Udder health outcomes in Irish herds participating in CellCheck dry cow consults.

The CellCheck dry cow consult (DCC) was developed by the CellCheck Technical Working Group to enable farmers to engage with their nominated veterinarian to develop farm-specific selective dry cow therapy (SDCT) plans, where appropriate. This study evaluated the effect of the DCC on farmer decision-making around dry cow therapy, and the udder health effects of implementing SDCT, in study herds over the 2019 and 2020 dry periods. The DCC was a 3-h consult, delivered and funded as part of the Targeted Advisory Service on Animal Health. Herds that completed a DCC were invited to register for a dry cow review the following year. The combined dataset for analysis across both years comprised 439 herds and 25,357 cows. Herd size ranged from 25 to 800. The median SCC of cows dried off with teat sealant only was 47,000 cells/mL before drying off in 2019 and 48,000 cells/mL at first milk recording in 2020, and 43,000 cells/mL before drying off in 2020 and 39,000 cells/mL at first milking recording in 2021. Following both the 2019 and 2020 dry periods, cows tended to converge toward a similar median SCC early in the following lactation, irrespective of prior dry cow treatment strategy. The uptake of SDCT was greater in review herds, with 21% of cows receiving teat sealant only in 2020, compared with 16.3% of cows in herds participating in a consult for the first time in 2020. At an individual cow level, in both years dry period new infection rate (NIR) was approximately 2.7% higher for cows treated with teat sealant only, than for those treated with both dry cow antibiotic tubes and teat sealant, and 1.2% higher than cows treated with antibiotic only. Regardless of treatment, a significant association was detectable between increasing parity and the risk of a dry period new infection. Increasing herd size had a significant effect on the risk of dry period NIR. At a herd level, no significant increase in NIR occurred when SDCT was used compared with herds where blanket dry cow therapy was used. Though not without risk, SDCT can be successfully implemented in Irish herds; however, constant attention to hygiene and management is essential. Despite the challenges, facilitating continued farmer education and engagement with professional guidance will be important.

Implications for the conservation of deep-water corals in the face of multiple stressors: A case study from the New Zealand region.

The waters around New Zealand are a global hotspot of biodiversity for deep-water corals; approximately one sixth of the known deep-water coral species of the world have been recorded in the region. Deep-water corals are vulnerable to climate-related stressors and from the damaging effects of commercial fisheries. Current protection measures do not account for the vulnerability of deep-water corals to future climatic conditions, which are predicted to alter the distribution of suitable habitat for them. Using recently developed habitat suitability models for 12 taxa of deep-water corals fitted to current and future seafloor environmental conditions (under different future climatic conditions: SSP2 - 4.5 and SSP3 - 7.0) we explore possible levels of spatial protection using the decision-support tool Zonation. Specifically, we assess the impact of bottom trawling on predictions of current distributions of deep-water corals, and then assess the effectiveness of possible protection for deep-water corals, while accounting for habitat refugia under future climatic conditions. The cumulative impact of bottom trawling was predicted to impact all taxa, but particularly the reef-forming corals. Core areas of suitable habitat were predicted to decrease under future climatic conditions for many taxa. We found that designing protection using current day predictions alone, having accounted for the impacts of historic fishing impacts, was unlikely to provide adequate conservation for deep water-corals under future climate change. Accounting for future distributions in spatial planning identified areas which may provide climate refugia whilst still providing efficient protection for current distributions. These gains in conservation value may be particularly important given the predicted reduction in suitable habitat for deep-water corals due to bottom fishing and climate change. Finally, the possible impact that protection measures may have on deep-water fisheries was assessed using a measure of current fishing value (kg km-2 fish) and future fishing value (predicted under future climate change scenarios).

Reproductive tract disease in Irish grazing dairy cows: Retrospective observational study examining its association with reproductive performance and accuracy of 2 diagnostic tests.

