Selective treatment of clinical mastitis: Assessment of the Net Cash Impact on Dairy Farms Under Diverse Scenarios. A European Perspective.

Selective treatment of clinical mastitis (STCM) potentially reduces antimicrobial use without negative implications on cow's milk production or health. However, this approach comes with additional costs. The aim of this study was to evaluate the net cash impact (NCI) of implementing STCM compared with blanket treatment of clinical mastitis (BTCM) under different diagnostic-test turnaround times (24 h, 14 h, and 8 h) using a stochastic partial budget analysis with Monte Carlo simulation. The target population was European commercial dairy herds; therefore, the model inputs were primarily from European sources. Additionally, variables associated with dairy management programs were obtained from USDA sources, worldwide multisite clinical trials, and expert opinion. The output was calculated by subtracting the cost of STCM from the cost of BTCM and it represented the expected NCI if a herd switched from BTCM to STCM. Depending on the time-to-treatment efficiency and diagnostic-test turnaround time, the expected mean NCI, assuming that STCM has no impact on the cow's future health or production, ranged from +€8.7 to +€12.4 per case with 72.4% to 84.8% of the iterations being ≥ €0. Moreover, using the numerically favorable health and production effects of STCM reported in the literature, the expected mean NCI ranged from +€44.5 to +€48.1 per case with 93.6% to 95.4% of the iterations being ≥ €0. The variables with the greatest contribution to NCI variance were proportion of gram-positive cases (39.2% of the variance) and days out of the tank for treated cows (22.0%). However, if future cow's health and production were accounted for, culling risk (24.6%), recurrence risk (19.4%), and milk yield (10.6%) would have the greatest contribution to NCI. The sensitivity analysis indicated that farms with high clinical mastitis incidence, low proportion of gram-positive cases, large number of days out of the tank for treated cows, higher milking frequency or using automatic milking systems, not using the highest priced diagnostic tests, and having high antimicrobial treatment costs are the best candidates for STCM. Improving time-to-treatment efficiency, for example, by using a rapid diagnostic test, leads to a favorable NCI, while high daily milk yield and milk price enhances the NCI in already positive scenarios. Finally, the cash flow entirely depends on future cow's health and milk yield. In conclusion, results indicate that overall, STCM is a practice that positively impacts the NCI of many herds.

Quantitative TMT-based proteomics revealing host, dietary and microbial proteins in bovine faeces including barley serpin Z4, a prominent component in the head of beer.

There has been little information about the proteome of bovine faeces or about the contribution to the faecal proteome of proteins from the host, the feed or the intestinal microbiome. Here, the bovine faecal proteome and the origin of its component proteins was assessed, while also determining the effect of treating barley, the major carbohydrate in the feed, with either ammonia (ATB) or sodium propionate (PTB) preservative. Healthy continental crossbreed steers were allocated to two groups and fed on either of the barley-based diets. Five faecal samples from each group were collected on Day 81 of the trial and analysed by quantitative proteomics using nLC-ESI-MS/MS after tandem mass tag labelling. In total, 281 bovine proteins, 199 barley proteins, 176 bacterial proteins and 190 archaeal proteins were identified in the faeces. Mucosal pentraxin, albumin and digestive enzymes were among bovine proteins identified. Serpin Z4 a protease inhibitor was the most abundant barley protein identified which is also found in barley-based beer, while numerous microbial proteins were identified, many originating bacteria from Clostridium, while Methanobrevibacter was the dominant archaeal genus. Thirty-nine proteins were differentially abundant between groups, the majority being more abundant in the PTB group compared to the ATB group. SIGNIFICANCE: Proteomic examination of faeces is becoming a valuable means to assess the health of the gastro-intestinal tract in several species, but knowledge on the proteins present in bovine faeces is limited. This investigation aimed to characterise the proteome of bovine faecal extracts in order to evaluate the potential for investigations of the proteome as a means to assess the health, disease and welfare of cattle in the future. The investigation was able to identify proteins in bovine faeces that had been (i) produced by the individual cattle, (ii) present in the barley-based feed eaten by the cattle or (iii) produced by bacteria and other microbes in the rumen or intestines. Bovine proteins identified included mucosal pentraxin, serum albumin and a variety of digestive enzymes. Barley proteins found in the faeces included serpin Z4, a protease inhibitor that is also found in beer having survived the brewing process. Bacterial and archaeal proteins in the faecal extracts were related to several pathways related to the metabolism of carbohydrates. The recognition of the range of proteins that can be identified in bovine faeces raises the possibility that non-invasive sample collection of this material could provide a novel diagnostic approach to cattle health and welfare.

