Bayesian estimation of sensitivity and specificity of a milk pregnancy-associated glycoprotein ELISA test for pregnancy diagnosis between 23 and 27 days after insemination in Holstein dairy cows.

Pregnancy diagnosis using pregnancy-associated glycoprotein (PAG) ELISA technology in blood or milk samples is validated from 28 d after insemination in dairy cows. The objective of this study was to estimate the sensitivity (Se) and specificity (Sp) of a commercial milk PAG-based ELISA in Holstein dairy cows between 23 and 27 d after insemination. Milk samples (n = 268) from 257 Holstein dairy cows 23 to 27 d after AI were submitted for PAG ELISA testing. Pregnancy status was confirmed by either a second milk PAG ELISA test conducted between 28 and 50 d after insemination (n = 200) or transrectal ultrasonography performed between 28 and 59 d after insemination (n = 68). A Bayesian latent class model was used to compare the paired results from the test at 23 to 27 d after AI test to the reference test. The latent class model typically used for comparing 2 or more imperfect tests was extended to include the possibility of pregnancy loss between the 23 to 27 d test and the reference test. Informative priors for the probability of pregnancy loss, and for the Se and Sp of the PAG and ultrasonography reference tests were obtained from the scientific literature. Estimated median Se and Sp of the PAG ELISA test conducted between 23 and 27 d after AI were 0.98 (95% credible interval 0.93 to 1.0) and 0.98 (0.89 to 1.0), respectively, when using a standardized corrected optical density threshold of 0.15. Although the accuracy of the test under investigation was excellent, more data will be needed to confirm the optimal diagnostic cut point for PAG in milk for early pregnancy diagnosis in this time window. The optimal timing of pregnancy diagnosis will depend on herd-specific logistics and the action to be taken to re-inseminate nonpregnant cows.

Prevalence of elevated milk ß-hydroxybutyrate concentrations in Holstein cows measured by Fourier-transform infrared analysis in Dairy Herd Improvement milk samples and association with milk yield and components.

The purpose was to describe the prevalence and effect of elevated milk ß-hydroxybutyrate (BHB) as detected by routine Fourier-transform infrared analysis in Dairy Herd Improvement milk samples. Data collected over 4 yr included cow information as well as milk yield and composition from 498,310 samples from postparturient Holstein cows (5-35d in milk) from 4,242 herds. The following thresholds were used to classify cows based on their early lactation milk BHB concentration: <0.15mmol/L=negative; 0.15 to 0.19mmol/L=suspect; and ≥0.20mmol/L=positive. Overall prevalence (suspect + positive) was 22.6% and was higher for older cows (18.7, 19.5, and 27.6%, for cows in their first, second, and third or greater lactation, respectively). Distribution with regards to days in milk was different among parity groups, with first-lactation cows having highest prevalence (30%) in the first week after calving; cows in their second and third and greater parity had the highest prevalence in the second week after calving, at 25.8 and 34.6%, respectively. Season of calving affected the prevalence of elevated milk BHB, with cows calving in the fall and spring seasons showing higher prevalence. Distribution among herds was highly variable, as 45% of herds had a prevalence of 20% or less, 47% of herds had a prevalence between 21 and 40%, 6% of herds had a prevalence between 40 and 50%, and 2% of herds had a prevalence of 50% or above. Positive cows had lower milk yield, protein concentration and yield, and lower Transition Cow Index than negative cows, but also higher fat concentration and yield, as well as higher somatic cell count than negative cows. Suspect cows were generally intermediate. The present analysis highlights the opportunity for elevated milk BHB monitoring at the herd level through routine BHB testing in Dairy Herd Improvement milk samples.

Genetic analysis of milk ß-hydroxybutyrate and its association with fat-to-protein ratio, body condition score, clinical ketosis, and displaced abomasum in early first lactation of Canadian Holsteins.