The detection of reproductive tract disease (RTD) 3 wk postpartum is important because of its effect on subsequent reproductive outcomes. Numerous methods for the diagnosis of RTD are described, some of which are more practical and instantaneous in terms of diagnosis. Two of these methods involve identification of purulent vaginal discharge (PVD) and evidence of ultrasonographic uterine changes indicative of endometritis (UE). The objectives of our retrospective observational study were (1) to assess the association of PVD or UE score at the prebreeding examination (PBE) with the hazard of pregnancy within the subsequent breeding season; (2) to determine the test sensitivity (Se) and specificity (Sp) at the point of sampling of both tests using a Bayesian latent class model; and (3) to determine the effect of varying positivity thresholds on test accuracy. To achieve these objectives, we analyzed an initial data set of 5,049 PBE from 2,460 spring-calved cows in 8 herds between 2014 and 2018. Each PBE was conducted once between 25 and 86 d in milk. At each PBE, vaginal discharge was obtained with a Metricheck device (Simcro) whereas uterine contents were assessed using transrectal ultrasonography. Purulent vaginal discharge was scored on a scale of 0 to 3 depending on discharge character, and UE was scored on a scale of 0 to 4 depending on the presence and consistency of intraluminal fluid. Cows with scores of ≥2 in either test had received treatment. Fertility data were available from 4,756 PBE after data exclusion. The association between PVD or UE score at the PBE and subsequent hazard of pregnancy was analyzed using a Cox proportional hazards model. Cows with a PVD score of 2 or 3 were less likely to conceive than cows with a PVD score 0 [score 2 hazard ratio (HR) = 0.74; 95% confidence interval (CI): 0.59-0.94; score 3 HR = 0.65; 95% CI: 0.51-0.84]. Cows with a UE score of 1, 2, 3, or 4 were less likely to conceive than cows with a UE score of 0 (score 1 HR = 0.82; 95% CI: 0.73-0.93; score 2 HR = 0.79; 95% CI: 0.62-1.00; score 3 HR = 0.43; 95% CI: 0.43-0.90; score 4 HR = 0.39; 95% CI: 0.26-0.58). To determine the Se and Sp of PVD or UE score for diagnosis of RTD at the time of PBE, a Bayesian latent class model was fitted on 2,460 individual cow PBE. Flat priors were used for the Se and Sp of UE, whereas informative priors were used for PVD Se (mode = 65%, 5th percentile = 45%) and Sp (mode = 90%, 5th percentile = 80%) and RTD prevalence (mode = 20%, 5th percentile = 10%). Posterior estimates (median and 95% Bayesian probability intervals; BPI) were obtained using 'rjags' (R Studio). The optimal test thresholds (PVD and UE score ≥1) were selected by assessing the effect of different thresholds on test estimates and using a misclassification cost analysis. Based on these, median (95% BPI) Se for PVD and UE score ≥1 were 44% (29-60%) and 67% (33-100%), respectively. Median Sp for PVD and UE score ≥1 were 90% (86-93%) and 91% (86-93%), respectively. Higher scores in both tests were associated with impaired fertility, and UE scoring with a threshold of ≥1 had the highest test Se and Sp estimates although test Se was conditional on days in milk when the PBE occurred.

Seroprevalence of Mycoplasma bovis in bulk milk samples in Irish dairy herds and risk factors associated with herd seropositive status.

