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 firstname.lastname@example.org
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.
Filarial nematodes possess glutathione transferases (GSTs), ubiquitous enzymes with the potential to detoxify xenobiotic and endogenous substrates, and modulate the host immune system, which may aid worm infection establishment, maintenance and survival in the host. Here we have identified and characterized a σ class glycosylated GST (OoGST1), from the cattle-infective filarial nematode Onchocerca ochengi, which is homologous (99% amino acid identity) with an immunodominant GST and potential vaccine candidate from the human parasite, O. volvulus, (OvGST1b). Onchocerca ochengi native GSTs were purified using a two-step affinity chromatography approach, resolved by 2D and 1D SDS-PAGE and subjected to enzymic deglycosylation revealing the existence of at least four glycoforms. A combination of lectin-blotting and mass spectrometry (MS) analyses of the released N-glycans indicated that OoGST1 contained mainly oligomannose Man5GlcNAc2 structure, but also hybrid- and larger oligommanose-type glycans in a lower proportion. Furthermore, purified OoGST1 showed prostaglandin synthase activity as confirmed by Liquid Chromatography (LC)/MS following a coupled-enzyme assay. This is only the second reported and characterized glycosylated GST and our study highlights its potential role in host-parasite interactions and use in the study of human onchocerciasis.
The value of the nosological distinction between non-affective and affective psychosis has frequently been challenged. We aimed to investigate the transdiagnostic dimensional structure and associated characteristics of psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic categories, we expected that positive symptoms occurred more frequently in ethnic minority groups and in more densely populated environments, and that negative symptoms were associated with indices of neurodevelopmental impairment.
This study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Symptom ratings were analysed using multidimensional item response modelling in Mplus to estimate five theory-based models of psychosis. We used multiple regression models to examine demographic and context factors associated with symptom dimensions.
A bifactor model, composed of one general factor and five specific dimensions of positive, negative, disorganization, manic and depressive symptoms, best-represented associations among ratings of psychotic symptoms. Positive symptoms were more common in ethnic minority groups. Urbanicity was associated with a higher score on the general factor. Men presented with more negative and less depressive symptoms than women. Early age-at-first-contact with psychiatric services was associated with higher scores on negative, disorganized, and manic symptom dimensions.
Our results suggest that the bifactor model of psychopathology holds across diagnostic categories of non-affective and affective psychosis at FEP, and demographic and context determinants map onto general and specific symptom dimensions. These findings have implications for tailoring symptom-specific treatments and inform research into the mood-psychosis spectrum.
Next-generation 21cm observations will enable imaging of reionization on very large scales. These images will contain more astrophysical and cosmological information than the power spectrum, and hence providing an alternative way to constrain the contribution of different reionizing sources populations to cosmic reionization. Using Convolutional Neural Networks, we present a simple network architecture that is sufficient to discriminate between Galaxy-dominated versus AGN-dominated models, even in the presence of simulated noise from different experiments such as the HERA and SKA.
Le Français commun dit régulièrement, comme chacun sait, C’est le plus beau blé qu’il yAITsur le marché, construisant au subjonctif le verbe de la proposition subordonnée. Un trait du parler populaire de la région de Québec — observé aussi ailleurs au Canada français — consiste à substituer ici au subjonctif, lorsque le verbe est un verbe d’existence, un indicatif accompagné de la négation (réduite à pas) et à dire: C’est le plus beau blé qu’il y A PAS sur le marché.
Cet emploi en apparence aberrant de la négation est-il une innovation du français canadien ou représente-t-il, au contraire, l’usage ancien d’un des divers parlers régionaux français apportés en Nouvelle-France aux XVIIe et XVIIIe siècles? Ce n’est pas notre intention d’éclairer ce point d’histoire. Notre propos est tout différent. Prenant acte des deux usages observés et de leur divergeance, nous démontrerons—en nous appuyant, pour ce faire, sur l’analyse psychomécanique du langage du linguiste français Gustave Guillaume — que, en face de la nuance de pensée à exprimer, les deux manières de dire s’équipollent, la négation d’une forme verbale indicative produisant en l’occurrence le même effet de sens que l’emploi affirmatif d’une forme de subjonctif.
