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Treatment options for Hepatitis C infection have greatly improved with direct-acting antiviral (DAA) combinations achieving high cure rates. Nevertheless, the cost of this treatment is still high and access to treatment in many countries has been preferentially reserved for patients with more severe fibrosis (F3 and F4). In this French nationwide study, we investigated the epidemiological characteristics and genotype distribution of hepatitis C virus (HCV) in treatment-naive patients with METAVIR fibrosis stages between F0 and F2 in order to identify patient profiles that became eligible for unrestricted treatment in a second period. Between 2015 and 2016 we collected data from nine French university hospitals on a total of 584 HCV positive patients with absent, mild or moderate liver fibrosis. The most represented genotypes were genotype 1b (159/584; 27.2%), followed by genotype 1a (150/584; 25.7%); genotype 3 (87/584: 14.9%); genotype 4 (80/584; 13.7%). Among genotype 4: 4a was predominantly encountered with 22 patients (27.5% of genotype 4). Genotypes 1b and 1a are currently the most frequent virus types present in treatment-naive patients with mild fibrosis in France. They can be readily cured using the available DAA. Nevertheless, non-a/non-d genotype 4 is also frequent in this population and clinical data on the efficacy of DAA on these subtypes is missing. The GEMHEP is the French group for study and evaluation of viral hepatitis on a national scale. Data collection on epidemiological and molecular aspects of viral hepatitis is performed on a regular basis in all main French teaching hospitals and serves as a basis for surveillance of these infections. Analysis and trends are regularly published on behalf of the GEMHEP group. Data collection was performed retrospectively over the 2015–2016 period, covering nine main university hospitals in France. A total of 584 hepatitis C positive patients were included in this study. Genotyping of the circulating viruses showed a high prevalence of genotypes 1b and 1a in our population. The epidemiology of hepatitis C is slowly changing in France, particularly as a consequence of the rise of ‘non-a non-d’ genotype 4 viruses mainly originating from African populations. More data concerning treatment efficacy of these genotypes is needed in order to guide clinical care.
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. It provides recommendations on the assessment and management of patients with cancer of the oral cavity and the lip.
• Surgery remains the mainstay of management for oral cavity tumours. (R)
• Tumour resection should be performed with a clinical clearance of 1 cm vital structures permitting. (R)
• Elective neck treatment should be offered for all oral cavity tumours. (R)
• Adjuvant radiochemotherapy in the presence of advanced neck disease or positive margins improves control rates. (R)
• Early stage lip cancer can be treated equally well by surgery or radiation therapy. (R)
Eight winter oilseed rape and two spring oilseed rape field experiments were performed in the UK in harvest years 2009–12. Each experiment consisted of at least one hybrid and one open-pollinated variety grown at five seed rates from 10 or 20 seeds/m2 to 160 or 200 seeds/m2. Linear plus exponential curves were used to describe the yield response to seed rate and to calculate economically optimal seed rates. Plant counts were then used to derive optimal plant population densities. These ranged from <10 to 39 plants/m2 for six winter oilseed rape experiments between 73 and >155 plants/m2 in two winter oilseed rape experiments with severe spring droughts, and from 47 to 65 plants/m2 for spring oilseed rape. Optimal plant population densities were lower for hybrid than for open-pollinated varieties, due to a combination of the higher cost of hybrid seed and, for some experimental sites, hybrid varieties compensating better for low plant populations. Across all sites, sowing winter oilseed rape at 30 seeds/m2 rather than common commercial rates of 70 seeds/m2 for hybrids and 100 seeds/m2 for open-pollinated varieties would have increased average gross margin by £29/ha. Sowing spring oilseed rape at 70 seeds/m2 rather than commonly used rates of 120 or 150 seeds/m2 would have increased average gross margin by £64/ha.
