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We investigated the long-term outcome of patients with proliferative LN treated with CSs and MMF.This was a single-centre retrospective study on patients with biopsy-proven class III/IV ± V LN treated with prednisolone and MMF continuously as both early and maintenance immunosuppression.Sixty-five patients were included, and followed for 91.9 (47.7) months. All received prednisolone and MMF as induction immunosuppression. In 31 patients, maintenance immunosuppression comprised prednisolone and MMF only (MMF-MMF group). MMF was replaced with AZA in 23 patients (MMF-AZA), and with calcineurin inhibitors (CNIs) in 11 patients (MMF-CNI) at sometime during follow-up. Ten-year patient and renal survival rates were 91% and 86%, respectively, and were similar in the three groups. MMF-MMF group showed better relapse-free survival than MMF-AZA and MMF-CNI patients (76% vs 56% vs 43%, respectively at 5 years; 69% vs 32% vs 0%, respectively at 10 years; MMF-MMF vs MMF-AZA or MMF-CNI, P = 0.049 or 0.019, respectively; MMF-AZA vs MMF-CNI, P = 0.490). Patients treated with MMF for24 months had better relapse-free survival than those treated for shorter durations (88% vs 48% at 5 years; 81% vs 28% at 10 years; P0.001). Renal function at 10 years was better in the MMF-MMF group. Anaemia was associated with MMF treatment. Other adverse events were comparable and relatively minor with MMF, AZA or CNI as maintenance.Long-term treatment with CSs and MMF from induction to maintenance phase is associated with relatively favourable long-term outcome in Chinese LN patients. Discontinuation of MMF before 24 months may increase the risk of flares.

Vitamin D deficiency is common globally. There is evidence that vitamin D status may be related to immune function and cardiovascular disease. The vitamin D status of Chinese kidney transplant recipients has never been investigated. We performed a cross-sectional study and measured the level of 25-hydroxyvitamin D [25(OH)D] in 94 Chinese renal transplant recipients with stable allograft function. Vitamin D deficiency and insufficiency were detected in 43.6% and 54.2% of patients, respectively. About 53.2% of the patients also had elevated parathyroid hormone (PTH) levels. The level of 25(OH)D was lower in kidney transplant recipients compared with healthy controls matched for age and sex (52.5 ± 15.6 nmol/L vs. 57.5 ± 19.0 nmol/L, p = 0.05), but the level of serum creatinine was higher in kidney transplant recipients (120.3 ± 48.5 μmol/L and 78.3 ± 15.3 μmol/L, p 0.01). The level of 25(OH)D was negatively correlated with that of PTH (p = 0.001). The latter was associated with serum creatinine (p = 0.001) and duration of dialysis (p = 0.001). Patients with a history of acute rejection showed lower levels of 25(OH)D (45.3 ± 11.9 nmol/L vs. 54.2 ± 16.0 nmol/L, p = 0.003). We conclude that vitamin D deficiency is prevalent among Chinese renal transplant recipients. In view of the potential immunomodulatory effect of vitamin D, the relationship between vitamin D level and rejection and the effect of vitamin D supplementation in renal transplant recipients warrant further investigations.

Past trends of the occurrences of extreme temperature and rainfall events in Hong Kong from 1885 to 2008 were examined using a suite of 27 extreme indices adopted from the core indices developed by the Expert Team on Climate Change Detection, Monitoring and Indices (ETCCDMI) under the auspices of the World Meteorological Organization (WMO), with appropriate modification to suit the sub-tropical climate of Hong Kong. Results showed that the extreme daily maximum and minimum temperatures, annual numbers of very hot days (daily maximum temperature ≥ 33.0 °C) and hot nights (daily minimum temperature ≥ 28.0 °C) as well as the warm spell duration index (WSDI) in Hong Kong exhibited statistically significant long-term rising trends, whereas the annual number of cold days (daily minimum temperatures ≤ 12.0 °C) and cold spell duration (CSDI) index had a statistically significant decreasing trend. Regarding rainfall, the frequency of occurrence of extreme hourly, 2- and 3-hourly rainfall amounts increased significantly. The fraction of annual total precipitation due to events exceeding the daily 95th percentile of the climatological normal (1971–2000) increased by 22 mm per decade in the same period, indicating that the contribution of heavy rain to the annual rainfall amount was increasing with time. However, the maximum length of dry spell in the summer months from April to September increased at a rate of 0.3 days per decade from 1885 to 2008. Using the time-dependent generalized extreme value (GEV) distribution technique, the return period for the daily minimum temperature of 4 °C or lower had significantly lengthened from 6 years in 1900 to 163 years in 2000. The return period for an hourly rainfall of 100 mm or more had shortened from 37 years in 1900 to 18 years in 2000. Copyright © 2010 Royal Meteorological Society

