Milk solids per kilogram of body weight (BW) is growing in popularity as a measure of dairy cow lactation efficiency. Little is known on the extent of genetic variability that exist in this trait but ...also the direction and strength of genetic correlations with other performance traits. Such genetic correlations are important to know if producers are to consider actively selecting cows excelling in milk solids per kilogram of BW. The objective of the present study was to use a large data set of commercial Irish dairy cows to quantify the extent of genetic variability in milk solids per kilogram of BW and related traits but also their genetic and phenotypic inter-relationships. Mid-lactation BW and body condition score (BCS), along with 305-d milk solids yield (i.e., fat plus protein yield) were available on 12,413 lactations from 11,062 cows in 85 different commercial dairy herds. (Co)variance components were estimated using repeatability animal linear mixed models. The genetic correlation between milk solids and body weight was only 0.05, which when coupled with the observed large genetic variability in both traits, indicate massive potential to select for both traits in opposite directions. The genetic correlations between both milk solids and BW with BCS; however, need to be considered in any breeding strategy. The genetic standard deviation, heritability, and repeatability of milk solids per kilogram of BW was 0.08, 0.37, and 0.57, respectively. The genetic correlation between milk solids per kilogram of BW with milk solids, BW, and BCS was 0.62, −0.75, and −0.41, respectively. Therefore, based on genetic regression, each increase of 0.10 units in genetic merit for milk solids per kilogram of BW is expected to result in, on average, an increase in 16.1 kg 305-d milk solids yield, a reduction of 25.6 kg of BW and a reduction of 0.05 BCS units (scale of 1–5 where 1 is emaciated). The genetic standard deviation (heritability) for 305-d milk solids yield adjusted phenotypically to a common BW was 27.3 kg (0.22). The genetic correlation between this adjusted milk solids trait with milk solids, BW, and BCS was 0.91, −0.12, and −0.26, respectively. Once also adjusted phenotypically to a common BCS, the genetic standard deviation (heritability) for milk solids adjusted phenotypically to a common BW was 26.8 kg (0.22) where the genetic correlation with milk solids, BW and BCS was 0.91, −0.21, and −0.07, respectively. The genetic standard deviation (heritability) of BW adjusted phenotypically for differences in milk solids was 35.3 kg (0.61), which reduced to 33.2 kg when also phenotypically adjusted for differences in BCS. Results suggest considerable opportunity exists to change milk solids yield independent of BW, and vice versa. The opportunity is reduced slightly once also corrected for differences in BCS. Inter-animal BCS differences should be considered if selection on such metrics is contemplated.
As land becomes a limiting resource for pasture-based dairy farming, the inclusion of purchased supplementary feeds to increase milk production per cow (through greater dry matter intake) and per ...hectare (through increased stocking rate) is often proposed as a strategy to increase profitability. Although a plausible proposition, virtually no analysis has been done on the effect of such intensification on the profitability of commercial pasture-based dairy farm businesses. The objective of this study was to characterize the average physical and financial performance of dairy systems differing in the proportion of the cow’s diet coming from grazed pasture versus purchased supplementary feeds over 4 yr, while accounting for any interaction with geographic region. Physical, genetic, and financial performance data from 1,561 seasonal-calving, pasture-based dairy farms in Ireland were available between the years 2008 and 2011; data from some herds were available for more than 1 yr of the 4-yr study period, providing data from 2,759 dairy farm-years. The data set was divided into geographic regions, based on latitude, rainfall, and soil characteristics that relate to drainage; these factors influence the length of the pasture growth season and the timing of turnout to pasture in spring and rehousing in autumn. Farms were also categorized by the quantity of feed purchased; farms in which cows received <10, 11–20, 21–30, or >30% of their annual feed requirements from purchased feed were