Metabolic-associated fatty liver disease and hepatocellular carcinoma: a prospective study of characteristics and response to therapy.

BACKGROUND AND AIM: The rising incidence of hepatocellular carcinoma (HCC) in Australia is related to increasing rates of metabolic-associated fatty liver disease (MAFLD). This study aimed to prospectively characterize the metabolic profile, lifestyle, biometric features, and response to treatment of HCC patients in an Australian population. METHOD: Multicenter prospective cohort analysis of newly diagnosed HCC patients at six multidisciplinary team meetings over a 2-year period. RESULTS: Three hundred and thirteen (313) newly diagnosed HCC patients with MAFLD (n = 77), MAFLD plus other liver disease (n = 57) (the "mixed" group), and non-MAFLD (n = 179) were included in the study. Alcohol-associated liver disease (ALD) (43%) and MAFLD (43%) were the most common underlying liver diseases. MAFLD-HCC patients were older (73 years vs 67 years vs 63 years), more likely to be female (40% vs 14% vs 20%), less likely to have cirrhosis (69% vs 88% vs 85%), showed higher ECOG, and were less likely to be identified by screening (29% vs 53% vs 45%). Metabolic syndrome was more prevalent in the MAFLD and mixed groups. The severity of underlying liver disease and HCC characteristics were the same across groups. While the MAFLD population self-reported more sedentary lifestyles, reported dietary patterns were no different across the groups. Dyslipidemia was associated with tumor size, and those taking statins had a lower recurrence rate. CONCLUSION: Equal to ALD, MAFLD is now the most common underlying liver disease seen in HCC patients in Australia. Future HCC prevention screening and treatment strategies need to take this important group of patients into consideration.

A survey of mastitis pathogens including antimicrobial susceptibility in southeastern Australian dairy herds.

The objectives for this study were to (1) describe the pathogen profile in quarters from cows with clinical mastitis and in cows with subclinical mastitis in southeastern Australia; and (2) describe antimicrobial susceptibility among isolated pathogens. As a secondary objective, we aimed to compare antimicrobial resistance prevalence in pathogens isolated from clinical and subclinical mastitis samples. A convenience sample of dairy herds (n = 65) from 4 regions in southeastern Australia (Gippsland, Northern Victoria, Tasmania, Western Victoria) were invited to submit milk samples from cows with clinical and subclinical mastitis over a 14-mo period (January 2011 to March 2012). Farmers were instructed to collect aseptic quarter milk samples from the first 10 cases of clinical mastitis for each month of the study. In addition, farmers submitted composite milk samples from cows with subclinical mastitis at 1 or 2 sampling occasions during the study period. Aerobic culture and biochemical tests were used to identify isolates. Isolates were classified as susceptible, intermediate, or resistant to a panel of antimicrobial agents based on the zone of growth inhibition around antimicrobial-impregnated disks, with antimicrobial resistance (AMR) classified as nonsusceptibility by combining intermediate and resistant groups into a single category. Generalized linear mixed models were used to compare the prevalence of AMR between clinical and subclinical mastitis isolates. For clinical mastitis samples (n = 3,044), 472 samples (15.5%) were excluded for contamination. Of the remaining samples (n = 2,572), the most common results were Streptococcus uberis (39.2%), no growth (27.5%), Staphylococcus aureus (10.6%), Escherichia coli (8.4%), and Streptococcus dysgalactiae (6.4%). For subclinical mastitis samples (n = 1,072), 425 (39.6%) were excluded due to contamination. Of the remaining samples (n = 647), the most common results were no growth (29.1%), Staph. aureus (29.1%), and Strep. uberis (21.6%). The prevalence of AMR among common isolates was low for the majority of antimicrobial agents. Exploratory analysis found that the probability of Staph. aureus demonstrating resistance to penicillin was 5.16 times higher (95% confidence interval: 1.68, 15.88) in subclinical isolates relative to clinical Staph. aureus isolates. A similar association was observed for amoxicillin with subclinical Staph. aureus isolates being 4.70 times (95% confidence interval: 1.49, 14.75) more likely to be resistant than clinical Staph. aureus isolates. We concluded that the most common bacteria causing clinical mastitis in dairy herds in Australia is likely to be Strep. uberis, whereas Staph. aureus is likely to be the most common cause of subclinical mastitis. Despite decades of antimicrobial use to control these organisms, AMR appears to be uncommon.

Lamb mortality and clostridial disease.

