1,981 research outputs found
The peptide motif of the single dominantly expressed class I molecule of the chicken MHC can explain the response to a molecular defined vaccine of infectious bursal disease virus (IBDV)
No full textIn contrast to typical mammals, the chicken MHC (the BF-BL region of the B locus) has strong genetic associations with resistance and susceptibility to infectious pathogens as well as responses to vaccines. We have shown that the chicken MHC encodes a single dominantly expressed class I molecule whose peptide-binding motifs can determine resistance to viral pathogens, such as Rous sarcoma virus and Marek’s disease virus. In this report, we examine the response to a molecular defined vaccine, fp-IBD1, which consists of a fowlpox virus vector carrying the VP2 gene of infectious bursal disease virus (IBDV) fused with ?-galactosidase. We vaccinated parental lines and two backcross families with fp-IBD1, challenged with the virulent IBDV strain F52/70, and measured damage to the bursa. We found that the MHC haplotype B15 from line 15I confers no protection, whereas B2 from line 61 and B12 from line C determine protection, although another locus from line 61 was also important. Using our peptide motifs, we found that many more peptides from VP2 were predicted to bind to the dominantly expressed class I molecule BF2*1201 than BF2*1501. Moreover, most of the peptides predicted to bind BF2*1201 did in fact bind, while none bound BF2*1501. Using peptide vaccination, we identified one B12 peptide that conferred protection to challenge, as assessed by bursal damage and viremia. Thus, we show the strong genetic association of the chicken MHC to a T cell vaccine can be explained by peptide presentation by the single dominantly expressed class I molecule
Artemether resistance in vitro is linked to mutations in PfATP6 that also interact with mutations in PfMDR1 in travellers returning with Plasmodium falciparum infections.
No full textBACKGROUND: Monitoring resistance phenotypes for Plasmodium falciparum, using in vitro growth assays, and relating findings to parasite genotype has proved particularly challenging for the study of resistance to artemisinins.
METHODS: Plasmodium falciparum isolates cultured from 28 returning travellers diagnosed with malaria were assessed for sensitivity to artemisinin, artemether, dihydroartemisinin and artesunate and findings related to mutations in pfatp6 and pfmdr1.
RESULTS: Resistance to artemether in vitro was significantly associated with a pfatp6 haplotype encoding two amino acid substitutions (pfatp6 A623E and S769N; (mean IC50 (95% CI) values of 8.2 (5.7 - 10.7) for A623/S769 versus 623E/769 N 13.5 (9.8 - 17.3) nM with a mean increase of 65%; p = 0.012). Increased copy number of pfmdr1 was not itself associated with increased IC50 values for artemether, but when interactions between the pfatp6 haplotype and increased copy number of pfmdr1 were examined together, a highly significant association was noted with IC50 values for artemether (mean IC50 (95% CI) values of 8.7 (5.9 - 11.6) versus 16.3 (10.7 - 21.8) nM with a mean increase of 87%; p = 0.0068). Previously described SNPs in pfmdr1 are also associated with differences in sensitivity to some artemisinins.
CONCLUSIONS: These findings were further explored in molecular modelling experiments that suggest mutations in pfatp6 are unlikely to affect differential binding of artemisinins at their proposed site, whereas there may be differences in such binding associated with mutations in pfmdr1. Implications for a hypothesis that artemisinin resistance may be exacerbated by interactions between PfATP6 and PfMDR1 and for epidemiological studies to monitor emerging resistance are discussed
Plasmodium berghei-infection induces volume-regulated anion channel-like activity in human hepatoma cells
No full textParasite infection can lead to alterations in the permeability of host plasma membranes. Presented here is the first demonstration that this phenomenon occurs in Plasmodium‐infected liver cells. Using the whole‐cell patch‐clamp technique, volume‐regulated anion channel (VRAC) activity was characterized in Huh‐7 cells (a human hepatoma cell line) before and after infection with Plasmodium berghei. Consistent with the presence of VRACs, hypotonic bath solution induced large ion currents in Huh‐7 cells that rectified outwardly, reversed close to the equilibrium potential for Cl‐ and were inhibited by tamoxifen, clomiphene, mefloquine and 5‐nitro‐2, 3‐(phenylpropylamino)‐benzoic acid (NPPB), with IC50 values of 4 ± 1, 4 ± 2, 2 ± 1 and 52 ± 12 μM respectively. In isotonic conditions, initial current recordings measured in uninfected and immature (24 h post invasion) parasite‐infected Huh‐7 cells were similar (with conductances of 14 ± 3 versus 19 ± 5 pS/pF). However, in mature (48–72 h post invasion) parasite‐infected Huh‐7 cells there was a sevenfold increase in currents (with a conductance of 98 ± 16 pS/pF). The elevated currents observed in the latter are consistent with VRAC‐like activity and the possible reasons for their activation are discussed