Les notes que nous avons réunies dans le présent article sur le schwa en franco-canadien, ont été rédigées d’après des textes oraux enregistrés sur ruban magnétique. Ces textes constituent quatre contes de folklore du comté de Charlevoix, et ils représentent approximativement deux heures et demie de débit oral. Les sujets parlants sont des cultivateurs originaires de cette région de la province de Québec qui se situe à quelques 70 milles au nord-est de la ville de Québec, sur la rive nord du fleuve Saint-Laurent. Nous tenons à ajouter que la plupart des faits que nous signalerons ont été notés également dans le parler populaire, et à un moindre degré, dans le parler familier de la ville de Québec.
National Institute for Health and Care Excellence have recommended faecal calprotectin (FC) testing as an option in adults with lower gastrointestinal symptoms for whom specialist investigations are being considered, if cancer is not suspected and it is used to support a diagnosis of inflammatory bowel disease (IBD) or irritable bowel syndrome. York Hospital and Vale of York Clinical Commissioning Group have developed an evidence-based care pathway to support this recommendation for use in primary care. It incorporates a higher FC cut-off value, a ‘traffic light’ system for risk and a clinical management pathway.
To evaluate this care pathway.
The care pathway was introduced into five primary care practices for a period of six months and the clinical outcomes of patients were evaluated. Negative and positive predictive values (NPV and PPV) were calculated. GP feedback of the care pathway was obtained by means of a web-based survey. Comparator gastroenterology activity in a neighbouring trust was obtained.
The care pathway for FC in primary care had a 97% NPV and a 40% PPV. This was better than GP clinical judgement alone and doubled the PPV compared with the standard FC cut-off (<50 mcg/g), without affecting the NPV. In total, 89% of patients with IBD had an FC>250 mcg/g and were diagnosed by ‘straight to test’ colonoscopy within three weeks. The care pathway was considered helpful by GPs and delivered a higher diagnostic yield after secondary care referral (21%) than the conventional comparator pathway (5%).
A care pathway for the use of FC that incorporates a higher cut-off value, a ‘traffic light’ system for risk and supports clinical decision making can be achieved safely and effectively. It maintains the balance between a high NPV and an acceptable PPV. A modified care pathway for the use of FC in primary care is proposed.
Inflammation and diet have been suggested to be important risk factors for hepatocellular cancer (HCC). This Italian multicentre hospital-based case–control study conducted between 1999 and 2002 and including 185 cases with incident, histologically confirmed HCC, and 404 controls hospitalised for acute non-neoplastic diseases provided an opportunity to investigate the association between HCC and the dietary inflammatory index (DII). The DII was computed on the basis of dietary intake assessed 2 years before the date of interview by a validated sixty-three-item FFQ. Logistic regression models were used to estimate OR adjusted for age, sex, study centre, education, BMI, smoking, physical activity, serum markers of hepatitis B and C infection and energy intake. Energy adjustment for DII was performed using the residual method. Participants in the highest tertile of DII scores (i.e. with a more pro-inflammatory diet) had a higher risk for HCC (ORtertile 3 v, 1 2·43; 95 % CI 1·27, 4·68; Ptrend=0·03). When stratified by the presence or absence of hepatitis B/C infection and sex, DII was strongly associated with HCC in hepatitis B- and C-negative participants (ORtertile 3 v. 1 4·18; 95 % CI 1·53, 11·39; Ptrend=0·02) and among males (ORtertile 3 v. 1 3·60; 95 % CI 1·65, 7·87; Ptrend=0·001). These results indicate that a pro-inflammatory diet is associated with increased risk for HCC, in those without a history of hepatitis B/C infection and among males.
