While higher intake of fish and lower consumption of red/processed meats have been suggested to play a protective role in the etiology of several cancers, prospective evidence for hepatocellular ...carcinoma (HCC) is limited, particularly in Western European populations.
The associations of fish and meats with HCC risk were analyzed in the EPIC cohort. Between 1992 and 2010, 191 incident HCC were identified among 477 206 participants. Baseline diet was assessed using validated dietary questionnaires. A single 24-h diet recall from a cohort subsample was used for calibration. Multivariable proportional hazard regression was utilized to estimate hazard ratios (HR) and 95% confidence intervals (CI). In a nested case–control subset (HCC = 122), HBV/HCV status and liver function biomarkers were measured.
HCC risk was inversely associated with intake of total fish (per 20 g/day increase, HR = 0.83, 95% CI 0.74–0.95 and HR = 0.80, 95% CI 0.69–0.97 before and after calibration, respectively). This inverse association was also suggested after adjusting for HBV/HCV status and liver function score (per 20-g/day increase, RR = 0.86, 95% CI 0.66–1.11 and RR = 0.74, 95% CI 0.50–1.09, respectively) in a nested case–control subset. Intakes of total meats or subgroups of red/processed meats, and poultry were not associated with HCC risk.
In this large European cohort, total fish intake is associated with lower HCC risk.
While host immune receptors detect pathogen-associated molecular patterns to activate immunity, pathogens attempt to deregulate host immunity through secreted effectors. Fungi employ LysM effectors ...to prevent recognition of cell wall-derived chitin by host immune receptors, although the mechanism to compete for chitin binding remained unclear. Structural analysis of the LysM effector Ecp6 of the fungal tomato pathogen Cladosporium fulvum reveals a novel mechanism for chitin binding, mediated by intrachain LysM dimerization, leading to a chitin-binding groove that is deeply buried in the effector protein. This composite binding site involves two of the three LysMs of Ecp6 and mediates chitin binding with ultra-high (pM) affinity. Intriguingly, the remaining singular LysM domain of Ecp6 binds chitin with low micromolar affinity but can nevertheless still perturb chitin-triggered immunity. Conceivably, the perturbation by this LysM domain is not established through chitin sequestration but possibly through interference with the host immune receptor complex. DOI:http://dx.doi.org/10.7554/eLife.00790.001.
The trend in synchrotron radiation (x-rays) is towards higher brilliance. This may lead to a very high power density, of the order of hundreds of watts per square millimetre at the x-ray optical ...elements. These elements are, typically, windows, polarizers, filters and monochromators. The preferred material for Bragg diffracting optical elements at present is silicon, which can be grown to a very high crystal perfection and workable size as well as rather easily processed to the required surface quality. This allows x-ray optical elements to be built with a sufficient degree of lattice perfection and crystal processing that they may preserve transversal coherence in the x-ray beam. This is important for the new techniques which include phase-sensitive imaging experiments like holo-tomography, x-ray photon correlation spectroscopy, coherent diffraction imaging and nanofocusing. Diamond has a lower absorption coefficient than silicon, a better thermal conductivity and lower thermal expansion coefficient which would make it the preferred material if the crystal perfection (bulk and surface) could be improved. Synthetic HPHT-grown (high pressure, high temperature) type Ib material can readily be produced in the necessary sizes of 4-8 mm square and with a nitrogen content of typically a few hundred parts per million. This material has applications in the less demanding roles such as phase plates: however, in a coherence-preserving beamline, where all elements must be of the same high quality, its quality is far from sufficient. Advances in HPHT synthesis methods have allowed the growth of type IIa diamond crystals of the same size as type Ib, but with substantially lower nitrogen content. Characterization of this high purity type IIa material has been carried out with the result that the crystalline (bulk) perfection of some of the HPHT-grown materials is approaching the quality required for the more demanding applications such as imaging applications and imaging applications with coherence preservation. The targets for further development of the type IIa diamond are size, crystal perfection, as measured by the techniques of white beam and monochromatic x-ray diffraction imaging (historically called x-ray topography), and also surface quality. Diamond plates extracted from the cubic growth sector furthest from the seed of the new low strain material produces no measurable broadening of the x-ray rocking curve width. One measures essentially the crystal reflectivity as defined by the intrinsic reflectivity curve (Darwin curve) width of a perfect crystal. In these cases the more sensitive technique of plane wave topography has been used to establish a local upper limit of the strain at the level of an 'effective misorientation' of 10(-7) rad.
