Search

Background In the past decade, catheter ablation (CA) has become a rapidly expanding treatment option for ventricular tachycardia (VT), however it is not commonly utilized for patients with post-myocarditis VT. We aimed to systematically review up-to-date evidence regarding feasibility, effectiveness, and safety of CA, with a specific focus on long-term relapse rate and procedural complications. Methods A structured electronic database search (PubMed, Embase, Cochrane) of the scientific literature was performed for studies describing outcomes at up to 7.3 years after CA. The primary outcome measured was VT recurrence post-ablation. Procedural success was defined as freedom of ventricular arrhythmias (at the end of follow-up after an ablation procedure). The secondary outcome was significant procedural complications which included procedural death, stroke, cardiac tamponade, acute myocardial infarction, major vascular complications, and major bleeding, assessed on a study-by-study basis. Results A total of 186 patients were included in analysis with most patients (88%) being male. Over the follow up period there was a 18% relapse rate (n=34) (Confidence Interval (CI); 0.12–0.24, I2≈0, p=0.77) with the majority of patients remaining VT free for the duration of follow up. Only one study recorded the percentage of re-do procedures. The overall procedural complication rate was 3.0% (n=7, (CI; 0.01–0.07, I2≈0, p=0.44) and of note, there were no peri-procedural deaths or heart transplant surgeries reported. However, a single study reported a mortality of 10% (n=2) during the follow up period. Conclusions CA is an effective and durable long-term therapeutic strategy for post myocarditis VT patients with limited relapse rate and very low complication rates based on these non-randomised data. Larger randomised-controlled trials with standardised treatment and long follow-up are required to compare CA versus conventional treatment in the post-acute myocardial phase. Funding Acknowledgement Type of funding sources: None. Relapse rate during follow-upProcedural complication rate

To enable the planned rapid growth of both government and private operators in space, including satellites, space tourism and manned missions to the Moon and to Mars, a realistic and holistic approach to radiation risk reduction is needed. In deep space, ionizing radiation from Galactic Cosmic Rays (GCRs), which originate outside the solar system and Solar Energetic Particles (SEPs) from the sun pose a critical threat to human life and equipment. The composition and energy spectra of the radiation from these two sources are different and must be considered separately. GCRs provide a chronic, slowly varying, highly energetic background source of High-Z high-Energy (HZE) particles, while the Sun's activity varies with an 11-year cycle during which the Sun produces Solar Wind (SW) at varying intensities. The SW influences GCRs, since the GCRs are at maximum intensity during solar minimum when the decreased intensity of the solar wind causes less attenuation. In addition to the SW, there are solar events such as solar flares and coronal mass ejections (CMEs), which increase during solar max. These events give rise to SEPs, which pose a danger both to humans and electronics in space. It is therefore very important to be able to predict, forecast and measure the SEPs to apply the best possible protection for humans and electronics. Currently, the only proven and practical countermeasure to reduce the exposure to GCRs and SEPs is passive shielding. However, the presence of passive shielding does not always reduce the radiation risks for HZE particle exposure, e.g. metal shielding can increase the effective dose behind the shielding. The basic physics to estimate the shielding efficiency is straightforward as the energy loss of heavy ions in the shield is caused by electron and nuclear interactions, which can be approximated by simple stopping power and total reaction cross section formulas. It is therefore easy to show that a hydrogen rich material is best for charge particle protection. To increase shielding against secondary neutrons, the shielding material should also contain additives with high neutron capture cross section, e.g. Boron-10. Cosmic Shielding Corporation (CSC) provides the first holistic commercial solution to radiation risk reduction for both humans and electronics. CSC can predict SEPs using a modified version of MAG4 program, developed for the NASA Space Radiation Analysis Group (SRAG), which gives the likelihood of major solar flares, CMEs, and SEPs occurring up to 48 hours in advance. Furthermore, simulations of radiation transport through the spacecraft material, electronics and crew can be performed to estimate what possible damage an event can cause. Finally, we offer an improved version of a state-of-the-art, ultra-high molecular weight (UHMW) polyethylene composite material RFX-1, developed by NASA and assigned to CSC, which can either act as the main structural element of a spacecraft or habitat, or as a shielding layer on top of other structural materials. The improved version of RFX-1 is a lightweight Polyethylene composite with multifunctional strength, thermal management, ballistic impact resistance, low flammability, a high melting point and almost three times higher Ultimate Tensile Strength (UTS) then traditional Al alloys used in spacecraft. We also offer sophisticated embedded radiation detectors systems and Fiber-Optic Bragg Grating sensors for real time Prognostics and Health Management (PHM) of the shielding efficiency and mechanical strength.