The mango blossom gall midge, Procontarinia mangiferae, is a multivoltine species that induces galls in inflorescences and leaves of the mango tree, Mangifera indica. In subtropical Reunion Island, populations of P. mangiferae are observed all-year round, but the pattern and the role of dormancy in their life cycle have never been documented. We performed field and laboratory experiments using more than 15,000 larvae. We demonstrated that a larval diapause may affect a part of the midge population, regardless of the season. The total duration of the diapause varied from 6 weeks to more than 1 year. One year of field monitoring showed that the highest incidence of diapause was observed in larvae collected during the summer from mango leaves, where it affected approximately one-third of the individuals. This facultative diapause allows the permanent presence of P. mangiferae in the orchards. By recording diapause duration during 22 weeks under controlled conditions, we showed that high temperatures (26 °C) increased diapause duration and extended the range of the dates of diapause emergence, whereas cool temperatures (20 °C) shortened diapause duration and shortened the range of the dates of emergence from diapause. A temperature decrease from 26 to 20 °C triggered the emergence of diapausing individuals. These mechanisms ensure the synchronization of the emergence of diapausing individuals with the appearance of mango inflorescences, which is also induced by cool winter temperatures.
The aim of the present study was to evaluate the effects on yield, oil concentration and nitrogen (N) uptake efficiency of N fertilizer applied to the foliage of oilseed rape during and soon after flowering. Four field experiments were conducted in the UK during the 2008/09 and 2009/10 seasons which investigated six rates of soil-applied N (ammonium nitrate) ranging from 0 to 280 or 320 kg N/ha with each treatment followed by 0 or 40 kg/ha of foliar N applied as a solution of urea at the end of flowering. Each experiment also investigated five rates of foliar N ranging from 0 to 120 kg N/ha applied at the end of flowering and five timings of foliar N (40 kg N/ha) from mid-flowering to 2 weeks after the end of flowering.
Foliar N at 40 kg N/ha applied at the end of flowering significantly increased the seed yield in three of the four experiments. The seed yield increase across all four experiments was 0·25 t/ha (range of 0–0·41 t/ha). In two experiments, the increase in seed yield in response to foliar N occurred irrespective of whether it followed sub-optimal or super-optimal rates of soil-applied N; in one experiment there was a greater response at sub-optimal soil-applied N rates. The foliar N treatment reduced the seed oil concentration by 11 g/kg and increased seed protein concentration by 11 g/kg. Similar yield responses were observed for foliar N applications between mid-flowering and 2 weeks after the end of flowering. The efficiency with which foliar N was taken up into the plant varied between 0 and 100% with an average uptake efficiency across the four experiments of 61%.
Synchrotron based μ-XRF, μ-XAS and μ-XRD have made a major impact in the field of environmental science in the last ten years. One of the first seven ‘day one’ beamlines on the Diamond Light Source is a microfocus spectroscopy beamline, beamline I18. Here the current status of the beamline and the opportunities it presents in the field of environmental science are described, with results from two of the first experiments also included. The first is based on the use of bonemeal to remediate soil. We used Zn K-edge and Pb L3-edge spectroscopy to characterize the speciation of these two elements on a soil after bonemeal treatment. The results are compared with bulk measurements taken on the whole soil and standard materials. The second experiment described here is a study of the speciation and association of Ni in a laterite from Moa Bay, Cuba. Here the differences in the Ni speciation associated with Mn oxides are examined and compared with Fe oxides phases.
The snow surface roughness at centimetre and millimetre scales is an important parameter related to wind transport, snowdrifts, snowfall, snowmelt and snow grain size. Knowledge of the snow surface roughness is also of high interest for analyzing the signal from radar sensors such as SAR, altimeters and scatterometers. Unfortunately, this parameter has seldom been measured over snow surfaces. The techniques used to measure the roughness of other surfaces, such as agricultural or sand soils, are difficult to implement in polar regions because of the harsh climatic conditions. In this paper we develop a device based on a laser profiler coupled with a GPS receiver on board a snowmobile. This instrumentation was tested successfully in midre Lovénbreen, Svalbard, in April 2006. It allowed us to generate profiles of 3 km sections of the snow-covered glacier surface. Because of the motion of the snowmobile, the roughness signal is mixed with the snowmobile signal. We use a distance/frequency analysis (the empirical mode decomposition) to filter the signal. This method allows us to recover the snow surface structures of wavelengths between 4 and 50 cm with amplitudes of >1 mm. Finally, the roughness parameters of snow surfaces are retrieved. The snow surface roughness is found to be dependent on the scales of the observations. The retrieved RMS of the height distribution is found to vary between 0.5 and 9.2 mm, and the correlation length is found to be between 0.6 and 46 cm. This range of measurements is particularly well adapted to the analysis of GHz radar response on snow surfaces.
