The use of oxytocin to cause cervical dilation for transcervical insemination in nulliparous goats: Improving pregnancy and kidding rates.

To evaluate the effect of oxytocin as a cervical dilator, a study was carried out on nulliparous goats inseminated transcervically at the beginning of the breeding season. One hundred sixteen nulliparous goats with a mean live weight of 33.4 ± 0.68 kg and an age of 13.7 ± 0.37 months were used. The goats were exposed to active bucks of proven fertility for a period of 14 d in order to induce oestrus. One week later, the Ovsynch protocol was applied, which consisted of the application of 20 mg of gonadorelin (Day Zero), 0.075 mg of cloprostenol (Day 7) and of a second dose of 20 mg of gonadorelin applied on Day 9. Artificial insemination (AI) was performed 16 hr later. Three treatments were evaluated: T1 = 50 IU saline, T2 = 25 IU oxytocin; T3 = 50 IU of oxytocin, intravenously applied 10-15 min before AI. The time required to inseminate each treated goat from groups T2 and T3 was 49.56 and 56.25 s, respectively, versus 85.78 s needed for the goats from group T1 (p < .0001). In the T1 group of goats, the insemination catheter was inserted 2.1 cm into the cervical canal and in goats from groups T2 and T3 it reached 3.41 and 3.77 cm into the cervical canal, respectively (p = .02). Pregnancy rates and prolificacy (kids/doe) were higher (p = .02) for groups T2 (82.93%; 1.16) and T3 (76.92%; 1.21) respectively than for control goats (61.11%; 0.69). In conclusion, the intravenous administration of oxytocin led to greater dilation and depth of cervical penetration, obtaining higher pregnancy rates and prolificacy.

Quantitative CT Characteristics of Cluster Phenotypes in the Severe Asthma Research Program Cohorts.

Background Clustering key clinical characteristics of participants in the Severe Asthma Research Program (SARP), a large, multicenter prospective observational study of patients with asthma and healthy controls, has led to the identification of novel asthma phenotypes. Purpose To determine whether quantitative CT (qCT) could help distinguish between clinical asthma phenotypes. Materials and Methods A retrospective cross-sectional analysis was conducted with the use of qCT images (maximal bronchodilation at total lung capacity [TLC], or inspiration, and functional residual capacity [FRC], or expiration) from the cluster phenotypes of SARP participants (cluster 1: minimal disease; cluster 2: mild, reversible; cluster 3: obese asthma; cluster 4: severe, reversible; cluster 5: severe, irreversible) enrolled between September 2001 and December 2015. Airway morphometry was performed along standard paths (RB1, RB4, RB10, LB1, and LB10). Corresponding voxels from TLC and FRC images were mapped with use of deformable image registration to characterize disease probability maps (DPMs) of functional small airway disease (fSAD), voxel-level volume changes (Jacobian), and isotropy (anisotropic deformation index [ADI]). The association between cluster assignment and qCT measures was evaluated using linear mixed models. Results A total of 455 participants were evaluated with cluster assignments and CT (mean age ± SD, 42.1 years ± 14.7; 270 women). Airway morphometry had limited ability to help discern between clusters. DPM fSAD was highest in cluster 5 (cluster 1 in SARP III: 19.0% ± 20.6; cluster 2: 18.9% ± 13.3; cluster 3: 24.9% ± 13.1; cluster 4: 24.1% ± 8.4; cluster 5: 38.8% ± 14.4; P < .001). Lower whole-lung Jacobian and ADI values were associated with greater cluster severity. Compared to cluster 1, cluster 5 lung expansion was 31% smaller (Jacobian in SARP III cohort: 2.31 ± 0.6 vs 1.61 ± 0.3, respectively, P < .001) and 34% more isotropic (ADI in SARP III cohort: 0.40 ± 0.1 vs 0.61 ± 0.2, P < .001). Within-lung Jacobian and ADI SDs decreased as severity worsened (Jacobian SD in SARP III cohort: 0.90 ± 0.4 for cluster 1; 0.79 ± 0.3 for cluster 2; 0.62 ± 0.2 for cluster 3; 0.63 ± 0.2 for cluster 4; and 0.41 ± 0.2 for cluster 5; P < .001). Conclusion Quantitative CT assessments of the degree and intraindividual regional variability of lung expansion distinguished between well-established clinical phenotypes among participants with asthma from the Severe Asthma Research Program study. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Verschakelen in this issue.

Effect of Palpable Udder Defects on Milk Yield, Somatic Cell Count, and Milk Composition in Non-Dairy Ewes.