The collagenase subfamily of matrix metalloproteinases (MMPs) have important roles in the remodeling of collagenous matrices. The proteinase-activated receptor (PAR) family has a unique mechanism of activation requiring proteolysis of an extracellular domain forming a neo-N terminus that acts as a tethered ligand, a process that has been associated with the development of arthritis. Canonical PAR2 activation typically occurs via a serine proteinase at Arg(36)-Ser(37), but other proteinases can cleave PARs downstream of the tethered ligand and “disarm” the receptor. To identify additional cleavage sites within PAR2, we synthesized a 42-amino-acid peptide corresponding to the extracellular region. We observed that all three soluble MMP collagenases, MMP-1, MMP-8, and MMP-13, cleave PAR2 and discovered a novel cleavage site (Ser(37)-Leu(38)). Metalloproteinases from resorbing bovine nasal cartilage and recombinant human collagenases could cleave a quenched fluorescent peptide mimicking the canonical PAR2 activation region, and kinetic constants were determined. In PAR2-overexpressing SW1353 chondrocytes, we demonstrated that the activator peptide SLIGKV-NH(2) induces rapid calcium flux, inflammatory gene expression (including MMP1 and MMP13), and the phosphorylation of extracellular signal-regulated kinase (ERK) and p38 kinase. The corresponding MMP cleavage-derived peptide (LIGKVD-NH(2)) exhibited no canonical activation; however, we observed phosphorylation of ERK, providing evidence of biased agonism. Importantly, we demonstrated that preincubation with active MMP-1 reduced downstream PAR2 activation by a canonical activator, matriptase, but not SLIGKV-NH(2). These results support a role for collagenases as proteinases capable of disarming PAR2, revealing a mechanism that suppresses PAR2-mediated inflammatory responses.

Many catabolic stimuli, including interleukin-1 (IL-1) in combination with oncostatin M (OSM), promote cartilage breakdown via the induction of collagen-degrading collagenases such as matrix metalloproteinase 1 (MMP1) and MMP13 in human articular chondrocytes. Indeed, joint diseases with an inflammatory component are characterised by excessive extracellular matrix (ECM) catabolism. Importantly, protein kinase C (PKC) signalling has a primary role in cytokine-induced MMP1/13 expression, and is known to regulate cellular functions associated with pathologies involving ECM remodelling. At present, substrates downstream of PKC remain undefined. Herein, we show that both IL-1- and OSM-induced phosphorylation of protein kinase D (PKD) in human chondrocytes is strongly associated with signalling via the atypical PKCι isoform. Consequently, inhibiting PKD activation with a pan-PKD inhibitor significantly reduced the expression of MMP1/13. Specific gene silencing of the PKD isoforms revealed that only PKD3 (PRKD3) depletion mirrored the observed MMP repression, indicative of the pharmacological inhibitor specifically affecting only this isoform. PRKD3 silencing was also shown to reduce serine phosphorylation of signal transducer and activator of transcription 3 (STAT3) as well as phosphorylation of all three mitogen-activated protein kinase groups. This altered signalling following PRKD3 silencing led to a significant reduction in the expression of the activator protein-1 (AP-1) genes FOS and JUN, critical for the induction of many MMPs including MMP1/13. Furthermore, the AP-1 factor activating transcription factor 3 (ATF3) was also reduced concomitant with the observed reduction in MMP13 expression. Taken together, we highlight an important role for PKD3 in the pro-inflammatory signalling that promotes cartilage destruction.