Summary Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons that results in progressive weakness and death from respiratory failure, commonly within about 3 years. Previous studies have shown association of a locus on chromosome 9p with ALS and linkage with ALS–frontotemporal dementia. We aimed to test whether this genomic region is also associated with ALS in an independent set of UK samples, and to identify risk factors associated with ALS in a further genome-wide association study that combined data from the independent analysis with those from other countries. Methods We collected samples from patients with sporadic ALS from 20 UK hospitals and obtained UK control samples from the control groups of the Depression Case Control study, the Bipolar Affective Case Control Study, and the British 1958 birth cohort DNA collection. Genotyping of DNA in this independent analysis was done with Illumina HumanHap550 BeadChips. We then undertook a joint genome-wide analysis that combined data from the independent set with published data from the UK, USA, Netherlands, Ireland, Italy, France, Sweden, and Belgium. The threshold for significance was p=0·05 in the independent analysis, because we were interested in replicating a small number of previously reported associations, whereas the Bonferroni-corrected threshold for significance in the joint analysis was p=2·20×10 −7 Findings After quality control, samples were available from 599 patients and 4144 control individuals in the independent set. In this analysis, two single nucleotide polymorphisms in a locus on chromosome 9p21.2 were associated with ALS: rs3849942 (p=2·22×10 −6 ; odds ratio [OR] 1·39, 95% CI 1·21–1·59) and rs2814707 (p=3·32×10 −6 ; 1·38, 1·20–1·58). In the joint analysis, which included samples from 4312 patients with ALS and 8425 control individuals, rs3849942 (p=4·64×10 −10 ; OR 1·22, 95% CI 1·15–1·30) and rs2814707 (p=4·72×10 −10 ; 1·22, 1·15–1·30) were associated with ALS. Interpretation We have found strong evidence of a genetic association of two single nucleotide polymorphisms on chromosome 9 with sporadic ALS, in line with findings from previous independent GWAS of ALS and linkage studies of ALS–frontotemporal dementia. Our findings together with these earlier findings suggest that genetic variation at this locus on chromosome 9 causes sporadic ALS and familial ALS–frontotemporal dementia. Resequencing studies and then functional analysis should be done to identify the defective gene. Funding ALS Therapy Alliance, the Angel Fund, the Medical Research Council, the Motor Neurone Disease Association of Great Britain and Northern Ireland, the Wellcome Trust, and the National Institute for Health Research Dementias and Neurodegenerative Diseases Research Network (DeNDRoN).

Aedes albopictus, which can transmit Dengue fever, is one of the common mosquitoes in Hong Kong. To study the effect of weather on the abundance of Aedes mosquitoes in Hong Kong, ovitraps were set up at an unperturbed experimental site for a period of 7 days every month to record the Ovitrap Index, an often-adopted parameter to indicate the abundance of mosquitoes at a site, from July 2007 to June 2009. Analysis of the Ovitrap Indices at the experimental site and the weather elements collected from a nearby automatic weather station in the same period showed that the Ovitrap Indices were highly correlated with the mean air temperature over a 22 day period comprising the preceding 15 days and the 7 days when the ovitraps were in place, as well as the total rainfall over the 15 day period prior to the setting up of the ovitraps. A Climate Aedes Mosquitoes Abundance Model was developed based on the observations to predict the abundance of Aedes mosquitoes in Hong Kong. The model can provide a useful tool for planning of preventive and control measures against Aedes mosquitoes in Hong Kong. Copyright © 2010 Royal Meteorological Society

Western social media platforms like Facebook, YouTube, etc are banned in China. In their places, Weibo, WeChat, Youku and more are the main social media channels in China and thus the main battlefields of social marketing for brands entering China Market. WeChat is the largest social network in China, with over 900 million users daily, for nearly all types of services, including booking flights, restaurant table reservation, shopping, paying bills, etc. To cater the needs of the new generation of Chinese digital natives, a mobile app eM++ was developed that creates new customer services and enables tailored fashion marketing. This new mobile app eM++ works well in China, will this be also well received in other countries? This research investigates consumers’ perception of this new fashion e-tailoring e-shopping concept in UK. Will this type of e-tailored services be welcome in UK? Will consumers welcome this type of e-shopping service in UK? Or they prefer the traditional way of tailoring and shopping? Which social media platforms should be used for promotion? The sample population of this research covers both male and females from China and UK aged 18 years old or above with experience of searching and/or buying clothing items online. Convenient sampling and snow-balling sampling methods are used. In UK, recruitment of volunteers for this project will be via emails to colleagues and previous students, as well as via posters of recruiting volunteers for this project posted on campus. Details of the project and experiment will be included in both emails and posters. Volunteered participants are asked to answer a pre-experiment online questionnaire. Based on their answers, suitable participants will be invited to participate the experimental part (which is trying a fashion app and then answer the post-experiment questionnaire). Participants successfully completed the experiment and post-experiment questionnaire will be given their own body measurements with a 3D model in user’s customised shape, as well as a discount coupon for future use when the app is officially launched. This research will have mainly quantitative data analysis, SPSS will be used to analyse the data. There will have a few open-ended questions that qualitative data analysis method will be employed. This research will explore the feasibility of this service in UK and formulate a cross-cultural comparison between China and UK.