The aim of this study was to estimate genetic parameters for milk ß-hydroxybutyrate (BHBA) in early first lactation of Canadian Holstein cows and to examine its genetic association with indicators of energy balance (fat-to-protein ratio and body condition score) and metabolic diseases (clinical ketosis and displaced abomasum). Data for milk BHBA recorded between 5 and 100 d in milk was obtained from Valacta (Sainte-Anne-de-Bellevue, Québec, Canada), the Canadian Dairy Herd Improvement organization responsible for Québec and Atlantic provinces. Test-day milk samples were analyzed by mid-infrared spectrometry using previously developed calibration equations for milk BHBA. Test-day records of fat-to-protein ratio were obtained from the routine milk recording scheme. Body condition score records were available from the routine type classification system. Data on clinical ketosis and displaced abomasum recorded by producers were available from the national dairy cattle health system in Canada. Data were analyzed using linear animal models. Heritability estimates for milk BHBA at different stages of early lactation were between 0.14 and 0.29. Genetic correlations between milk BHBA were higher between adjacent lactation intervals and decreased as intervals were further apart. Correlations between breeding values for milk BHBA and routinely evaluated traits revealed that selection for lower milk BHBA in early lactation would lead to an improvement of several health and fertility traits, including SCS, calving to first service, number of services, first service to conception, and days open. Also, lower milk BHBA was associated with a longer herd life, better conformation, and better feet and legs. A higher genetic merit for milk yield was associated with higher milk BHBA, and, therefore, a greater susceptibility to hyperketonemia. Milk BHBA at the first test-day was moderately genetically correlated with fat-to-protein ratio (0.49), body condition score (-0.35), and clinical ketosis (0.48), whereas the genetic correlation with displaced abomasum was near zero (0.07). Milk BHBA can be routinely analyzed in milk samples at test days, and, therefore, provides a practical tool for breeding cows less susceptible to hyperketonemia.

Eyeblinks and visual suppression.

A technique for bypassing the eyelids permits equivalent visual stimulation of the retina before, during, or after a blink. Sensitivity to these stimuli decreases during voluntary blinks. This indicates that the source of the deficit is neural rather than optical. Such a visual loss may help to explain the common experience that most blinks go unnoticed.

Multiple pseudo-abscesses following aortic valve replacement.

Prosthetic aortic valve endocarditis is associated with valve ring abscess, conduction abnormalities and a grave prognosis. Aortic root abscess is a serious complication of infective endocarditis with high mortality. We report a case of a patient who had echocardiographic features resembling aortic root abscess along with severe aortic regurgitation, 6 weeks following aortic valve replacement. Valvular dehiscence led to perivalvular abscess like appearance. Infective endocarditis was exluded. He underwent a successful redo aortic valve surgery with slow recovery.

Genetic analysis of milk urea nitrogen and lactose and their relationships with other production traits in Canadian Holstein cattle.

The objective of this research was to estimate heritabilities of milk urea nitrogen (MUN) and lactose in the first 3 parities and their genetic relationships with milk, fat, protein, and SCS in Canadian Holsteins. Data were a random sample of complete herds (60,645 test day records of 5,022 cows from 91 herds) extracted from the edited data set, which included 892,039 test-day records of 144,622 Holstein cows from 4,570 herds. A test-day animal model with multiple-trait random regression and the Gibbs sampling method were used for parameter estimation. Regression curves were modeled using Legendre polynomials of order 4. A total of 6 separate 4-trait analyses, which included MUN, lactose, or both (yield or percentage) with different combinations of production traits (milk, fat and protein yield, fat and protein percentages, and somatic cell score) were performed. Average daily heritabilities were moderately high for MUN (from 0.384 to 0.414), lactose kilograms (from 0.466 to 0.539), and lactose percentage (from 0.478 to 0.508). Lactose yield was highly correlated with milk yield (0.979). Lactose percentage and MUN were not genetically correlated with milk yield. However, lactose percentage was significantly correlated with somatic cell score (-0.202). The MUN was correlated with fat (0.425) and protein percentages (0.20). Genetic correlations among parities were high for MUN, lactose percentage, and yield. Estimated breeding values (EBV) of bulls for MUN were correlated with fat percentage EBV (0.287) and EBV of lactose percentage were correlated with lactation persistency EBV (0.329). Correlations between lactose percentage and MUN with fertility traits were close to zero, thus diminishing the potential of using those traits as possible indicators of fertility.

E-therapies in England for stress, anxiety or depression: what is being used in the NHS? A survey of mental health services.

OBJECTIVE: To document the range of web and smartphone apps used and recommended for stress, anxiety or depression by the National Health Service (NHS) in England. DESIGN: The study was conducted using Freedom of Information (FOI) requests and systematic website searches. DATA SOURCES: Data were collected via FOI requests to NHS services between 13 February 2015 and 31 March 2015, and searches conducted on NHS apps library websites between 26 March 2015 and 2 November 2015. DATA COLLECTION/EXTRACTION METHODS: Data were compiled from responses to: (1) FOI requests sent to all Improving Access to Psychological Therapies (IAPT) services and NHS Mental Health Trusts in England and (2) NHS apps library search results. RESULTS: A total of 61 (54.95%) out of the then 111 IAPT service providers responded, accounting for 191 IAPT services, and all 51 of the then NHS Mental Health Trusts responded. The results were that 13 different web apps and 35 different smartphone apps for depression, anxiety or stress were available through either referral services or the online NHS Apps Libraries. The apps used and recommended vary by area and by point of access (online library/IAPT/trust). CONCLUSIONS: Future research is required to establish the evidence base for the apps that are being used in the NHS in England. There is a need for service provision to be based on evidence and established guidelines.

