To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Despite the much improved therapeutic approaches for cancer treatment that have been developed over the past 50 years, cancer remains a major cause of mortality globally. Considerable epidemiological and experimental evidence has demonstrated an association between ingestion of food and nutrients with either an increased risk for cancer or its prevention. There is rising interest in exploring agents derived from natural products for chemoprevention or for therapeutic purposes. Honey is rich in nutritional and non-nutritional bioactive compounds, as well as in natural antioxidants, and its potential beneficial function in human health is becoming more evident. A large number of studies have addressed the anti-cancer effects of different types of honey and their phenolic compounds using in vitro and in vivo cancer models. The reported findings affirm that honey is an agent able to modulate oxidative stress and has anti-proliferative, pro-apoptotic, anti-inflammatory, immune-modulatory and anti-metastatic properties. However, despite its reported anti-cancer activities, very few clinical studies have been undertaken. In the present review, we summarise the findings from different experimental approaches, including in vitro cell cultures, preclinical animal models and clinical studies, and provide an overview of the bioactive profile and bioavailability of the most commonly studied honey types, with special emphasis on the chemopreventive and therapeutic properties of honey and its major phenolic compounds in cancer. The implications of these findings as well as the future prospects of utilising honey to fight cancer will be discussed.
Tick-borne diseases (TBDs) can sometimes cause severe symptoms and lead to hospitalisation, but they often go unnoticed in the Emergency Department (ED). The aim of this study was twofold: (i) to describe the profile of patients hospitalised by TBDs; and (ii) to evaluate the data collected in the medical records from the ED in order to analyse their potential clinical consequences. A total of 84 cases that included all TBD diagnoses registered in the ED records were identified and analysed. These corresponded to all the hospitalisations by TBDs in the last 10 years (2009–2019) in two tertiary hospitals in Granada, Spain. Statistical analyses were made using RStudio. Coinciding with the absence of patient's report of exposure to ticks, 64.3% of TBDs were not suspected in the ED. Intensive care unit admission was required in 8.3% of cases, and the mortality rate was 2.4%. Non-suspected cases showed longer hospital stay (P < 0.001), treatment duration (P = 0.02) and delay in the initiation of antibiotic treatment (P < 0.001). Our findings indicate that symptoms associated with TBDs are highly non-specific. In the absence of explicit information related to potential tick exposure, TBDs are not initially suspected. As a consequence, elective treatment administration is delayed and hospitalisation time is prolonged. In conclusion, our results highlight the importance of addressing potential exposure to ticks during the ED contact with patients presenting with febrile syndrome.
The present study investigated the effects of nutritional programming through parental feeding on offspring performance and expression of selected genes related to stress resistance in a marine teleost. Gilthead seabream broodstock were fed diets containing various fish oil (FO)/vegetable oil ratios to determine their effects on offspring performance along embryogenesis, larval development and juvenile on-growing periods. Increased substitution of dietary FO by linseed oil (LO) up to 80 % LO significantly reduced the total number of eggs produced by kg per female per spawn. Moreover, at 30 d after hatching, parental feeding with increasing LO up to 80 % led to up-regulation of the fatty acyl desaturase 2 gene (fads2) that was correlated with the increase in conversion rates of related PUFA. Besides, cyclo-oxygenase 2 (cox2) and TNF-α (tnf-α) gene expression was also up-regulated by the increase in LO in broodstock diets up to 60 or 80 %, respectively. When 4-month-old offspring were challenged with diets having different levels of FO, the lowest growth was found in juveniles from broodstock fed 100 % FO. An increase in LO levels in the broodstock diet up to 60LO raised LC-PUFA levels in the juveniles, regardless of the juvenile’s diet. The results showed that it is possible to nutritionally programme gilthead seabream offspring through the modification of the fatty acid profiles of parental diets to improve the growth performance of juveniles fed low FO diets, inducing long-term changes in PUFA metabolism with up-regulation of fads2 expression. The present study provided the first pieces of evidence of the up-regulation of immune system-related genes in the offspring of parents fed increased FO replacement by LO.
There is a long history of exploitation of the South American river turtle Podocnemis expansa. Conservation efforts for this species started in the 1960s but best practices were not established, and population trends and the number of nesting females protected remained unknown. In 2014 we formed a working group to discuss conservation strategies and to compile population data across the species’ range. We analysed the spatial pattern of its abundance in relation to human and natural factors using multiple regression analyses. We found that > 85 conservation programmes are protecting 147,000 nesting females, primarily in Brazil. The top six sites harbour > 100,000 females and should be prioritized for conservation action. Abundance declines with latitude and we found no evidence of human pressure on current turtle abundance patterns. It is presently not possible to estimate the global population trend because the species is not monitored continuously across the Amazon basin. The number of females is increasing at some localities and decreasing at others. However, the current size of the protected population is well below the historical population size estimated from past levels of human consumption, which demonstrates the need for concerted global conservation action. The data and management recommendations compiled here provide the basis for a regional monitoring programme among South American countries.
