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Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
From 2007 to 2010, the largest reported Q-fever epidemic occurred in the Netherlands with 4026 notified laboratory-confirmed cases. During the course of the epidemic, health-seeking behaviour changed and awareness among health professionals increased. Changes in laboratory workflows were implemented. The aim of this study was to analyse how these changes instigated adjustments of notification criteria and how these adjustments affected the monitoring and interpretation of the epidemic. We used the articles on laboratory procedures related to the epidemic and a description of the changes that were made to the notification criteria. We compared the output of a regional laboratory with notifications to the regional Public Health Service and the national register of infectious diseases. We compared the international notification criteria for acute Q-fever. Screening with ELISA IgM phase II and PCR was added to the diagnostic workflow. In the course of the epidemic, serology often revealed a positive IgG/IgM result although cases were not infected recently. With increasing background seroprevalence, the presence of IgM antibodies can only be suggestive for acute Q-fever and has to be confirmed either by seroconversion of IgG or a positive PCR result. Differences in sero-epidemiology make it unlikely that full harmonisation of notification criteria between countries is feasible.
A total of eight ileal and caecal cannulated Yorkshire barrows were used to determine the interactions of dietary fibre (DF) and lipid types on apparent digestibility of DM and fatty acids (FA) and FA flows in gastrointestinal segments. Pigs were offered four diets that contained either pectin or cellulose with or without beef tallow or maize oil in two Youden square designs (n 6). Each period lasted 15 d. Faeces, ileal and caecal contents were collected to determine apparent ileal digestibility (AID), apparent caecal digestibility and apparent total tract digestibility (ATTD) of dietary components. The interactions between DF and lipid types influenced (P <0·05) the digestibility of DM and FA flows. The addition of maize oil decreased (P <0·05) AID of DM in pectin diets, and the addition of beef tallow depressed (P <0·001) ATTD of DM in cellulose diets. Dietary supplementation with beef tallow decreased (P <0·05) the AID of FA in pectin-containing diets but had no effects in cellulose-containing diets. Dietary supplementation with beef tallow increased (P <0·05) AID of SFA and PUFA and the flow of ileal oleic, vaccenic, linolenic and eicosadienoic acids and reduced the flow of faecal lauric, docosatetraenoic and docosapentaenoic acids in pectin- and cellulose-containing diets. In conclusion, the interaction between DF type and lipid saturation modulates digestibility of DM and lipids and FA flows but differs for soluble and insoluble fibre sources, SFA and unsaturated fatty acids and varies in different gastrointestinal segments.
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.
Effective integrated weed management in agricultural landscapes depends on the ability to identify and manage processes that drive weed dynamics. The current study reports the effects of grazing management and crop rotation strategies on the seedbank and emerged weed flora in an integrated crop-livestock system (ICLS) experiment during a 12-year period under no-tillage in sub-tropical southern Brazil. During winter, Italian ryegrass cover crops were grazed by sheep: grazing management treatments included two stocking methods (continuous and rotational) and two forage allowances (10 and 20 kg of herbage dry matter available per 100 kg animal live weight). During summer, the crop rotation treatments involved either soybean-maize or soybean-soybean in succession with winter-grazed cover crops. The treatments were part of a factorial randomized complete block design. Treatment effects were evaluated on the weed seedbank and emerged weed flora populations during winter-grazed cover crop and summer crop growth as well as during the harvest phase. The current results demonstrate that crop rotation and grazing management exhibited interactive effects on the determination of weed outcomes in an ICLS. However, overall, compared with moderate forage allowance, high forage allowance during the winter-grazed cover crop caused lower emerged weed flora in subsequent crops (20% reduction during crop growth and 90% reduction at crop harvest) and 48% reduction in seedbank size. High forage allowance promoted more residue from winter-grazed cover crop biomass, which remained during the summer crop phases and probably resulted in a physical barrier to weed emergence.