Mycoplasma bovis is a serious disease of cattle worldwide; mastitis, pneumonia, and arthritis are particularly important clinical presentations in dairy herds. Mycoplasma bovis was first identified in Ireland in 1994, and the reporting of Mycoplasma-associated disease has substantially increased over the last 5 years. Despite the presumed endemic nature of M. bovis in Ireland, there is a paucity of data on the prevalence of infection, and the effect of this disease on the dairy industry. The aim of this observational study was to estimate apparent herd prevalence for M. bovis in Irish dairy herds using routinely collected bulk milk surveillance samples and to assess risk factors for herd seropositivity. In autumn 2018, 1,500 herds out of the 16,858 herds that submitted bulk tank milk (BTM) samples to the Department of Agriculture testing laboratory for routine surveillance were randomly selected for further testing. A final data set of 1,313 sampled herds with a BTM ELISA result were used for the analysis. Testing was conducted using an indirect ELISA kit (ID Screen Mycoplasma bovis). Herd-level risk factors were used as explanatory variables to determine potential risk factors associated with positive herd status (reflecting past or current exposure to M. bovis). A total of 588 of the 1,313 BTM samples were positive to M. bovis, providing an apparent herd prevalence of 0.45 (95% CI: 0.42, 0.47) in Irish dairy herds in autumn 2018. Multivariable analysis was conducted using logistic regression. The final model identified herd size, the number of neighboring farms, in-degree and county as statistically significant risk factors for herd BTM seropositivity to M. bovis. The results suggest a high apparent herd prevalence of seropositivity to M. bovis, and evidence that M. bovis infection is now endemic in the Irish dairy sector. In addition, risk factors identified are closely aligned to what we would expect of an infectious disease. Awareness raising and education about this important disease is warranted given the widespread nature of exposure and likely infection in Irish herds. Further work on the validation of diagnostic tests for herd-level diagnosis should be undertaken as a matter of priority.

Synthesis and biological evaluation of a novel anticancer agent CBISC that induces DNA damage response and diminishes levels of mutant-p53.

A novel nitrogen mustard CBISC has been synthesized and evaluated as an anticancer agent. CBISC has been shown to exhibit enhanced cell proliferation inhibition properties against mutant p53 cell lines colorectal cancer WiDr, pancreatic cancer (MIAPaCa-2 and PANC-1), and triple negative breast cancer (MDA-MB-231 and MDA-MB-468). In vitro mechanism of action studies revealed perturbations in the p53 pathway and increased cell death as evidenced by western blotting, immunofluorescent microscopy and MTT assay. Further, in vivo studies revealed that CBISC is well tolerated in healthy mice and exhibited significant in vivo tumor growth inhibition properties in WiDr and MIAPaCa-2 xenograft models. These studies illustrate the potential utility of CBISC as an anticancer agent.

Synthesis and biological evaluation of N, N-dialkylcarboxy coumarin-NO donor conjugates as potential anticancer agents.

A series of nitric oxide (NO) donor furoxan conjugates of N, N-dialkylcarboxy coumarins have been synthesized as potential anticancer agents. The synthesized compounds have been tested for their in vitro antiproliferative activities on various cancer and noncancerous cell lines. The candidate derivatives exhibit selectivity towards cancer cells with excellent activities in low nM to µM concentrations. In vitro mechanistic studies indicate that the candidate compounds generate substantial NO, inhibit colony formation, and cause apoptosis in cancer cells. A preliminary in vivo tolerance study of the lead candidate 10 in mice indicates that it is well-tolerated, evidenced by zero mortality and normal body weight gains in treated mice. Further translation of the lead derivative 10 using MDA-MB-231 based tumor xenograft model shows good tumor growth reduction.

A survey of biosecurity and health management practices on Irish dairy farms engaged in contract-rearing.

A survey was conducted to investigate potential differences in biosecurity and health management practices on Irish dairy farms that sent their heifers for contract-rearing (source dairy farms, SDF; n = 62) and those rearing their own heifers (control farms, CF; n = 50). Participating farmers were surveyed by postal questionnaire between September and November 2018. The overall response rate was 93%. Results show that structurally, SDF were larger, less fragmented, and more specialized than CF. Outsourcing of labor-intensive activities to external contractors was more common among SDF than CF, exposing them to potentially increased biosecurity risks associated with animal movements, use of shared equipment, and increased frequency of farm visitors. The majority of SDF sent heifers to a single-origin rearing facility (70%), with heifers most commonly arriving at the rearing unit between 2 and 4 mo (53%) and returning to the dairy farm between 18 and 21 mo of age (56%). Despite the increased biosecurity risk associated with contract-rearing, implementation of disease prevention measures was not superior on SDF compared with CF. For both farm types, there was scope for improvement to visitor biosecurity protocols, quarantine procedures, colostrum feeding practices, and hygiene of calving areas. This research provides an overview of the demographics and farm management practices implemented by dairy farmers engaged in contract-rearing of replacement heifers, and will serve to inform farmers, veterinary advisors, and policy makers.