considered to be categories representative of increasing levels of system intensification. Geographic region was associated with differences in grazing days, pasture harvested per hectare, milk production per cow and per hectare, and farm profitability. Farms in regions with longer grazing seasons harvested a greater amount of pasture an additional 19kg of dry matter (DM)/ha per grazing day per hectare, and greater pasture harvested was associated with increased milk component yield per hectare (58.4kg of fat and 51.4kg of protein more per tonne of DM pasture harvested/ha) and net profit per hectare (€268/ha more per tonne of DM harvested). Milk yield and yield of milk components per cow and per hectare increased linearly with increased use of purchased feed (additional 30.6kg of milk fat and 26.7kg of milk protein per tonne of DM purchased feed per hectare), but, on average, pasture harvested/hectare and net profit/hectare declined (−0.60 t of DM/ha and −€78.2/ha, respectively) with every tonne of DM supplementary feed purchased per hectare. The results indicate an effect of purchased feeds not usually accounted for in marginal economic analyses (e.g., milk to feed price ratio): the decline in pasture harvested/hectare, with the costs of producing the unutilized pasture in addition to the cost of feed resulting in a lower profit. In conclusion, greater milk component yields per cow were associated with increased profit per hectare, and a greater use of purchased feeds was associated with an increase in the yield of milk components. However, on average, increasing yield of milk components through the supply of purchased feeds to pasture-based cows was associated with a decline in pasture harvested per hectare and profitability. The decline in pasture harvested per hectare with increased use of purchased supplements per cow is probably the primary reason for the low milk production response and the failure to capitalize on the potential benefits of purchased supplements, with the associated costs of growing the unutilized pasture, in conjunction with increased nonfeed variable and fixed costs outweighing the increased milk production and revenue from supplementation. Farmers considering intensification through use of purchased supplements to increase the stock-carrying capacity of the farm (i.e., stocking rate) must ensure that they focus on management of pasture and total cost control to capture the potential benefits of supplementary feed use.
There is renewed interest in dairy cow crossbreeding in Ireland as a means to further augment productivity and profitability. The objective of the present study was to compare milk production and ...fertility performance for Holstein, Friesian, and Jersey purebred cows, and their respective crosses in 40 Irish spring-calving commercial dairy herds from the years 2008 to 2012. Data on 24,279 lactations from 11,808 cows were available. The relationship between breed proportion, as well as heterosis and recombination coefficients with performance, was quantified within a mixed model framework that also contained the fixed effects of parity; cow and contemporary group of herd-year-season of calving were both included as random effects in the mixed model. Breed proportion was associated with all milk production parameters investigated. Milk yield was greatest for Holstein (5,217kg), intermediate for Friesian (4,591kg), and least for Jersey (4,230kg), whereas milk constituents (i.e., fat and protein concentration) were greatest for Jersey (9.38%), intermediate for Friesian (7.91%), and least for Holstein (7.75%). Yield of milk solids in crossbred cows exceeded their respective parental average performance; greatest milk solids yield (i.e., fat kg + protein kg) was observed in the Holstein × Jersey first-cross, yielding 25kg more than the mid-parent mean. There was no consistent breed effect on the reproductive traits investigated. Relative to the mid-parent mean, Holstein × Jersey cows calved younger as heifers and had a shorter calving interval. Friesian × Jersey first-cross cows also had a shorter calving interval relative to their mid-parent mean. Results were consistent with findings from smaller-scale controlled experiments. Breed complementarity and heterosis attainable from crossbreeding resulted in superior animal performance and, consequently, greater expected profitability in crossbred cows compared with their respective purebreds.