AIMS: To determine the level and timing of lamb loss that occurs during the first year of life on a typical hill country sheep and beef farm in the central North Island of New Zealand and to determine how much of this loss can be prevented through vaccination against the five main clostridial diseases using a commercially available multivalent clostridial vaccine. METHODS: The study was conducted on a single commercial hill country sheep and beef farm in the central North Island of New Zealand, with a history of never vaccinating their stock against clostridial disease. Lambs were blocked on sex and randomly selected at docking into treatment (n = 1,705 lambs) and control (n = 1,709 lambs) groups. Treated lambs were vaccinated at docking and 4 weeks later with 1 mL of multivalent clostridial vaccine. Control lambs were not vaccinated. Different coloured ear tags were used to identify the lambs in the treatment and control groups. All lambs were counted at docking (October 2019) and at six other management event times between docking and when the replacement hoggets were set stocked for lambing (August 2020). The number of lambs sold between each management event, from each group was also counted. The difference in the number of lambs from one management event to another, minus the lambs sold between these events was regarded as the lamb losses for that period. RESULTS: The total percentage of lamb losses from docking to pre-lamb was 4.8% (81/1,705) and 6.2% (106/1,709) in the vaccinated and unvaccinated lambs respectively OR = 0.75 (95% CI = 0.56-1.02; p = 0.06). Most lamb loss occurred in the period after docking, followed by the period between weaning and the first post-weaning drench. Less lamb loss occurred in the vaccinated lambs (27/1,705; 1.6%) after docking than in the unvaccinated lambs (66/1,709; 3.9%). This was mainly due to lower female lamb losses in the vaccinated (5/868; 0.6%) compared to the unvaccinated (38/868; 4.4%) group (p < 0.001). CONCLUSIONS: Vaccination of lambs at docking and 4 weeks later, with a multivalent 5-in-1 clostridial vaccine was associated with a 23.6% (25/106) reduction in total lamb loss from docking to pre-lambing. In female lambs, vaccination was associated with an 87% (33/38) reduction in lamb loss after docking and a 37% (22/59) reduction over the total trial period.

Nanomaterials by design: a review of nanoscale metallic multilayers.

Nanoscale metallic multilayers have been shown to have a wide range of outstanding properties, which differ to a great extent from those observed in monolithic films. Their exceptional properties are mainly associated with the large number of interfaces and the nanoscale layer thicknesses. Many studies have investigated these materials focusing on magnetic, mechanical, optical, or radiation tolerance properties. Thus, this review provides a summary of the findings in each area, including a description of the general attributes, the adopted synthesis methods and most common characterization techniques used. This information is followed by a compendium of the material properties and a brief discussion of related experimental data, as well as existing and promising applications. Other phenomena of interest, including thermal stability studies, self-propagating reactions and the progression from nano multilayers to amorphous and/or crystalline alloys, are also covered. In general, this review highlights the use of nano multilayer architectures as viable routes to overcome the challenges of designing and implementing new engineering materials at the nanoscale.

Vitamin B6 catabolism and lung cancer risk: results from the Lung Cancer Cohort Consortium (LC3).

BACKGROUND: Increased vitamin B6 catabolism related to inflammation, as measured by the PAr index (the ratio of 4-pyridoxic acid over the sum of pyridoxal and pyridoxal-5'-phosphate), has been positively associated with lung cancer risk in two prospective European studies. However, the extent to which this association translates to more diverse populations is not known. MATERIALS AND METHODS: For this study, we included 5323 incident lung cancer cases and 5323 controls individually matched by age, sex, and smoking status within each of 20 prospective cohorts from the Lung Cancer Cohort Consortium. Cohort-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PAr and lung cancer risk were calculated using conditional logistic regression and pooled using random-effects models. RESULTS: PAr was positively associated with lung cancer risk in a dose-response fashion. Comparing the fourth versus first quartiles of PAr resulted in an OR of 1.38 (95% CI: 1.19-1.59) for overall lung cancer risk. The association between PAr and lung cancer risk was most prominent in former smokers (OR: 1.69, 95% CI: 1.36-2.10), men (OR: 1.60, 95% CI: 1.28-2.00), and for cancers diagnosed within 3 years of blood draw (OR: 1.73, 95% CI: 1.34-2.23). CONCLUSION: Based on pre-diagnostic data from 20 cohorts across 4 continents, this study confirms that increased vitamin B6 catabolism related to inflammation and immune activation is associated with a higher risk of developing lung cancer. Moreover, PAr may be a pre-diagnostic marker of lung cancer rather than a causal factor.

