements of coastal boulder deposits. Importantly there are no data reporting shore platform erosion, boulder entrainment and/or boulder transport during storm events – rock coast dynamics during storm events are currently unexplored. Here, we use high-resolution (daily) field data to measure and characterize coastal boulder transport before, during and after the extreme Northeast Atlantic extra-tropical cyclone Johanna in March 2008. Forty-eight limestone fine-medium boulders (n = 46) and coarse cobbles (n = 2) were tracked daily over a 0.1 km2 intertidal area during this multi-day storm. Boulders were repeatedly entrained, transported and deposited, and in some cases broken down (n = 1) or quarried (n = 3), during the most intense days of the storm. Eighty-one percent (n = 39) of boulders were located at both the start and end of the storm. Of these, 92% were entrained where entrainment patterns were closely aligned to wave parameters. These data firmly demonstrate rock coasts are dynamic and vulnerable under storm conditions. No statistically significant relationship was found between boulder size (mass) and net transport distance. Graphical analyses suggest that boulder size limits the maximum longshore transport distance but that for the majority of boulders lying under this threshold, other factors influence transport distance. Paired analysis of 20 similar sized and shaped boulders in different morphogenic zones demonstrates that geomorphological control affects entrainment and transport distance – where net transport distances were up to 39 times less where geomorphological control was greatest. These results have important implications for understanding and for accurately measuring and modelling boulder entrainment and transport. Coastal managers require these data for assessing erosion risk.This paper benefitted from: comments from J. Hansom, S. Etienne and anonymous reviewers; student volunteers at Atlantic United World College; cartography from Sue Rouillard and Mike Shand; funding from a Royal Geographical Society EPSRC small grant and a NERC grant NE/M010546/1 (Dr Naylor) and an Australian Research Council Discovery grant DP0557205 (Dr Stephenson); permission from the Countryside Council for Wales

Antipsychotics and Torsadogenic Risk: Signals Emerging from the US FDA Adverse Event Reporting System Database

Background: Drug-induced torsades de pointes (TdP) and related clinical entities represent a current regulatory and clinical burden. Objective: As part of the FP7 ARITMO (Arrhythmogenic Potential of Drugs) project, we explored the publicly available US FDA Adverse Event Reporting System (FAERS) database to detect signals of torsadogenicity for antipsychotics (APs). Methods: Four groups of events in decreasing order of drug-attributable risk were identified: (1) TdP, (2) QT-interval abnormalities, (3) ventricular fibrillation/tachycardia, and (4) sudden cardiac death. The reporting odds ratio (ROR) with 95 % confidence interval (CI) was calculated through a cumulative analysis from group 1 to 4. For groups 1+2, ROR was adjusted for age, gender, and concomitant drugs (e.g., antiarrhythmics) and stratified for AZCERT drugs, lists I and II (http://www.azcert.org, as of June 2011). A potential signal of torsadogenicity was defined if a drug met all the following criteria: (a) four or more cases in group 1+2; (b) significant ROR in group 1+2 that persists through the cumulative approach; (c) significant adjusted ROR for group 1+2 in the stratum without AZCERT drugs; (d) not included in AZCERT lists (as of June 2011). Results: Over the 7-year period, 37 APs were reported in 4,794 cases of arrhythmia: 140 (group 1), 883 (group 2), 1,651 (group 3), and 2,120 (group 4). Based on our criteria, the following potential signals of torsadogenicity were found: amisulpride (25 cases; adjusted ROR in the stratum without AZCERT drugs = 43.94, 95 % CI 22.82-84.60), cyamemazine (11; 15.48, 6.87-34.91), and olanzapine (189; 7.74, 6.45-9.30). Conclusions: This pharmacovigilance analysis on the FAERS found 3 potential signals of torsadogenicity for drugs previously unknown for this risk

The differential hormonal milieu of morning versus evening, may have an impact on muscle hypertrophic potential

Substantial gains in muscle strength and hypertrophy are clearly associated with the routine performance of resistance training. What is less evident is the optimal timing of the resistance training stimulus to elicit these significant functional and structural skeletal muscle changes. Therefore, this investigation determined the impact of a single bout of resistance training performed either in the morning or evening upon acute anabolic signalling (insulin-like growth factor-binding protein-3 (IGFBP-3), myogenic index and differentiation) and catabolic processes (cortisol). Twenty-four male participants (age 21.4±1.9yrs, mass 83.7±13.7kg) with no sustained resistance training experience were allocated to a resistance exercise group (REP). Sixteen of the 24 participants were randomly selected to perform an additional non-exercising control group (CP) protocol. REP performed two bouts of resistance exercise (80% 1RM) in the morning (AM: 0800 hrs) and evening (PM: 1800 hrs), with the sessions separated by a minimum of 72 hours. Venous blood was collected immediately prior to, and 5 min after, each resistance exercise and control sessions. Serum cortisol and IGFBP-3 levels, myogenic index, myotube width, were determined at each sampling period. All data are reported as mean ± SEM, statistical significance was set at P≤0.05. As expected a significant reduction in evening cortisol concentration was observed at pre (AM: 98.4±10.5, PM: 49.8±4.4 ng/ml, P0.05). Timing of resistance training regimen in the evening appears to augment some markers of hypertrophic potential, with elevated IGFBP-3, suppressed cortisol and a superior cellular environment. Further investigation, to further elucidate the time course of peak anabolic signalling in morning vs evening training conditions, are timely