Analysis of milk urea nitrogen and lactose and their effect on longevity in Canadian dairy cattle.

The aim of this study was to assess the phenotypic level of lactose and milk urea nitrogen concentration (MUN) and the association of these traits with functional survival of Canadian dairy cattle using a Weibull proportional hazards model. A total of 1,568,952 test-day records from 283,958 multiparous Holstein cows from 4,758 herds, and 79,036 test-day records from 26,784 multiparous Ayrshire cows from 384 herds, calving from 2001 to 2004, were used for the phenotypic analysis. The overall average lactose percentage and MUN for Ayrshires were 4.49% and 12.20 mg/dL, respectively. The corresponding figures for Holsteins were 4.58% and 11.11 mg/dL. Concentration of MUN increased with parity number, whereas lactose percentage decreased in later parities. Data for survival analysis consisted of 39,536 first-lactation cows from 1,619 herds from 2,755 sires for Holsteins and 2,093 cows in 228 herds from 157 sires for Ayrshires. Test-day lactose percentage and MUN were averaged within first lactation. Average lactose percentage and MUN were grouped into 5 classes (low, medium-low, medium, medium-high, and high) based on mean and standard deviation values. The statistical model included the effects of stage of lactation, season of production, the annual change in herd size, type of milk-recording supervision, age at first calving, effects of milk, fat, and protein yields calculated as within herd-year-parity deviations, herd-year-season of calving, lactose percentage and MUN classes, and sire. The relative culling rate was calculated for animals in each class after accounting for the remaining effects included in the model. Results showed that there was a statistically significant association between lactose percentage and MUN in first lactation with functional survival in both breeds. Ayrshire cows with high and low concentration of MUN tended to be culled at a higher than average rate. Instead, Holstein cows had a linear association, with decreasing relative risk of culling with increasing levels of MUN concentration. The relationship between lactose percentage and survival was similar across breeds, with higher risk of culling at low level of lactose, and lower risk of culling at high level of lactose percentage.

Health related quality of life of patients with refractory angina before and one year after enrolment onto a refractory angina program.

OBJECTIVE: This study was designed to assess the impact of a refractory angina programme on the health related quality of life for patients with chronic refractory angina (CRA) one year following enrolment. DESIGN: A one year prospective audit. SETTING: Specialist refractory angina clinic at a tertiary cardiac referral centre. PATIENTS: 69 consecutive refractory angina patients referred to a regional refractory angina centre from 1/03/2001 to 1/09/2002. INTERVENTIONS: Pain treatment algorithm in accordance with the recommendations of the national refractory angina guideline committee. MAIN OUTCOME MEASURES: Improvements in quality of life indices were assessed using Seattle angina questionnaire (SAQ), and short form-12 (SF-12) with changes in mood determined using the hospital anxiety and depression (HAD) questionnaire. RESULTS: All dimensions of the SF-12 and SAQ were superior at one year with significant improvement seen with the mental component of SF-12 (p = 0.023), and four of the five SAQ domains, angina stability (p = 0.028), angina frequency (p=0.02), treatment satisfaction (p=0.001) and quality of life (p < 0.001). All the significant changes within the SAQ domains were large enough to be considered clinically relevant. At one year the anxiety and depression domains were significantly improved from baseline (p = 0.015, 0.018) with clinical anxiety levels falling significantly from 55% to 40%, a relative reduction of 28% (p = 0.008). CONCLUSIONS: Implementation of the national refractory angina guidelines in a prospective study of 69 consecutive CRA patients significantly improved health related quality of life status at one year.

Blink-related eye movements.

Eye movements that accompany a blink have been measured in human subjects by the use of a visual-persistence method. With straight-ahead binocular viewing, each eye typically rotates nasalward and downward 1-2 deg during the closing phase of a blink. These eye movements are more rapid than the lid movements as recorded by high-speed photography. In fact, the eyes have already completed their initial rotation and started back again before the lids are fully closed. With off-center viewing, a blink causes each eye to rotate toward its primary position of regard. Indeed, if the eye is already in that position when the blink starts, the eye moves very little. With eyelids taped open, an eye tracker can be used, and records confirming the visual persistence tracings are obtained. Sequential photography of the cornea in profile reveals that the eye moves inward and back out again during a blink. The amplitude of this retraction is typically less than 1 mm; and its time course, slower than that of the rotational eye movements, parallels the closure and opening of the lids. In normal conditions of viewing there is no evidence of conjugate saccades, or of any large, upward rotation of the eyes (Bell's phenomenon) that was once believed to take place during a blink.