This study analyzes the relationship between the two intrapersonal perfectionism dimensions (i.e., Self-Oriented Perfectionism-Critical, SOP-C, and Self-Oriented Perfectionism-Strivings, SOP-S) and the components of aggressive behavior (cognitive, emotional and motor) in a sample of 804 (48.3% females) Spanish students between the ages of 8 and 11 (M = 9.57; DE = 1.12). The Spanish versions of the SOP-C and SOP-S subscales of the Child/Adolescent Perfectionism Scale and the Aggression Questionnaire were used. Students with high SOP-C scored significantly higher (p < .001) than their peers with low SOP-C on all components of aggressive behavior. The magnitude of these differences (Cohen’s d index) ranged from .40 to .59. In contrast, non-significant statistical differences were found between students with high and low SOP-S. Moreover, logistic regression analysis revealed that SOP-C significantly and positively predicted high Hostility, Anger and Physical and Verbal Aggression, whereas none of these components were significantly predicted by SOP-S (95% CI). Results are discussed, taking into account the debate on the conceptualization and nature of intrapersonal perfectionism.
We prove that if
-triple and not a Cartan factor of rank two, then
satisfies the Mazur–Ulam property, that is, every surjective isometry from the unit sphere of
onto the unit sphere of another real Banach space
extends to a surjective real linear isometry from
Corrections for scattering on XRF intensity have commonly used integral approaches and isotropic approximations, which give a limited knowledge on this subject. An exact theoretical expression for XRF enhancement due to coherent and incoherent scattering is presented in this paper. It has been obtained as a solution of the Boltzmann transport equation for photons. This equation describes the diffusion of photons in an infinite homogeneous target. Both the excitation and the emission beams have been assumed to be well collimated. The solution accounts for the mixed, scattering and photoelectric interactions. Complete kernels including atomic form factors have been used for both types of scattering. An appropriate kernel has been written for the photoelectric interaction. The correction is computed for several pure elements and is compared with isotropic approximations.
The climate of north-western Spain, with high temperatures and relative humidity during the grapevine vegetative cycle, can especially favour the development of fungal diseases in vineyards. One of the most important diseases is downy mildew, caused by the fungus Plasmopara viticola. The aim of the current study is to propose a system containing phenological data, biological sensors of pathogen indicator and the agrometeorological Goidanich Index in order to optimize the application of downy mildew fungicide treatments. The study was conducted in a vineyard of the ‘Ribeiro’ Designation of Origin region from 2005 to 2016 during the Vitis vegetative period. Aerobiological sampling was performed using a LANZONI VPPS-2000 volumetric trap. The highest number of infection cycles was recorded during the 2009 harvest, with a total of 16 cycles. Years with fewer infection cycles were 2008, 2011 and 2012 (13 cycles). Primary infections were produced during the third fortnight of April and a high amount of secondary infection cycles were detected by the Goidanich algorithm during the fruit development and berry ripening stages. The best estimators of the P. viticola spore concentrations were the fungus spore levels during the previous day, the average temperature 5 days before and rainfall 2 days before. The regression equation obtained accounted for the 95.9% of the spore concentration variation. The combination of the Goidanich index and biological sensors provides a valuable tool to establish an accurate, modern, integrated downy mildew pest-management strategy.
