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1.
Can J Cardiol ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32504546

RESUMO

BACKGROUND: Drivers at risk of sudden incapacitation from syncope pose a potential threat to themselves and to society. The purpose of this systematic review is to synthesize the risk of motor vehicle collisions (MVCs) for patients with a history of syncope. METHODS: We systematically searched Medline (1946-2019) as well as Cinahl, Embase, Psychinfo, and the Transportation Research Information Documentation (1806-2017) for articles on MVCs and drivers with vasovagal syncope (VVS), arrhythmic syncope, or syncope not yet diagnosed (NYD). Quality ratings were assigned by team consensus. RESULTS: Eleven studies of moderate quality were included (n = 42,972). Compared with the general populations of Canada, the United States, and the United Kingdom (0.49%-2.29% per driver-year), the prospective MVC risk was lower for VVS (0.0%-0.31% per driver-year; 3 studies; n = 782) and higher for arrhythmic syncope (1.9%-3.4% per driver-year; 2 studies; n = 730). The results were more variable for syncope NYD (0.0%-6.9% per driver-year prospectively; 6 studies; n = 41,460). Patients with syncope NYD had an almost 2-fold increased MVC risk in the largest study, although the smaller studies showed contradictory findings. CONCLUSIONS: VVS patients appear to be at very low risk for MVCs, supporting current guidelines which do not recommend driving suspension for these patients in most cases. Although the data for other forms of syncope are too limited for definitive conclusions and must be improved, arrhythmic syncope appears to be associated with nontrivial risk.

2.
Science ; 368(6497)2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32439657

RESUMO

Although perovskite solar cells have produced remarkable energy conversion efficiencies, they cannot become commercially viable without improvements in durability. We used gas chromatography-mass spectrometry (GC-MS) to reveal signature volatile products of the decomposition of organic hybrid perovskites under thermal stress. In addition, we were able to use GC-MS to confirm that a low-cost polymer/glass stack encapsulation is effective in suppressing such outgassing. Using such an encapsulation scheme, we produced multi-cation, multi-halide perovskite solar cells containing methylammonium that exceed the requirements of the International Electrotechnical Commission 61215:2016 standard by surviving more than 1800 hours of the Damp Heat test and 75 cycles of the Humidity Freeze test.

3.
Sci Rep ; 10(1): 8002, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409668

RESUMO

Variable selection in inferential modelling is problematic when the number of variables is large relative to the number of data points, especially when multicollinearity is present. A variety of techniques have been described to identify 'important' subsets of variables from within a large parameter space but these may produce different results which creates difficulties with inference and reproducibility. Our aim was evaluate the extent to which variable selection would change depending on statistical approach and whether triangulation across methods could enhance data interpretation. A real dataset containing 408 subjects, 337 explanatory variables and a normally distributed outcome was used. We show that with model hyperparameters optimised to minimise cross validation error, ten methods of automated variable selection produced markedly different results; different variables were selected and model sparsity varied greatly. Comparison between multiple methods provided valuable additional insights. Two variables that were consistently selected and stable across all methods accounted for the majority of the explainable variability; these were the most plausible important candidate variables. Further variables of importance were identified from evaluating selection stability across all methods. In conclusion, triangulation of results across methods, including use of covariate stability, can greatly enhance data interpretation and confidence in variable selection.

4.
J Cardiovasc Nurs ; 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32453274

RESUMO

BACKGROUND: Decision support can help patients facing implantable cardioverter-defibrillator (ICD) replacement understand their options and reach an informed decision reflective of their preferences. OBJECTIVE: The aim of this study was to evaluate the feasibility of a decision support intervention for patients faced with the decision to replace their ICD. METHODS: A pilot feasibility randomized trial was conducted. Patients approaching ICD battery depletion were randomized to decision support intervention or usual care. Feasibility outcomes included recruitment rates, intervention use, and completeness of data; secondary outcomes were knowledge, values-choice concordance, decisional conflict, involvement in decision making, and choice. RESULTS: A total of 30 patients were randomized to intervention (n = 15) or usual care (n = 15). The intervention was used as intended, with 2% missing data. Patients in the intervention arm had better knowledge (77.4% vs 51.1%; P = .002). By 12 months, 8 of 13 (61.5%) in the intervention arm and 10 of 14 (71.4%) in the usual care arm accepted ICD replacement; 1 per arm declined (7.7% vs 7.1%, respectively). CONCLUSION: It was feasible to deliver the intervention, collect data, despite slow recruitment. The decision support intervention has the potential to improve ICD replacement decision quality.