An assessment of the impact of possible CAP reform scenarios on Romanian agriculture
No full textUsing a simplified model, with key-variable the prices of two different possible scenarios of CAP reform after 2013 (moderate and radical), this paper present a comparison between the price effects of implementation of each reform scenario at 2015 horizon on Romanian agriculture. This short analysis shows that, under the presented hypotheses, the net welfare effect, due to the price changes, for the selected products, is positive in both reform scenarios, yet greater in the case of the radical reform. Integrated in the large context of Romanian development, it seems that the influence of CAP reform upon agriculture and rural areas will be most likely a gradual one: an interpenetration between the two scenarios is foreseeable, starting with the moderate reform that will dominate the period around 2013, the reform measures acquiring a more radical character afterwards.CAP reform, Romania, welfare effects, Agricultural and Food Policy,
Prevalence and clinical picture of celiac disease in Turner syndrome
No full textPrevalence and clinical picture of celiac disease in Turner syndrome.
Bonamico M1, Pasquino AM, Mariani P, Danesi HM, Culasso F, Mazzanti L, Petri A, Bona G; Italian Society Of Pediatric Gastroenterology Hepatology (SIGEP); Italian Study Group for Turner Syndrom (ISGTS).
Author information 1Department of Pediatrics, University of Rome La Sapienza, 00161 Roma, Italy.
Abstract
A multicenter study of Turner syndrome (TS) patients was carried out to estimate the prevalence of celiac disease (CD) and to detect clinical characteristics and laboratory data of affected patients. Three hundred eighty-nine girls with TS were screened by IgA antigliadin antibodies and/or antiendomysial antibodies. Intestinal biopsy was offered to positive cases. CD was diagnosed in 25 patients. In celiac subjects, anemia, anorexia, and delayed growth (with respect to Italian TS curves) were frequently present; whereas distended abdomen, chronic diarrhea, constipation, and vomiting occurred more rarely. In addition, low serum iron levels, hemoglobinemia, and high values of aminotransferases were observed. Ten patients showed classic CD, 8 showed atypical symptoms, and 7 showed a silent CD. In 11 symptomatic patients, the diagnosis of CD was made at the onset of symptoms, whereas 7 of them showed a median delay of 79 months in diagnosis. Other autoimmune disorders were observed in 40% of the patients. Our study confirms the high prevalence (6.4%) of CD in a large series of TS patients. Moreover, the subclinical picture in 60% of the cases, the diagnostic delay, and the incidence of other autoimmune disorders suggest that routine screening of CD in TS is indicated
Documenting Impacts of Hydro-Meteorological Events Using Earth Observation
No full textThe ambition of H2020 OPERANDUM project is to develop and document Nature Based Solutions (NBS) to mitigate risks associated with hydro-meteorological (HM) hazards. NBS mitigate risks by reducing the vulnerability of a particular system. The aim of this work is to demonstrate the use of multisource remote sensing data in documenting the impact of extreme HM events to advance knowledge on vulnerability and exposure. In particular the focus is to document past impacts due to extreme events selected from a characterization of recent (3 0 years) HM events in 11 Open Air Laboratories (OALs) where co-design, co-development and deployment of NBS are taking place. The impacts were documented by applying a wide spectrum of satellite image data and other, close - range, remote sensing techniques. A better understanding of the consequences due to extreme HM events in a particular area (OALs) is essential to identify elements at risk and expected to provide a reference to evaluate the reduction of vulnerability and mitigation of risks past the completion of NBS.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Optical and Laser Remote SensingGeo-engineerin
The progress and outcomes of black and minority ethnic (BME) nurses through the Nursing and Midwifery Council's "Fitness to Practise" process: Final report
No full textBACKGROUND
This is the first investigation of the relationship between ethnicity and regulation of the nursing profession conducted internationally. The study was commissioned by the Nursing and Midwifery Council which is the regulator of the professions in the UK.