Background: Amiodarone-induced thyrotoxicosis (AIT) is a clinical condition that is notoriously difficult to manage; the relative risk of adverse cardiovascular events in these patients compared with euthyroid patients is largely unknown. Objective: We compared the clinical characteristics and major adverse cardiovascular events (MACE) in AIT and euthyroid patients. Method: Patients at a tertiary referral center who had been prescribed amiodarone for at least 3 months were retrospectively analyzed. Baseline clinical characteristics, laboratory parameters, and outcome events were evaluated. MACE was defined as cardiovascular mortality, myocardial infarction, stroke and heart failure, or ventricular arrhythmias that required hospitalization. Results: A total of 354 patients (61.8 ± 14.1 yr; 64.7% male) with a mean follow-up of 48.6 ± 26.7 months were studied. AIT, euthyroid status, and amiodarone-induced hypothyroidism were identified in 57 (16.1%), 224 (63.3%), and 73 (20.6%) patients, respectively. No differences in baseline clinical characteristics were observed between AIT and euthyroid patients. Nonetheless AIT patients demonstrated a higher MACE rate (31.6 vs. 10.7%, P < 0.01), mostly driven by a higher rate of ventricular arrhythmias that required admission (7.0 vs. 1.3%, P = 0.03). Cox-regression multivariate analysis revealed that AIT (hazard ratio 2.68; confidence interval 1.53–4.68; P < 0.01) and left ventricular ejection fraction less than 45% (hazard ratio 2.52; confidence interval 1.43–4.42; P < 0.01) were independent predictors of MACE. Conclusion: In patients prescribed long-term amiodarone therapy, occurrence of AIT is associated with a 2.7-fold increased risk of MACE. Regular and close biochemical surveillance is thus advisable to identify and treat this high-risk group of patients.

Although the 2003 severe acute respiratory syndrome (SARS) outbreak was controlled, repeated transmission of SARS coronavirus (CoV) over several years makes the development of a SARS vaccine desirable. We performed a comparative evaluation of two SARS vaccines for their ability to protect against live SARS-CoV intranasal challenge in ferrets. Both the whole killed SARS-CoV vaccine (with and without alum) and adenovirus-based vectors encoding the nucleocapsid (N) and spike (S) protein induced neutralizing antibody responses and reduced viral replication and shedding in the upper respiratory tract and progression of virus to the lower respiratory tract. The vaccines also diminished haemorrhage in the thymus and reduced the severity and extent of pneumonia and damage to lung epithelium. However, despite high neutralizing antibody titres, protection was incomplete for all vaccine preparations and administration routes. Our data suggest that a combination of vaccine strategies may be required for effective protection from this pathogen. The ferret may be a good model for SARS-CoV infection because it is the only model that replicates the fever seen in human patients, as well as replicating other SARS disease features including infection by the respiratory route, clinical signs, viral replication in upper and lower respiratory tract and lung damage.

Plasma loops in solar active regions have been observed in EUV and soft X-rays for decades. Their formation mechanism and properties, however, are still not fully understood. Predictions by early models, based on 1D hydrostatic equilibria with uniform plasma heating, are not consistent with high-resolution measurements. In this Letter, we demonstrate, via 3D simulations, that a class of heating models can lead to the dynamic formation of plasma loops provided the plasma is heated sufficiently to match SXT soft X-ray measurements. We show that individual flux tubes in a 3D magnetic structure tend to stand out against their neighbors. The loops have large aspect ratios and nearly uniform cross sections in the corona, similar to those observed by EIT and TRACE. The coronal EUV emission from these thermally unstable solutions is roughly consistent with EIT measurements. The solution oscillates in time through a large-amplitude, nonlinear cycle, leading to repeated brightening and fading of the loops.

Summary Fungal contamination occurred on the salted Amazonian fish Osteoglossum bicirrhosum which were air dried in the shade. The human pathogenic fungus Exophiala werneckii was recovered as the sole contaminant from all salted fish. It was implicated for the first time as a halophilic saprophyte causing food spoilage.

OBJECTIVE To examine the effectiveness of Integrated Care and Discharge Support for elderly patients in reducing accident and emergency department attendance, acute hospital admissions, and hospital bed days after discharge. Factors that compromise its effectiveness were investigated and cost analysis was performed. DESIGN Cohort prospective study. SETTING Integrated Care and Discharge Support for elderly patients in Hong Kong West Cluster. PARTICIPANTS Home-dwelling patients recruited between April 2012 and March 2013 into Integrated Care and Discharge Support for elderly patients in Hong Kong West Cluster. RESULTS A total of 1090 older patients were studied. The Integrated Care and Discharge Support for elderly patients programme reduced accident and emergency department attendance by 40% (P

Two different severe acute respiratory syndrome (SARS) vaccine strategies were evaluated for their ability to protect against live SARS coronavirus (CoV) challenge in a murine model of infection. A whole killed (inactivated byβ-propiolactone) SARS-CoV vaccine and a combination of two adenovirus-based vectors, one expressing the nucleocapsid (N) and the other expressing the spike (S) protein (collectively designated Ad S/N), were evaluated for the induction of serum neutralizing antibodies and cellular immune responses and their ability to protect against pulmonary SARS-CoV replication. The whole killed virus (WKV) vaccine given subcutaneously to 129S6/SvEv mice was more effective than the Ad S/N vaccine administered either intranasally or intramuscularly in inhibiting SARS-CoV replication in the murine respiratory tract. This protective ability of the WKV vaccine correlated with the induction of high serum neutralizing-antibody titres, but not with cellular immune responses as measured by gamma interferon secretion by mouse splenocytes. Titres of serum neutralizing antibodies induced by the Ad S/N vaccine administered intranasally or intramuscularly were significantly lower than those induced by the WKV vaccine. However, Ad S/N administered intranasally, but not intramuscularly, significantly limited SARS-CoV replication in the lungs. Among the vaccine groups, SARS-CoV-specific IgA was found only in the sera of mice immunized intranasally with Ad S/N, suggesting that mucosal immunity may play a role in protection for the intranasal Ad S/N delivery system. Finally, the sera of vaccinated mice contained antibodies to S, further suggesting a role for this protein in conferring protective immunity against SARS-CoV infection.