Cow-level risk factors for reproductive tract disease diagnosed by 2 methods in pasture-grazed dairy cattle in Ireland.

The cow-side diagnosis of reproductive tract disease (RTD) involves identifying the presence of purulent vaginal discharge (PVD) and ultrasonographic endometritis (UE). The objectives of our study were to obtain prevalence estimates for RTD diagnosed by 2 methods (PVD and UE scoring) and to investigate the risk factors for increased probability of RTD if these methods are used in isolation or in combination. Our retrospective observational cohort study tested the hypothesis that RTD assessed by 2 methods would have similar risk factors, and that those would be mainly cow- and calving-related factors. We analyzed data from 5,049 pre-breeding examinations (PBE) from 2,460 spring-calved cows on 8 farms between 2014 and 2018. Cow-related details assessed were days in milk at PBE, breed, lactation number, dry period length, body condition score at calving and PBE, 305-d milk yield, predicted transmitting ability for production and fertility, the presence of a corpus luteum at PBE, and positive diagnosis the previous year. Calving details assessed were type of sire, calf sex, twinning, stillbirth, calving difficulty score, and retained fetal membranes. We conducted statistical analyses using 4 multivariable logistic regression models to identify the risk of RTD diagnosed by (1) PVD in isolation, (2) UE in isolation, (3) the presence of either PVD or UE; and (4) the presence of both PVD and UE. We accounted for herd, cow, and year as random effects in all 4 models. The overall prevalence of RTD in models 1, 2, 3, and 4 were 7.5, 6.7, 11.6, and 2.6%, respectively. Days in milk at PBE, the interaction between days in milk and retained fetal membranes, twinning, and the predicted transmitting ability for calving interval were consistently significant risk factors for positive scores in all 4 models. Considerable calving difficulty [adjusted odds ratio (AOR) = 13.64], Holstein Friesian dam breed (AOR = 2.58), first lactation (AOR = 2.39), and body condition score at PBE (AOR = 1.64) were risk factors for a positive PVD score but not for a positive UE score. Fifth lactation (AOR = 1.69), a beef-sired calf (AOR = 1.46), and the absence of a corpus luteum at PBE (AOR = 1.57) were risk factors for a positive UE score but not for a positive PVD score. These results support the hypothesis that most of the risk factors for PVD and UE are the same but some are distinctly different, implying that in some instances the 2 methods diagnose separate components of the RTD complex.

The effect of growth rate on reproductive outcomes in replacement dairy heifers in seasonally calving, pasture-based systems.

The effect of average daily gain (ADG) on reproductive outcomes in replacement dairy heifers was investigated. All heifers were managed in the typical Irish spring calving, pasture-based system, where the herd calves in 1 block between January and April and the majority of the diet comprises grazed grass. Heifer calves (n = 399) from 7 herds were weighed at birth and at the beginning of the breeding season, and ADG was calculated. Service dates and pregnancy diagnosis results were recorded, and conception dates were calculated. Days open (DO) was defined as the number of days between the beginning of the breeding season and conception. Genetic data were retrieved from the Irish Cattle Breeding Federation database. A Cox proportional hazard model was constructed to identify variables with a significant effect on DO. An accelerated failure time model was used to predict survival curves and median survival times for different combinations of the significant variables. The ADG ranged from 0.41 to 0.91 kg/d, with a median of 0.70 kg/d. Frailty effect of farm within year, maintenance subindex of the economic breeding index, and ADG had a significant effect on DO. Derived from the final accelerated failure time model, the predicted median DO for a heifer with an ADG of 0.40, 0.70, or 0.90 kg/d aged 443 d at the beginning of the breeding season and with a maintenance subindex in the second tercile were 27, 16, and 11 d, respectively.