Increasing evidence implicates serine proteinases in the proteolytic cascades leading to the pathological destruction of extracellular matrices such as cartilage in osteoarthritis (OA). We have previously demonstrated that the type II transmembrane serine proteinase (TTSP) matriptase acts as a novel initiator of cartilage destruction via the induction and activation of matrix metalloproteinases (MMPs). Hepsin is another TTSP expressed in OA cartilage such that we hypothesized this proteinase may also contribute to matrix turnover. Herein, we demonstrate that addition of hepsin to OA cartilage in explant culture induced significant collagen and aggrecan release and activated proMMP-1 and proMMP-3. Furthermore, hepsin directly cleaved the aggrecan core protein at a novel cleavage site within the interglobular domain. Hepsin expression correlated with synovitis as well as tumour necrosis factor α expression, and was induced in cartilage by a pro-inflammatory stimulus. However, a major difference compared to matriptase was that hepsin demonstrated markedly reduced capacity to activate proteinase-activated receptor-2. Overall, our data suggest that hepsin, like matriptase, induces potent destruction of the extracellular matrix whilst displaying distinct efficiencies for the cleavage of specific substrates.

Interpreting spatial patterns in the abundance of species over time is a fundamental cornerstone of ecological research. For many species, this type of analysis is hampered by datasets that contain a large proportion of zeros, and data that are overdispersed and spatially autocorrelated. This is particularly true for insects, for which abundance data can fluctuate from zero to many thousands in the space of weeks. Increasingly, an understanding of the ways in which environmental variation drives spatial and temporal patterns in the distribution, abundance and phenology of insects is required for management of pests and vector-borne diseases. In this study, we combine the use of smoothing techniques and generalised linear mixed models to relate environmental drivers to key phenological patterns of two species of biting midges, Culicoides pulicaris and C. impunctatus, of which C. pulicaris has been implicated in transmission of bluetongue in Europe. In so doing, we demonstrate analytical tools for linking the phenology of species with key environmental drivers, despite using a relatively small dataset containing overdispersed and zero-inflated data. We demonstrate the importance of landcover and climatic variables in determining the seasonal abundance of these two vector species, and highlight the need for more empirical data on the effects of temperature and precipitation on the life history traits of palearctic Culicoides spp. in Europe.

Since the early 20th century, much of the urban history of medieval and early modern Scotland has focused on the purpose behind, and functionality of, the pre-modern burgh. As a result of contemporary urban concerns, in the 1970s scholars began to ask new questions of the surviving documentary sources and engage cartographic, geographical and archaeological evidence. As a result of newer interdisciplinary approaches to the field, the 1980s and 1990s witnessed a growing interest in pre-modern burghs as more than trade hubs and administrative centres; they were increasingly seen as places where individuals lived, worked and prayed. But while this ‘urban aspect of local history’ received attention from urban historians of Scotland, very little research has been undertaken in the areas of urbanization, urban networks and urban hierarchies since two important articles were published in 1989 and 1992. This article surveys the development of the field of pre-modern Scottish urban history and traces the impact made by other disciplines.

Advanced cervical cancer continues to present a major health care challenge in the developing world. In contrast, in our own culture, the incidence of the disease is falling. However, the condition is presenting at an earlier stage and to younger patients who may wish to preserve their fertility, if possible. The traditional treatment, of radical surgery with adjuvant chemo-radiotherapy or primary chemo-radiotherapy, conflicts with such wishes. Therefore, techniques have been developed in the last 10 years, which aim to preserve fertility without compromising clinical outcome. The newer techniques, which have been evaluated range from cone biopsy with or without lymphadenectomy through to radical trachelectomy. The latter technique is accumulating evidence of satisfactory oncological outcome, acceptable complication data and successful maternity outcome. However, the obstetric course for these patients is not guaranteed or straightforward. Most recently, treatments incorporating pre-operative chemotherapy followed by cone biopsy with lymphadenectomy have been described. Such a policy is likely to produce more obstetric gains but it must not be at the expense of oncological outcome, unless requested by the patient. The need for consistent high-quality imaging, histopathology and clinical decision-making supports the concept that such care should only be developed and available in highly specialized centres. The requirement for comprehensive data collection and follow up of oncological variables, obstetric outcome and complication rates should be mandatory. New more conservative methods should only be developed under strict scientific control, using the traditional methods as comparators. However, it is possible that such fertility preserving techniques may be very attractive to some patients, even if they are increasing their risk of recurrent cervical cancer.