In recent years there has been an increasing interest in the issue of farm animal welfare. This interest stems from a belief that many modern livestock production systems do not allow animals to perform a natural range of behaviour, leading to a possible decline in welfare. One method of determining the value of natural behaviours is to perform preference tests. In dairy cows, choices relating to various treatments, including feeding, shouting, electric shock, hitting (Pajor et al., 2003) and being milked (Prescott et al., 1998) have been assessed using Y-maze methodology. This is a process that involves training animals to anticipate receiving a treatment if they enter one arm of the Y and an alternative treatment if they enter the other. We used preference tests as a tool to determine how dairy cows perceive aspects of their feeding environment, with specific emphasis on understanding what difficulties low ranking animals face at the feed-face. We hypothesised that subordinate cows would trade-off proximity to a dominant individual at the feed-face with access to food of a high quality.
Recent evidence shows that the serotonin 2A receptor (5-hydroxytryptamine2A receptor, 5-HT2AR) is critically involved in the formation of visual hallucinations and cognitive impairments in lysergic acid diethylamide (LSD)-induced states and neuropsychiatric diseases. However, the interaction between 5-HT2AR activation, cognitive impairments and visual hallucinations is still poorly understood. This study explored the effect of 5-HT2AR activation on response inhibition neural networks in healthy subjects by using LSD and further tested whether brain activation during response inhibition under LSD exposure was related to LSD-induced visual hallucinations.
In a double-blind, randomized, placebo-controlled, cross-over study, LSD (100 µg) and placebo were administered to 18 healthy subjects. Response inhibition was assessed using a functional magnetic resonance imaging Go/No-Go task. LSD-induced visual hallucinations were measured using the 5 Dimensions of Altered States of Consciousness (5D-ASC) questionnaire.
Relative to placebo, LSD administration impaired inhibitory performance and reduced brain activation in the right middle temporal gyrus, superior/middle/inferior frontal gyrus and anterior cingulate cortex and in the left superior frontal and postcentral gyrus and cerebellum. Parahippocampal activation during response inhibition was differently related to inhibitory performance after placebo and LSD administration. Finally, activation in the left superior frontal gyrus under LSD exposure was negatively related to LSD-induced cognitive impairments and visual imagery.
Our findings show that 5-HT2AR activation by LSD leads to a hippocampal–prefrontal cortex-mediated breakdown of inhibitory processing, which might subsequently promote the formation of LSD-induced visual imageries. These findings help to better understand the neuropsychopharmacological mechanisms of visual hallucinations in LSD-induced states and neuropsychiatric disorders.
In order to accurately estimate body composition at slaughter and to meet specific market targets, the influence of age at time of castration (surgical or immunological) on body composition and boar taint indicators must be determined for male pigs. In all, 48 males were randomly assigned to one of four management regimens: (1) entire male pigs (EM), (2) EM surgically castrated at ~40 kg BW and 10 weeks of age (late castrates; LC), (3) conventional, early surgical castrates (within 4 days of birth; EC) and (4) EM immunized with a gonadotropin-releasing hormone (GnRH) analog (primary dose at 30 kg BW and 8 weeks of age; booster dose at 70 kg and 14 weeks of age; IM). Pigs were fed corn and soybean meal-based diets that were not limiting in essential nutrients. Back fat was sampled on days −3, 8, 18 and 42, relative to administering the booster dose of GnRH analog at day 0, to determine androstenone concentrations (n=8 or 9/group). Fat androstenone concentrations in IM were lower than EM between days 8 and 42 after administering the booster dose (173 v. 863 ng/g, respectively; P<0.01), and were not different from surgically castrated males (EC and LC) after day 18. Slaughter occurred at ~115 kg BW, 42 days (6 weeks) after administering the booster dose for IM, and 10 and 20 weeks after surgical castration for LC and EC, respectively (n=8 or 9/group). At slaughter, live BW, liver weight as a percent of live BW, dissectible bone as a percent of cold carcass side, body protein and water contents and whole-body protein deposition decreased with time after surgical castration (linear; P<0.05), whereas dressing percentage, dissectible fat, probe fat depth and body fat content increased with time after surgical castration (linear; P<0.05). The IM had intermediate dressing percentage and dissected fat to EM and EC, whereas liver weight as a percent of live BW and body protein and lipid contents were not different from EM. Whole-body lipid deposition tended to be greater in IM than in EM between 14 and 20 weeks of age (373 v. 286 g/d; P=0.051). In conclusion, castration of male pigs after 6 weeks of age has a lasting effect on physical and chemical body composition. The relationship between time after castration and body composition may be developed to predict carcass composition and can be used to determine the ideal immunization schedule aimed at specific markets in the future.
