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Both blood- and milk-based biomarkers have been analysed for decades in research settings, although often only in one herd, and without focus on the variation in the biomarkers that are specifically related to herd or diet. Biomarkers can be used to detect physiological imbalance and disease risk and may have a role in precision livestock farming (PLF). For use in PLF, it is important to quantify normal variation in specific biomarkers and the source of this variation. The objective of this study was to estimate the between- and within-herd variation in a number of blood metabolites (β-hydroxybutyrate (BHB), non-esterified fatty acids, glucose and serum IGF-1), milk metabolites (free glucose, glucose-6-phosphate, urea, isocitrate, BHB and uric acid), milk enzymes (lactate dehydrogenase and N-acetyl-β-D-glucosaminidase (NAGase)) and composite indicators for metabolic imbalances (Physiological Imbalance-index and energy balance), to help facilitate their adoption within PLF. Blood and milk were sampled from 234 Holstein dairy cows from 6 experimental herds, each in a different European country, and offered a total of 10 different diets. Blood was sampled on 2 occasions at approximately 14 days-in-milk (DIM) and 35 DIM. Milk samples were collected twice weekly (in total 2750 samples) from DIM 1 to 50. Multilevel random regression models were used to estimate the variance components and to calculate the intraclass correlations (ICCs). The ICCs for the milk metabolites, when adjusted for parity and DIM at sampling, demonstrated that between 12% (glucose-6-phosphate) and 46% (urea) of the variation in the metabolites’ levels could be associated with the herd-diet combination. Intraclass Correlations related to the herd-diet combination were generally higher for blood metabolites, from 17% (cholesterol) to approximately 46% (BHB and urea). The high ICCs for urea suggest that this biomarker can be used for monitoring on herd level. The low variance within cow for NAGase indicates that few samples would be needed to describe the status and potentially a general reference value could be used. The low ICC for most of the biomarkers and larger within cow variation emphasises that multiple samples would be needed - most likely on the individual cows - for making the biomarkers useful for monitoring. The majority of biomarkers were influenced by parity and DIM which indicate that these should be accounted for if the biomarker should be used for monitoring.
We studied trends in the incidence of health care-associated infections (HAIs) in LTCFs between 2009 and 2015 and determined the effect of participation in our network. Elder-care physicians reported weekly the number of cases of influenza-like illness, gastroenteritis, (probable) pneumonia, urinary tract infections (UTIs) and all-cause mortality. Trends in the incidence of infection and mortality in relation to LTCF characteristics were calculated using multilevel univariate and multivariate logistic regression. Thirty LTCF participated for 3 years or more, 16 for 2 years and the remaining 12 LTCF for 1 year. During the study period, the median number of beds decreased from 158 to 139, whereas the percentage of residents with private bedrooms increased from 14% to 87%. UTIs were the most frequently reported infections, followed by (probable) pneumonia and gastroenteritis. Adjusted for calendar year and season, we observed a statistically significant decrease in the incidence of influenza-like illness (odds ratio (OR) = 0.8, P < 0.01) and (probable) pneumonia (OR = 0.8, P < 0.01) for each extra year an LTCF participated. Although there are other likely contributors, such as more private rooms and enhanced infection control measures, the decreasing trend of HAI in LTCFs participating in surveillance implies that surveillance is a valuable addition to current strategies to optimise infection control.
Unbalanced metabolic status in the weeks after calving predisposes dairy cows to metabolic and infectious diseases. Blood glucose, IGF-I, non-esterified fatty acids (NEFA) and β-hydroxybutyrate (BHB) are used as indicators of the metabolic status of cows. This work aims to (1) evaluate the potential of milk mid-IR spectra to predict these blood components individually and (2) to evaluate the possibility of predicting the metabolic status of cows based on the clustering of these blood components. Blood samples were collected from 241 Holstein cows on six experimental farms, at days 14 and 35 after calving. Blood samples were analyzed by reference analysis and metabolic status was defined by k-means clustering (k=3) based on the four blood components. Milk mid-IR analyses were undertaken on different instruments and the spectra were harmonized into a common standardized format. Quantitative models predicting blood components were developed using partial least squares regression and discriminant models aiming to differentiate the metabolic status were developed with partial least squares discriminant analysis. Cross-validations were performed for both quantitative and discriminant models using four subsets randomly constituted. Blood glucose, IGF-I, NEFA and BHB were predicted with respective R2 of calibration of 0.55, 0.69, 0.49 and 0.77, and R2 of cross-validation of 0.44, 0.61, 0.39 and 0.70. Although these models were not able to provide precise quantitative values, they allow for screening of individual milk samples for high or low values. The clustering methodology led to the sharing out of the data set into three groups of cows representing healthy, moderately impacted and imbalanced metabolic status. The discriminant models allow to fairly classify the three groups, with a global percentage of correct classification up to 74%. When discriminating the cows with imbalanced metabolic status from cows with healthy and moderately impacted metabolic status, the models were able to distinguish imbalanced group with a global percentage of correct classification up to 92%. The performances were satisfactory considering the variables are not present in milk, and consequently predicted indirectly. This work showed the potential of milk mid-IR analysis to provide new metabolic status indicators based on individual blood components or a combination of these variables into a global status. Models have been developed within a standardized spectral format, and although robustness should preferably be improved with additional data integrating different geographic regions, diets and breeds, they constitute rapid, cost-effective and large-scale tools for management and breeding of dairy cows.