No association between circulating concentrations of vitamin D and risk of lung cancer: an analysis in 20 prospective studies in the Lung Cancer Cohort Consortium (LC3).

Background: There is observational evidence suggesting that high vitamin D concentrations may protect against lung cancer. To investigate this hypothesis in detail, we measured circulating vitamin D concentrations in prediagnostic blood from 20 cohorts participating in the Lung Cancer Cohort Consortium (LC3). Patients and methods: The study included 5313 lung cancer cases and 5313 controls. Blood samples for the cases were collected, on average, 5 years before lung cancer diagnosis. Controls were individually matched to the cases by cohort, sex, age, race/ethnicity, date of blood collection, and smoking status in five categories. Liquid chromatography coupled with tandem mass spectrometry was used to separately analyze 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] and their concentrations were combined to give an overall measure of 25(OH)D. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 25(OH)D as both continuous and categorical variables. Results: Overall, no apparent association between 25(OH)D and risk of lung cancer was observed (multivariable adjusted OR for a doubling in concentration: 0.98, 95% CI: 0.91, 1.06). Similarly, we found no clear evidence of interaction by cohort, sex, age, smoking status, or histology. Conclusion: This study did not support an association between vitamin D concentrations and lung cancer risk.

Novel associations between blood DNA methylation and body mass index in middle-aged and older adults.

BACKGROUND/OBJECTIVES: There is increasing evidence of a relationship between blood DNA methylation and body mass index (BMI). We aimed to assess associations of BMI with individual methylation measures (CpGs) through a cross-sectional genome-wide DNA methylation association study and a longitudinal analysis of repeated measurements over time. SUBJECTS/METHODS: Using the Illumina Infinium HumanMethylation450 BeadChip, DNA methylation measures were determined in baseline peripheral blood samples from 5361 adults recruited to the Melbourne Collaborative Cohort Study (MCCS) and selected for nested case-control studies, 2586 because they were subsequently diagnosed with cancer (cases) and 2775 as controls. For a subset of 1088 controls, these measures were repeated using blood samples collected at wave 2 follow-up, a median of 11 years later; weight was measured at both time points. Associations between BMI and blood DNA methylation were assessed using linear mixed-effects regression models adjusted for batch effects and potential confounders. These were applied to cases and controls separately, with results combined through fixed-effects meta-analysis. RESULTS: Cross-sectional analysis identified 310 CpGs associated with BMI with P<1.0 × 10-7, 225 of which had not been reported previously. Of these 225 novel associations, 172 were replicated (P<0.05) using the Atherosclerosis Risk in Communities (ARIC) study. We also replicated using MCCS data (P<0.05) 335 of 392 associations previously reported with P<1.0 × 10-7, including 60 that had not been replicated before. Associations between change in BMI and change in methylation were observed for 34 of the 310 strongest signals in our cross-sectional analysis, including 7 that had not been replicated using the ARIC study. CONCLUSIONS: Together, these findings suggest that BMI is associated with blood DNA methylation at a large number of CpGs across the genome, several of which are located in or near genes involved in ATP-binding cassette transportation, tumour necrosis factor signalling, insulin resistance and lipid metabolism.

An epigenome-wide association study meta-analysis of educational attainment.

The epigenome is associated with biological factors, such as disease status, and environmental factors, such as smoking, alcohol consumption and body mass index. Although there is a widespread perception that environmental influences on the epigenome are pervasive and profound, there has been little evidence to date in humans with respect to environmental factors that are biologically distal. Here we provide evidence on the associations between epigenetic modifications-in our case, CpG methylation-and educational attainment (EA), a biologically distal environmental factor that is arguably among the most important life-shaping experiences for individuals. Specifically, we report the results of an epigenome-wide association study meta-analysis of EA based on data from 27 cohort studies with a total of 10 767 individuals. We find nine CpG probes significantly associated with EA. However, robustness analyses show that all nine probes have previously been found to be associated with smoking. Only two associations remain when we perform a sensitivity analysis in the subset of never-smokers, and these two probes are known to be strongly associated with maternal smoking during pregnancy, and thus their association with EA could be due to correlation between EA and maternal smoking. Moreover, the effect sizes of the associations with EA are far smaller than the known associations with the biologically proximal environmental factors alcohol consumption, body mass index, smoking and maternal smoking during pregnancy. Follow-up analyses that combine the effects of many probes also point to small methylation associations with EA that are highly correlated with the combined effects of smoking. If our findings regarding EA can be generalized to other biologically distal environmental factors, then they cast doubt on the hypothesis that such factors have large effects on the epigenome.