Synthesis and biological evaluation of 2-alkoxycarbonylallyl esters as potential anticancer agents.

The reaction of carboxylic acids with Baylis-Hillman reaction derived α-bromomethyl acrylic esters readily provide 2-(alkoxycarbonyl)allyl esters in good to excellent yields. These functionalized allyl esters have been evaluated for their cell proliferation inhibition properties against breast cancer (MDA-MB-231 and 4T1) and pancreatic cancer (MIAPaCa-2) cell lines to explore their potential as anticancer agents. Several of the synthesized derivatives exhibit good potency against all three cancer cell lines. Our structure activity relationship (SAR) studies on 2-carboxycarbonyl allyl esters indicate that substituted aromatic carboxylic acids provide enhanced activity compared to substituted aliphatic carboxylic acid analogs. Di- and tri-allyl esters derived from di-and tri-carboxylic acids exhibit higher inhibition of cell proliferation than mono esters. Further SAR studies indicate that the double bond in the 2-(alkoxycarbonyl)allyl ester is required for its activity, and there is no increase in activity with increased chain length of the alkoxy group. Two lead candidate compounds have been identified from the cell proliferation inhibition studies and their preliminary mechanism of action as DNA damaging agents has been evaluated using epifluorescence and western blot analysis. One of the lead compounds has been further evaluated for its systemic toxicity in healthy CD-1 mice followed by anticancer efficacy in a triple negative breast cancer MDA-MB-231 xenograft model in NOD-SCID mice. These two in vivo studies indicate that the lead compound is well tolerated in healthy CD-1 mice and exhibits good tumor growth inhibition compared to breast cancer drug doxorubicin.

The life cycle stages of Pneumocystis murina have opposing effects on the immune response to this opportunistic, fungal pathogen.

The cyst cell wall ß-glucans of Pneumocystis have been shown to stimulate immune responses in lung epithelial cells, dendritic cells, and alveolar macrophages. Little is known about how the trophic life forms, which do not have a fungal cell wall, interact with these innate immune cells. Here, we report differences in the responses of both neonatal and adult mice to the trophic and cystic life cycle stages of Pneumocystis murina The adult and neonatal immune responses to infection with Pneumocystis murina trophic forms were less robust than the response to infection with a physiologically normal mixture of cysts and trophic forms. Cysts promoted the recruitment of nonresident innate immune cells and T and B cells into the lungs. Cysts, but not trophic forms, stimulated increased IFN-γ cytokine concentrations in the alveolar spaces, and an increase in IFN-γ-producing CD4+ T cells. In vitro, bone marrow-derived dendritic cells (BMDCs) stimulated with cysts produced the proinflammatory cytokines IL-1ß and IL-6. In contrast, trophic forms suppressed ß-glucan-, LTA-, and LPS-induced IL-1ß, IL-6, and TNFα production by BMDCs and antigen presentation to CD4+ T cells. The negative effects of trophic forms were not due to ligation of mannose receptor. Our results indicate that optimal innate and adaptive immune responses to Pneumocystis species are dependent on stimulation with the cyst life cycle stage. Conversely, trophic forms suppress ß-glucan-induced proinflammatory responses in vitro, suggesting that the trophic forms dampen cyst-induced inflammation in vivo.

Coumarin carboxylic acids as monocarboxylate transporter 1 inhibitors: In vitro and in vivo studies as potential anticancer agents.