AIMS OF THE STUDY
“To establish whether the progress and outcomes of Black and minority ethnic (BME) nurses in relation to fitness to practice, from the point of referral to the point of case closure, is different from that of White nurses and midwives (N&M); and whether we can from the data account for any differences identified” (Call for research, NMC 2015). The study was designed to investigate whether BME N&M nurses are more likely to be referred and whether they were more likely to progress through the stages of the Fitness to Practise (FtP) process (screening, investigation or adjudication) and whether they were more likely to receive a severe penalty at the end of the process.
DATA
The NMC made available a copy of the register which had socio-demographic information on 681,258 nurses and midwives between April 2012 and December 2014 as well as data on referrals from April 2012 to December 2014 which totalled 5,851. Over that period the total number of cases that went to adjudication was 946.
VARIABLES
The main independent variable is ethnicity which we divided into Black, Asian, White, Other and Unknown. The latter category accounted for 40% of all referrals. The outcomes studied were rates of referral, the imposition of interim orders (where the referred individual is not allowed to work, progression through screening, investigation, adjudication and final outcome, which was dichotomised into “can work” or “cannot work”. The regression models also controlled for: age, gender, source of referral (9 categories), region of qualification (Africa, Asia, Europe, Other, UK), country of referral (4 counties of the UK) and whether or not the individual referred had a representative, such as a Union.
METHODS OF ANALYSIS
Descriptive statistics, cross-tabulation analysis, logistic regression and ordinal logistic regression
FINDINGS
Descriptive statistics showed that BME nurses are more likely to be referred than white nurses and to progress through the FtP process. Having trained in Africa is also a risk factor for referral. Older N&M and males are more likely to be referred. Most referrals come from employers but members of the public are also an important source of referral. Inferential statistics show that relative to Whites, being Asian, Black or of Unknown ethnicity is associated with progressing through FtP process. However, when “source of referral” is entered into the regression model only the “Unknown ethnicity” category remains significantly more likely to progress than White N&M. Males are more likely to progress through the FtP process but age, though positive, is not significant. There were few significant differences among the countries of the UK. The imposition of interim orders did not vary by ethnicity. The presence of a representative seems to reflect the stage of the FtP process rather than being a factor that contributes to the outcome. Finally, at adjudication, being Asian or Black is associated with a less severe penalty than White. Only those of Unknown ethnicity are more likely than Whites to get a severe penalty. These results are not altered by controlling for the source of referral.
STRENGTHS AND WEAKNESSES OF THE STUDY
The strengths include: the fact that this is the first study of its kind, the datasets analysed are large and the statistics are appropriate. Weakness include the fact that in 40% cases the ethnicity of the referred individual is not known. Some of the registered N&M may not be working which means that their risk of being referred to the NMC is low which could be a threat to the comparison of different ethnic groups. The administrative data which we analysed did not provide information about the specialty (e.g. mental health, maternity), job setting (care home, acute hospital) or level of seniority (staff nurse or Director of Nursing of the individuals referred were not amenable to analysis.
RECOMMENDATIONS
The analysis reported here could be enhanced in the future if the information on ethnicity, the setting in which the referred individual is working and their grade is made available. Some jobs may simply carry a higher risk of referral to the NMC and BME nurses may disproportionately occupy those positions. The main finding, which is that the relationship between ethnicity and FtP is mediated by referral by the employer, directs our attention to the need for further research to understand how the working environment leads to an over-representation of BME nurses in the FtP process. Within the NMC, further research needs to be conducted to understand why White nurses are more likely to be given a severe penalty at adjudication even though they are underrepresented in referrals and less likely to progress through the process. With the introduction of the NMC code and revalidation, the collection of data by the NMC and the FtP process will undoubtedly change. At the same time, the NHS has introduced policies to directly affect the working environment of BME nurses and midwives. This means that this study should be repeated to take account of these changes in the wider environment
Thermal characteristics of InGaP/GaAs HBT ballasted with extended ledge
No full textA InGaP/GaAs heterojunction bipolar transistor structure is proposed in which the base epi-layer underneath the extended ledge works as a base ballast resistor. The structure eliminates the critical alignment for a passivation ledge formation as well as additional process steps for external base ballast resistor. Both ballasted and unballasted devices were fabricated and compared. Small signal equivalent circuit gives us the magnitude of the effective ballast resistance. The thermal characteristics, including gain-collapsed I-V and Vb, regression curve are shown and modeled. The temperature dependency of base sheet resistance and its influence on the device performance are also discussed.The author would like to thank Dr. H. Koo and Mr. S. Cho of the
Hanmirotek Corp. for their valuable suggestions and participation in
the fabrication of devices
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