Modulating Oncolytic Adenovirus Immunotherapy by Driving Two Axes of the Immune System by Expressing 4-1BBL and CD40L.

Oncolytic viruses (OVs) can have utility for direct killing of cancer cells, but may also serve to activate the immune system against cancer cells. While viruses alone can serve as immune stimulators, there is great interest in arming OVs with genes encoding immune stimulatory proteins to amplify their effects. In this work, we have tested the efficacy of conditionally-replicating adenoviruses (CRAds) with and without selected immunostimulatory payloads, murine CD40L (mCD40L) or 4-1BBL (m4-1BBL), in an immune competent mouse model of melanoma. When CRAd657-m4-1BBL and CRAd657-mCD40L were injected into B16-hCAR murine melanoma tumors, both single vectors delayed tumor growth and prolong survival compared to empty CRAd657. However, combined injection of both CRAd-m4-1BBL and CRAd-mCD40L mediated significantly better control of tumor growth. All of the payloads increased immune cell infiltration into tumors and notably reduced expression of PD-1 exhaustion marker on T cells. Tumor volumes were negatively associated with total infiltrating T cell population. We found that the payloads increased immune cell infiltration into tumors with some specificities: recruitment of CD8+ T cells was higher with m4-1BBL expression, while mCD40L expression induced more CD4+ T cell infiltration. Importantly, the combination of CRAd657-m4-1BBL and CRAd657-mCD40L induced the highest immune cells/T cell infiltration and the highest anti-TRP-2 tumor-associated antigen T cell responses than empty or single gene vector. This combination also caused depigmentation in areas adjacent to the tumor sites in more animals. These data indicate that driving two axes of the immune system with combined immune stimulatory payloads can lead to improved anticancer immune responses and better tumor control in an immune competent model of cancer.

Chemistry and world food supplies.

Much of the unprecedented increase in developing countries' food production in the past two decades is due to chemical-based technologies and to the use of agricultural chemicals. However, these successes were won under generally favorable conditions of soil, climate, and irrigation water availability. The challenge of the future is to broaden the base of increased food production to include areas less well endowed with natural and economic resources. Chemistry and chemicals must play vital roles in this venture. Innovative chemical and biochemical approaches must be called upon to produce crop varieties, animal strains, and associated technologies to overcome constraints such as insects and diseases, acid and alkaline soils, and drought conditions. Genetic engineering will probably be a primary mechanism to achieve this goal.

Response to myocardial ischemia/reperfusion injury involves Bnip3 and autophagy.

Ischemia and reperfusion (I/R) injury is associated with extensive loss of cardiac myocytes. Bnip3 is a mitochondrial pro-apoptotic Bcl-2 protein which is expressed in the adult myocardium. To investigate if Bnip3 plays a role in I/R injury, we generated a TAT-fusion protein encoding the carboxyl terminal transmembrane deletion mutant of Bnip3 (TAT-Bnip3DeltaTM) which has been shown to act as a dominant negative to block Bnip3-induced cell death. Perfusion with TAT-Bnip3DeltaTM conferred protection against I/R injury, improved cardiac function, and protected mitochondrial integrity. Moreover, Bnip3 induced extensive fragmentation of the mitochondrial network and increased autophagy in HL-1 myocytes. 3D rendering of confocal images revealed fragmented mitochondria inside autophagosomes. Enhancement of autophagy by ATG5 protected against Bnip3-mediated cell death, whereas inhibition of autophagy by ATG5K130R enhanced cell death. These results suggest that Bnip3 contributes to I/R injury which triggers a protective stress response with upregulation of autophagy and removal of damaged mitochondria.

Pointing perception is precise.

The spontaneity and ease with which we point understates the gesture's significance to understanding cognition. Onset of pointing in infancy predicts early word acquisition and signals a capacity for shared intentionality. Yet, notwithstanding its importance, there is little research on the perception of pointing and its referents. Here we show that perceptual acuity for discerning where another person is pointing is remarkably accurate. Thresholds, as low as 0.5° of visual angle across an interpersonal distance of ∼2 m, are modulated by the referent's location in space and the hand used to point and remain constant when the pointer's eyes are occluded from view and when 'embodiment' cues are enhanced or minimized. Pointing with the index finger not only directs attention toward a general region of space but the morphology of arm, hand and finger can be used to discern the location of the pointer's attention with precision.