In non-dairy ewes, udder defects hinder the survival and weight gain of their pre-weaned lambs. The objectives of this study were to determine the effects of palpable udder defects on milk yield, somatic cell count (SCC), and milk composition in non-dairy Romney ewes. Ewes with a history of udder defects or normal udders were selected for the study. Of a total of 48 ewes that lambed, 30 ewes reared at least one lamb, and were milked six times, once weekly, for the first six weeks of lactation. Udder halves were palpated and scored at each milking event. Multivariate linear mixed models examined the impacts of udder defects on udder-half and whole-udder milk yield, SCC, and milk composition (fat, protein, lactose, total solids, and solids non-fat (SNF)). Across the six examinations, 24.7% of the total 352 udder-half examinations were observed to be defective. Udder halves that were defective at least once produced on average 57.9% less (p < 0.05) milk than normal udder halves, while normal udder halves with a contralateral defective half yielded 33.5% more (p < 0.05) milk than normal udder halves. Successive occurrence of both hard and lump udder defect categories in an udder-half, udder defect detection early in lactation, and a high frequency of udder defect detection were all associated with udder-half milk yield loss (p < 0.05). At the whole-udder level, no differences in milk yield (p > 0.05) were observed between those with one udder-half defective and both normal udder-halves. However, udders in which one udder half was categorised as hard but progressed to lump and remained as lump until 42 days of lactation produced less (p < 0.05) milk compared with normal udders. With the exception of SNF, there were no significant associations (p > 0.05) between milk composition parameters and udder defect. Overall, these findings emphasise the importance of udder health in non-dairy ewes and the potential effect of udder defects on their lambs.

Associations among Mammary Ultrasound Measurements, Milk Yield of Non-Dairy Ewe Lambs and the Growth of Their Single Lambs.

Mammary cistern size was positively correlated with milk yield of mature dairy ewes, but the association in ewe lambs is unknown. This experiment aimed to examine the associations between mammary ultrasound measurements and the milk yield of ewe lambs at one year of age and to determine the accuracy of using maternal mammary ultrasound to predict single lamb growth rates. Single-bearing ewe lambs (n = 45) were randomly selected and 30 were milked once at weeks three (W3), five (W5), and seven (W7) of lactation. Mammary ultrasound scans were performed at day 110 of pregnancy, W3, W5, W7, and weaning (L69). Single lambs (n = 30) were weighed at birth and at each mammary scanning event. Udder measurements explained 26.8%, 21.4%, and 38.4% of the variation in milk yield at W3, W5 and W7, respectively, and 63.5% and 36.4% of the variation in single lamb growth to W3 and to L69. This ultrasound technique was more accurate in predicting single lamb growth to W3 than milk yield and may enable the identification of pregnant ewe lambs whose progeny would have greater growth rates. More research is needed to identify accurate indicators of superior milk yield and determine whether ultrasound could be used to select ewe lambs.

Association of Computed Tomography Densitometry with Disease Severity, Functional Decline, and Survival in Systemic Sclerosis-associated Interstitial Lung Disease.

Rationale: Measuring disease extent and progression of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is challenging, with recent studies suggesting potential utility of quantitative measurements from computed tomography (CT) scans.Objectives: To determine the associations of quantitative computed tomography (qCT) density-based measures with physiological parameters, visual CT scores, and survival in patients with SSc-ILD.Methods: Patients with SSc-ILD and volumetric high-resolution CT images with ≤1.25-mm slice thickness were retrospectively identified. Cardiothoracic radiologists produced visual CT scores of ground glass, reticulation, and honeycombing, with visual fibrosis score equaling the sum of reticulation and honeycombing. qCT measurements included high-attenuation areas (HAA), skewness, kurtosis, and mean lung attenuation (MLA). Associations of qCT measures with pulmonary physiology, visual CT scores, and mortality were analyzed using Spearman's rank correlation and Cox regression.Results: A total of 503 CT scans from 170 patients with SSc-ILD were included. qCT HAA, skewness, kurtosis, and MLA were associated with lung function and visual fibrosis scores, independent of age, sex, and pack-years, using both baseline and change data. Baseline and changes in qCT measures (except ∆skewness) were associated with mortality on unadjusted analysis. Changes in all qCT variables remained associated with survival after adjustment for baseline age, sex, pack-years, and lung function, but not when adjusting for changes in lung function. ∆HAA and ∆MLA were associated with survival after adjustment for age, sex, pack-years, and change in visual CT scores.Conclusions: CT density measurements correlate with physiologic impairment and visual CT scores in patients with SSc-ILD; however, they were not associated with survival independent of changes in pulmonary physiology. The clinical utility of more sophisticated qCT measures should be explored.