In dairy goats, the kid rearing system can have critical importance in financial returns. Commonly used criteria for the choice of rearing system are not always clear due to the high number of factors involved. The aim of this study was to quantify all those factors to facilitate decision making. So, the effect of two different kid rearing systems, mixed rearing system (MRS) and artificial rearing system (ARS), on milk yield, milk composition and somatic cell count (SCC), milk yield loss at weaning for MRS, kid growth and costs of the different traits on the financial returns in Murciano-Granadina breed goats was studied. Twenty-four goats per group were used. In the MRS, goats reared only one kid, which had free access to goat milk 24 h a day and were weaned at week 6 of lactation, whereas kids in the ARS were separated from their mothers at kidding, colostrum and artificially reared. In both systems, dams were machine-milked once a day throughout lactation and the records took place weekly. Potential milk yield was estimated according to the oxytocin method up to week 12 of lactation, and was similar for both rearing systems, although a 12.3% drop in potential milk yield at weaning was observed for MRS. During the first 6 weeks of lactation, marketable milk was lower for dams in MRS compared to those in ARS (72.1 v. 113.0 l), but similar for the rest of the experiment (101.5 v. 99.4 l, respectively). Marketable milk composition and SCC throughout the 12 weeks of lactation were unaffected by the rearing system. Artificial rearing system entailed an increment in production cost of 22.2€ per kid compared to the rearing by MRS. A similar economic return per goat and kid was obtained from ARS and MRS in this experiment, although, due to one herd’s prolificacy of 1.8, the actual results would be 16.2€ per goat in favour of MRS. The real interest of this experiment may be the possibility of extrapolation to different flocks with diverse levels of milk production, prolificacy and prices and costs for incomes and outputs, to estimate the production system that increases returns. In conclusion, the results showed an increase in the cost of €22.2 per kid bred in the ARS, compared to the MRS, and a final return of 16.2€ per goat in favour of the mixed system.
With the recent discovery of a dozen dusty star-forming galaxies and around 30 quasars at z > 5 that are hyper-luminous in the infrared (μ LIR > 1013 L⊙, where μ is a lensing magnification factor), the possibility has opened up for SPICA, the proposed ESA M5 mid-/far-infrared mission, to extend its spectroscopic studies toward the epoch of reionisation and beyond. In this paper, we examine the feasibility and scientific potential of such observations with SPICA’s far-infrared spectrometer SAFARI, which will probe a spectral range (35–230 μm) that will be unexplored by ALMA and JWST. Our simulations show that SAFARI is capable of delivering good-quality spectra for hyper-luminous infrared galaxies at z = 5 − 10, allowing us to sample spectral features in the rest-frame mid-infrared and to investigate a host of key scientific issues, such as the relative importance of star formation versus AGN, the hardness of the radiation field, the level of chemical enrichment, and the properties of the molecular gas. From a broader perspective, SAFARI offers the potential to open up a new frontier in the study of the early Universe, providing access to uniquely powerful spectral features for probing first-generation objects, such as the key cooling lines of low-metallicity or metal-free forming galaxies (fine-structure and H2 lines) and emission features of solid compounds freshly synthesised by Population III supernovae. Ultimately, SAFARI’s ability to explore the high-redshift Universe will be determined by the availability of sufficiently bright targets (whether intrinsically luminous or gravitationally lensed). With its launch expected around 2030, SPICA is ideally positioned to take full advantage of upcoming wide-field surveys such as LSST, SKA, Euclid, and WFIRST, which are likely to provide extraordinary targets for SAFARI.
Laser-based compact MeV X-ray sources are useful for a variety of applications such as radiography and active interrogation of nuclear materials. MeV X rays are typically generated by impinging the intense laser onto ~mm-thick high-Z foil. Here, we have characterized such a MeV X-ray source from 120 TW (80 J, 650 fs) laser interaction with a 1 mm-thick tantalum foil. Our measurements show X-ray temperature of 2.5 MeV, flux of 3 × 1012 photons/sr/shot, beam divergence of ~0.1 sr, conversion efficiency of ~1%, that is, ~1 J of MeV X rays out of 80 J incident laser, and source size of 80 m. Our measurement also shows that MeV X-ray yield and temperature is largely insensitive to nanosecond laser contrasts up to 10−5. Also, preliminary measurements of similar MeV X-ray source using a double-foil scheme, where the laser-driven hot electrons from a thin foil undergoing relativistic transparency impinging onto a second high-Z converter foil separated by 50–400 m, show MeV X-ray yield more than an order of magnitude lower compared with the single-foil results.
The Coneybury ‘Anomaly’ is an Early Neolithic pit located just south-east of Stonehenge, Wiltshire. Excavations recovered a faunal assemblage unique in its composition, consisting of both wild and domestic species, as well as large quantities of ceramics and stone tools, including a substantial proportion of blades/bladelets. We present a suite of new isotope analyses of the faunal material, together with ancient DNA sex determination, and reconsider the published faunal data to ask: What took place at Coneybury, and who was involved? We argue on the basis of multiple lines of evidence that Coneybury represents the material remains of a gathering organised by a regional community, with participants coming from different areas. One group of attendees provided deer instead of, or in addition to, cattle. We conclude that the most likely scenario is that this group comprised local hunter-gatherers who survived alongside local farmers.