Efficacy and adverse effects of buprenorphine in acute pain management: systematic review and meta-analysis of randomised controlled trials.

Buprenorphine appears to have a ceiling effect on respiratory depression, but not analgesia in healthy young patients. However, the efficacy and side-effects of buprenorphine in the setting of acute pain are poorly characterized. The aim of this study was to characterize the analgesic efficacy and adverse effects of buprenorphine compared with morphine in the acute pain setting. A systematic review of five databases was performed. Randomised controlled trials (RCTs) comparing buprenorphine with morphine in acute pain management were included. Studies performed outside of the hospital setting were excluded. The a priori primary outcomes included pain, respiratory depression, and sedation. Secondary outcomes included requirement for rescue analgesia, time to rescue analgesia, nausea, vomiting, dizziness, hypotension, and pruritus. Twenty-eight RCTs with 2210 patients met the inclusion criteria. There was no difference in pain [visual analogue scale weighted mean difference (WMD)=-0.29; 95% confidence interval (CI)=-0.62 to 0.03; I2=99%; P=0.07], incidence of respiratory depression [odds ratio (OR)=2.07; 95% CI=0.78-5.51; I2=30%; P=0.14], or sedation (OR=1.44; 95% CI=0.76-2.74; I2=23%; P=0.26). There was only one secondary outcome with an overall significant difference; buprenorphine use was associated with significantly less pruritus (OR=0.31; 95% CI=0.12-0.84; I2=6%; P=0.02). Whilst a theoretical ceiling effect may exist with respect to buprenorphine and respiratory depression, in a clinical setting, it can still cause significant adverse effects on respiratory function. However, given that buprenorphine is an equally efficacious analgesic agent, it is a useful alternative opioid because of its ease of administration and reduced incidence of pruritus.

Dietary inflammatory index or Mediterranean diet score as risk factors for total and cardiovascular mortality.

BACKGROUND AND AIMS: Dietary patterns are associated with risk of cardiovascular disease (CVD). We aimed to examine associations of the Dietary Inflammatory Index (DII) and the Mediterranean Diet Score (MDS) with total, cardiovascular disease (CVD) and coronary heart disease (CHD) mortality in the Melbourne Collaborative Cohort Study; and compare the strengths of the associations. METHODS AND RESULTS: In our prospective cohort study of 41,513 men and women aged 40-69 years, a food frequency questionnaire was completed at baseline and mortality data were obtained via linkage with local and national registries over an average of 19 years follow up. At baseline, questionnaires were completed and physical measures and blood samples taken. Cox proportional hazards models, adjusting for age, alcohol consumption, sex, region of origin, personal history of CVD or diabetes and family history of CVD, were used to assess associations between dietary scores and mortality. More Mediterranean or less inflammatory diets were associated with lower total, CVD and CHD mortality. The hazard ratio for total mortality comparing the highest and lowest quintiles was 1.16 (95%CI: 1.08-1.24) for DII; and 0.86 (95%CI: 0.80-0.93) comparing the highest and lowest three categories of MDS. Using the Bayesian information criterion, there was no evidence that the DII score was more strongly associated with total and CVD mortality than was the MDS. CONCLUSIONS: The MDI and the DII show similar associations with total and cardiovascular mortality, consistent with the consensus that plant-based diets are beneficial for health.

Exploring the provision of alcohol advice by clinicians to breast cancer patients.

Interactions between clinicians and patients along the cancer trajectory provide an opportunity to deliver key messages regarding drinking behaviours and long-term health. This study aimed to explore the extent and nature of clinician-patient discussions regarding alcohol intake and cancer outcomes in the clinical breast cancer setting, using a qualitative research design involving semi-structured interviews. Purposive sampling was used to recruit 27 breast cancer clinicians (eight dietitians, nine breast care nurses, 10 oncologists) across Victoria, Australia. Interview data were analysed using descriptive statistics and a content analysis approach. Clinicians' knowledge of national alcohol recommendations was found to be inconsistent. Clinicians reported a lack of patient awareness of the link between alcohol and breast cancer. Current frameworks for assessing and advising on patient alcohol intake were felt to be impractical. The extent and nature of advice provided about alcohol was influenced by several patient and clinician factors. The provision of alcohol advice in the clinical breast cancer setting is not practiced systematically by any professional group. New approaches are needed to support patient education about alcohol intake and survivorship in the clinical oncology setting.