Using Novel Computed Tomography Analysis to Describe the Contribution and Distribution of Emphysema and Small Airways Disease in Chronic Obstructive Pulmonary Disease.

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation, caused by emphysema and small airways disease (SAD). Computed tomography (CT) coupled with image analysis enables the quantification of these abnormalities; however, the optimum method for doing so has not been determined.Objectives: This study aims to compare two CT quantitative analysis techniques, disease probability measure (DPM) and parametric response mapping (PRM), and assess their relationship with specific physiological measures of SAD.Methods: Subjects with mild to moderate COPD, never smokers, and healthy ex-smokers were recruited. Each had airway oscillometry and multiple-breath nitrogen washout, measuring peripheral airway resistance, peripheral airway reactance, and acinar airway inhomogeneity. Subjects also had an inspiratory and expiratory chest CT, with DPM and PRM analysis performed by coregistering images and classifying each voxel as normal, emphysema, or nonemphysematous gas trapping related to SAD.Results: Thirty-eight subjects with COPD, 18 never smokers, and 23 healthy ex-smokers were recruited. There were strong associations between DPM and PRM analysis when measuring gas trapping (ρ = 0.87; P < 0.001) and emphysema (ρ = 0.99; P < 0.001). DPM assigned significantly more voxels as emphysema and gas trapped than PRM (P < 0.001). Both techniques showed significantly greater emphysema and gas trapping in subjects with COPD than in never smokers and ex-smokers (P < 0.001). All CT measures had significant associations with peripheral airway resistance and reactance, with disease probability measure of nonemphysematous gas trapping related to SAD having the strongest independent association with peripheral airway resistance (ß = 0.42; P = 0.001) and peripheral airway reactance (ß = 0.41; P = 0.001). Emphysema measures had the strongest associations with acinar airway inhomogeneity (ß = 0.35-0.38).Conclusions: These results provide further validation for the use of DPM/PRM analysis in COPD by demonstrating significant relationships with specific physiological measures of SAD.

PLGA nanoparticle encapsulation reduces toxicity while retaining the therapeutic efficacy of EtNBS-PDT in vitro.

Photodynamic therapy regimens, which use light-activated molecules known as photosensitizers, are highly selective against many malignancies and can bypass certain challenging therapeutic resistance mechanisms. Photosensitizers such as the small cationic molecule EtNBS (5-ethylamino-9-diethyl-aminobenzo[a]phenothiazinium chloride) have proven potent against cancer cells that reside within acidic and hypoxic tumour microenvironments. At higher doses, however, these photosensitizers induce "dark toxicity" through light-independent mechanisms. In this study, we evaluated the use of nanoparticle encapsulation to overcome this limitation. Interestingly, encapsulation of the compound within poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA-EtNBS) was found to significantly reduce EtNBS dark toxicity while completely retaining the molecule's cytotoxicity in both normoxic and hypoxic conditions. This dual effect can be attributed to the mechanism of release: EtNBS remains encapsulated until external light irradiation, which stimulates an oxygen-independent, radical-mediated process that degrades the PLGA nanoparticles and releases the molecule. As these PLGA-encapsulated EtNBS nanoparticles are capable of penetrating deeply into the hypoxic and acidic cores of 3D spheroid cultures, they may enable the safe and efficacious treatment of otherwise unresponsive tumour regions.

Algorithm Variability in the Estimation of Lung Nodule Volume From Phantom CT Scans: Results of the QIBA 3A Public Challenge.

RATIONALE AND OBJECTIVES: Quantifying changes in lung tumor volume is important for diagnosis, therapy planning, and evaluation of response to therapy. The aim of this study was to assess the performance of multiple algorithms on a reference data set. The study was organized by the Quantitative Imaging Biomarker Alliance (QIBA). MATERIALS AND METHODS: The study was organized as a public challenge. Computed tomography scans of synthetic lung tumors in an anthropomorphic phantom were acquired by the Food and Drug Administration. Tumors varied in size, shape, and radiodensity. Participants applied their own semi-automated volume estimation algorithms that either did not allow or allowed post-segmentation correction (type 1 or 2, respectively). Statistical analysis of accuracy (percent bias) and precision (repeatability and reproducibility) was conducted across algorithms, as well as across nodule characteristics, slice thickness, and algorithm type. RESULTS: Eighty-four percent of volume measurements of QIBA-compliant tumors were within 15% of the true volume, ranging from 66% to 93% across algorithms, compared to 61% of volume measurements for all tumors (ranging from 37% to 84%). Algorithm type did not affect bias substantially; however, it was an important factor in measurement precision. Algorithm precision was notably better as tumor size increased, worse for irregularly shaped tumors, and on the average better for type 1 algorithms. Over all nodules meeting the QIBA Profile, precision, as measured by the repeatability coefficient, was 9.0% compared to 18.4% overall. CONCLUSION: The results achieved in this study, using a heterogeneous set of measurement algorithms, support QIBA quantitative performance claims in terms of volume measurement repeatability for nodules meeting the QIBA Profile criteria.