Severe acute respiratory syndrome (SARS) is a recently recognized and highly contagious pneumonic illness, caused by a novel coronavirus. While developments in diagnostic, clinical and other aspects of SARS research are well underway, there is still great difficulty for frontline clinicians as validated rapid diagnostic tests or effective treatment regimens are lacking. This article attempts to summarize some of the recent developments in this newly recognized condition from the Asia Pacific perspective.

Apart from the spatial resolution enhancement, scaling of temporal resolution, equivalently the imaging throughput, of fluorescence microscopy is of equal importance in advancing cell biology and clinical diagnostics. Yet, this attribute has mostly been overlooked because of the inherent speed limitation of existing imaging strategies. To address the challenge, we employ an all-optical laser-scanning mechanism, enabled by an array of reconfigurable spatiotemporally-encoded virtual sources, to demonstrate ultrafast fluorescence microscopy at line-scan rate as high as 8 MHz. We show that this technique enables high-throughput single-cell microfluidic fluorescence imaging at 75,000 cells/second and high-speed cellular 2D dynamical imaging at 3,000 frames per second, outperforming the state-of-the-art high-speed cameras and the gold-standard laser scanning strategies. Together with its wide compatibility to the existing imaging modalities, this technology could empower new forms of high-throughput and high-speed biological fluorescence microscopy that was once challenged.

To the Editor: The purpose of our review[1][1] was to neither promulgate nor suppress the Pharmacy Curriculum Outcomes Assessment (PCOA) examination but rather to review available data and inform the Academy. We appreciate the authors’ rigorous and spirited defense of the examination and explicit

GTP cyclohydrolase 1, encoded by the GCH1 gene, is an essential enzyme for dopamine production in nigrostriatal cells. Loss-of-function mutations in GCH1 result in severe reduction of dopamine synthesis in nigrostriatal cells and are the most common cause of DOPA-responsive dystonia, a rare disease that classically presents in childhood with generalized dystonia and a dramatic long-lasting response to levodopa. We describe clinical, genetic and nigrostriatal dopaminergic imaging ([(123)I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) tropane single photon computed tomography) findings of four unrelated pedigrees with DOPA-responsive dystonia in which pathogenic GCH1 variants were identified in family members with adult-onset parkinsonism. Dopamine transporter imaging was abnormal in all parkinsonian patients, indicating Parkinson's disease-like nigrostriatal dopaminergic denervation. We subsequently explored the possibility that pathogenic GCH1 variants could contribute to the risk of developing Parkinson's disease, even in the absence of a family history for DOPA-responsive dystonia. The frequency of GCH1 variants was evaluated in whole-exome sequencing data of 1318 cases with Parkinson's disease and 5935 control subjects. Combining cases and controls, we identified a total of 11 different heterozygous GCH1 variants, all at low frequency. This list includes four pathogenic variants previously associated with DOPA-responsive dystonia (Q110X, V204I, K224R and M230I) and seven of undetermined clinical relevance (Q110E, T112A, A120S, D134G, I154V, R198Q and G217V). The frequency of GCH1 variants was significantly higher (Fisher's exact test P-value 0.0001) in cases (10/1318 = 0.75%) than in controls (6/5935 = 0.1%; odds ratio 7.5; 95% confidence interval 2.4-25.3). Our results show that rare GCH1 variants are associated with an increased risk for Parkinson's disease. These findings expand the clinical and biological relevance of GTP cycloydrolase 1 deficiency, suggesting that it not only leads to biochemical striatal dopamine depletion and DOPA-responsive dystonia, but also predisposes to nigrostriatal cell loss. Further insight into GCH1-associated pathogenetic mechanisms will shed light on the role of dopamine metabolism in nigral degeneration and Parkinson's disease.

The mechanism of the dynamic emergence of current-carrying magnetic loops into the corona is examined by three-dimensional MHD simulations. By simultaneously modeling the spacetime profiles of the normal components of the emerging magnetic field and current density on the photosphere, we demonstrate that this process can qualitatively reproduce observations that show the emergence of a helically twisted magnetic structure with a suitable field-current combination. The flux-tube structure rises into the initially nearly field-free corona and gradually relaxes into a nearly force-free, steady state, magnetic loop.

Cytotoxic T cells are believed to be an important immune response in HIV infection, both in the initial response to viraemia, and in controlling HIV replication and maintaining clinical stability. We report here the detailed findings in two vertically infected children, from the Edinburgh perinatal cohort. Both were clinically stable for the first 7 years of life. One had vigorous HIV-specific cytotoxic T lymphocyte (CTL) responses, and non-lytic suppression, measured in vitro, while the second had no CTL activity against HIV. Despite her HIV-specific immunity, the first child had a declining CD4 count, and a high and fluctuating viral load, whereas the second child maintained a stable CD4 count, a low viral load and had a virus which could not be cultured in peripheral blood mononuclear cells (PBMC) in vitro. The first child subsequently progressed to AIDS and has now died, while the second remains clinically well. More detailed investigations showed the clinically stable child to be heterozygous for the CCR5 receptor, and to be HLA-B49--both of which markers have been associated with slow HIV disease progression. These findings question the role of CTL in maintaining stable HIV disease, and stress the need for immunological investigations to be considered in the light of the genetic make-up of the patient. They may also reflect a different immunopathogenesis of HIV disease in children compared with adults.