Introduction: Redirecting low acuity patients from emergency departments to primary care walk-in clinics has been identified as a priority by many health authorities. Promoting family physicians for the management of ambulatory patients with urgent health concerns reflects the assumption that primary care facilities can offer high-quality and more affordable ambulatory emergency care. However, no performance assessment framework has been developed for ambulatory emergency care and consequently, quality of care provided in these alternate settings has never been formally compared. Primary objective: To identify structure, process and outcome indicators for ambulatory emergency care. Methods: We will identify and develop quality indicators (QIs) for ambulatory emergency care using a RAND/UCLA Appropriateness Method (RAM) composed of three different steps. First, we will perform a scoping literature review to inventory 1) all previously recommended QIs assessing care provided to ambulatory emergency patients in the ED or the primary care settings; 2) all conditions evaluated with the retrieved QIs; and 3) all outcomes measured by the same QIs. Second, a steering committee composed of the research team and of international experts in performance assessment in emergency and primary care will be presented with the lists of QI-related conditions and outcomes. They will be asked to identify potential outcome indicators for ambulatory emergency care by generating any relevant combinations of one condition and one outcome (e.g. acute asthma exacerbation/re-consultation). Committee members will be given the latitude to use and pair any conditions or outcomes not included in the lists as long as they think the resulting indicators are compatible with the study objectives. Using a structured nominal group approach, they will combine their suggestions and refine the list of potential QIs. This list of potential outcome indicators composed of pairs “condition/outcome” will be merged with the list of already published QIs identified during the literature review. Third, as per the RAM standards, we will assemble an international multidisciplinary panel (n=20) of patients, emergency and primary care providers, researchers and decision makers, after recommendations from international emergency and primary care associations, and from the Canadian Strategy for Patient-Oriented Research (SPOR) Support Units. Through iterative rounds of ratings using both web-based survey tools and videoconferencing, panelists will independently assess all candidate QIs. They will be asked to rate on a nine-level scale to what extent each QI is a relevant and useful measure of ambulatory emergency care quality. From one round to the next, QIs with a median panelist rating score of one to three will be excluded. Those with a median score of seven or more will be automatically included in the final list. QIs with median score of four to six will be retained for future deliberations among the panelists. Rounds of ratings will be conducted until all QIs are classified. Impact: The QIs identified will be used to develop a performance assessment framework for ambulatory emergency care. This will represent an essential step toward testing the assumption that EDs and primary care walk-in clinics provide equivalent care quality to low acuity patients.
Acoustic emissions in the audio spectrum are reported from observations of laboratory experiments conducted on snow samples in uniaxial compression. A number of tests show the pattern of acoustic emissions to be a function of the rate of deformation. Over the frequency range 20 to 7 000 Hz acoustic emissions are associated with rates of deformation corresponding to brittle fracture of the snow sample. Though probably present, no acoustic emissions were detected from samples deforming plastically.
In the 1998-99 flight, BOOMERanG has produced maps of ∼4% of the sky at high Galactic latitudes, at frequencies of 90, 150, 240 and 410 GHz, with resolution ≳ 10'. The faint structure of the Cosmic Microwave Background at horizon and sub-horizon scales is evident in these maps. These maps compare well to the maps recently obtained at lower frequencies by the WMAP experiment. Here we compare the amplitude and morphology of the structures observed in the two sets of maps. We also outline the polarization sensitive version of BOOMERanG, which was flown early this year to measure the linear polarization of the microwave sky at 150, 240 and 350 GHz.