Accounting Problems Under the Excess Profits Tax

DNA vaccines based on subunits from pathogens have several advantages over other vaccine strategies. DNA vaccines can easily be modified, they show good safety profiles, are stable and inexpensive to produce, and the immune response can be focused to the antigen of interest. However, the immunogenicity of DNA vaccines which is generally quite low needs to be improved. Electroporation and co-delivery of genetically encoded immune adjuvants are two strategies aiming at increasing the efficacy of DNA vaccines. Here, we have examined whether targeting to antigen-presenting cells (APC) could increase the immune response to surface envelope glycoprotein (Env) gp120 from Human Immunodeficiency Virus type 1 (HIV- 1). To target APC, we utilized a homodimeric vaccine format denoted vaccibody, which enables covalent fusion of gp120 to molecules that can target APC. Two molecules were tested for their efficiency as targeting units: the antibody-derived single chain Fragment variable (scFv) specific for the major histocompatilibility complex (MHC) class II I-E molecules, and the CC chemokine ligand 3 (CCL3). The vaccines were delivered as DNA into muscle of mice with or without electroporation. Targeting of gp120 to MHC class II molecules induced antibodies that neutralized HIV-1 and that persisted for more than a year after one single immunization with electroporation. Targeting by CCL3 significantly increased the number of HIV-1 gp120-reactive CD8(+) T cells compared to non-targeted vaccines and gp120 delivered alone in the absence of electroporation. The data suggest that chemokines are promising molecular adjuvants because small amounts can attract immune cells and promote immune responses without advanced equipment such as electroporation.Funding Agencies|Research Council of Norway; Odd Fellow</p

Late pulmonary metastases of renal cell carcinoma immediately after post-transplantation immunosuppressive treatment: a case report

Introduction We report a case of pulmonary metastatic recurrence of renal adenocarcinoma soon after radical nephrectomy that was followed by renal transplant and immunosuppressive medication. Increased risk of metastatic recurrence of renal cell carcinoma should be considered in the immediate post-transplant period when immunosuppressive medication is administered, even if nephrectomy had been performed many years earlier.Case presentation In 1986 the patient demonstrated renal insufficiency secondary to mesangial glomerulonephritis. In 1992 he underwent left side radical nephrectomy with histopathological diagnosis of clear cell adenocarcinoma. Mesangial glomerulonephritis in the remaining right kidney progressed to end-stage renal failure. In October 2000 he received a kidney transplant from a cadaver and commenced immunosuppressive medication. Two months later, several nodules were found in his lungs, which were identified as metastases from the primary renal tumor that had been removed with the diseased kidney 8 years earlier.Conclusion Recurrence of renal cell carcinoma metastases points to tumor dormancy and reflects a misbalance between effective tumor immune surveillance and immune escape. This case demonstrates that a state of tumor dormancy can be interrupted soon after administration of immunosuppressant medication.This work was partially supported by the Fondo de Investigaciones Sanitarias (PI 02/0175), the plan Andaluz de Investigacion, and the Instituto de Salud Carlos III-Red de centros de Cancer, Spain

Recovery of Barotrauma Injuries in Chinook Salmon, Oncorhynchus tshawytscha from Exposure to Pile Driving Sound

Juvenile Chinook salmon, Oncorhynchus tshawytscha, were exposed to simulated high intensity pile driving signals to evaluate their ability to recover from barotrauma injuries. Fish were exposed to one of two cumulative sound exposure levels for 960 pile strikes (217 or 210 dB re 1 µPa2·s SELcum; single strike sound exposure levels of 187 or 180 dB re 1 µPa2⋅s SELss respectively). This was followed by an immediate assessment of injuries, or assessment 2, 5, or 10 days post-exposure. There were no observed mortalities from the pile driving sound exposure. Fish exposed to 217 dB re 1 µPa2·s SELcum displayed evidence of healing from injuries as post-exposure time increased. Fish exposed to 210 dB re 1 µPa2·s SELcum sustained minimal injuries that were not significantly different from control fish at days 0, 2, and 10. The exposure to 210 dB re 1 µPa2·s SELcum replicated the findings in a previous study that defined this level as the threshold for onset of injury. Furthermore, these data support the hypothesis that one or two Mild injuries resulting from pile driving exposure are unlikely to affect the survival of the exposed animals, at least in a laboratory environment

High resolution 3-Dimensional imaging of the human cardiac conduction system from microanatomy to mathematical modeling