Novel N,N-dialkyl carboxy coumarins have been synthesized as potential anticancer agents via inhibition of monocarboxylate transporter 1 (MCT1). These coumarin carboxylic acids have been evaluated for their in vitro MCT1 inhibition, MTT cancer cell viability, bidirectional Caco-2 cell permeability, and stability in human and liver microsomes. These results indicate that one of the lead candidate compounds 4a has good absorption, metabolic stability, and a low drug efflux ratio. Systemic toxicity studies with lead compound 4a in healthy mice demonstrate that this inhibitor is well tolerated based on zero animal mortality and normal body weight gains compared to the control group. In vivo tumor growth inhibition studies in mice show that the candidate compound 4a exhibits significant single agent activity in MCT1 expressing GL261-luc2 syngraft model but doesn't show significant activity in MCT4 expressing MDA-MB-231 xenograft model, indicating the selectivity of 4a for MCT1 expressing tumors.

Synthesis and evaluation of functionalized benzoboroxoles as potential anti-tuberculosis agents.

Several derivatives of aminobenzoboroxole have been prepared starting from 2-boronobenzaldehyde. All of these derivatives have been evaluated for their anti-mycobacterial activity on Mycobacterium smegmatis and cytotoxicity on breast cancer cell line MCF7. Based on these studies, all the tested molecules have been found to be generally non-toxic and benzoboroxoles with unsubstituted (primary) amines have been found to exhibit good anti-mycobacterial activity. Some of the key compounds have been evaluated for their anti-tubercular activity on Mycobacterium tuberculosis H37Rv using 7H9 and GAST media. 7-Bromo-6-aminobenzoboroxole 4 has been identified as the lead candidate compound for further development.

Surfactant-Modified Soil Amendments Reduce Nitrogen and Phosphorus Leaching in a Sand-Based Rootzone.

United States Golf Association putting greens are susceptible to nitrogen (N) and phosphorus (P) leaching. Inorganic soil amendments are used to increase moisture and nutrient retention and may influence N and P leaching. This study was conducted to determine whether N and P leaching could be reduced using soil amendments and surfactant-modified soil amendments. Treatments included a control (sand), sand-peat, zeolite, calcined clay, hexadecyltrimethylammonium-zeolite, and hexadecyltrimethylammonium-calcined clay. Lysimeters were filled with a 30-cm rootzone layer of sand-peat (85:15 by volume), below which a 5-cm treatment layer of amendments was placed. A solution of NO-N, NH-N, and orthophosphate-P (2300, 2480, and 4400 µg mL, respectively) was injected at the top of each lysimeter, and leachate was collected using an autocollector set to collect a 10-mL sample every min until four pore volumes were collected. Uncoated amendments, sand, and peat had no influence on NO-N retention, whereas hexadecyltrimethylammonium-coated amendments reduced NO-N leaching to below detectable limits. Both coated and uncoated amendments reduced NH-N leaching, with zeolite reducing NH-N leached to near zero regardless of hexadecyltrimethylammonium coating. Pure sand resulted in a 13% reduction of applied orthophosphate-P leaching, whereas peat contributed to orthophosphate-P leaching. Surfactant-modified amendments reduced orthophosphate-P leaching by as much as 97%. Surfactant-modified soil amendments can reduce NO-N, NH-N, and orthophosphate-P leaching and, thus, may be a viable option for removing leached N and P before they enter surface or ground waters.

A Mannose Family Phosphotransferase System Permease and Associated Enzymes Are Required for Utilization of Fructoselysine and Glucoselysine in Salmonella enterica Serovar Typhimurium.