Almost nothing is known about the potential negative effects of Internet-based psychological treatments for depression. This study aims at investigating deterioration and its moderators within randomized trials on Internet-based guided self-help for adult depression, using an individual patient data meta-analyses (IPDMA) approach.
Studies were identified through systematic searches (PubMed, PsycINFO, EMBASE, Cochrane Library). Deterioration in participants was defined as a significant symptom increase according to the reliable change index (i.e. 7.68 points in the CES-D; 7.63 points in the BDI). Two-step IPDMA procedures, with a random-effects model were used to pool data.
A total of 18 studies (21 comparisons, 2079 participants) contributed data to the analysis. The risk for a reliable deterioration from baseline to post-treatment was significantly lower in the intervention v. control conditions (3.36 v. 7.60; relative risk 0.47, 95% confidence interval 0.29–0.75). Education moderated effects on deterioration, with patients with low education displaying a higher risk for deterioration than patients with higher education. Deterioration rates for patients with low education did not differ statistically significantly between intervention and control groups. The benefit–risk ratio for patients with low education indicated that 9.38 patients achieve a treatment response for each patient experiencing a symptom deterioration.
Internet-based guided self-help is associated with a mean reduced risk for a symptom deterioration compared to controls. Treatment and symptom progress of patients with low education should be closely monitored, as some patients might face an increased risk for symptom deterioration. Future studies should examine predictors of deterioration in patients with low education.
We show how estimates of parameters characterizing inflation-based theories of structure formation localized over the past year when large scale structure (LSS) information from galaxy and cluster surveys was combined with the rapidly developing cosmic microwave background (CMB) data, especially from the recent Boomerang and Maxima balloon experiments. All current CMB data plus a relatively weak prior probability on the Hubble constant, age and LSS points to little mean curvature (Ωtot = 1.08±0.06) and nearly scale invariant initial fluctuations (ns = 1.03±0.08), both predictions of (non-baroque) inflation theory. We emphasize the role that degeneracy among parameters in the Lpk = 212 ± 7 position of the (first acoustic) peak plays in defining the Ωtot range upon marginalization over other variables. Though the CDM density is in the expected range (Ωcdmh2 = 0.17 ± 0.02), the baryon density Ωbh2 = 0.030 ± 0.005 is somewhat above the independent 0.019 ± 0.002 nucleosynthesis estimates. CMB+LSS gives independent evidence for dark energy (ΩΛ = 0.66 ± 0.06) at the same level as from supernova (SN1) observations, with a phenomenological quintessence equation of state limited by SN1+CMB+LSS to wQ < −0.7 cf. the wQ=−1 cosmological constant case.
BOOMERanG has recently resolved structures on the last scattering surface at redshift ˜ 1100 with high signal to noise ratio. We review the technical advances which made this possible, and we focus on the current results for maps and power spectra, with special attention to the determination of the total mass-energy density in the Universe and of other cosmological parameters.
Fermentative catabolism (FAAC) of dietary and endogenous amino acids (AA) in the small intestine contributes to loss of AA available for protein synthesis and body maintenance functions in pigs. A continuous isotope infusion study was performed to determine whole body urea flux, urea recycling and FAAC in the small intestine of ileal-cannulated growing pigs fed a control diet (CON, 18.6% CP; n=6), a high fibre diet with 12% added pectin (HF, 17.7% CP; n=4) or a low-protein diet (LP, 13.4% CP; n=6). 15N-ammonium chloride and 13C-urea were infused intragastrically and intravenously, respectively, for 4 days. Recovery of ammonia at the distal ileum was increased by feeding additional fibre when compared with the CON (P<0.05) but was not affected by dietary protein (0.24, 0.39 and 0.14 mmol nitrogen/kg BW/day for CON, HF and LP, respectively; P<0.05). Lowering protein intake reduced urea flux (25.3, 25.7 and 10.3 mmol nitrogen/kg BW/day; P<0.01), urinary urea excretion (14.4, 15.0 and 6.2 mmol N/kg BW/day; P<0.001) and urea recycling (12.1, 11.3 and 3.23 mmol nitrogen/kg BW/day; P<0.01) compared with CON. There was a rapid reduction in 15N-ammonia enrichment in digesta along the small intestine suggesting rapid absorption of ammonia before the distal ileum and lack of uniformity of enrichment in the digesta ammonia pool. A two-pool model was developed to determine possible value ranges for nitrogen flux in the small intestine assuming rapid absorption of ammonia. Maximum estimated FAAC based on this model was significantly lower when dietary protein content was decreased (32.9, 33.4 and 17.4 mmol nitrogen/kg BW/day; P<0.001). There was no impact of dietary fibre on estimates of small intestine nitrogen flux (P>0.05) compared with CON. The two-pool model developed in the present study allows for estimation of FAAC but still has limitations. Quantifying FAAC in the small intestine of pigs, as well as other non-ruminants and humans, offers a number of challenges but warrants further investigation.