The vast majority of piglets reared in the European Union (EU) and worldwide is tail docked to reduce the risk of being tail bitten, even though EU animal welfare legislation bans routine tail ...docking. Many conventional herds experience low levels of tail biting among tail docked pigs, however it is not known, what the prevalence would have been had the pigs not been tail docked. The aim of this study was to compare the prevalence of tail lesions between docked and undocked pigs in a conventional piggery in Denmark with very low prevalence of tail biting among tail docked pigs. The study included 1922 DanAvl Duroc×(Landrace×Large White) female and castrated male pigs (962 docked and 960 undocked). Docked and undocked pigs were housed under the same conditions in the same room but in separate pens with 20 (±0.03) pigs/pen. Pigs had ad libitum access to commercial diets in a feed dispenser. Manipulable material in the form of chopped straw was provided daily on the floor (~10 g/pig per day), and each pen had two vertically placed soft wood boards. From weaning to slaughter, tail wounds (injury severity and freshness) were scored every 2nd week. No clinical signs of injured tails were observed within the tail docked group, whereas 23.0% of the undocked pigs got a tail lesion. On average, 4.0% of the pigs with undocked tails had a tail lesion on tail inspection days. More pens with tail lesions were observed among pigs weighing 30 to 60 kg (34.3%; P<0.05) than in pens with pigs weighing 7 to 30 kg (13.0%) and 60 to 90 kg (12.8%). Removal of pigs to a hospital pen was more likely in undocked pens (P<0.05, 47.7% undocked pens and 22.9% docked pens). Finally, abattoir meat inspection data revealed more tail biting remarks in undocked pigs (P<0.001). In conclusion, this study suggests that housing pigs with intact tails in conventional herds with very low prevalence of tail biting among tail docked pigs, will increase the prevalence of pigs with tail lesions considerably, and pig producers will need more hospital pens. Abattoir data indicate that tail biting remarks from meat inspection data severely underestimate on-farm prevalence of tail lesions.
The entrainment and impingement of fish into water diversion infrastructure is one of the several factors contributing to their decline. Here, controlled experiments assessed the potential for a ...behavioral guidance device a light-emitting diode (LED) light array strobing at various spectra to reduce the entrainment of juvenile Chinook salmon (
Oncorhynchus tshawytscha
) into a water diversion pipe. Fish were tested during the day and night, and under control conditions (light off) and red, blue, and white spectra strobing at 2 Hz. Fish entrainment into the diversion pipe was evaluated. Results indicated greater entrainment at night compared to day. All trials at night with the LED light strobing had higher entrainment than the control, with blue and white spectra corresponding to greater entrainment than red spectra. During the day, the white spectra treatment was different from the red treatment, with lower entrainment. LED lights employed to repel migratory juvenile salmon away from water intake structures may be ineffectual but there is potential for the light to be used as an attractant to guide fish towards desirable features such as “safe” areas (bypass channels or fishways).
Mutations in the gene for desmoplakin (DSP) may cause arrhythmogenic right ventricular cardiomyopathy (ARVC) and Carvajal syndrome (CS). Desmoplakin is part of all desmosomes, which are abundantly ...expressed in both myocardial and epidermal tissue and serve as intercellular mechanical junctions. This study aimed to investigate protein expression in myocardial and epidermal tissue of ARVC and CS patients carrying DSP mutations in order to elucidate potential molecular disease mechanisms. Genetic investigations identified three ARVC patients carrying different heterozygous DSP mutations in addition to a homozygous DSP mutation in a CS patient. The protein expression of DSP in mutation carriers was evaluated in biopsies from myocardial and epidermal tissue by immunohistochemistry. Keratinocyte cultures were established from skin biopsies of mutation carriers and characterized by reverse transcriptase polymerase chain reaction, western blotting, and protein mass spectrometry. The results showed that the mutation carriers had abnormal DSP expression in both myocardial and epidermal tissue. The investigations revealed that the disease mechanisms varied accordingly to the specific types of DSP mutation identified and included haploinsufficiency, dominant‐negative effects, or a combination hereof. Furthermore, the results suggest that the keratinocytes cultured from patients are a valuable and easily accessible resource to elucidate the effects of desmosomal gene mutations in humans.