Due primarily to a lack of phenotypic data, little research has been undertaken on the genetics of reproductive performance in beef cattle. The objective of this study was to quantify, using data ...from the Irish national cattle herd, the contribution of additive genetics to phenotypic differences in reproductive performance in beef cattle and to investigate whether routinely available early predictors of genetic merit for reproductive performance exist. Up to 218,718 parity records from 156,506 animals were used to estimate variance components for a range of reproductive traits using repeatability animal linear mixed models. Covariances with performance traits were estimated using bivariate sire linear mixed models. The reproductive traits were age at first calving, calving in the first 42 d of the calving seasons (defined separately in heifers and cows), calving interval between consecutive calving events, and survival to the next lactation. Performance traits included calving dystocia, linear type traits describing the skeletal, muscular, and functional characteristics of an animal, live weight and price, carcass traits, and producer subjectively scored traits of weanling quality and docility. Heritability for age at first calving was 0.31 while the heritability of the remaining reproductive traits ranged from 0.01 to 0.06; repeatability estimates varied from 0.02 to 0.06. Increased muscularity, measured either by trained assessors or producers on live animals, or by mechanical grading machines on slaughtered animals (i.e., carcass conformation), was genetically correlated with reduced reproductive performance for some of the reproductive variables assessed. This is one of the largest studies undertaken on the genetics of reproduction in beef herds and clearly shows that genetic selection for improved reproductive performance in beef herds is feasible. However, breeding goals that select for muscularity and live weight or growth rate should be cognizant of indirect response to selection that may cause any deterioration in reproductive performance.
Introduction/Aims
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative illness with great unmet patient need. We aimed to evaluate whether mesenchymal stem cells induced to secrete high ...levels of neurotrophic factors (MSC‐NTF), a novel autologous cell‐therapy capable of targeting multiple pathways, could safely slow ALS disease progression.
Methods
This randomized, double‐blind, placebo‐controlled study enrolled ALS participants meeting revised El Escorial criteria, revised ALS Functional Rating Scale (ALSFRS‐R) ≥25 (screening) and ≥3 ALSFRS‐R points decline prior to randomization. Participants received three treatments of MSC‐NTF or placebo intrathecally. The primary endpoint evaluated efficacy of MSC‐NTF through a responder analysis and safety. A change in disease progression post‐treatment of ≥1.25 points/mo defines a clinical response. A pre‐specified analysis leveraged baseline ALSFRS‐R of 35 as a subgroup threshold.
Results
Overall, MSC‐NTF treatment was well tolerated; there were no safety concerns. Thirty‐three percent of MSC‐NTF and 28% of placebo participants met clinical response criteria at 28 wk (odds ratio OR = 1.33, P = .45); thus, the primary endpoint was not met. A pre‐specified analysis of participants with baseline ALSFRS‐R ≥ 35 (n = 58) showed a clinical response rate at 28 wk of 35% MSC‐NTF and 16% placebo (OR = 2.6, P = .29). Significant improvements in cerebrospinal biomarkers of neuroinflammation, neurodegeneration, and neurotrophic factor support were observed with MSC‐NTF, with placebo unchanged.
Discussion
The study did not reach statistical significance on the primary endpoint. However, a pre‐specified subgroup suggests that MSC‐NTF participants with less severe disease may have retained more function compared to placebo. Given the unmet patient need, the results of this trial warrant further investigation.
Molecular genetic analyses of lung adenocarcinoma have recently become standard of care for treatment selection. The Lung Cancer Mutation Consortium was formed to enable collaborative ...multi-institutional analyses of 10 potential oncogenic driver mutations. Technical aspects of testing and clinicopathologic correlations are presented.
Mutation testing in at least one of the eight genes (epidermal growth factor receptor EGFR, KRAS, ERBB2, AKT1, BRAF, MEK1, NRAS, and PIK3CA) using SNaPshot, mass spectrometry, Sanger sequencing+/− peptide nucleic acid and/or sizing assays, along with anaplastic lymphoma kinase (ALK) and/or MET fluorescence in situ hybridization, were performed in six labs on 1007 patients from 14 institutions.