A method for determining threshold from single-unit neural activity.

A computationally straightforward method is described for determining the latency, duration and magnitude of stimulus-evoked single-unit neural activity. A unique feature of the method is its ability to define the neural response without reference to stimulus parameters. First, the temporal component of the spike train that represents the response is located and then that component is analyzed to determine the magnitude of the response. Intensity-response functions can then be constructed, using the number of extra spikes above baseline activity as a measure of response magnitude. Threshold can be defined as any point on the intensity-response function.

A retinal smear technique for varying grating contrast.

We present here a technique for modulating contrast in gratings seen in Maxwellian-view or on a projection screen. The method can be used with achromatic or chromatic grating stimuli. It is based on a high frequency oscillatory displacement of the grating image, which in turn produces a smearing of the image on the observer's retina. The waveform of the displacement and its amplitude determine the appearance and contrast of the image produced on the retina.

Changes in the human visually evoked cortical potential in response to chromatic modulation of a sinusoidal grating.

Human visually evoked cortical potentials (VECPs) were recorded from 4 subjects in response to the counterphase alternation of an equal brightness chromatic grating pattern. The pattern was constructed from 2 monochromatic sinusoidal gratings registered 180 deg out of phase. Eleven wavelengths from 450 to 650 nm (at 20 nm intervals) were used. Each wavelength was paired in the grating stimulus with every other to produce a total of 55 different chromatic gratings. The chromatic modulation depth (contrast) of each grating was varied and resulting VECPs were recorded. VECP amplitude was found to vary linearly with log chromatic modulation depth. VECP threshold values were inferred by extrapolation of linear regression lines to zero VECP amplitude. Chromatic modulation sensitivity functions were derived and a multidimensional scaling analysis of the data for each subject was performed. The data were adequately described by a two-dimensional geometric configuration of the 11 wavelengths used. The configurations were similar in shape to those obtained psychophysically by Butler and Riggs (1978) Vision Res. 18, 1407-1416, who used a similar stimulus pattern. Their shapes are consistent with an opponent-color model of color vision.

Perception of suprathreshold stimuli during saccadic eye movements.

We have investigated the extent to which a graded series of suprathreshold stimuli are perceptually weakened by saccadic suppression. Stimuli were brief decrements of variable amplitude in the illumination of a Ganzfeld. For each of several decrements presented during fixation, we determined a matching amplitude of decrement presented during saccades. The measure of saccadic suppression was the ratio of these two amplitudes. The matches made by three observers exhibit ratios as high as 6:1 (0.8 log unit of suppression) near the threshold. Suppression decreases systematically as the strength of the stimulus increases, reaching 0.1 log unit or less for stimuli 2 log units above threshold.

Measurements of visual suppression during opening, closing and blinking of the eyes.

We have previously shown that the sensitivity of human vision, as measured with a stimulus that bypasses the eyelids, is briefly impaired at the time of an eyeblink. We now find that the visual loss is almost equally extensive during eye closure if the eyes then remained closed. But little impairment occurs during eye opening when the eyes then remain open. We have previously concluded that, in blinking, visual suppression is associated with an inhibitory signal sent out by the brain. We now conclude that this signal arises primarily as a corollary to the efferent discharge that closes the eyelids.

A dynamic programming algorithm for the distance between two finite areas.

The problems of speech recognition and orthographic word correction have been greatly mitigated by the use of dynamic programming techniques for finding the distance between two finite sequences. This paper extends the technique into two dimensions, and presents an algorithm for finding the distance between two finite areas. Applications of the algorithm are suggested.

Isolated word recognition of silent speech using magnetic implants and sensors.

There are a number of situations where individuals wish to communicate verbally but are unable to use conventional means-so called 'silent speech'. These include speakers in noisy and covert situations as well as patients who have lost their voice as a result of a laryngectomy or similar procedure. This paper focuses on those who are unable to speak following a laryngectomy and assesses the possibility of speech recognition based on a magnetic implant/sensors system. Permanent magnets are placed on the tongue and lips and the changes in magnetic field resulting from movement during speech are monitored using a set of magnetic sensors. The sensor signals are compared to sets of pre-recorded templates using the dynamic time warping (DTW) method, and the best match is identified. Experimental trials are reported for subjects with intact larynx, typically using 500-1000 utterances used for speaker dependant training and testing. It is shown that recognition rates of over 90% are achievable for vocabularies of at least 57 isolated words: sufficient to drive command-and-control applications.