Microleakage associated with a silver-reinforced restorative glass-ionomer cement (Hi-Dense) used with a composite resin (Z100) in a modified Class II bonded-base technique restoration was evaluated. The influence of long-term artificial saliva storage, thermal and load cycling was also determined. Class II composite (Z100) restorations used with a new dental adhesive system (Scotchbond Multi-Purpose Dental Adhesive) were used as controls. Results showed that the bonded-base technique can reduce the leakage observed with the direct composite technique. Thermocycling decreased the leakage at the composite-enamel interface but had no effect on the leakage at the composite-dentine interface or on the leakage patterns of bonded-base restorations. Load cycling had no significant influence on leakage patterns of either type of restorative mode. Storage in artificial saliva resulted in decreased leakage at the composite-enamel interface but had a minor adverse effect at the glass-ionomer-dentine interface.

A dose ratio of 1:1 was recommended for the conversion from Standard-release Tacrolimus (Prograf) to Prolonged-release Tacrolimus (Advagraf). We investigated the trough tacrolimus blood level in Chinese kidney transplant recipients after conversion, including subjects receiving concomitant treatment with diltiazem. Eighteen stable renal allograft recipients were followed prospectively for 12 weeks after conversion from Prograf to Advagraf at the same daily dose. Tacrolimus blood trough level decreased significantly within 8 weeks after conversion (p 0.01). Twelve patients required escalation of the Advagraf dose by 1.10 ± 0.36 mg. For the whole group the daily tacrolimus dose was increased from 0.057 ± 0.032 mg/kg to 0.068 ± 0.033 mg/kg (p 0.0001). At week 12 the daily dose of Advagraf was 127 ± 32% of the original daily dose of Prograf. In the subgroup of patients receiving diltiazem, their tacrolimus trough level decreased significantly after conversion (p = 0.001), and the daily tacrolimus dose was increased from 0.060 ± 0.036 mg/kg to 0.073 ± 0.036 mg/kg (p 0.0001). At week 12, their daily dose of Advagraf was 131 ± 34% of the original daily dose before conversion. To conclude, conversion from Prograf to Advagraf in renal allograft recipients with or without diltiazem co-treatment necessitated an increase in the daily dose by approximately 30% to maintain the target blood trough level unchanged.

Summary form only given. A, pulsed hot dense compact plasma torus (CT) in a Field Reversed Configuration (FRC), of few keV temperature, density (1023-1024) m-3, and a life time of several microseconds is of great interest for fusion research as an alternative to already canonical inertial, magnetic stationary approaches and magnetized target fusion [1-3]. This paper provides a brief description of prototypical experiments on formation of two FRCs, their transport in a sequence of multistage compressions and final collision in the center of device. The goal of this experiment is to test various alternative pulsed power technologies for FRC formation as well as the evolution of formed CTs at higher stored energies. Furthermore, the experiment may provide a preliminary assessment of the feasibility of such a scheme of distributed magnetic compression/acceleration of plasma CTs for controlled thermonuclear fusion. Analysis of first experimental results with stored energy in the 0.5-1 MJ and their comparison with respective computer simulations will be given.

Rotavirus is a leading cause of severe infectious diarrhea in infants and young children aged5 years. Rotavirus infections have minimal to strong seasonality depending on geographical locations. In this study, a comprehensive retrospective analysis was performed to evaluate the association between rotavirus admission and multiple key meteorological variables, including air temperature, relative humidity, atmospheric pressure, and solar radiation over a 15-year period from 1995 to 2009 in Hong Kong. Rotavirus infections were found to show a distinct cyclical pattern with an annual peak in cold season. The weekly number of cases showed the strongest correlation with average air temperature of the previous 7 days (rho=-0.69; P0.0001), followed by atmospheric pressure (rho=+0.67; P0.0001); whereas only weak correlation with relative humidity (rho=-0.252; P0.0001) and solar radiation (rho=-0.312; P0.0001) was observed. Curve fitting regression analysis suggested that the correlation was nonlinear in nature in which the effect was more profound towards lower air temperature and higher atmospheric pressure conditions. In binary logistic regression analysis, a final model that included air temperature (≤ 20°C) and atmospheric pressure (≥ 1,013 hPa) predicted correctly 85.3% and 82.6% of weeks with rotavirus activity above and below the baseline level, respectively. In multivariate Poisson model, air temperature and solar radiation were independent factors associated with the weekly number of rotavirus cases, adjusted for seasonal variation. In summary, the current study provides evidence suggesting that local seasonal activity of rotavirus correlated strongly with air temperature, followed by atmospheric pressure but only minimally with relative humidity in pre-vaccine era.

Pleiotrophin (PTN) is a growth factor with both pro-angiogenic and limited pro-tumorigenic activity. We evaluated the potential for PTN to be used for safe angiogenic gene therapy using the full length gene and a truncated gene variant lacking the domain implicated in tumorigenesis. Mouse myoblasts were transduced to express full length or truncated PTN (PTN or T-PTN), along with a LacZ reporter gene, and injected into mouse limb muscle and myocardium. In cultured myoblasts, PTN was expressed and secreted via the Golgi apparatus, but T-PTN was not properly secreted. Nonetheless, no evidence of uncontrolled growth was observed in cells expressing either form of PTN. PTN gene delivery to myocardium, and non-ischemic skeletal muscle, did not result in a detectable change in vascularity or function. In ischemic hindlimb at 14 days post-implantation, intramuscular injection with PTN-expressing myoblasts led to a significant increase in skin perfusion and muscle arteriole density. We conclude that (1) delivery of the full length PTN gene to muscle can be accomplished without tumorigenesis, (2) the truncated PTN gene may be difficult to use in a gene therapy context due to inefficient secretion, (3) PTN gene delivery leads to functional benefit in the mouse acute ischemic hindlimb model.