UNLABELLED: Salmonella enteric serovar Typhimurium, a major cause of food-borne illness, is capable of using a variety of carbon and nitrogen sources. Fructoselysine and glucoselysine are Maillard reaction products formed by the reaction of glucose or fructose, respectively, with the ε-amine group of lysine. We report here that S. Typhimurium utilizes fructoselysine and glucoselysine as carbon and nitrogen sources via a mannose family phosphotransferase (PTS) encoded by gfrABCD (glucoselysine/fructoselysine PTS components EIIA, EIIB, EIIC, and EIID; locus numbers STM14_5449 to STM14_5454 in S. Typhimurium 14028s). Genes coding for two predicted deglycases within the gfr operon, gfrE and gfrF, were required for growth with glucoselysine and fructoselysine, respectively. GfrF demonstrated fructoselysine-6-phosphate deglycase activity in a coupled enzyme assay. The biochemical and genetic analyses were consistent with a pathway in which fructoselysine and glucoselysine are phosphorylated at the C-6 position of the sugar by the GfrABCD PTS as they are transported across the membrane. The resulting fructoselysine-6-phosphate and glucoselysine-6-phosphate subsequently are cleaved by GfrF and GfrE to form lysine and glucose-6-phosphate or fructose-6-phosphate. Interestingly, although S. Typhimurium can use lysine derived from fructoselysine or glucoselysine as a sole nitrogen source, it cannot use exogenous lysine as a nitrogen source to support growth. Expression of gfrABCDEF was dependent on the alternative sigma factor RpoN (σ(54)) and an RpoN-dependent LevR-like activator, which we designated GfrR. IMPORTANCE: Salmonella physiology has been studied intensively, but there is much we do not know regarding the repertoire of nutrients these bacteria are able to use for growth. This study shows that a previously uncharacterized PTS and associated enzymes function together to transport and catabolize fructoselysine and glucoselysine. Knowledge of the range of nutrients that Salmonella utilizes is important, as it could lead to the development of new strategies for reducing the load of Salmonella in food animals, thereby mitigating its entry into the human food supply.

Synthesis, in vitro, and in vivo evaluation of novel functionalized quaternary ammonium curcuminoids as potential anti-cancer agents.

Novel functionalized quaternary ammonium curcuminoids have been synthesized from piperazinyl curcuminoids and Baylis-Hillman reaction derived allyl bromides. These molecules are found to be highly water soluble with increased cytotoxicity compared to native curcumin against three cancer cell lines MIAPaCa-2, MDA-MB-231, and 4T1. Preliminary in vivo toxicity evaluation of a representative curcuminoid 5a in healthy mice indicates that this molecule is well tolerated based on normal body weight gains compared to control group. Furthermore, the efficacy of 5a has been tested in a pancreatic cancer xenograft model of MIAPaCa-2 and has been found to exhibit good tumor growth inhibition as a single agent and also in combination with clinical pancreatic cancer drug gemcitabine.

Effect of exposure to Neospora caninum, Salmonella, and Leptospira interrogans serovar Hardjo on the economic performance of Irish dairy herds.

The objective of the current study was to quantify the effects of exposure to Salmonella, Neospora caninum, and Leptospira interrogans serovar Hardjo (L. hardjo) on dairy farm profitability and to simulate the effect of vaccination for Salmonella and L. hardjo on dairy farm profitability. The production effects associated with exposure to each of these pathogens in study herds were defined under 3 categories: (1) milk production effects, (2) reproduction effects (including culling), and (3) mortality effects. The production effects associated with exposure to Salmonella, N. caninum, and L. hardjo were incorporated into the Moorepark Dairy Systems Model. In the analysis, herds negative for exposure to Salmonella, N. caninum, and L. hardjo were assumed baseline herds, with all results presented relative to this base. In simulations examining the effect of vaccination for Salmonella and L. hardjo on farm profitability, vaccinated herds (vaccination costs included) were considered as baseline herds and results were presented relative to this base. Total annual profits in unvaccinated herds were reduced by €77.31, €94.71, and €112.11 per cow at milk prices of €0.24, €0.29, and €0.34/L, respectively, as a result of exposure to Salmonella. In the current study, herds positive for exposure to Salmonella recorded a 316-kg reduction in milk yield, whereas no association was detected between exposure to N. caninum or L. hardjo and milk production. Exposure to both N. caninum and L. hardjo was associated with compromised reproductive performance. Herds positive for exposure to N. caninum and Salmonella had greater rates of adult cow mortality and calf mortality, respectively. Vaccination for both Salmonella and L. hardjo was associated with improved performance in study herds. Exposure to N. caninum resulted in a reduction in annual farm profits of €11.55, €12, and €12.44 per cow at each milk price, whereas exposure to L. hardjo resulted in a reduction in annual farm profits of €13.83, €13.78, and €13.72 per cow at each milk price. Herds that tested positive for exposure to Salmonella and L. hardjo were compared with herds vaccinated for the respective pathogens. Herds vaccinated for Salmonella generated €67.09, €84.48, and €101.89 per cow more profit at each milk price compared with herds positive for exposure. Similarly, herds vaccinated for L. hardjo generated €9.74, €9.69, and €9.63 per cow more profit compared with unvaccinated exposed herds. However, herds that tested negative for exposure to Salmonella and L. hardjo generated additional profits of €10.22 and €4.09 per cow, respectively, compared with vaccinated baseline herds.