In all, 1007 specimens had mutation analysis performed, and 733 specimens had all 10 genes analyzed. Mutation identification rates did not vary by analytic method. Biopsy and cytology specimens were inadequate for testing in 26% and 35% of cases compared with 5% of surgical specimens. Among the 1007 cases with mutation analysis performed, EGFR, KRAS, ALK, and ERBB2 alterations were detected in 22%, 25%, 8.5%, and 2.4% of cases, respectively. EGFR mutations were highly associated with female sex, Asian race, and never-smoking status; and less strongly associated with stage IV disease, presence of bone metastases, and absence of adrenal metastases. ALK rearrangements were strongly associated with never-smoking status and more weakly associated with presence of liver metastases. ERBB2 mutations were strongly associated with Asian race and never-smoking status. Two mutations were seen in 2.7% of samples, all but one of which involved one or more of PIK3CA, ALK, or MET.
Multi-institutional molecular analysis across multiple platforms, sample types, and institutions can yield consistent results and novel clinicopathological observations.
Kelp forests form an important biogenic habitat that responds to natural and human drivers. Global concerns exist about threats to kelp forests, yet long-term information is limited and research ...suggests that trends are geographically distinct. We examined distribution of the bull kelp Nereocystis luetkeana over 145 years in South Puget Sound (SPS), a semi-protected inner basin in a fjord estuary complex in the northeast Pacific Ocean. We synthesized 48 historical and modern Nereocystis surveys and examined presence/absence within 1-km segments along 452 km of shoreline. Compared to the earliest baseline in 1878, Nereocystis extent in 2017 decreased 63%, with individual sub-basins showing up to 96% loss. Losses have persisted for decades, across a range of climate conditions. In recent decades, Nereocystis predominantly occurred along shorelines with intense currents and mixing, where temperature and nutrient concentrations did not reach thresholds for impacts to Nereocystis performance, and high current speeds likely excluded grazers. Losses predominated in areas with elevated temperature, lower nutrient concentrations, and relatively low current velocities. The pattern of long-term losses in SPS contrasts with stability in floating kelp abundance during the last century in an area of the Salish Sea with greater wave exposure and proximity to oceanic conditions. These findings support the hypothesis that kelp beds along wave-sheltered shorelines exhibit greater sensitivity to environmental stressors. Additionally, shorelines with strong currents and deep-water mixing may provide refugia within sheltered systems.
Few data are available comparing cardiovascular disease (CVD) biomarker profiles between women and men in the general population. We analyzed sex-based differences in multiple biomarkers reflecting ...distinct pathophysiological pathways, accounting for differences between women and men in CVD risk factors, body composition, and cardiac morphology.
A cross-sectional analysis was performed using data from the Dallas Heart Study, a multiethnic population-based study. Associations between sex and 30 distinct biomarkers representative of 6 pathophysiological categories were evaluated using multivariable linear regression adjusting for age, race, traditional CVD risk factors, kidney function, insulin resistance, MRI and dual-energy x-ray absorptiometry measures of body composition and fat distribution, and left ventricular mass.
After excluding participants with CVD, the study population included 3439 individuals, mean age 43 years, 56% women, and 52% black. Significant sex-based differences were seen in multiple categories of biomarkers, including lipids, adipokines, and biomarkers of inflammation, endothelial dysfunction, myocyte injury and stress, and kidney function. In fully adjusted models, women had higher levels of high-density lipoprotein cholesterol and high-density lipoprotein particle concentration, leptin, d-dimer, homoarginine, and N-terminal pro B-type natriuretic peptide, and lower levels of low-density lipoprotein cholesterol, adiponectin, lipoprotein-associated phospholipase A2 mass and activity, monocyte chemoattractant protein-1, soluble endothelial cell adhesion molecule, symmetrical dimethylarginine, asymmetrical dimethylarginine, high-sensitivity troponin T, and cystatin C.
Biomarker profiles differ significantly between women and men in the general population. Sex differences were most apparent for biomarkers of adiposity, endothelial dysfunction, inflammatory cell recruitment, and cardiac stress and injury. Future studies are needed to characterize whether pathophysiological processes delineated by these biomarkers contribute to sex-based differences in the development and complications of CVD.
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