We investigated the effect of postfabrication annealing on optical and photocatalytic properties of hydrothermally grown zinc oxide nanorods. Three annealing conditions (oxygen flow, forming gas flow, and zinc ambient) were performed at 250 °C and 350 °C. Optical properties (photoluminescence spectra) and photocatalytic activities of the rods were examined. Effects of annealing on the optical properties and photocatalytic activities of hydrothermally grown ZnO nanorods were discussed in detail.

Objective. A review was conducted to determine implementation strategies, utilities, score interpretation, and limitations of the Pharmacy Curriculum Outcome Assessment (PCOA) examination. Methods. Articles were identified through the PubMed and American Journal of Pharmaceutical Education, and International Pharmaceutical Abstracts databases using the following terms: "Pharmacy Curriculum Outcomes Assessment," "pharmacy comprehensive examination," and "curricular assessment." Studies containing information regarding implementation, utility, and predictive values for US student pharmacists, curricula, and/or PGY1/PGY2 residents were included. Publications from the Academic Medicine Journal, the Accreditation Council for Pharmacy Education (ACPE), and the American Association of Colleges of Pharmacy (ACCP) were included for background information and comparison of predictive utilities of comprehensive examinations in medicine. Results. Ten PCOA and nine residency-related publications were identified. Based on published information, the PCOA may be best used as an additional tool to identify knowledge gaps for third-year student pharmacists. Conclusion. Administering the PCOA to students after they have completed their didactic coursework may yield scores that reflect student knowledge. Predictive utility regarding the North American Pharmacy Licensure Examination (NAPLEX) and potential applications is limited, and more research is required to determine ways to use the PCOA.

The dynamical properties of a realisticthermal-structure interface between a coronal loop and the chromosphere/photosphere are investigated by numerical simulations using acoustic and Alfvenic excitations. These properties are relevant to the end conditions seen by coronal MHD perturbations (e.g., waves or instabilities), in the absence of much slower energetics effects. Analytic studies of coronal-loop hydromagnetics have often made simplifying assumptions about the boundary conditions at the loop base in order to make their calculations tractable. However, in the presence of a transition region and chromosphere with rapidly varying plasma conditions, it is not clear how valid these heuristic assumptions are. In this study, we find that the discontinuous fluid-density model approximately represents the reflection/ transmission scaling with respect to varying transition-region density and temperature (i.e., dynamic impedance) ratios, although it does not quantitatively predict the chromospheric response to wave-like coronal activity. This disagreement is partially due to the finite width of the corona-to-photosphere transition.

The location and frequency of coronal energy release provide a significant constraint on the coronal heating mechanism. The evolution of the intensity observed in coronal structures found from time lag analysis of Atmospheric Imaging Assembly (AIA) data has been used to argue that heating must occur sporadically. Recently, we have demonstrated that quasi-steady, highly stratified (footpoint) heating can produce results qualitatively consistent with the evolution of observed coronal structures. The goals of this paper are to demonstrate that time lag analysis of 3D simulations of footpoint heating are qualitatively consistent with time lag analysis of observations and to use the 3D simulations to further understand whether time lag analysis is a useful tool in defining the evolution of coronal structures. We find the time lag maps generated from simulated data are consistent with the observed time lag maps. We next investigate several example points. In some cases, the calculated time lag reflects the evolution of a unique loop along the line of sight, though there may be additional evolving structures along the line of sight. We confirm that using the multi-peak AIA channels can produce time lags that are difficult to interpret. We suggest using a different high temperature channel, such as an X-ray channel. Finally, we find that multiple evolving structures along the line of sight can produce time lags that do not represent the physical properties of any structure along the line of sight, although the cross-correlation coefficient of the lightcurves is high. Considering the projected geometry of the loops may reduce some of the line-of-sight confusion.

In the present study, we use a forward modeling method to construct a 3D thermal structure encompassing active region 7986 of 1996 August. The extreme ultraviolet (EUV) emissions are then computed and compared with observations. The heating mechanism is inspired by a theory on Alfven wave turbulence dissipation. The magnetic structure is built from a Solar and Heliospheric Observatory (SOHO)/MDI magnetogram and an estimated torsion parameter deduced from observations. We found that the solution to the equations in some locations is in a thermal nonequilibrium state. The time variation of the density and temperature profiles leads to time dependent emissions, which appear as thin, loop-like structures with uniform cross-section. Their timescale is consistent with the lifetime of observed coronal loops. The dynamic nature of the solution also leads to plasma flows that resemble observed coronal rain. The computed EUV emissions from the coronal part of the fan loops and the high loops compare favorably with SOHO/EIT observations in a quantitative comparison. However, the computed emission from the lower atmosphere is excessive compared to observations, a symptom common to many models. Some factors for this discrepancy are suggested, including the use of coronal abundances to compute the emissions and the neglect of atmospheric opacity effects.