Delays in rotavirus vaccine schedule could improve performance in low- and middle-income countries (LMICs). However, delaying the first dose could be detrimental if infants experience severe rotavirus gastroenteritis (RVGE) early in life. Our objective was to describe the timing and predictors of severe RVGE in unvaccinated children in LMICs. We analysed the placebo arms from two clinical trials (cohort 1: NCT00241644; cohort 2: NCT00362648). We estimated the rate, cumulative incidence (per 1000 infants) and age distribution of severe RVGE episodes. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals (CI) for the association between baseline factors and severe RVGE. Cumulative incidence at 6 months of age was 23/1000 (95% CI 15–30) in cohort 1 and 6/1000 (95% CI 3–8) in cohort 2. Early antibiotic use (compared with no use) was associated with 2.03 (95% CI 1.18–3.48) and 1.41 (95% CI 0.80–2.51) times the rate of severe RVGE in cohorts 1 and 2, respectively. The cumulative incidence of severe RVGE was low at 6 months of age, suggesting that a 4-week delay in the vaccination schedule may not result in a large number of severe RVGE episodes prior to vaccine receipt.
Norovirus is detected in one in five diarrhoea episodes in children, yet little is known about environmental risk factors associated with this disease, especially in low-income settings. The objective of this study was to examine environmental risk factors, and spatial and seasonal patterns of norovirus diarrhoea episodes in children in León, Nicaragua. We followed a population-based cohort of children under age 5 years for norovirus diarrhoea over a 1-year period. At baseline, characteristics of each household were recorded. Households were geocoded and spatial locations of garbage dumps, rivers, and markets were collected. In bivariate analysis we observed younger children and those with animals in their households were more likely to have experienced norovirus episodes. In adjusted models, younger children remained at higher risk for norovirus episodes, but only modest associations were observed with family and environmental characteristics. We next identified symptomatic children living in the same household and within 500 m buffer zones around the household of another child infected with the same genotype. Norovirus diarrhoea episodes peaked early in the rainy season. These findings contribute to our understanding of environmental factors and norovirus infection.
One of the observing modes available with the ESO Very Large Telescope will be coherent combination of the light received by up to four 8 m unit telescopes and several 1.8 m auxiliary telescopes. The location of the main telescopes is fixed, while auxiliary telescopes can be moved among some 30 observing stations. The locations of these stations were chosen to augment the (u, v) coverage of the unit telescopes as well as to function as an independent interferometric array.
The 8 m telescopes will be equipped with adaptive optics to correct for seeing-induced wavefront aberrations. This wavefront correction will be complete at near-infrared wavelengths, giving the interferometer very high sensitivity in this spectral regime. This paper gives a brief description of the VLT Interferometer and an update on its status.
Since our publication of the high-precision calibration curve for the larger part of the 4th millennium BC (de Jong, Becker & Mook, 1986), we found that the dendrochronologic scale (cal bc) needs a correction of 26 years. Instead of using the zero-point of the Niederwill chronology (4039 bc) which was floating at the time, our dendrochronologic scale was erroneously based on the zero-point of the Hohenheim master chronology, which, in its 1986 stage, extended to 4065 bc.