Early outcomes in youth with psychogenic nonsyncopal collapse.

OBJECTIVE: To evaluate several early outcome measures following diagnosis of psychogenic nonsyncopal collapse (PNSC). METHODS: Over a 34-month period, a prospective cohort study was conducted of patients referred for tilt-table evaluation of fainting and orthostatic intolerance. Clinical histories were obtained and anxiety and depressive symptom questionnaires were completed prior to testing. Among 539 patients referred, 100 (18.6%) were diagnosed with PNSC. Outcome data were collected by telephone or during routine follow-up a median of 572 days postdiagnosis. RESULTS: Eighty-four patients (84%) provided outcome data. Following communication of the diagnosis, 32 patients (38%) had immediate PNSC resolution. Attack resolution occurred in 44% by 1 month, 51% by 6 months, 52% by 12 months, 69% after 12 months, and 31% continued to have PNSC at the time of follow-up. Patients with continued PNSC had higher anxiety scores than patients with immediate resolution (p = 0.047). Following diagnosis, emergency department visits for fainting decreased from 78.6% to 20.2% (p = 0.017), and management by psychology or psychiatry increased from 26.2% to 76.2% (p < 0.001). During the follow-up period, 8 patients (9.5%) were hospitalized for suicidal ideation, a median of 253 (range 33-470) days postdiagnosis; 12 patients (14.3%) developed new (non-PNSC) conversion disorders, a median of 86 (range 9-504) days postdiagnosis. Suicidal ideation was associated with higher anxiety (p = 0.007) but not higher depression scores. CONCLUSIONS: The diagnostic rate of PNSC parallels that of PNES among patients referred for tertiary care evaluations. The improvements in attack frequency following PNSC diagnosis must be tempered by the potential risks of self-harm and the development of new conversion disorders.

Identifying Aß-specific pathogenic mechanisms using a nematode model of Alzheimer's disease.

Multiple gene expression alterations have been linked to Alzheimer's disease (AD), implicating multiple metabolic pathways in its pathogenesis. However, a clear distinction between AD-specific gene expression changes and those resulting from nonspecific responses to toxic aggregating proteins has not been made. We investigated alterations in gene expression induced by human beta-amyloid peptide (Aß) in a Caenorhabditis elegans AD model. Aß-induced gene expression alterations were compared with those caused by a synthetic aggregating protein to identify Aß-specific effects. Both Aß-specific and nonspecific alterations were observed. Among Aß-specific genes were those involved in aging, proteasome function, and mitochondrial function. An intriguing observation was the significant overlap between gene expression changes induced by Aß and those induced by Cry5B, a bacterial pore-forming toxin. This led us to hypothesize that Aß exerts its toxic effect, at least in part, by causing damage to biological membranes. We provide in vivo evidence consistent with this hypothesis. This study distinguishes between Aß-specific and nonspecific mechanisms and provides potential targets for therapeutics discovery.

Selectivity, scope, and simplicity of models: a lesson from fitting judgments of perceived depth.

When comparing psychological models a researcher should assess their relative selectivity, scope, and simplicity. The third of these considerations can be measured by the models' parameter counts or equation length, the second by their ability to fit random data, and the first by their differential ability to fit patterned data over random data. These conclusions are based on exploration of integration models reflecting depth judgments. Replication of Massaro's (1988a) results revealed an additive model (Bruno & Cutting, 1988), and Massaro's fuzzy-logical model of perception (FLMP) fit data equally well, but further exploration showed that the FLMP fit random data better. The FLMP's successes may reflect not its sensitivity in capturing psychological process but its scope in fitting any data and its complexity as measured by equation length.

Community psychiatric nurse aftercare for alcoholics: a five-year follow-up study.