As a profession, we have an ethical responsibility to improve standards of clinical care and performance. Revalidation provides a new method to achieve such an aspiration. To achieve this, an emphasis on the development of robust outcome measures is vital. The needs of the patient are central to all these developments and the fundamental principle of good medical practice should underwrite our professionalism.

ALAN D. FALCONER (**) Impulses for the study on "The Nature and Purpose of the Church" In the responses of the churches to the Faith and Order study Baptism, Eucharist, Ministry (BEM), many church commissions detected that there had been an implicit ecclesiology, and called for a more explicit and focused study on the church. (1) While BEM itself had not specifically addressed the nature, purpose or form of the church, affirmations in each section of the statement about the church led readers to suggest that a baptismal or eucharistic ecclesiology was an implicit framework for the text, and that the threefold ministry as evident in some Christian traditions was being proposed as a sine qua non of the church. In the light of those reactions, the Plenary Commission on Faith and Order, meeting in Budapest in 1989, proposed that the overall programme of Faith and Order (F&O) should focus on "The Nature and Mission of the Church - Ecumenical Perspectives of Ecclesiology". (2) The commission felt that such a study might provide a coherent and comprehensive ecclesiological framework for the studies on BEM, apostolic faith, and unity and renewal being undertaken by the commission. The study might also respond to some of the critical comments to BEM, and could draw on the increasing ecumenical discussions on the understanding of the church evident in a number of international bilateral dialogues. (3) The recommendation was that previous work on the topic be brought into consideration alongside that on koinonia, which was the subject of a number of bilateral dialogues, to provide basic ecumenical perspectives on ecclesiology which could serve as an impetus for the renewal and enrichment of the ecclesiologies of the differe nt Christian traditions, and thus for their convergence in the movement towards visible unity. Various themes for the development of the study were suggested - the church as the body of Christ, the temple of the Spirit, the people of God, the kingdom of God and the covenant. The intention was therefore not to develop a detailed ecclesiological system or even an "ecumenical ecclesiology". The commission also found itself seeking to articulate for the Canberra assembly of the World Council of Churches (WCC) a statement on "The Church as koinonia: Gift and Calling". This statement, which was adopted at the assembly after a number of emendations, had been a response to a request from the central committee of the WCC. The statement begins with a reflection on the purpose of the church, rooted in the action of the Holy Trinity. It notes that the unity of the church to which we are called is a koinonia given and expressed in faith, worship, ministry and life, and then identifies a number of common actions which might help the churches to realize more faithfully the character and purposes of the church. (4) A further reflection on koinonia also emerged from a series of essays published by the Joint Working Group between the WCC and the Roman Catholic Church. This was designed as an interpretative study on the Canberra text, setting it in the context of previous ecumenical statements on unity. It was also to be a contribution to the Fifth World Conference on Faith and Order in Santiago de Compostela, August 1993. (5) After the Canberra assembly, the major work undertaken by the F&O Commission was the organization of the Fifth World Conference on Faith and Order. This was the first such conference for thirty years, and also the first to draw on the fruits of full Roman Catholic participation in the ecumenical movement. The major theme was that of koinonia, and the conference sought to reflect on the theological and biblical understanding of koinonia, and on koinonia in faith, life and witness. A preparatory discussion paper was prepared and examined in a number of regional conferences. (6) The conference itself explored the importance of an understanding of the Holy Trinity for an understanding of koinonia, and called for a study on the nature of the church -- a community confessing the one faith to God's glory, sharing sacramental and ministerial life, and engaging in common witness. …

Millennium Development Goal 5 incorporates targets related to improving maternal mortality in resource poor countries with universal access to reproductive healthcare. The complex interrelationship between causation and solution of these problems is expounded together with strategies of care. Healthcare modelling based on the provision of skilled birth attendants and emergency obstetric care facilities will reduce the terrible tragedy of maternal mortality. Currently 500,000 women die annually in childbirth, and the majority of these deaths are avoidable. The large majority occur in resource poor countries. With the current slow progress, it is unlikely that the necessary improvement will be achieved by 2015. Major initiatives aimed at education, increasing workforce and improving local facilities and availability of drugs will help. The solutions are simple, but progress requires political desire.