The relation between inflammation deriving from diet and endometrial cancer risk has not yet been investigated. In this study, we explored the association between the dietary inflammatory index (DII) and endometrial cancer risk in an Italian case–control study. Cases comprised 454 patients with incident, histologically confirmed carcinoma of the endometrium, and controls comprised 908 subjects admitted to the same network of hospitals as cases for a wide spectrum of acute, non-neoplastic conditions. DII scores were computed on the basis of dietary intake assessed using a reproducible and valid seventy-eight-item FFQ. OR were calculated through logistic regression models conditioned on age and study centre and adjusted for recognised confounding factors, including total energy intake. Women with the most pro-inflammatory diet had a higher risk for endometrial cancer compared with women with the most anti-inflammatory diet (ORQuartile 4 v. 1 1·46; 95 % CI 1·02, 2·11; Ptrend=0·04). A pro-inflammatory diet may increase the risk for endometrial cancer.
Only one prospective study has analysed the relationship between the inflammatory properties of diet and risk of depression thus far. The aim of this study was to assess the association between the dietary inflammatory index (DII) and the incidence of depression. In a cohort study of 15 093 university graduates, participants completed a validated FFQ at baseline and after 10 years of follow-up. The DII was calculated based on the FFQ. Each of the twenty-eight nutrients or foods received a score based on findings from the peer-reviewed literature reporting on the relationships between diet and inflammatory biomarkers (IL-1β, IL-4, IL-6, IL-10, TNF-α and C-reactive protein). Participants were classified as having depression if they reported a new clinical diagnosis of depression by a physician, antidepressant drugs, or both. Multivariable Cox regression models were used to estimate hazard ratios (HR) of depression according to quintiles of the DII. After a median 8·5 years of follow-up, we observed 1051 incident cases of depression. The HR for participants in the highest quintile of DII (strongly pro-inflammatory) was 1·47 (95 % CI 1·17, 1·85) compared with those in the bottom quintile, with a significant dose–response relationship (Ptrend=0·01). In the subgroup analyses, the association between DII and depression was stronger among participants >55 years and among those with cardiometabolic comorbidities (HR 2·70; 95 % CI 1·22, 5·97 and HR 1·80; 95 % CI 1·27, 2·57, respectively). A pro-inflammatory diet was associated with a significantly higher risk of depression in a Mediterranean population. This association was stronger among older subjects and subjects with cardiometabolic diseases.
Diet and inflammation have been suggested to be important risk factors for colorectal cancer (CRC). In the present study, we examined the association between the dietary inflammatory index (DII) and the risk of CRC in a multi-centre case–control study conducted between 1992 and 1996 in Italy. The study included 1225 incident colon cancer cases, 728 incident rectal cancer cases and 4154 controls hospitalised for acute non-neoplastic diseases. The DII was computed based on dietary intake assessed using a validated seventy-eight-item FFQ that included assessment of alcohol intake. Logistic regression models were used to estimate the OR adjusted for age, sex, study centre, education, BMI, alcohol drinking, physical activity and family history of CRC. Energy intake was adjusted using the residual method. Subjects with higher DII scores (i.e. with a more pro-inflammatory diet) had a higher risk of CRC, with the DII being used both as a continuous variable (ORcontinuous 1·13, 95 % CI 1·09, 1·18) and as a categorical variable (ORquintile 5 v. 1 1·55, 95 % CI 1·29, 1·85; P for trend < 0·0001). Similar results were observed when the analyses were carried out separately for colon and rectal cancer cases. These results indicate that a pro-inflammatory diet is associated with an increased risk of CRC.