Measurements in the infrared wavelength domain allow direct assessment of the physical state and energy balance of cool matter in space, enabling the detailed study of the processes that govern the formation and evolution of stars and planetary systems in galaxies over cosmic time. Previous infrared missions revealed a great deal about the obscured Universe, but were hampered by limited sensitivity.
SPICA takes the next step in infrared observational capability by combining a large 2.5-meter diameter telescope, cooled to below 8 K, with instruments employing ultra-sensitive detectors. A combination of passive cooling and mechanical coolers will be used to cool both the telescope and the instruments. With mechanical coolers the mission lifetime is not limited by the supply of cryogen. With the combination of low telescope background and instruments with state-of-the-art detectors SPICA provides a huge advance on the capabilities of previous missions.
SPICA instruments offer spectral resolving power ranging from R ~50 through 11 000 in the 17–230 μm domain and R ~28.000 spectroscopy between 12 and 18 μm. SPICA will provide efficient 30–37 μm broad band mapping, and small field spectroscopic and polarimetric imaging at 100, 200 and 350 μm. SPICA will provide infrared spectroscopy with an unprecedented sensitivity of ~5 × 10−20 W m−2 (5σ/1 h)—over two orders of magnitude improvement over what earlier missions. This exceptional performance leap, will open entirely new domains in infrared astronomy; galaxy evolution and metal production over cosmic time, dust formation and evolution from very early epochs onwards, the formation history of planetary systems.
This is the first report on the development and characterization of eight monoclonal antibodies (MABs) generated against whole- and membrane-enriched tachyzoite extracts of the apicomplexan parasite Besnoitia besnoiti. Confocal laser scanning immunofluorescence microscopy was used to localize respective epitopes in B. besnoiti tachyzoites along the lytic cycle. A pattern compatible with dense granule staining was observed with MABs 2.A.12, 2.F.3 and 2.G.4, which could be confirmed by immunogold electron microscopy for MABs 2.A.12 and 2.F.3. In particular, MABs 2.F.3 and 2.G.4 were secreted during early invasion, proliferation and egress phases. MABs 3.10.8 and 5.5.11 labelled the tachyzoite surface, whilst MABs 1.17.8, 8.9.2 and 2.G.A recognized the apical tip, which is reminiscent for microneme localization. Besides, the epitopes recognized by the latter two (MABs 8.9.2 and 2.G.A) exhibited a redistribution from the anterior part across the parasite surface towards the posterior end during invasion. Most MABs developed were genus-specific. Indeed, the MABs cross-reacted neither with T. gondii nor with N. caninum tachyzoites. In summary, we have generated MABs that will be useful to study the key processes in the lytic cycle of the parasite and with additional promising diagnostic value. However, the molecular identity of the antigens recognized remains to be elucidated.
Early, conforming antibiotic treatment in elderly patients hospitalised for community-acquired pneumonia (CAP) is a key factor in the prognosis and mortality. The objective was to examine whether empirical antibiotic treatment was conforming according to the Spanish Society of Pulmonology and Thoracic Surgery guidelines in these patients. Multicentre study in patients aged ⩾65 years hospitalised due to CAP in the 2013–14 and 2014–15 influenza seasons. We collected socio-demographic information, comorbidities, influenza/pneumococcal vaccination history and antibiotics administered using a questionnaire and medical records. Bivariate analyses and multilevel logistic regression were made. In total, 1857 hospitalised patients were included, 82 of whom required intensive care unit (ICU) admission. Treatment was conforming in 51.4% (95% confidence interval (CI) 49.1–53.8%) of patients without ICU admission and was associated with absence of renal failure without haemodialysis (odds ratio (OR) 1.49, 95% CI 1.15–1.95) and no cognitive dysfunction (OR 1.71, 95% CI 1.25–2.35), when the effect of the autonomous community was controlled for. In patients with ICU admission, treatment was conforming in 45.1% (95% CI 34.1–56.1%) of patients and was associated with the hospital visits in the last year (<3 vs. ⩾3, OR 2.70, 95% CI 1.03–7.12) and there was some evidence that this was associated with season. Although the reference guidelines are national, wide variability between autonomous communities was found. In patients hospitalised due to CAP, health services should guarantee the administration of antibiotics in a consensual manner that is conforming according to clinical practice guidelines.