We present a system architecture for a broadband indoor wireless digital communications system, capable of supporting ATM at transport bit rates up to about 160 Mb/s for broadband LANs. Access is via a radio system with carrier frequencies within the 20 to 60 GHz range, because of the relative abundance of available bandwidth in this range. The system design is shaped by a set of service requirements, by the characteristics of indoor millimeter wave radio channels, and by the constraints and opportunities of the relevant device technologies. The design includes a multi-access microcellular architecture accommodating ATM traffic with a wide range of broadband and narrowband bit rates and services in an office environment. A modern configuration incorporating bandwidth spreading, signal processing, and coding measures to provide immunity to the effects of radio channel fading, multipath, shadowing, interference and noise, and millimeter-wave component limitations has been developed. The architecture exploits millimeter-wave and SAW device technologies to design and realize the various transceiver components in low-cost, low-power monolithic and/or hybrid form.

Culicoides biting midges (Diptera: Ceratopogonidae) vector a wide variety of internationally important arboviral pathogens of livestock and represent a widespread biting nuisance. This study investigated the influence of landscape, host and remotely-sensed climate factors on local abundance of livestock-associated species in Scotland, within a hierarchical generalized linear model framework. The Culicoides obsoletus group and the Culicoides pulicaris group accounted for 56% and 41%, respectively, of adult females trapped. Culicoides impunctatus Goetghebuer and C. pulicaris s.s. Linnaeus were the most abundant and widespread species in the C. pulicaris group (accounting for 29% and 10%, respectively, of females trapped). Abundance models performed well for C. impunctatus, Culicoides deltus Edwards and Culicoides punctatus Meigen (adjusted R(2) : 0.59-0.70), but not for C. pulicaris s.s. (adjusted R(2) : 0.36) and the C. obsoletus group (adjusted R(2) : 0.08). Local-scale abundance patterns were best explained by models combining host, landscape and climate factors. The abundance of C. impunctatus was negatively associated with cattle density, but positively associated with pasture cover, consistent with this species' preference in the larval stage for lightly grazed, wet rush pasture. Predicted abundances of this species varied widely among farms even over short distances (less than a few km). Modelling approaches that may facilitate the more accurate prediction of local abundance patterns for a wider range of Culicoides species are discussed.

INTRODUCTION: The maternal mortality ratio (MMR) is a key indicator for measurement of progress against Millennium Development Goal 5 (MDG 5). For many countries especially those with a presumed high number of maternal deaths only estimates are available. SOURCES OF DATA: Recent global estimates and the reasons for high maternal mortality are reviewed. AREAS OF AGREEMENT: There is international consensus that efforts to reduce maternal mortality globally need to be intensified. AREAS OF CONTROVERSY: Many countries lack accurate data on number of deaths in women of reproductive age and number of births. Therefore statistical modelling has been used to calculate estimates which generally have wide confidence intervals and may be disputed by individual countries. GROWING POINTS: There is renewed focus on MMR as 2015 approaches. AREAS TIMELY FOR DEVELOPING RESEARCH: There is a need to adapt and implement methods for measuring maternal mortality to generate more accurate estimates. More data on cause of death are needed.

A preliminary analysis of zonally averaged, ozone concentration data obtained from commercial (GASP) aircraft between the equator and 60 deg North indicates that ozone in the upper troposphere exhibits a primary maximum during the spring, and, in middle latitudes, a secondary maximum in the summer of both 1975 and 1976. A late-fall/early-winter minimum also appears and seems consistent with previous upper air measurements. The April ozone maximum has been well documented and appears at the time when the stratospheric ozone content is greatest and cyclogenetic activity is most vigorous. However, the secondary maximum in June has not been widely observed or quoted as a unique feature. It is hypothesized that the rapid ascent of the tropopause between midspring and summer could account for the incorporation of ozone-rich, stratospheric air into the upper troposphere with a subsequent dilution during the following months. This may explain certain aspects of the annual ozone cycle in the lower troposphere which occasionally exhibit a bimodal distribution during the warm season.