Previous studies have shown that various dietary components may be implicated in the aetiology of pancreatic cancer. However, the possible relationship between diet-related inflammation and the risk of pancreatic cancer has not yet been investigated. We examined the ability of a newly developed literature-derived dietary inflammatory index (DII) to predict the risk of pancreatic cancer in a case–control study conducted in Italy between 1991 and 2008. This included 326 incident cases and 652 controls admitted to the major teaching and general hospitals for non-neoplastic diseases, frequency-matched to cases by study centre, sex and age. The DII was computed based on dietary intake assessed using a validated and reproducible seventy-eight-item FFQ. Logistic regression models were used to estimate multivariable OR adjusted for age, sex, study centre, education, BMI, smoking status, alcohol drinking and history of diabetes. Energy adjustment was performed using the residual method. Subjects with higher DII scores (i.e. representing a more pro-inflammatory diet) had a higher risk of pancreatic cancer, with the DII being used as both a continuous variable (ORcontinuous 1·24, 95 % CI 1·11, 1·38) and a categorical variable (i.e. compared with the subjects in the lowest quintile of the DII, those in the second, third, fourth and fifth quintiles had, respectively, ORquintile2 v. 1 1·70, 95 % CI 1·02, 2·80; ORquintile3 v. 1 1·91, 95 % CI 1·16, 3·16; ORquintile4 v. 1 1·98, 95 % CI 1·20, 3·27; ORquintile5 v. 1 2·48, 95 % CI 1·50, 4·10; Ptrend= 0·0015). These data suggest that a pro-inflammatory diet increases the risk of pancreatic cancer.
Previous studies have shown that various dietary components may be implicated in the aetiology of prostate cancer, although the results remain equivocal. The possible relationship of inflammation derived from dietary exposures with prostate cancer risk has not been investigated. We examined the ability of a newly developed dietary inflammatory index (DII) to predict prostate cancer risk in a case–control study conducted in Italy between 1991 and 2002. A total of 1294 patients aged < 75 years with incident, histologically confirmed carcinoma of the prostate served as cases. A total of 1451 subjects aged < 75 years who were admitted to the same hospitals as cases for a wide spectrum of acute, non-neoplastic conditions served as controls. The DII was computed based on dietary intake assessed using a previously validated seventy-eight-item FFQ. Logistic regression models were used to estimate multivariable OR adjusted for age, study centre, years of education, social class, BMI, smoking status, family history of prostate cancer and total energy intake. Men with higher DII scores had a higher risk of prostate cancer when analysed using the DII as both continuous (OR 1·06, 95 % CI 1·00, 1·13) and categorical, i.e. compared with men in the lowest quartile of the DII, men in the third and fourth quartiles were at elevated risk (ORQuartile 3 v. 1 1·32, 95 % CI 1·03, 1·69 and ORQuartile 4 v. 1 1·33, 95 % CI 1·01, 1·76; Ptrend= 0·04). These data suggest that a pro-inflammatory diet, as indicated by the increasing DII score, is a risk factor of prostate cancer in Italian men.
We reviewed photographic images of fishes from depths of 381–2282 m in Marguerite Bay and 405–2007 m in the Amundsen Sea. Marguerite Bay fishes were 33% notothenioids and 67% non-notothenioids. Channichthyids (47%) and nototheniids (44%) were the most abundant notothenioids. The deep-living channichthyid Chionobathyscus dewitti (74%) and the nototheniid genus Trematomus (66%) were the most abundant taxa within these two families. The most abundant non-notothenioids were the macrourid Macrourus whitsoni (72%) and zoarcids (18%). Amundsen Sea fishes were 87% notothenioids and 13% non-notothenioids, the latter exclusively Macrourus whitsoni. Bathydraconids (38%) and artedidraconids (30%) were the most abundant notothenioids. We observed that Macrourus whitsoni was benthopelagic and benthic and infested by large ectoparasitic copepods. Juvenile (42 cm) Dissostichus mawsoni was not neutrally buoyant and resided on the substrate at 1277 m. Lepidonotothen squamifrons was seen near and on nests of eggs in early December. A Pogonophryne sp. from 2127 m was not a member of the deep-living unspotted P. albipinna group. Chionobathyscus dewitti inhabited the water column as well as the substrate. The pelagic zoarcid Melanostigma gelatinosum was documented in the water column a few metres above the substrate. The zoogeographic character of the Marguerite Bay fauna was West Antarctic or low-Antarctic and the Amundsen Sea was East Antarctic or high-Antarctic.