This paper briefly describes the principle of operation and science goals of the AMANDA high energy neutrino telescope located at the South Pole, Antarctica. Results from an earlier phase of the telescope, called AMANDA-BIO, demonstrate both reliable operation and the broad astrophysical reach of this device, which includes searches for a variety of sources of ultrahigh energy neutrinos: generic point sources, Gamma-Ray Bursts and diffuse sources. The predicted sensitivity and angular resolution of the telescope were confirmed by studies of atmospheric muon and neutrino backgrounds. We also report on the status of the analysis from AMANDA-II, a larger version with far greater capabilities. At this stage of analysis, details of the ice properties and other systematic uncertainties of the AMANDA-II telescope are under study, but we have made progress toward critical science objectives. In particular, we present the first preliminary flux limits from AMANDA-II on the search for continuous emission from astrophysical point sources, and report on the search for correlated neutrino emission from Gamma Ray Bursts detected by BATSE before decommissioning in May 2000. During the next two years, we expect to exploit the full potential of AMANDA-II with the installation of a new data acquisition system that records full waveforms from the in-ice optical sensors.
A huge gap exists between the production of evidence and its take-up in clinical practice settings. To fill this gap, treatment guidelines, based on explicit assessments of the evidence base, are commonly employed in several fields of medicine, including schizophrenia and related psychotic disorders. It remains unclear, however, whether treatment guidelines have any impact on provider performance and patient outcomes, and how implementation should be conducted to maximise benefit.
For people with schizophrenia, non-adherence to antipsychotic medications may result in high use of health and other services. The objective of our research was to examine the economic consequences of non-adherence in patients with schizophrenia taking antipsychotic medication.
Data were taken from QUATRO, a randomized controlled trial that drew a sample of adults with schizophrenia receiving psychiatric services in four European cities: Amsterdam, Leipzig, London and Verona. Trial inclusion criteria were a clinical diagnosis of schizophrenia, requiring on-going antipsychotic medication for at least 1-year following baseline assessment, and exhibiting evidence of clinical instability in the year prior to baseline. The patient-completed Medication Adherence Questionnaire (MAQ) was used to calculate the 5-point Morisky index of adherence. Generalized linear models (GLM) were developed to determine the effect of adherence on (i) health and social care and (ii) societal costs before and after treatment, taking into account other potential cost-influencing factors.
The effect of non-adherence on costs was mixed. For different groups of services, and according to treatment group assignment, non-adherence was both negatively and positively associated with costs.
The impact of non-adherence on costs varies across the types of services used by individuals with schizophrenia.
Children with sickle cell anaemia (SCA) might carry hospital-associated bacterial lineages due to frequent hospital stays and antibiotic treatments. In this study we compared Staphylococcus aureus from SCA patients (n = 73) and healthy children (n = 143) in a cross-sectional study in Gabon. S. aureus carriage did not differ between children with SCA (n = 34, 46·6%) and controls matched for age, residence and sex (n = 67, 46·9%). Both groups shared similar S. aureus genotypes. This finding points towards a transmission of S. aureus between both groups in the community. We conclude that resistance rates from population-based studies with healthy participants could therefore also be used to guide treatment and prophylaxis of endogenous infections in children with SCA despite a different selection pressure.
Methicillin-resistant Staphylococcus aureus (MRSA) commonly causes infection in hospitalized patients. Resistance is due to the acquisition of mecA gene located on the chromosomal element SCCmec and to date 12 types have been identified. Specific epidemic clones of MRSA have emerged with enhanced ability to spread within and among hospitals and to cross national boundaries. We studied 30 isolates from patients with MRSA infections at two hospitals in Porto Alegre city from April to December, 2008 and determined their SCCmec type by PCR. Representative strains were typed by PFGE. Eighteen (60%) isolates carried SCCmec type III and had PFGE profiles clonally related to the previously characterized Brazilian epidemic clone, and 11 (36·7%) isolates with pulsotypes closely related to the Cordobes/Chilean clone harboured SCCmec type I. To the best of our knowledge, this is the first report of the appearance of Cordobes/Chilean clone involved in nosocomial infection in Brazil.
We present a scalable, continuous manufacturing method of nanoparticle production based on laser ablation of an aerosol generated from an aqueous precursor solution. A Collison nebulizer is used to generate a mist of ~10 μm diameter water droplets containing dissolved transition metal salts, suspended in 1 atmosphere of buffer gas. Water from the droplets quickly evaporates, leaving solid particles ~2 μm in diameter for a typical solution concentration. These microparticles are then ablated by a pulsed KrF excimer laser (10 ns, λ = 248 nm, 2 J/cm2 at focus). Ablation results in plasma breakdown of the microparticle and photothermal decomposition of the precursor material. Following ablation, nanoparticles 5-20 nm in diameter are formed and collected. For AgNO3 ablated in He gas, metal Ag nanoparticles were produced. For Cu(NO3)2 ablated in He, crystalline Cu2O nanoparticles were produced. For Ni(NO3)2 ablated in He, crystalline NiO nanoparticles were produced. A combination of AgNO3 and Cu(NO3)2 ablated in a reducing atmosphere of 10% H2 and 90% He yielded Ag-Cu alloy nanoparticles. In contrast to conventional wet-chemical synthesis processes, our nanoparticles are formed ‘bare,’ without surfactants or organic material contaminating the surface. Owing to their small size and high free surface area, nanoparticles produced by this process are ideally suited for applications that include catalysis and facilitated transport membranes.