The aim of this study was to determine if community psychiatric nurse (CPN) aftercare for 1 year improved the 5-year outcome in patients following inpatient treatment for alcohol dependence. A 5-year follow-up study, observer blind, with non-random allocation of subjects to aftercare by CPN for 1 year or standard outpatient care, was used. Subjects had all received inpatient treatment for 6 weeks in a rural alcohol treatment unit. Subjects were traced and assessed in the community 5 years after the index admission. The participants consisted of 127 white male alcoholics. All were first admissions, who had been selected for inpatient treatment and who completed a 6-week inpatient stay. Seventy-three subjects received intensive aftercare by CPN for 1 year, 54 subjects received standard outpatient appointments not due to random allocation but because no CPN was available. Data were collected by semi-structured interview at entry to the trial, namely background epidemiological information, details of drinking history, previous hospital admission, educational, employment and criminal information. At 5-year follow-up, data on drinking status, use of other drugs, hospital admissions, criminal behaviour and gambling, attendance at self-help groups, relationships and employment were collected. Thirty-six per cent of the CPN aftercare group was completely abstinent during the 5 years after treatment compared to 6% of the standard aftercare group (p < 0.001). Subjects receiving CPN aftercare were less likely to report blackouts (p < 0.05) or gambling (p < 0.05). They were more likely to attend hospital meetings (p < 0.0001). CPN aftercare is an effective way of maximizing the effects of inpatient treatment. The effects endured for 5 years after treatment.

Visual sensitivity, blur and the sources of variability in the amplitude spectra of natural scenes.

A number of researchers have suggested that in order to understand the response properties of cells in the visual pathway, we must consider the statistical structure of the natural environment. In this paper, we focus on one aspect of that structure, namely, the correlational structure which is described by the amplitude or power spectra of natural scenes. We propose that the principle insight one gains from considering the image spectra is in understanding the relative sensitivity of cells tuned to different spatial frequencies. This study employs a model in which the peak sensitivity is constant as a function of frequency with linear bandwith increasing (i.e., approximately constant in octaves). In such a model, the "response magnitude" (i.e., vector length) of cells increases as a function of their optimal (or central) spatial frequency out to about 20 cyc/deg. The result is a code in which the response to natural scenes, whose amplitude spectra typically fall as 1/f, is roughly constant out to 20 cyc/deg. An important consideration in evaluating this model of sensitivity is the fact that natural scenes show considerable variability in their amplitude spectra, with individual scenes showing falloffs which are often steeper or shallower than 1/f. Using a new measure of image structure (the "rectified contrast spectrum" or "RCS") on a set of calibrated natural images, it is shown that a large part of the variability in the spectra is due to differences in the sparseness of local structure at different scales. That is, an image which is "in focus" will have structure (e.g., edges) which has roughly the same magnitude across scale. That is, the loss of high frequency energy in some images is due to the reduction of the number of regions that contain structure rather than the amplitude of that structure. An "in focus" image will have structure (e.g., edges) across scale that have roughly equal magnitude but may vary in the area covered by structure. The slope of the RCS was found to provide a reasonable prediction of physical blur across a variety of scenes in spite of the variability in their amplitude spectra. It was also found to produce a good prediction of perceived blur as judged by human subjects.

What's constant in contrast constancy? The effects of scaling on the perceived contrast of bandpass patterns.

"Contrast constancy" refers to the ability to perceive objects as maintaining a constant contrast independent of size or distance. When tested with high contrast sinusoidal gratings, contrast constancy has been shown to hold for a wide range of spatial frequencies, suggesting that sensitivity is constant across the spectrum at suprathreshold. In this study, we show that contrast constancy also holds for relatively broadband patterns. We describe how the frequency spectra of such functions change as the patterns scale in size. In particular, we emphasize how these changes in the spectra depend on whether the functions are localized (coherent phase) or spatially distributed (incoherent phase). In Fourier terms, the scaling properties depend on the phase spectra of the patterns. Contrast constancy is shown to hold for both localized Gabor patches (coherent phase spectra) and bandpass noise patterns (incoherent phase spectra). Constancy holds over a wide range of suprathreshold contrasts; in fact, matching is quite accurate as soon as the pattern is suprathreshold. These results are explained with a model in which mechanism bandwidths increase with frequency (constant in octaves) and peak spectral sensitivity is equal across frequency out to around 16 c/deg. In the case of the Gabor stimuli, perceived contrast is assumed to be mediated by a mechanism centered on the patch. For the bandpass noise, contrast is determined by the average response of units distributed across the stimulus. This model can account for the matching data without assuming that the contrast-response gain of the underlying channels changes with spatial frequency. Neither does the model assume "response pooling". In addition to explaining the experimental results, the model also predicts that perceived contrast will be approximately constant across scale for scenes whose spectra fall as 1/f, as is typical of natural scenes.

Independent coding across spatial scales in moving fractal images..