A synthetic cubic pyrochlore, Gd2Ti2O7 (Fd3̅m) irradiated with swift heavy ions is compared with a compositionally-related composition La2Ti2O7 (P21), which has a monoclinic, layered, perovskite-type structure. Irradiation experiments were performed at the GSI Helmholtz Center with 181Ta ions and 129Xe ions at specific energies of 11MeV/amu. At these energies the ions pass entirely through the sample thickness of ∼ 40 μm. Angle-dispersive synchrotron powder x-ray diffraction (XRD) measurements were completed and an increasing ion-induced amorphization with increasing ion fluence was for both phases. The ion track cross-sections for the radiation-induced crystalline-to-amorphous transformation, as determined from the evolution of the integrated peak intensities as a function of fluence, reveal that La2Ti2O7 (track diameter, d ∼ 7.2 nm with 181Ta and 5.1 nm with 129Xe) is more susceptible to amorphization than Gd2Ti2O7 (d ∼ 6.2 nm with 181Ta and 4.6 nm with 129Xe). The radiation response of the two titanate compounds can be understood in the context of their different structures and cation ionic radius ratios rA/rB, where the susceptibility of radiation of titanate pyrochlores is proportionate with this radius ratio. The higher electronic linear energy loss of the 181Ta ions as compared with 129Xe ions leads to a consistent increase of volume amorphized per ion in both materials, which manifests as a larger track diameter.
Recent findings suggest there is a complex interaction between the IGF system and the inflammatory immune response. The objective of this study was to determine whether gene expression of growth factors (IGF-1, IGF-binding protein-3 (IGFBP-3) and growth hormone receptors (GHR)) in the liver is associated with gene expression of immunomodulators in the liver, including C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp), interferon-α (IFN-α), IFN-γ, tumour necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-10 and IL-18, as well as with the presence of Salmonella spp., Lawsonia intracellularis, Brachyspira spp., enterotoxigenic Escherichia coli, methicillin-resistant Staphylococcus aureus, swine influenza virus, and porcine reproductive and respiratory syndrome virus (PRRSV) in nursery pigs (n=74) from commercial farms (n=4). Gene expression was quantified using reverse transcription quantitative-PCR (RT-qPCR) and the data were modelled using logistic regression methods. Pigs with elevated IGF-1 expression were less likely to have increased expression of TNF-α (odds ratio (OR)=0.14, P<0.01) and IL-18 (OR=0.19, P<0.05), and less likely to be colonized with PRRSV (OR=0.03, P<0.01). Pigs with increased expression of IGFBP-3 were more likely to have elevated IL-6 expression (OR=8.5, P<0.05). It was also observed that IGFBP-3 and IGF-1 were significantly associated when Hp expression was low (OR=30, P<0.05), but this association was not significant when Hp expression was high (P=0.54). Pigs with increased expression of GHR were less likely to have elevated expression of SAA (OR=0.01, P<0.05) and IL-1β (OR=0.03, P<0.05), but more likely to have increased expression of CRP (OR=290, P<0.01). Overall, there appears to be an inverse association between the hepatic expression of the IGF system (IGF-1, IGFBP-3, GHR) and certain cytokines (IL-1β, IL-18, TNF-α) and acute-phase proteins (SAA, Hp).