Cardiac arrhythmias and conduction disturbances are accompanied by structural remodelling of the specialised cardiomyocytes known collectively as the cardiac conduction system. Here, using contrast enhanced micro-computed tomography, we present, in attitudinally appropriate fashion, the first 3-dimensional representations of the cardiac conduction system within the intact human heart. We show that cardiomyocyte orientation can be extracted from these datasets at spatial resolutions approaching the single cell. These data show that commonly accepted anatomical representations are oversimplified. We have incorporated the high-resolution anatomical data into mathematical simulations of cardiac electrical depolarisation. The data presented should have multidisciplinary impact. Since the rate of depolarisation is dictated by cardiac microstructure, and the precise orientation of the cardiomyocytes, our data should improve the fidelity of mathematical models. By showing the precise 3-dimensional relationships between the cardiac conduction system and surrounding structures, we provide new insights relevant to valvar replacement surgery and ablation therapies. We also offer a practical method for investigation of remodelling in disease, and thus, virtual pathology and archiving. Such data presented as 3D images or 3D printed models, will inform discussions between medical teams and their patients, and aid the education of medical and surgical trainees

A simple and rapid flow cytometry-based assay to identify a competent embryo prior to embryo transfer

Multiple pregnancy is a risk for prematurity and preterm birth. The goal of assisted reproduction is to achieve a single pregnancy, by transferring a single embryo. This requires improved methods to identify the competent embryo. Here, we describe such a test, based on flow cytometric determination of the nucleic acid (PI+) containing extracellular vesicle (EV) count in day 5 embryo culture media. 88 women undergoing IVF were included in the study. More than 1 embryos were transferred to most patients. In 58 women, the transfer resulted in clinical pregnancy, whereas in 30 women in implantation failure. In 112 culture media of embryos from the "clinical pregnancy" group, the number of PI+ EVs was significantly lower than in those of 49 embryos, from the "implantation failure" group. In 14 women, transfer of a single embryo resulted in a singleton pregnancy, or, transfer of two embryos in twin pregnancy. The culture media of 19 out of the 20 "confirmed competent" embryos contained a lower level of PI+ EVs than the cut off level, suggesting that the competent embryo can indeed be identified by low PI+ EV counts. We developed a noninvasive, simple, inexpensive, quick test, which identifies the embryos that are most likely to implant

Role of radiography, MRI and FDG-PET/CT in diagnosing, staging and therapeutical evaluation of patients with multiple myeloma

Multiple myeloma is a malignant B-cell neoplasm that involves the skeleton in approximately 80% of the patients. With an average age of 60 years and a 5-years survival of nearly 45% Brenner et al. (Blood 111:2516–2520, 35) the onset is to be classified as occurring still early in life while the disease can be very aggressive and debilitating. In the last decades, several new imaging techniques were introduced. The aim of this review is to compare the different techniques such as radiographic survey, multidetector computed tomography (MDCT), whole-body magnetic resonance imaging (WB-MRI), fluorodeoxyglucose positron emission tomography- (FDG-PET) with or without computed tomography (CT), and 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy. We conclude that both FDG-PET in combination with low-dose CT and whole-body MRI are more sensitive than skeleton X-ray in screening and diagnosing multiple myeloma. WB-MRI allows assessment of bone marrow involvement but cannot detect bone destruction, which might result in overstaging. Moreover, WB-MRI is less suitable in assessing response to therapy than FDG-PET. The combination of PET with low-dose CT can replace the golden standard, conventional skeletal survey. In the clinical practise, this will result in upstaging, due to the higher sensitivity

The community impact of the 2009 influenza pandemic in the WHO European Region: a comparison with historical seasonal data from 28 countries

Contains fulltext : 109779.pdf (publisher's version ) (Open Access)BACKGROUND: The world has recently experienced the first influenza pandemic of the 21st century that lasted 14 months from June 2009 to August 2010. This study aimed to compare the timing, geographic spread and community impact during the winter wave of influenza pandemic A (H1N1) 2009 to historical influenza seasons in countries of the WHO European region. METHODS: We assessed the timing of pandemic by comparing the median peak of influenza activity in countries of the region during the last seven influenza seasons. The peaks of influenza activity were selected by two independent researchers using predefined rules. The geographic spread was assessed by correlating the peak week of influenza activity in included countries against the longitude and latitude of the central point in each country. To assess the community impact of pandemic influenza, we constructed linear regression models to compare the total and age-specific influenza-like-illness (ILI) or acute respiratory infection (ARI) rates reported by the countries in the pandemic season to those observed in the previous six influenza seasons. RESULTS: We found that the influenza activity reached its peak during the pandemic, on average, 10.5 weeks (95% CI 6.4-14.2) earlier than during the previous 6 seasons in the Region, and there was a west to east spread of pandemic A(H1N1) influenza virus in the western part of the Region. A regression analysis showed that the total ILI or ARI rates were not higher than historical rates in 19 of the 28 countries. However, in countries with age-specific data, there were significantly higher consultation rates in the 0-4 and/or 5-14 age groups in 11 of the 20 countries. CONCLUSIONS: Using routine influenza surveillance data, we found that pandemic influenza had several differential features compared to historical seasons in the region. It arrived earlier, caused significantly higher number of outpatient consultations in children in most countries and followed west to east spread that was previously observed during some influenza seasons with dominant A (H3N2) ifluenza viruses. The results of this study help to understand the epidemiology of 2009 influenza pandemic and can be used for pandemic preparedness planning