5.
ACS Appl Mater Interfaces ; 12(20): 22825-22834, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32326702

RESUMO

The one-dimensional photovoltaic absorber material Sb2S3 requires crystal orientation engineering to enable efficient carrier transport. In this work, we adopted the vapor transport deposition (VTD) method to fabricate vertically aligned Sb2S3 on a CdS buffer layer. Our work shows that such a preferential vertical orientation arises from the sulfur deficit of the CdS surface, which creates a beneficial bonding environment between exposed Cd2+ dangling bonds and S atoms in the Sb2S3 molecules. The CdS/VTD-Sb2S3 interface recombination is suppressed by such properly aligned ribbons at the interface. Compared to typical [120]-oriented Sb2S3 films deposited on CdS by the rapid thermal evaporation (RTE) method, the VTD-Sb2S3 thin film is highly [211]- and [121]-oriented and the performance of the solar cell is increased considerably. Without using any hole transportation layer, a conversion efficiency of 4.73% is achieved with device structure of indium tin oxide (ITO)/CdS/Sb2S3/Au. This work provides a potential way to obtain vertically aligned thin films on different buffer layers.

6.
Sci Rep ; 10(1): 4289, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152401

RESUMO

Mastitis in dairy cattle is extremely costly both in economic and welfare terms and is one of the most significant drivers of antimicrobial usage in dairy cattle. A critical step in the prevention of mastitis is the diagnosis of the predominant route of transmission of pathogens into either contagious (CONT) or environmental (ENV), with environmental being further subdivided as transmission during either the nonlactating "dry" period (EDP) or lactating period (EL). Using data from 1000 farms, random forest algorithms were able to replicate the complex herd level diagnoses made by specialist veterinary clinicians with a high degree of accuracy. An accuracy of 98%, positive predictive value (PPV) of 86% and negative predictive value (NPV) of 99% was achieved for the diagnosis of CONT vs ENV (with CONT as a "positive" diagnosis), and an accuracy of 78%, PPV of 76% and NPV of 81% for the diagnosis of EDP vs EL (with EDP as a "positive" diagnosis). An accurate, automated mastitis diagnosis tool has great potential to aid non-specialist veterinary clinicians to make a rapid herd level diagnosis and promptly implement appropriate control measures for an extremely damaging disease in terms of animal health, productivity, welfare and antimicrobial use.

7.
J Am Chem Soc ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32129999

RESUMO

For the fabrication of perovskite solar cells (PSCs) using a solution process, it is essential to understand the characteristics of the perovskite precursor solution to achieve high performance and reproducibility. The colloids (iodoplumbates) in the perovskite precursors under various conditions were investigated by UV-visible absorption, dynamic light scattering, photoluminescence, and total internal reflection fluorescence microscopy techniques. Their local structure was examined by in situ X-ray absorption fine structure studies. Perovskite thin films on a substrate with precursor solutions were characterized by transmission electron microscopy, X-ray diffraction analysis, space-charge-limited current, and Kelvin probe force microscopy. The colloidal properties of the perovskite precursor solutions were found to be directly correlated with the defect concentration and crystallinity of the perovskite film. This work provides guidelines for controlling perovskite films by varying the precursor solution, making it possible to use colloid-engineered lead halide perovskite layers to fabricate efficient PSCs.

8.
Int J Toxicol ; 39(2): 151-164, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32174281

RESUMO

The liver is primarily thought of as a metabolic organ; however, the liver is also an important mediator of immunological functions. Key perspectives on this emerging topic were presented in a symposium at the 2018 annual meeting of the American College of Toxicology entitled "Beyond metabolism: Role of the immune system in hepatic toxicity." Viral hepatitis is an important disease of the liver for which insufficient preventive vaccines exist. Host immune responses inadequately clear these viruses and often potentiate immunological inflammation that damages the liver. In addition, the liver is a key innate immune organ against bacterial infection. Hepatocytes and immune cells cooperatively control systemic and local bacterial infections. Conversely, bacterial infection can activate multiple types of immune cells and pathways to cause hepatocyte damage and liver injury. Finally, the immune system and specifically cytokines and drugs can interact in idiosyncratic drug-induced liver injury. This rare disease can result in a disease spectrum that ranges from mild to acute liver failure. The immune system plays a role in this disease spectrum.