Tail biting is a welfare and economical concern in modern pig production. One common preventive measure used throughout the world is tail docking, which is generally considered one of the most ...effective methods for limiting tail biting. However, tail docking is a painful mutilation and systematic tail docking is not allowed in the EU. Therefore, the aim was to compare pig behaviour and the prevalence of tail biting in finishing pigs with intact tails housed in two different pen designs under Danish commercial conditions. PEN1 was a traditional Danish pen and PEN2 was inspired by Swedish finisher pen design and had a larger proportion of solid floor area (PEN1: 1/3 and PEN2: 2/3), reduced group size (PEN1: 15 and PEN2: 12), increased space allowance per head (PEN1: 0.7 m2 and PEN2: 0.89 m2) and straw allocated on the floor (PEN2) whereas straw was provided in a straw rack in PEN1. Tail damage observations were carried out daily by the stockperson and every 2 weeks one trained research technician assessed tail damages according to a tail scoring system. Tail lesions were observed in 51% of PEN1 and in 11% of PEN2 (P < 0.001). PEN1 had higher prevalence of tail damages than PEN2 (23% v. 5%, P < 0.001). Behavioural observations were carried out by the use of video recordings. Pigs in PEN2 tended to spend more time on tail-directed behaviour than pigs in PEN1 (P = 0.07), whereas pigs in PEN1 tended to spend more time on ear-directed behaviour (P = 0.08). Pigs in PEN2 spent more time on straw-directed behaviour compared to pigs in PEN1 (P < 0.001). Pen design did not affect time spent on other penmate-directed behaviour. In addition, the level of welfare between the two pen designs was compared using the Welfare Quality® protocol. PEN2 received an overall score of ‘excellent’ while PEN1 scored ‘enhanced’. PEN2 scored higher on all principles besides ‘good health’, where PEN1 scored better on lameness and wounds. The main measurements accounting for the differences were water supply, huddling, tail biting, social behaviour and fear of humans. In conclusion, the combination of increased space allowance, increased area of solid flooring, straw allocated onto the floor and reduced group size (PEN2) resulted in fewer tail damaged pigs and a better overall welfare assessment, despite a tendency for more tail-directed behaviour.
Summary
To address uncertainty of whether clinical stage groupings (cTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report ...data—simple descriptions of patient characteristics, cancer categories, and non–risk‐adjusted survival—for clinically staged patients from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty‐three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all‐cause mortality from first management decision. Of 22,123 clinically staged patients, 8,156 had squamous cell carcinoma, 13,814 adenocarcinoma, 116 adenosquamous carcinoma, and 37 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (18.5–25 mg/kg2, 47%), little weight loss (2.4 ± 7.8 kg), 0‐1 ECOG performance status (67%), and history of smoking (67%). Cancers were cT1 (12%), cT2 (22%), cT3 (56%), cN0 (44%), cM0 (95%), and cG2‐G3 (89%); most involved the distal esophagus (73%). Non–risk‐adjusted survival for squamous cell carcinoma was not distinctive for early cT or cN; for adenocarcinoma, it was distinctive for early versus advanced cT and for cN0 versus cN+. Patients with early cancers had worse survival and those with advanced cancers better survival than expected from equivalent pathologic categories based on prior WECC pathologic data. Thus, clinical and pathologic categories do not share prognostic implications. This makes clinically based treatment decisions difficult and pre‐treatment prognostication inaccurate. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient characteristics, cancer categories, and treatment characteristics and should direct 9th edition data collection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Our objective was to determine if methods for preparing total mixed ration TMR; horizontal paddle mixer with knives (PK) vs. vertical auger (VA) mixer would alter the physical form of the TMR and ...affect utilization of diets with increasing amounts of modified wet distillers grains with solubles (MWDGS). Holstein cows (n = 24 with 12 ruminally cannulated; 144 d in milk ± 31 d at start) were used in a split-plot design with mixer type as the whole plot and MWDGS concentrations as subplots in a replicated 3 × 3 Latin square arrangement with 35-d periods. Inclusion rates of MWDGS were 10, 20, and 30% of dietary dry matter, primarily replacing corn, soybean meal, soyhulls, and whole cottonseed. Feed dry matter intake (DMI) was less for PK (23.8 kg/d) than for VA (25.7 kg/d), but was unaffected by MWDGS concentration. Milk production did not differ by concentration of MWDGS or by interaction of MWDGS × mixer. Milk fat percentage declined with increasing MWDGS but the interaction between mixer and MWDGS showed that decreases were larger with VA mixing. Cows fed the diet containing 30% MWDGS mixed with PK averaged 3.45% (1.24 kg/d) milk fat, whereas cows fed the same diet mixed with VA averaged 2.81% (1.10 kg/d) fat. Concentrations of trans-10,cis-12 C18:2 in milk fat likely explain the differences observed in milk fat yield; the concentration of trans-10,cis-12 C18:2 increased as MWDGS was increased and the MWDGS × mixer interaction showed that VA had greater concentrations. Greater mean particle size and increased variation in particle size with VA may partially explain differences in milk fat via increased sorting that allowed for an altered rumen environment and favored alternative biohydrogenation pathways. Feed conversion efficiency (FCE; energy-corrected milk/DMI) decreased linearly as MWDGS increased, but FCE tended to be maintained when higher MWDGS diets were mixed using PK rather than VA. Ruminal pH and ammonia concentration decreased linearly as MWDGS increased. The PK mixer resulted in greater FCE when higher amounts of MWDGS were fed, primarily because milk fat content and yield were not as depressed and DMI was lower at similar milk yields.
Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, ...including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways.
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