Functional development of the adult ovine mammary gland--insights from gene expression profiling.

BACKGROUND: The mammary gland is a dynamic organ that undergoes dramatic physiological adaptations during the transition from late pregnancy to lactation. Investigation of the molecular basis of mammary development and function will provide fundamental insights into tissue remodelling as well as a better understanding of milk production and mammary disease. This is important to livestock production systems and human health. Here we use RNA-seq to identify differences in gene expression in the ovine mammary gland between late pregnancy and lactation. RESULTS: Between late pregnancy (135 days of gestation ± 2.4 SD) and lactation (15 days post partum ± 1.27 SD) 13 % of genes in the sheep genome were differentially expressed in the ovine mammary gland. In late pregnancy, cell proliferation, beta-oxidation of fatty acids and translation were identified as key biological processes. During lactation, high levels of milk fat synthesis were mirrored by enrichment of genes associated with fatty acid biosynthesis, transport and lipogenesis. Protein processing in the endoplasmic reticulum was enriched during lactation, likely in support of active milk protein synthesis. Hormone and growth factor signalling and activation of signal transduction pathways, including the JAK-STAT and PPAR pathways, were also differently regulated, indicating key roles for these pathways in functional development of the ovine mammary gland. Changes in the expression of epigenetic regulators, particularly chromatin remodellers, indicate a possible role in coordinating the large-scale transcriptional changes that appear to be required to switch mammary processes from growth and development during late pregnancy to synthesis and secretion of milk during lactation. CONCLUSIONS: Coordinated transcriptional regulation of large numbers of genes is required to switch between mammary tissue establishment during late pregnancy, and activation and maintenance of milk production during lactation. Our findings indicate the remarkable plasticity of the mammary gland, and the coordinated regulation of multiple genes and pathways to begin milk production. Genes and pathways identified by the present study may be important for managing milk production and mammary development, and may inform studies of diseases affecting the mammary gland.

Inter-Method Performance Study of Tumor Volumetry Assessment on Computed Tomography Test-Retest Data.

RATIONALE AND OBJECTIVES: Tumor volume change has potential as a biomarker for diagnosis, therapy planning, and treatment response. Precision was evaluated and compared among semiautomated lung tumor volume measurement algorithms from clinical thoracic computed tomography data sets. The results inform approaches and testing requirements for establishing conformance with the Quantitative Imaging Biomarker Alliance (QIBA) Computed Tomography Volumetry Profile. MATERIALS AND METHODS: Industry and academic groups participated in a challenge study. Intra-algorithm repeatability and inter-algorithm reproducibility were estimated. Relative magnitudes of various sources of variability were estimated using a linear mixed effects model. Segmentation boundaries were compared to provide a basis on which to optimize algorithm performance for developers. RESULTS: Intra-algorithm repeatability ranged from 13% (best performing) to 100% (least performing), with most algorithms demonstrating improved repeatability as the tumor size increased. Inter-algorithm reproducibility was determined in three partitions and was found to be 58% for the four best performing groups, 70% for the set of groups meeting repeatability requirements, and 84% when all groups but the least performer were included. The best performing partition performed markedly better on tumors with equivalent diameters greater than 40 mm. Larger tumors benefitted by human editing but smaller tumors did not. One-fifth to one-half of the total variability came from sources independent of the algorithms. Segmentation boundaries differed substantially, not ony in overall volume but also in detail. CONCLUSIONS: Nine of the 12 participating algorithms pass precision requirements similar to what is indicated in the QIBA Profile, with the caveat that the present study was not designed to explicitly evaluate algorithm profile conformance. Change in tumor volume can be measured with confidence to within ±14% using any of these nine algorithms on tumor sizes greater than 10 mm. No partition of the algorithms was able to meet the QIBA requirements for interchangeability down to 10 mm, although the partition comprising best performing algorithms did meet this requirement for a tumor size of greater than approximately 40 mm.