9.
J Dairy Sci ; 103(4): 3250-3263, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32057434

RESUMO

Conflicting views between the dairy industry and the public about how dairy cows should be managed, together with an increase in the availability of alternatives to dairy foods, challenge future markets for milk producers. Members of the public value animal welfare as well as naturalness and grazing, but neither the relative importance of specific aspects of management nor the diversity of views underlying these preferences have been established. To better understand these issues, 2,054 UK citizens recruited through a research panel took part in an online survey. They were asked to rank 17 attributes relating to dairy cow management and milk production through the novel application of best-worst scaling, a discrete choice methodology that allows a trade-off between items. Hierarchical Bayesian analysis of the results revealed 3 attributes of equal top importance: (1) access to grazing, (2) cow health and welfare, and (3) cow comfort. Alongside this overarching ranking, underlying differences in preferences were identified in 6 approximately equally sized citizen groups within the sample, which were identified through latent class analysis. Each latent class expressed significantly different priorities from the other, and each had different indicative sociodemographic, attitudinal, experiential, and value-oriented characteristics, as established through a multinomial logistic model. If the diversity of preference between the citizen groups found in the sample is reflected within wider populations, there may be opportunities for the dairy industry to improve communication about positive practices, develop new dairy product markets, and consider changes to dairy farming systems to better meet different citizens' needs. Furthermore, the defining characteristics and priorities of each group raise the question of whether grazing in particular, but also other attributes presented within the study, is understood in different ways by different subgroups of citizens.

10.
Can J Cardiol ; 36(4): 509-517, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31924453

RESUMO

BACKGROUND: There exists limited evidence on managing atrial fibrillation (AF) with rapid ventricular response in the emergency department. We sought to better understand the burden of disease in patients with AF for whom rhythm control was not successful or not attempted and identify opportunities for improved care. METHODS: We conducted a health records review of consecutive visits of patients with AF at 2 academic emergency departments. We included patients ≥ 18 years with AF, heart rate ≥ 100 beats per minute (bpm), and who were not successfully cardioverted or not attempted cardioversion. Outcomes were: (1) incidence given rate control, (2) management practices, (3) adverse events, (4) compliance with guidelines, and (5) outcomes. We performed descriptive statistics. RESULTS: We included 665 visits, with mean age ± standard deviation 77.4 ± 12.9, female 51.6%, mean ± standard deviation heart rate 121.6 ± 17.4 bpm, AF status (permanent 53.4%; paroxysmal 29.5%; persistent 17.1%), admitted 61.4%. Of all cases, 147 (22.1%) had primary AF and 518 (77.9%) had a rapid rate secondary to a medical cause (heart failure 12.8%; pneumonia 11.7%; sepsis 8.4%). In 117 with primary AF given rate control, 59.0% had a final rate ≤ 100 bpm and 7.7% suffered adverse events. Suboptimal use of rate control occurred in 47.0% (agent 2.6%; route 27.4%; dosage 9.4%; timing 7.7%). At discharge, 11.5% with CHADS-65 risk factors were still not anticoagulated. CONCLUSIONS: Most patients had a rapid rhythm secondary to a medical cause. There were a concerning number of adverse events related to suboptimal use of rate control. Better awareness of guidelines will ensure safer use of rate control.