Current assessments of bioburden embedded in spacecraft materials are based on work performed in the Viking era (1970s), and the ability to culture organisms extracted from such materials. To circumvent the limitations of such approaches, DNA-based techniques were evaluated alongside established culturing techniques to determine the recovery and survival of bacterial spores encapsulated in spacecraft-qualified polymer materials. Varying concentrations of Bacillus pumilus SAFR-032 spores were completely embedded in silicone epoxy. An organic dimethylacetamide-based solvent was used to digest the epoxy and spore recovery was evaluated via gyrB-targeted qPCR, direct agar plating, most probably number analysis, and microscopy. Although full-strength solvent was shown to inhibit the germination and/or outgrowth of spores, dilution in excess of 100-fold allowed recovery with no significant decrease in cultivability. Similarly, qPCR (quantitative PCR) detection sensitivities as low as ∼103 CFU ml−1 were achieved upon removal of inhibitory substances associated with the epoxy and/or solvent. These detection and enumeration methods show promise for use in assessing the embedded bioburden of spacecraft hardware.
Raman spectroscopy is used to characterize silicon implanted with boron at a dose of 1014/cm2 or less and thermally annealed. The Raman scattering strengths and band shapes of the first-order optical mode at 520 cm-1 and of the second-order phonon modes are investigated to determine which modes are sensitive to the boron implant. The asimplanted samples show diminishing Raman scattering strength as the boron dose increases when the incident laser beam is 60° with respect to the sample normal. Thermal annealing restores some of the Raman scattering strength. Three excitation wavelengths are used and the shortest, 457.9 nm, yields the greatest spectral differences from unimplanted silicon. The backscattering geometry shows a variety of changes in the Raman spectrum upon boron implantation. These involve band shifts of the first-order optical mode, bandwidth variations of the first-order optical mode, and the intensity of the second-order mode at 620 cm-1.
The Fast Multipole Method (FMM) offers an efficient way (order O(N)) to handle long range electrostatic interactions, thus enabling more realistic molecular dynamics simulations of large molecular systems. The performance of the fast molecular dynamics (FMD) code, a parallel MD code being developed in our group, using the three-dimensional fast multipole method, shows a good speedup. The application to the full atomic-scale molecular dynamics simulation of a liquid crystalline droplet of 4-n-pentyl-4'-cyanobiphenyl (5CB) molecules, of size 35,872 atoms, shows strong surface effects on various orientational order parameters.
The science of extra-solar planets is one of the most rapidly changing areas of astrophysics and since 1995 the number of planets known has increased by almost two orders of magnitude. A combination of ground-based surveys and dedicated space missions has resulted in 560-plus planets being detected, and over 1200 that await confirmation. NASA's Kepler mission has opened up the possibility of discovering Earth-like planets in the habitable zone around some of the 100,000 stars it is surveying during its 3 to 4-year lifetime. The new ESA's Gaia mission is expected to discover thousands of new planets around stars within 200 parsecs of the Sun. The key challenge now is moving on from discovery, important though that remains, to characterisation: what are these planets actually like, and why are they as they are?
In the past ten years, we have learned how to obtain the first spectra of exoplanets using transit transmission and emission spectroscopy. With the high stability of Spitzer, Hubble, and large ground-based telescopes the spectra of bright close-in massive planets can be obtained and species like water vapour, methane, carbon monoxide and dioxide have been detected. With transit science came the first tangible remote sensing of these planetary bodies and so one can start to extrapolate from what has been learnt from Solar System probes to what one might plan to learn about their faraway siblings. As we learn more about the atmospheres, surfaces and near-surfaces of these remote bodies, we will begin to build up a clearer picture of their construction, history and suitability for life.
The Exoplanet Characterisation Observatory, EChO, will be the first dedicated mission to investigate the physics and chemistry of Exoplanetary Atmospheres. By characterising spectroscopically more bodies in different environments we will take detailed planetology out of the Solar System and into the Galaxy as a whole.
EChO has now been selected by the European Space Agency to be assessed as one of four M3 mission candidates.