Integrating rapid habitat mapping with community metrics and functional traits to assess estuarine ecological conditions: A New Zealand case study.

Estuarine ecosystems are under pressure from anthropogenic stressors in many parts of the world. In a New Zealand estuary, we integrated rapid habitat mapping, univariate and multivariate benthic community metrics and functional traits-based metrics to provide a holistic assessment of its ecological condition. Our integrative approach identified 11 different habitat classes across the study estuary and revealed how univariate, multivariate, and functional traits-based metrics varied spatially. Variation was driven mainly by sedimentary conditions, particularly, the sediment's organic matter and silt-clay content. Degraded conditions were apparent in several parts of the estuary, which overlapped with areas showing high concentrations of decaying algae, anoxic conditions, and low values of univariate and functional metrics. Our holistic approach, integrating mapping and quantitative community assessments, provided a more complete picture of estuarine conditions and enabled us to identify locations across the estuary with the greatest potential for restoration success.

Investigating a dilution effect between somatic cell count and milk yield and estimating milk production losses in Irish dairy cattle.

Increased somatic cell counts (SCC) are associated with reduced milk yield. Additionally, it has been hypothesized that as milk yield increases, SCC is diluted in cattle without an intramammary infection (IMI). If the hypothesis is correct, estimates of SCC from high-yielding cattle without an IMI are likely to be lower than those from low-yielding cattle without an IMI. The objectives of this paper were to investigate the presence of a potential dilution effect between SCC and milk yield, overall and by parity, and to estimate lactation milk production losses with increasing SCC in Irish dairy cattle. The data consisted of 100 randomly selected herds from all milk recording herds between 2008 and 2010. The data set comprised 8,229 cows, of which approximately 90% were Holstein or Holstein crossbred animals. Various adjustments were used to investigate the presence of a potential dilution effect between SCC and milk yield; additionally, lactation milk production losses with increasing SCC and parity were estimated. The data had an inherent hierarchical structure, with lactations nested within cows and cows within herds; thus, a linear mixed model with 2 random effects was used. We found no evidence of a dilution effect of SCC with increasing milk yield in Irish dairy cattle. Average milk production losses were estimated, and they increased with increasing SCC compared with the referent of ≤ 50,000 cells/mL. Additionally, for all SCC values for parities 1 to 3, this production loss increased significantly with increasing parity. Estimated milk losses for parities 4 and 5 did not differ, and differences between parities 3 and 4 were significant only for SCC values <300,000 cells/mL. The estimated milk loss with increasing SCC varies greatly across studies, with the results from the current study exceeding most previously published results (except for results from the UK). Several factors could explain these differences, including geographic factors such as milk yield and predominant mastitis pathogens. The dilution effect warrants further work, as does the effect of prior duration of increased SCC on milk yield and the potential for compensation of milk yield losses over a lactation.