11.
J Dairy Sci ; 103(3): 2615-2623, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31954578

RESUMO

National bodies in Great Britain (GB) have expressed concern over young stock health and welfare and identified calf survival as a priority; however, no national data have been available to quantify mortality rates. The aim of this study was to quantify the temporal incidence rate, distributional features, and factors affecting variation in mortality rates in calves in GB since 2011. The purpose was to provide information to national stakeholder groups to inform resource allocation both for knowledge exchange and future research. Cattle birth and death registrations from the national British Cattle Movement Service were analyzed to determine rates of both slaughter and on-farm mortality. The number of births and deaths registered between 2011 and 2018 within GB were 21.2 and 21.6 million, respectively. Of the 3.3 million on-farm deaths, 1.8 million occurred before 24 mo of age (54%) and 818,845 (25%) happened within the first 3 mo of age. The on-farm mortality rate was 3.87% by 3 mo of age, remained relatively stable over time, and was higher for male calves (4.32%) than female calves (3.45%). Dairy calves experience higher on farm mortality rates than nondairy (beef) calves in the first 3 mo of life, with 6.00 and 2.86% mortality rates, respectively. The 0- to 3-mo death rate at slaughterhouse for male dairy calves has increased from 17.40% in 2011 to 26.16% in 2018, and has remained low (<0.5%) for female dairy calves and beef calves of both sexes. Multivariate adaptive regression spline models were able to explain a large degree of the variation in mortality rates (coefficient of determination = 96%). Mean monthly environmental temperature and month of birth appeared to play an important role in neonatal on-farm mortality rates, with increased temperatures significantly reducing mortality rates. Taking the optimal month of birth and environmental temperature as indicators of the best possible environmental conditions, maintaining these conditions throughout the year would be expected to result in a reduction in annual 0- to 3-mo mortality of 37,571 deaths per year, with an estimated economic saving of around £11.6 million (USD $15.3 million) per annum. National cattle registers have great potential for monitoring trends in calf mortality and can provide valuable insights to the cattle industry. Environmental conditions play a significant role in calf mortality rates and further research is needed to explore how to optimize conditions to reduce calf mortality rates in GB.


Assuntos
Doenças dos Bovinos/mortalidade , Matadouros , Animais , Animais Recém-Nascidos , Bovinos , Fazendas , Feminino , Masculino , Parto , Gravidez , Reino Unido/epidemiologia
12.
Prev Vet Med ; 174: 104822, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31751855

RESUMO

In light of current concerns about the sustainability of red meat production in a world with increasing global demand for food from animal origin there is a need for a better understanding of factors that influence the growth rate and feed conversion efficiency of animals on commercial farms. The primary objective of this observational study was to use longitudinal data to quantify the simultaneous effects of multiple ewe and lamb factors on lamb growth rate. A secondary aim was to evaluate model structures that specifically account for lamb grouping effects during the growth period and compare these to classical hierarchical growth rate models. A total of 4172 weight recordings from 805 lambs and data on disease events were collected over a 6-month period from a commercial pedigree sheep flock. Three mixed model structures were compared, hierarchical, cross classified and multiple membership, and final estimates determined within a Bayesian framework. The multiple membership structure provided the best model fit and was used for final inference; taking account of the effect of lamb grouping over time provided the best estimates of lamb growth rate. Ewe lameness and mastitis cases had a deleterious impact on lamb growth. Lambs from ewes identified with mastitis during lactation were on average 3.0 (standard error (SE) 1.6) kg lighter during the four month growth period than lambs from unaffected ewes. Lambs from ewes that were not lame during pregnancy were 3.0 (SE 1.2) kg heavier at eight weeks of age than lambs from ewes with a least one lameness case during the same period. Lambs from ewes lame either during the first 4 weeks or between 4-8 weeks of a lamb's life (but not lame during pregnancy) were also significantly heavier at 56 days of age, than lambs reared by ewes that were lame during pregnancy (2.8 (SE 1.2) and 3.4 (SE 1.2) kg respectively). Cases of pneumonia and bacterial arthritis in lambs had a significant negative impact on lamb growth with affected lambs being on average 5.5 (SE 1.1) kg and 2.2 (SE 1.2) kg less than non-affected lambs respectively after the disease event. Prior to a case of lameness or pneumonia, lambs were significantly heavier than unaffected lambs suggesting a possible trade-off between growth and immune function. Overall, the study provides evidence that that a combination of ewe and lamb characteristics and disease events play an important role in determining lamb growth rate and that heavier lambs may be more susceptible to disease.