Motivation: Exome sequencing has proven to be an effective tool to discover the genetic basis of Mendelian disorders. It is well established that copy number variants (CNVs) contribute to the etiology of these disorders. However, calling CNVs from exome sequence data is challenging. A typical read depth strategy consists of using another sample (or a combination of samples) as a reference to control for the variability at the capture and sequencing steps. However, technical variability between samples complicates the analysis and can create spurious CNV calls. Results: Here, we introduce ExomeDepth, a new CNV calling algorithm designed to control for this technical variability. ExomeDepth uses a robust model for the read count data and uses this model to build an optimized reference set in order to maximize the power to detect CNVs. As a result, ExomeDepth is effective across a wider range of exome datasets than the previously existing tools, even for small (e.g. one to two exons) and heterozygous deletions. We used this new approach to analyse exome data from 24 patients with primary immunodeficiencies. Depending on data quality and the exact target region, we find between 170 and 250 exonic CNV calls per sample. Our analysis identified two novel causative deletions in the genes GATA2 and DOCK8. Availability: The code used in this analysis has been implemented into an R package called ExomeDepth and is available at the Comprehensive R Archive Network (CRAN). Contact: v.plagnol@ucl.ac.uk Supplementary Information: Supplementary data are available at Bioinformatics online.

Lentiviral latency remains a principal obstacle to curative AIDS therapy. Transcriptional repression and latency permits lentiviruses to evade host immune responses and antiretroviral drugs. We have established a model of peripheral CD4+ T cell lentiviral latency in cats experimentally infected with feline immunodeficiency virus (FIV). Multiple mechanisms of lentiviral transcriptional repression have been proposed including epigenetic mechanisms resulting in promoter hypermethylation and/or chromatin condensation. Methylation of promoter-associated cytosines in the cytosine-guanine dinucleotide (CpG) has been associated with transcriptional repression in both eukaryotic promoters and integrated retroviral genomes. Using methylcytosine mapping, we examined the CpG methylation patterns in both the 5′ and 3′ long terminal repeats (LTR) of the FIV provirus in peripheral blood mononuclear cells, monocytes and CD4+ T cells isolated during the acute and asymptomatic phases of infection. Here we report no evidence that proviral promoter hypermethylation is associated with lentiviral latency in peripheral CD4+ T cells and monocytes obtained from experimentally FIV-infected cats.

Field reversed configurations (FRCs) with high confinement are obtained in the C-2 device by combining plasma gun edge biasing and neutral beam injection. The plasma gun creates an inward radial electric field that counters the usual FRC spin-up. The $n=2$ rotational instability is stabilized without applying quadrupole magnetic fields. The FRCs are nearly axisymmetric, which enables fast ion confinement. The plasma gun also produces $E\ifmmode\times\else\texttimes\fi{}B$ shear in the FRC edge layer, which may explain the observed improved particle transport. The FRC confinement times are improved by factors 2 to 4, and the plasma lifetimes are extended from 1 to up to 4 ms.

Tropical Singapore's meterological profile makes it one of the world's lightning capitals. This study aims to assess the profile of the at-risk patient, and possibly identify factors predicting the length of hospital stay in patients with lightning injuries over a period of 11 years.

Intronic expansion of the GGGGCC hexanucleotide repeat within the C9ORF72 gene causes frontotemporal dementia and amyotrophic lateral sclerosis/motor neuron disease in both familial and sporadic cases. Initial reports indicate that this variant within the frontotemporal dementia/amyotrophic lateral sclerosis spectrum is associated with transactive response DNA binding protein (TDP-43) proteinopathy. The amyotrophic lateral sclerosis/motor neuron disease phenotype is not yet well characterized. We report the clinical and pathological phenotypes associated with pathogenic C9ORF72 mutations in a cohort of 563 cases from Northern England, including 63 with a family history of amyotrophic lateral sclerosis. One hundred and fifty-eight cases from the cohort (21 familial, 137 sporadic) were post-mortem brain and spinal cord donors. We screened DNA for the C9ORF72 mutation, reviewed clinical case histories and undertook pathological evaluation of brain and spinal cord. Control DNA samples (n = 361) from the same population were also screened. The C9ORF72 intronic expansion was present in 62 cases [11% of the cohort; 27/63 (43%) familial, 35/500 (7%) cases with sporadic amyotrophic lateral sclerosis/motor neuron disease]. Disease duration was significantly shorter in cases with C9ORF72-related amyotrophic lateral sclerosis (30.5 months) compared with non-C9ORF72 amyotrophic lateral sclerosis/motor neuron disease (36.3 months, P

In the present study we aimed to determine the prevalence of C9ORF72 GGGGCC hexanucleotide expansion in our cohort of 53 frontotemporal lobar degeneration (FTLD) patients and 174 neurologically normal controls. We identified the hexanucleotide repeat, in the pathogenic range, in 4 (2 bv-frontotemporal dementia (FTD) and 2 FTD-amyotrophic lateral sclerosis [ALS]) out of 53 patients and 1 neurologically normal control. Interestingly, 2 of the C9ORF72 expansion carriers also carried 2 novel missense mutations in GRN (Y294C) and in PSEN-2(I146V). Further, 1 of the C9ORF72 expansion carriers, for whom pathology was available, showed amyloid plaques and tangles in addition to TAR (trans-activation response) DNA-binding protein (TDP)-43 pathology. In summary, our findings suggest that the hexanucleotide expansion is probably associated with ALS, FTD, or FTD-ALS and occasional comorbid conditions such as Alzheimer's disease. These findings are novel and need to be cautiously interpreted and most importantly replicated in larger numbers of samples.