The isotope dilution technique is the most important way to study the metabolism of minerals. With the use of radiophosphorus (32P), it is possible to describe the kinetics of P including the endogenous fraction. The aim of this work was to study the metabolism of supplemented P using the isotope dilution technique and to apply bio mathematical model to investigate its kinetics.
Calcium is needed for bone formation, muscle contraction, nerve transmission and a variety of other functions in the organism. Experiments has been carried out to study phosphorus metabolism in sheep and cattle, by using isotope dilution techniques however, there is very little information on Ca metabolism in sheep. The objective of this experiment was to study the effects of various Ca sources on the Ca flows in sheep by two models.
The ESA observatory INTEGRAL (International Gamma-Ray Astrophysics Laboratory) is dedicated to fine imaging and spectroscopy in the energy range 15 keV to 10 Mev with concurrent X-ray (3-35 keV) and optical monitoring. It was launched on October 17, 2002 and has been succesfully operating ever since. Its two main instruments the spectrometer SPI – optimized for high resolution spectroscopy – and the imager IBIS – optimized for for high resolution imaging – are complemented by the X-ray monitor JEM-X and the optical monitor OMC. All the high energy instruments use coded mask techniques, allowing imaging in the gamma-ray range and combining wide fields of view with high spatial resolution. The presentation gives an overview of the unique properties of INTEGRAL.
The in vitro gas production is a widely used technique for the evaluation of feeds for ruminant animals. Although it measures rate and extension of gas production during feed fermentation in culture medium, rumen inoculum from operated animals (fistulae) is required. Faecal microorganisms function similarly to those in the rumen; they decompose feed and do not require operated animals. The objective of the present experiment was to compare rumen liquor and equine faeces as source of inoculum in the gas production technique.
Concentrate mixtures fed ruminants generally are composed by cereals where phosphorus is present mainly in phytate form or phytin (Maga, 1982). Phytate phosphorus is thought to be completely available to ruminants due to the presence of phytase enzyme that hydrolyzes phytate phosphorus making it available for absorption. Researches have shown that this fact is not always true, depending on different conditions (Park et al., 2000). The aim of this paper was to study the influence of phytate phosphorus on calcium availability.
Phosphorus and calcium deficiency in horses represents an important factor responsible for the low equine production in Brazil. The basic mechanisms of P and Ca metabolism differ substantially among species. Regulation of P and Ca metabolism is less well understood in horses than in others species. With the use of the isotopic dilution technique is possible to evaluate the metabolism for this mineral. The aim of the present experiment was to study the effect of different Ca levels in the diet on P and Ca metabolism in horses.
Toxoplasma gondii is the aetiological agent of toxoplasmosis and is the most frequent and best known of the parasitic diseases. In the United States, a serological survey from the Third National Health and Nutrition Examination Survey found that an estimated 23% of adolescents and adults have laboratory evidence of infection with T. gondii. Although toxoplasmosis is asymptomatic or shows self-limited symptoms in adults, in pregnant women infections can cause severe health problems to the fetus if the parasites are transmitted. Also, in immunodeficient patients, chronic infection with T. gondii can reactivate and produce encephalitis, which is frequently lethal. In addition, in veterinary medicine, T. gondii infection is of economic importance due to abortion and neonatal loss in sheep and goats. Recently, the development of vaccines against toxoplasmosis has progressed considerably. The live attenuated S48 strain of Toxoplasma has been broadly used for veterinary purposes. DNA vaccines containing the full-length of SAG1/P30, ROP2 or ROP 1 genes have proved to be a promising candidate to induce protection against toxoplasmosis. Viral vectors have proved to be the best candidates for vaccination in different diseases. A recombinant Herpes virus carrying the ROP2 gene is able to induce protective immunity in cats. In the present work we describe the potential of the MVA ROP2 recombinant vaccinia virus as a vaccine against toxoplasmosis. MVA ROP2 induces antibodies against the ROP2 protein in similar amount and types as the thermo-sensible strain ts-4 of T. gondii, which is able to fully protect mice against challenge with the virulent RH strain of T. gondii. Also, the life-span of mice is increased in MVA ROP2 vaccinated animals. We conclude that MVA ROP2 vaccine can possibly generate an immune response, which could be useful in protection against toxoplasmosis.