13.
Prev Vet Med ; 174: 104851, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31778947

RESUMO

The profitability of UK sheep farms is variable with many farms making a net loss. For economic sustainability, farms have to be profitable, therefore it is important to maximise income whilst controlling costs. The most important source of income in sheep flocks is from lamb production but there is little information on factors that explain variability between farms in revenue from lamb sales. The aim of this research was to identify farm, farmer and management factors likely to have the largest, most reliable associations with lamb-derived revenue. From a population of 830 sheep farms, 408 farmers completed an online questionnaire comprising over 300 variables. Total lamb-derived revenue was calculated for each farm using abattoir information including carcass classification. The median flock size was 560 ewes, median land size 265 acres, median revenue per acre from lambs sold was £197 (IQR = 120-296) and median revenue per ewe £95 (IQR = 72-123). A robust analytic approach using regularised (elastic net) regression with bootstrapping was implemented to account for multicollinearity in the data and to reduce the likelihood of model over-fitting. To provide model inference and allow ranking of variables in terms of relevance, covariate stability and coefficient distributions were evaluated. Factors with high stability and relatively large positive associations with revenue per acre were (median effect size (£); 95 % bootstrap probability interval); an increased stocking rate of 0.2 ewe/acre (13; 6-17), fertilizer being used on most of the grazing land (18; 0.1-37), the use of rotational grazing (13; 0.3-34), decreased proportion of ewes with prolapses (4; 0.3-9), separation of lame sheep from the rest of the flock (16; 0.9-37), selecting ewes for culling based on prolapses (20; 0.2-55) and infertility (20; 2-46), conducting body condition scoring of ewes at lambing (28; 3-58), early lactation (21; 1-54) or weaning (25; 2-70), increased farmer education (20; 2-54) and farmers with a positive business attitude (15; 0.2-38). Additional factors with a high stability and relatively large associations with increased revenue per ewe were; never trimming diseased feet of lame ewes (9; 0.8-22) and making use of farm records (5; 0.3-12). This is the first study in animal health epidemiology to use bootstrapped regularised regression to evaluate a wide dataset to provide a ranking of the importance of explanatory covariates. We conclude that the relatively small set of variables identified, with a potentially large influence on lamb-derived revenue, should be considered prime candidates for future intervention studies.

14.
Int J Environ Health Res ; : 1-14, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31829725

RESUMO

We examined whether exercising indoors vs. outdoors reduced the cardio-respiratory effects of outdoor air pollution. Adults ≥55 were randomly assigned to exercise indoors when the Air Quality Health Index was ≥5 and outdoors on other days (intervention group, n = 37), or outdoors everyday (control group, n = 35). Both groups completed cardio-respiratory measurements before and after exercise for up to 10 weeks. Data were analyzed using linear mixed effect regression models. In the control group, an interquartile range increase in fine particulate matter (PM2.5) was associated with increases of 1.4% in heart rate (standard error (SE) = 0.7%) and 5.6% (SE = 2.6%) in malondialdehyde, and decreases of 5.6% (SE = 2.5%) to 16.5% (SE = 7.5%) in heart rate variability measures. While the hypothesized benefit of indoor vs. outdoor exercise could not be demonstrated due to an insufficient number of intervention days (n = 2), the study provides evidence of short-term effects of air pollution in older adults. ISRCTN #26552763.

15.
J Electrocardiol ; 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31668635

RESUMO

BACKGROUND: Current LBBB definitions cannot always distinguish LBBB from left ventricular conduction delay. Only patients with LBBB are expected to normalize with His bundle pacing. Patients who develop new LBBB immediately post transcatheter aortic valve replacement (TAVR) provide an excellent model to define electrocardiogram (ECG) features of LBBB. We sought to describe their ECG features and develop a new ECG definition of LBBB. METHODS: We screened ECGs from 264 consecutive patients who underwent TAVR at the University of Ottawa Heart Institute. Patients with a baseline QRS of ≤100 ms who developed QRS ≥120 ms immediately after TAVR were included. Two electrocardiologists reviewed all ECG independently. Baseline demographics and echocardiographic data were retrospectively collected. RESULTS: 36 patients were included in the analysis. The median age was 85.5 years (IQR, 81.8-89 years) and 52.8% were males. The minimum QRS duration was 126 ms. The median QRS axis was -18° (IQR, -40-4.5°), which is 18.5° leftward compared to the median QRS axis before TAVR. Fourteen patients (38.9%) had left axis deviation. All patients had a notched/slurred R wave in at least one lateral lead and an R wave duration of ≤20 ms in V1 when present. CONCLUSION: We developed a new ECG definition of LBBB that includes 2 novel findings: notching/slurring of the R wave in at least one lateral lead and an R wave ≤20 ms in V1. Further larger studies are warranted to confirm these findings.