An expanded hexanucleotide repeat in the C9ORF72 gene has recently been identified as a major cause of familial frontotemporal lobar degeneration and motor neuron disease, including cases previously identified as linked to chromosome 9. Here we present a detailed retrospective clinical, neuroimaging and histopathological analysis of a C9ORF72 mutation case series in relation to other forms of genetically determined frontotemporal lobar degeneration ascertained at a specialist centre. Eighteen probands (19 cases in total) were identified, representing 35% of frontotemporal lobar degeneration cases with identified mutations, 36% of cases with clinical evidence of motor neuron disease and 7% of the entire cohort. Thirty-three per cent of these C9ORF72 cases had no identified relevant family history. Families showed wide variation in clinical onset (43-68 years) and duration (1.7-22 years). The most common presenting syndrome (comprising a half of cases) was behavioural variant frontotemporal dementia, however, there was substantial clinical heterogeneity across the C9ORF72 mutation cohort. Sixty per cent of cases developed clinical features consistent with motor neuron disease during the period of follow-up. Anxiety and agitation and memory impairment were prominent features (between a half to two-thirds of cases), and dominant parietal dysfunction was also frequent. Affected individuals showed variable magnetic resonance imaging findings; however, relative to healthy controls, the group as a whole showed extensive thinning of frontal, temporal and parietal cortices, subcortical grey matter atrophy including thalamus and cerebellum and involvement of long intrahemispheric, commissural and corticospinal tracts. The neuroimaging profile of the C9ORF72 expansion was significantly more symmetrical than progranulin mutations with significantly less temporal lobe involvement than microtubule-associated protein tau mutations. Neuropathological examination in six cases with C9ORF72 mutation from the frontotemporal lobar degeneration series identified histomorphological features consistent with either type A or B TAR DNA-binding protein-43 deposition; however, p62-positive (in excess of TAR DNA-binding protein-43 positive) neuronal cytoplasmic inclusions in hippocampus and cerebellum were a consistent feature of these cases, in contrast to the similar frequency of p62 and TAR DNA-binding protein-43 deposition in 53 control cases with frontotemporal lobar degeneration-TAR DNA-binding protein. These findings corroborate the clinical importance of the C9ORF72 mutation in frontotemporal lobar degeneration, delineate phenotypic and neuropathological features that could help to guide genetic testing, and suggest hypotheses for elucidating the neurobiology of a culprit subcortical network.

Delivery of bone marrow cells (BMCs) to the heart has substantially improved cardiac function in most rodent models of myocardial infarction (MI), but clinical trials of BMC therapy have led to only modest improvements. Rodent models typically involve intramyocardial injection of BMCs from distinct donor individuals who are healthy. In contrast, autologous BMCs from individuals after MI are used for clinical trials. Using BMCs from donor mice after MI, we discovered that recent MI impaired BMC therapeutic efficacy. MI led to myocardial inflammation and an increased inflammatory state in the bone marrow, changing the BMC composition and reducing their efficacy. Injection of a general anti-inflammatory drug or a specific interleukin-1 inhibitor to donor mice after MI prevented this impairment. Our findings offer an explanation of why human trials have not matched the success of rodent experiments and suggest potential strategies to improve the success of clinical autologous BMC therapy.

To study the predictive value of coronary calcification score (CCS) for future cardiovascular (CVS) events as detected by multi-detector computed tomography (MDCT) in patients with rheumatoid arthritis(RA) and systemic lupus erythematosus (SLE).A total of 152 patients with RA and SLE, and 106 healthy controls underwent MDCT to measure CCS. All patients were prospectively followed up for major CVS events.Compared with controls, patients with RA and SLE had a significantly higher mean CCS (42.2±154.3 vs. 1.4±13.0, p0.01) and prevalence of CCS 1-10, CCS 11-100 and CCS100 (all p0.05). After a mean period of 4.3±0.6 years, major CVS events occurred in 10 patients with RA and SLE. In patients with RA and SLE, a higher major CVS events rate occurred in patients with CCS 1-10 (5.0%), CCS 11-100 (14.3%) and CCS100 (40.0%) than those with CCS=0 (1.0%, p0.01). Multivariate Cox regression analysis revealed that hypercholesterolemia (hazard ratio (HR) 11.2, confidence interval (CI 1.4-89.3, p=0.02) and CCS100 (HR 11.1, CI 1.31-95.0, p=0.03) were independent predictors of combined events.Coronary calcification detected by MDCT independently predicts CVS events in patients with RA and SLE. Risk stratification by assessment of CCS may have an important role in patients with systemic inflammatory disease.

A high temperature field reversed configuration (FRC) has been produced in the newly built, world’s largest compact toroid (CT) facility, C-2, by colliding and merging two high-β CTs produced using the advanced field-reversed θ-pinch technology. This long-lived, stable merged state exhibits the following key properties: (1) apparent increase in the poloidal flux from the first pass to the final merged state, (2) significantly improved confinement compared to conventional θ-pinch FRCs with flux decay rates approaching classical values in some cases, (3) strong conversion from kinetic energy into thermal energy with total temperature (Te + Ti) exceeding 0.5 keV, predominantly into the ion channel. Detailed modeling using a new 2-D resistive magnetohydrodynamic (MHD) code, LamyRidge, has demonstrated, for the first time, the formation, translation, and merging/reconnection dynamics of such extremely high-β plasmas.