The close association of calcium and phosphorus in bone, and the narrow relationship between these minerals makes this subject always an important aim of study for researches on animal nutrition (Braithwaite, 1984). The utilization of alternative sources of calcium has been studied in Brazil in the last years however there is a lack of information about the effects of these sources on phosphorus metabolism. The aim of this study was to evaluate phosphorus metabolism in sheep fed four different sources of calcium through determination of true absorption and endogenous faecal loss of phosphorus by using the isotope dilution technique (Vitti et al., 2000).
The conversion of the single-stranded RNA genome into
double-stranded DNA by virus-coded reverse transcriptase (RT)
is an essential step of the retrovirus life cycle. In human
immunodeficiency virus type 1 (HIV-1), RT uses the cellular
tRNA3Lys to initiate
the (−) strand DNA synthesis. Placement of the primer
binding of its 3′-terminal 18 nt to a complementary
region of genomic RNA termed PBS. However, the PBS sequence
is not the unique determinant of primer usage and additional
contacts are important. This placement is believed to be achieved
in vivo by the nucleocapsid domain of Gag or by the mature protein
NCp. Up to now, structural information essentially arose from
heat-annealed primer-template complexes (Isel et al., J
Mol Biol, 1995, 247:236–250; Isel et al.,
EMBO J, 1999, 18:1038–1048). Here, we
investigated the formation of the primer–template complex
mediated by NCp and compared structural and functional properties
of heat- and NCp-annealed complexes. We showed that both heat-
and NCp-mediated procedures allow comparable high yields of
annealing. Then, we investigated structural features of both
kinds of complexes by enzymatic probing, and we compared their
relative efficiency in (−) strong stop DNA synthesis.
We did not find any significant differences between these
complexes, suggesting that information derived from the
heat-annealed complex can be transposed to the NCp-mediated
complex and most likely to complexes formed in vivo.
The pain-suppressive effect of morphine is related to the interaction of this alkaloid with binding sites located in the central nervous system (CNS) and more precisely within structures known for their involvement in the regulation of nociceptive stimuli. Moreover, the wide distribution of opioid receptors in the brain accounts for the multiplicity of pharmacologic responses elicited by morphine administration. Psychic dependence and respiratory depression, which are among the major side effects of narcotics, are related to overstimulation of brain receptors, respectively, in behavioral and bulbar respiratory controls. The reduction in intestinal transit is another drawback frequently associated with chronic morphine treatment. Thus, despite the considerable interest in morphine and surrogates for treatment of severe pain, there is a crucial need for new analgesics to fill the gap between opioid analgesics and antalgics, such as aspirin and paracetamol. Such compounds may be of major interest for the treatment of various pain syndromes (postoperative, neurogenic, osteoarthritic) and more easily used in children, the elderly, and patients with respiratory problems.
Although many factors seem to be involved in pain control, the prevailing role of the opioid μ receptor type in analgesia has hampered the discovery of analgesics devoid of the severe morphine side effects, which were proposed to result from the stimulation of μ receptors. This hypothesis has recently been firmly established using transgenic mice with a deletion of the μ-receptor gene (Matthes et al., 1996).
Numerous mediators are involved in both the control and the transmission of nociceptive messages, and several lines of research have been developed in the management of pain. Complete enkephalin- degrading enzyme inhibitors, which produce naloxone-reversible analgesia in all tests where morphine has been found to be active, remains the most promising way. CCK compounds, especially the CCKB antagonists also may be interesting drugs. Indeed, they are able to strongly potentiate the antinociceptive effects of the opioids. [dickenson, wiesenfeld-hallin et al.]