16.
JACC Clin Electrophysiol ; 5(9): 1059-1067, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31537335

RESUMO

OBJECTIVES: This study sought to examine outcomes of our approach to managing a large cohort of patients with Sprint Fidelis (Medtronic, Minneapolis, Minnesota) leads. BACKGROUND: The optimal management approach for patients with leads under advisory is unknown. Concerns regarding the risk of device infection and complications associated with delaying lead extraction have recently been suggested to argue against abandoning leads under advisory. METHODS: All patients with a Sprint Fidelis lead implanted at our institute were included. Lead management options were discussed with patients who presented for device surgery at the time of device upgrade, lead fracture, or elective replacement indicator. Implantation of a new lead with abandonment of the Sprint Fidelis lead was the recommended strategy. Patients were subsequently followed at the device clinic at 6-month intervals and were enrolled prospectively in a longitudinal registry. RESULTS: A total of 520 patients had Sprint Fidelis leads implanted between December 2003 and October 2007 at the study center; 217 patients underwent lead replacement (213 underwent a lead abandonment strategy and 4 underwent a lead extraction strategy). Mean follow-up after lead replacement was 55 ± 33 months. In patients undergoing lead abandonment, 10 of 213 (4.7%) had a procedural complication and 3 of 213 (1.4%) developed subsequent device infection requiring system extraction. CONCLUSIONS: In patients with a Sprint Fidelis lead, implanting a new lead without prophylactic extraction may be a feasible and safe strategy but requires longer follow-up.

17.
Vet Rec ; 185(14): 442, 2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31431521

RESUMO

Oestrus detection is an important part of maintaining efficient reproductive performance in dairy herds. Both lameness and mastitis are common diseases of dairy cows that may impact oestrus detection. A set of data from 28 herds identified as having good recording of clinical mastitis and lameness incidents was used for the study. Logistic regression was used to identify associations between disease episodes within 100 days of insemination and changes in the probability of reinsemination at either 18-24 or 19-26 days after an unsuccessful insemination. Population attributable risk was calculated to understand the impact these diseases may have at a herd level. Lameness 0-28 days after the first insemination of the interval decreased the odds of a reinsemination at an appropriate time by approximately 20 per cent. Clinical mastitis 1-28 days prior to the first insemination of the interval increased the odds of reinsemination at the expected time by approximately 20 per cent. The associations were similar for either interservice interval outcome. Population attributable risk suggested that the effect of these diseases on the probability of reinsemination at the expected time at a population level would likely be extremely small.

18.
J Dairy Sci ; 102(11): 10471-10482, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31447153

RESUMO

In this study, we assessed for the first time the use of a reticuloruminal temperature bolus and a thresholding method to detect drinking events and investigated different factors that can affect drinking behavior. First, we validated the detection of drinking events using 16 cows that received a reticuloruminal bolus. For this, we collected continuous drinking behavior data for 4 d using video recordings and ambient and water temperature for the same 4 d. After all the data were synchronized, we performed 2 threshold algorithms: a general-fixed threshold and a cow-day specific threshold algorithm. In the general-fixed threshold, a positive test was considered if the temperature of any cow fell below a fixed threshold; in the cow-day specific threshold, a positive test was considered when the temperature of specific cows fell below the threshold value deviations around the mean temperature of the cow for that day. The former was evaluated using a threshold varying between 35.7 and 39.5°C, and the latter using the formula µ-n10σ, where µ = mean of the temperature of each cow for one day, n = 1, 2, …, 20, and σ = standard deviation of the temperature of each cow on that day. The performance of the validation of detection using each of the threshold types was computed using different metrics, including overall accuracy, precision, recall (also known as sensitivity), F-score, positive predictive value, negative predictive value, false discovery rate, false omission rate, and Cohen's kappa statistic. The findings of the first study showed that the cow-day specific threshold of n = 10 performed better (true positives = 466; false positives = 167; false negatives = 165; true negatives = 8,416) than using a general-fixed threshold of 38.1°C (true positives = 449; false positives = 181; false negatives = 182; true negatives = 8,402). With the information gained in this first study, we investigated the different factors associated with temperature drop characteristics per cow: number of drops, mean amplitude of the drop, and mean recovery time. For this, we used data from 54 cows collected for almost 1 yr to build a mixed-effect multilevel model that included days in milk, parity, average monthly milk production, and ambient temperature as explanatory variables. Cow characteristics and ambient temperature had significant effects on drinking events. Our results provide a platform for automated monitoring of drinking behavior, which has potential value in prediction of health and welfare in dairy cattle.