In this work we searched for evidence of low level photoionization effects in the solid phase epitaxial regrowth (SPER) of intrinsic amorphous silicon on (100) silicon during isothermal furnace annealing. We used in situ cw laser interferometry to measure the changes in the rate at 500 °C as the laser power was varied from 20 mW-80 mW. Calculation showed that laser heating increased the sample temperature by a maximum of 6 °C at 80 mW. The measured change of the SPER rate with laser power in this range was always smaller than the change computed from an Arrhenius calculation using the measured activation energy, and the calculated value of the laser-produced increment in the sample temperature. The result indicates that there are negligible low level photoionization effects in silicon SPER.
In this work we measured the functional dependence of the solid phase epitaxial regrowth (SPER) of amorphous silicon on NAI, the concentration of implanted aluminum (p-type). The SPER rates of self-ion amorphized layers in silicon wafers with (100) substrate orientation were measured by in situ high precision, isothermal, cw laser interferometry for temperatures from 470 °C to 550 °C, and concentrations in the range 3×1018 cm−3 ≤NAI≤ 4.7×1020 cm−3 obtained from samples implanted with three different doses.
In the concentration range 3×1018 cm−3 ≤NAI≤ 2.3×1019 cm−3, we observed a “compensation effect” in which, with increasing NAI, the SPER rate decreased below the regrowth rate in intrinsic silicon and the activation energy of SPER increased to 2.85 eV, compared to 2.72 eV for intrinsic silicon. In the range 3.3×1019 cm−3 ≤NAI≤ 5.6×1019 cm−3, the regrowth rate increased linearly with NAI as previously observed for SPER in boron, phosphorus, and arsenic implanted samples. However, due to the compensation effect, the aluminum data could not be fit to the normalized equation; V/Vi = 1 + N/Ni, as was done previously for data obtained for boron, phosphorus, and arsenic. The regrowth rate increased nonlinearly to the maximum implanted concentration of 4.7× 1020 cm−3 at which the regrowth rate was more than double the previously observed maximum rate in boron doped silicon. In the high concentration range, the SPER rate enhancement could be fit by a quadratic equation whose curvature was positive as was the case for boron. This contrasts with the negative curvature required to fit the nonlinear dependence of the SPER rate on the concentration of donor impurities such as phosphorus and arsenic.
We made high precision cw laser interferometric measurements of the variations of the rate of solid phase epitaxial regrowth (SPER) of amorphous layers on (100) silicon implanted with both boron and phosphorus. Depth profiles of SPER were correlated with the implanted boron and phosphorus distributions measured by secondary ion mass spectroscopy (SIMS). The results showed that: (1) the minimum (SPER) rate did not occur at the depth where the implanted impurity concentrations were equal; (2) the maximum activation energy for SPER (∼2.9 eV; ≈0.18 eV greater than for SPER in intrinsic Si) occurred at the depth where the regrowth rate was a minimum; (3) the regrowth rates in the dual implanted sample were different from those of the samples doped only with phosphorus at the same net phosphorusc concentration; and (4) the rate at the depth where the impurity concentrations were equal was different from the intrinsic rate. Further interpretation of the results suggests that the SPER rate in the dual implanted samples is equal to the value for intrinsic silicon at a depth where the net ionized impurity concentration is compensated. The SPER rate was a minimum at a depth where the net ionized impurity concentration was slightly p type.
In this work we measured the functional dependence of the solid phase epitaxial (SPE) regrowth of amorphous silicon on the implanted phosphorous concentration, Np. The growth rates of self-ion amorphized layers in silicon wafers with (100) substrate orientation were measured by in situ, high precision, isothermal cw laser interferometry for temperatures from 460°C to 590°C, and concentrations in the range 2x1017 cm-3<Np<4x1020 cm-3. For low impurity concentrations, the fractional increase in the intrinsic SPE growth velocity ΔV/Vi depended linearly on Np as previously established for boron. For a given impurity concentration, the relative change V/Vi decreased with increasing annealing temperature.