Objective The objective of this study was to assess the impact of reorganisation of gynaecological services in southwest England following adoption of regionally agreed evidence-based guidelines and publication of the National Improving Outcomes Guidance in 1999. Design Prospective audit with cross-checking against histological reports. Setting All 19 acute hospitals in the four Cancer Networks of southwest England. Sample All subjects with squamous or verrucous vulval cancer diagnosed between 1997 and 2002. Method A one-page minimum data set proforma agreed by the South West Gynaecology Tumour Panel was completed by surgeons after treatment of each patient, and was sent to South West Cancer Intelligence Service for entry, collation and analysis. Data are presented for the years 1997 to 2002 inclusive, and comparisons were made between each of the three 2-year cohorts. Main outcome measures These are standards derived from the guidance. Results There were 436 squamous or verrucous vulval cancers registered. Recording of staging was missing in 20% of subjects. The percentage of subjects operated upon by lead gynaecological cancer surgeons increased from 78% in cohort 1 to 93% in cohort 3 (P < 0.001). There is a trend towards more conservative operations, which have lower co-morbidity. High activity surgeons achieved better rates of tumour-free skin margins, but even these were adequate only in 49% of operations. Lymphadenectomy rates did not follow guidance. Conclusion Centralisation of care of this rare cancer should continue, but specialists need to increase their efforts to ensure adequate skin margins and lymphadenectomy rates while balancing morbidity and the likelihood of recurrence in both fit and frail patients.

Summary In this study, we evaluated the management of postmenopausal bleeding at our one-stop clinic where the first line investigations were a transvaginal ultrasound scan and a pipelle endometrial biopsy. The records of 212 women seen in this clinic in 1994 were reviewed. One hundred and forty-four women (67.9%) were evaluated and reassured in one visit. The mean waiting period following referral to the clinic by the general practitioner was 36 days (range 6-157 days), and only 45 women (21%) required a hysteroscopy. The commonest diagnosis made was endometrial atrophy or no significant endometrial pathology (130 women (61.3%). Endometrial cancer was diagnosed in 12 women (5.6%), and one case of previously unsuspected ovarian cancer was detected. Our findings show that most women with post-menopausal bleeding can be assessed in one visit, and hysteroscopy is not always necessary in the initial assessment of this complaint.

Wireless bandwidth is a limited and scarce shared resource in MANETs. In our work, we are interested in the "end-to-end capacity" of the network, which we define to be the sum of the throughputs for each flow. This represents the service a network provides to its users. In this paper, we propose a routing protocol, called TB for traffic balancing, which increases the end-to-end capacity by more aggressively routing data through underutilized areas of a MANET. Simulation results show that TB performs better than other load-balancing protocols proposed in the literature. We also compare the experimental performance against lower bounds of maximum end-to-end capacity, discuss reasons for the performance gap, and identify possible future improvements to the protocol.

Several access points may be put into wireless ad hoc networks for people connecting to WWW or other Internet services. This kind of wireless network is called wireless mesh networks (WMNs) that still needs users to relay packets for other users. The meshed topology provides good reliability, market coverage, and scalability, as well as low upfront investment. However, due to the nature of routing algorithm the traffic load for a access point may be extremely heavy during particular periods while the other access points are in very light load. Consequently, the overall performance of the network are poor even the total traffic load is far below the system capacity. Traffic balancing proposed for wireless ad hoc networks provides an efficient solution to this problem. With right placement of the access points, the performance can be improved dramatically by traffic balancing.

This paper treats analytically and experimentally the response of RLS {Recursive Least Squares} adaptive filters with exponential windows to stationary and nonstationary inputs. A new formula for the "estimation-noise" has been derived involving second- and fourth-order statistics of the filter input as well as the exponential windowing factor and filter length. Under general time-varying conditions it is shown that the time constant associated with "lag effects" depends solely on the exponential weighting parameter λ. In addition the calculation of the excess mean square error due to the lag for an assumed Markov channel provides the necessary information about tradeoffs between speed of adaptation and steady-state error. In the simple case of channel identification it is shown that the LMS and RLS adaptive filters have the same tracking behavior.

The main objective of this research is to investigate, based upon the measured outdoor channel characteristics, if an equalizer is required in the LMCS/LIMDS system receiver over a range of bit rates and if any, then of what type and complexity? Then the viability and complexity of applying maximum likelihood sequence estimation (MLSE) as an alternative to DFE is studied and the error bounds obtained by applying DFE and MLSE are compared.