Assuntos
Algoritmos , Temperatura Corporal/fisiologia , Bovinos/fisiologia , Comportamento de Ingestão de Líquido/fisiologia , Retículo/metabolismo , Rúmen/metabolismo , Criação de Animais Domésticos/métodos , Animais , Feminino , Lactação/fisiologia , Funções Verossimilhança , Leite , Paridade , Valor Preditivo dos Testes , Gravidez , Curva ROC , Gravação em Vídeo
19.
Anal Chem ; 91(13): 8564-8573, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31141659

RESUMO

Improvements in the performance and availability of commercial instrumentation have made ion mobility-mass spectrometry (IM-MS) an increasingly popular approach for the structural analysis of ionic species as well as for separation of complex mixtures. Here, a new research instrument is presented which enables complex experiments, extending the current scope of IM technology. The instrument is based on a Waters SYNAPT G2-S i IM-MS platform, with the IM separation region modified to accept a cyclic ion mobility (cIM) device. The cIM region consists of a 98 cm path length, closed-loop traveling wave (TW)-enabled IM separator positioned orthogonally to the main ion optical axis. A key part of this geometry and its flexibility is the interface between the ion optical axis and the cIM, where a planar array of electrodes provides control over the TW direction and subsequent ion motion. On either side of the array, there are ion guides used for injection, ejection, storage, and activation of ions. In addition to single and multipass separations around the cIM, providing selectable mobility resolution, the instrument design and control software enable a range of "multifunction" experiments such as mobility selection, activation, storage, IMS n, and importantly custom combinations of these functions. Here, the design and performance of the cIM-MS instrument is highlighted, with a mobility resolving power of approximately 750 demonstrated for 100 passes around the cIM device using a reverse sequence peptide pair. The multifunction capabilities are demonstrated through analysis of three isomeric pentasaccharide species and the small protein ubiquitin.

20.
Regul Toxicol Pharmacol ; 105: 62-68, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30981719

RESUMO

The draft Step 2 ICH S5(R3) guideline includes an exposure-based endpoint as an option for selecting the high-dose in reproductive and developmental toxicity studies. To help determine an appropriate exposure margin for embryofetal developmental toxicity testing, a retrospective analysis was undertaken to determine what threshold would have been sufficient to detect hazards to embryofetal development in rats and rabbits for 18 known and 4 presumed human teratogens. The analysis showed that using a high dose that provided at least a 6-fold exposure margin in the developmental toxicity studies would have been sufficient to detect the teratogenic hazard with relevance for humans for all these therapeutics. With regards to human risk assessment practices for developmental toxicity, the analysis showed that, after excluding lenalidomide and pomalidomide data in rats, all available AUC margins at the NOAEL for the induction of malformations or embryofetal lethality were <4-fold of the exposure at the MRHD for all 22 therapeutics. These data support the proposed general approach of increased level of concern for human risk when exposure margins of the NOAEL to the MRHD are <10-fold, reduced concern when the exposure margins are 10- to 25-fold, and minimal concern when the exposure margin is > 25-fold.


Assuntos
Embrião de Mamíferos/efeitos dos fármacos , Medição de Risco/métodos , Teratogênios/toxicidade , Testes de Toxicidade/métodos , Animais , Área Sob a Curva , Relação Dose-Resposta a Droga , Feminino , Humanos , Nível de Efeito Adverso não Observado , Gravidez , Coelhos , Ratos , Estudos Retrospectivos , Especificidade da Espécie
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