Background: In RRMS patients with inadequate response to prior therapy, 2 alemtuzumab courses (12 mg/day; baseline: 5 days; 12 months later: 3 days) significantly improved outcomes versus SC IFNB-1a over 2 years (CARE-MS II [NCT00548405]). Efficacy remained durable in a 4-year extension (NCT00930553); patients could receive as-needed alemtuzumab retreatment (≥12 months apart) for disease activity, or another disease-modifying therapy (DMT). Through Year 6, 88% remained on study; 50% received neither alemtuzumab retreatment nor another DMT; 16% received ≥4 courses; 3% received ≥5 courses. We evaluated Course 4 (C4) efficacy in patients receiving ≥4 courses. Methods: Annualized relapse rate (ARR); improved/stable Expanded Disability Status Scale (EDSS) score (versus baseline); 6-month confirmed disability improvement (CDI). 11% of patients met inclusion criteria: ≥4 courses within 60 months of baseline; no DMT. Those receiving C5 were censored at that time. Results: ARR decreased after C4 (12 months pre-C4 [-12M]: 0.75; 12 months post-C4 [+12M]: 0.19; P<0.0001), remaining low (0.23) at Year 3 post-C4. More patients had stable/improved EDSS scores +12M (67.5%) versus at C4 administration (53.5%). Percentage with CDI increased post-C4 (-12M: 10.0%; +12M: 26.7%). Conclusions: C4 reduced relapses and stabilized/improved disability in patients with disease activity after initial treatment (C1, C2) plus one additional course (C3).
A novel method to perform small-scale laboratory experiments that reproduce concrete–bentonite and concrete–groundwater interactions has been developed. Such interfaces will prevail in engineered barrier systems used for isolation of nuclear waste. With the goal of optimizing the experimental method, this work has analysed the geochemical interaction of distilled water, low-pH cement mortar and FEBEX-bentonite for 75 days. Limited but evident reactivity between the materials was observed, mainly decalcification in cement mortar, carbonation at the interface with bentonite and Mg enrichment in bentonite. These results are consistent with the state-of-the-art literature and were used to validate this small-scale pilot laboratory experiment to establish the basis for further studies comparing the behaviour of different buffer and cement materials.
The Morrón de Mateo bentonite deposit has been studied as a natural analogue of the thermal effect on the bentonite barrier of a geological radioactive waste repository. This deposit was intruded by a volcanic dome that induced hydrothermal activity affecting the smectite clay minerals close to the dome. Previous studies of proximal bentonites indicated that Al-montmorillonites were transformed into Fe-rich smectites with intermediate composition between beidellite and saponite through gradual steps formed by smectites increasingly rich in Mg and Fe. In order to confirm the suggested transformation and the Fe distribution into the smectites, infrared and Mössbauer spectroscopy studies were performed. Infrared spectra of samples away from the dome show typical bands for montmorillonite type with prevailing Al in octahedral positions, while proximal samples also show bands of Fe-rich smectites. Mössbauer data confirm that Fe present in the fine fraction of bentonites is fundamentally located in the smectites structure, mainly as octahedrally coordinated Fe(III). Proximal smectites have a considerably more distorted octahedral environment for Fe(III) which probably stemmed from a significant degree of substitution of Al by Fe(III). These results confirm that an alteration process occurred related to the volcanic intrusion which produced an increase in temperature and Fe-rich solutions responsible for the transformation of Al-montmorillonites.
The present study was designed to describe the effects of early feed restriction of Merino lambs on feed efficiency during the fattening period by examining ruminal microbiota and fermentation parameters, gastrointestinal morphology, digestibility or liver proteome. In total, 24 male Merino lambs were randomly assigned to two experimental treatments (n=12 per treatment). Lambs of the first group (ad libitum (ADL)) were kept permanently with the dams, whereas the other 12 lambs (restricted (RES)) were milk restricted. When lambs reached a live BW (LBW) of 15 kg, all the animals were offered the same complete pelleted diet (35 g dry matter/kg LBW per day) until slaughter at a LBW of 27 kg. The RES lambs showed poorer feed efficiency during the fattening period when compared with the ADL group (feed to gain ratio, 3.69 v. 3.05, P<0.001). No differences were observed in ruminal microbiota, fermentation parameters or apparent digestibility. However, the proportion of the small intestine and the length of ileal villi were reduced in the RES lambs. In total, 26 spots/proteins were identified in the liver proteomic profile, with significant differences (P<0.05) between experimental treatments, suggesting a higher catabolism of proteins and a reduction in β-oxidation of fatty acids in RES lambs when compared with the ADL animals. In conclusion, early feed restriction of Merino lambs during the suckling period promotes long-term effects on the small intestine and the proteomic profile of the liver, which may influence the metabolic use of nutrients, thus negatively affecting feed efficiency during the fattening phase.