We compared observers' ability to discriminate the direction of apparent motion using images which varied in their spatial characteristic; white or flat spectrum noise, and 1/f noise which has an amplitude spectrum characteristic of natural scenes. The upper spatial limit for discrimination (dmax) was measured using a two-flash random dot kinematogram (RDK), which consisted either of a pair of bandpass filtered images or of a bandpass filtered image and its broadband counterpart. Six bandpass central frequencies were used, ranging from 0.25 to 5.66 cyc/deg. Subjects could perform the direction discrimination task for all six central frequencies in both the bandpass-bandpass and bandpass-broadband sequences for the 1/f images, and dmax values were found to be approximately equal in these two conditions at all spatial scales. However, for the white noise images, direction discrimination was not possible at the lowest central frequencies in the bandpass-broadband task. These data show that information from a wide range of spatial scales is equally salient to the human motion system in images whose amplitude spectra fall as 1/f. However, for white noise images, information at the higher spatial frequencies is more salient and dominates performance in the direction discrimination task. These results are consistent with a model in which spatial frequency filters in the input lines of motion detectors have octave constant spatial frequency bandwidths and equal peak sensitivity. In line with a number of recent studies, this suggests that the spatial properties of motion sensitive cells are matched to the statistical properties of natural scenes.

Is human motion detection subserved by a single or multiple channel mechanism?

Two recent versions of a single channel model of motion perception have had impressive success in explaining direction discrimination by human observers for spatially filtered noise images in two-flash apparent motion. It has been argued that the dramatic breakdown in motion perception which occurs when one image in the two-flash sequence is low-pass filtered can be explained only by a single channel model. We show that neither version of the single channel model which has been proposed can explain performance for noise images chosen to provide comparable stimulation in the spatial channels known to subserve human vision. A multi-channel model of motion perception has little difficulty in explaining these results.

Reported communication abilities of individuals with severe mental retardation.

Little is known about the distribution of communication skills among individuals with severe mental retardation. The present study was designed to obtain basic descriptive information about the reported expressive communication status and other associated sensory and behavioral characteristics of four representative samples of this overall population. These samples include both children and adults and individuals living in large residential facilities as well as those living at home or in smaller, more natural community environments. Results of this study, based on completed questionnaires for 211 subjects, revealed a wide range of communication abilities in this population, with a significantly larger percentage of adults than children communicating at symbolic levels.

The commitment to breastfeeding.

The Agency for International Development (A.I.D.) is increasing its efforts to promote breastfeeding, as part of its child survival initiatives in child spacing, diarrheal disease control, and nutrition. Research suggests that promotion can increase breastfeeding rates. The Agency, for the first time, has set aside funds specifically for breastfeeding promotion and is working to identify places in its programs where such promotion can take place.

Communication forms and functions of children and adults with severe mental retardation in community and institutional settings.

The forms and functions of expressive communication produced by 84 individuals with severe mental retardation were assessed, using a structured communication sampling procedure. Symbolic communication acts were produced by 39 participants, and 27 of these symbolic communicators produced one or more multiword/multisymbol utterances. Of the remaining participants, 38 produced intentional but nonsymbolic communication acts; 7 were not observed to produce any intentional communication. For all participants who produced intentional communication, there were significantly more imperative than declarative communication acts. Significant differences in the frequencies and functions of communication acts produced by these participants were associated with differences in their communication levels (contact gesture, distal gesture, or symbolic), age (child vs. adult), and residential status (community home vs. large facility).

Catch-up head growth and motor performance in very-low-birthweight infants.

The relationship between catch-up head growth and motor performance was examined in 48 very-low-birthweight (< 1,500 g) infants. All infants were nonasphyxiated, normocephalic, and appropriately grown for gestational age at birth. Serial cranial ultrasonography during the first month of life revealed no intracranial pathology. The age of catch-up head growth, defined as the corrected age when the head circumference recovered to the 5th percentile, was determined for each infant. At 12 months corrected age, the infants were evaluated and grouped according to normal (n = 37) or abnormal (n = 11) motor assessments. The abnormal group achieved catch-up head growth by 7.7 +/- 2.1 months vs 3.7 +/- 3.1 months for the normal group (P < .05). Only 27% of the motor-delayed infants achieved catch-up head growth by 6 months corrected age, as compared with 89% of the normal infants (P < .05). Premature infants who have achieved catch-up head growth by 6 months corrected age, corresponding to the period of maximal postnatal brain growth, have fewer motor abnormalities than infants who attain catch-up head growth later. There is a significant relationship between head circumference at 6 months corrected age and motor development in very-low-birthweight infants.