Protection of sheep by vaccination against experimental challenge with Leptospira borgpetersenii serovar Hardjo and L. interrogans serovar Pomona.

AIMS: To evaluate a multivalent leptospiral and clostridial vaccine for prevention of renal colonisation and urinary shedding in sheep, following experimental challenge with New Zealand strains of Leptospira borgpetersenii serovar Hardjo type Hardjobovis and L. interrogans serovar Pomona. METHODS: Two separate but similarly designed studies were conducted. In both studies, Romney-cross lambs, aged 9-11 weeks, were randomly allocated to a vaccinated group and a control group. Vaccinated lambs each received two 1.5-mL S/C doses of a multivalent leptospiral and clostridial vaccine, 4 weeks apart, and animals in the control groups received the same dose of saline. Groups of 12 vaccinated and 12 control lambs were randomly selected in each study for challenge with serovars Hardjo or Pomona. Challenge was initiated 16 weeks following the second vaccination with three daily doses of live leptospires by intranasal and conjunctival routes. Following challenge, urine samples were collected weekly for 6 weeks, for dark field microscopy and leptospiral culture; 6 weeks after challenge the lambs were slaughtered and kidneys collected for leptospiral culture. RESULTS: In lambs challenged with serovar Hardjo, 8/12 unvaccinated lambs had ≥1 urine or kidney sample that was positive for leptospires following culture, compared with 0/12 lambs in the vaccinated group (p=0.001). In lambs challenged with serovar Pomona, 9/12 unvaccinated lambs had ≥1 urine or kidney sample that was positive following culture, compared with 0/12 lambs in the vaccinated group (p<0.001). Prevention of renal colonisation and urinary shedding, expressed as the prevented fraction, was 100 (95% CI=61.7-100)% and 100 (95% CI=68.3-100)% against challenge with serovars Hardjo and Pomona, respectively, at 4 months after vaccination. CONCLUSIONS AND CLINICAL RELEVANCE: Use of a multivalent leptospiral and clostridial vaccine demonstrated protection against challenge from New Zealand strains of serovars of Hardjo and Pomona 4 months after vaccination in lambs first vaccinated at 9-11 weeks of age. Further studies are required to assess the duration of immunity against challenge in sheep.

Associations between hip bone mineral density, aortic calcification and cardiac workload in community-dwelling older Australians.

In older adults, lower bone density in the proximal femur was associated with increased heart burden, and this association was linked to calcification in the aorta. These results were seen in women but not in men. PURPOSE: To determine whether there is an association between lower bone mineral density (BMD) and increased cardiac workload in older adults, and if this association was independent of abdominal aortic calcification (AAC). METHODS: Three hundred thirty-seven participants [mean ± SD age = 70 ± 5 years and BMI = 28 ± 5 kg/m2, 61% females] had BMD determined by dual-energy X-ray absorptiometry and AAC determined by radiography. Aortic calcification score (ACS) was determined visually in the L1-L4 vertebrae (range 0-24). Systolic blood pressure (BP) and heart rate (HR) were measured. The rate pressure product (RPP), a measure of cardiac workload, was determined by multiplying BP and HR. RESULTS: AAC was present in 205 (61%) participants. Mean ± SD RPP was 9120 ± 1823; range was 5424-18,537. In all participants, ACS was positively associated with log-transformed RPP [LnRPP] (ß = 0.011, p < 0.001), and severe calcification was positively associated with LnRPP (ß = 0.083, p = 0.004 relative to no calcification). In sex-stratified analyses, these associations were significant only in females. Lower odds of any AAC were observed per 1 g/cm2 increment in femoral neck BMD (OR = 0.08, 95% CI 0.01-0.95). A similar trend was evident in women separately (OR = 0.05, 95% CI 0-1.17) but not men. In all participants, femoral neck (ß = -0.20, p = 0.04) and total hip BMD (ß = -0.17, p = 0.04) were inversely associated with LnRPP after multivariate adjustment. Adjusting additionally for AAC reduced the strength of the association in femoral neck (ß = -0.19, p = 0.05) but not total hip BMD (ß = -0.17, p = 0.04). CONCLUSION: Lower BMD was marginally, but significantly with increased LnRPP, and this relationship was partially mediated by AAC suggesting that older adults, particularly females, with osteoporosis may have an increased cardiovascular risk.

Comparison of two long acting pre-lambing anthelmintic treatments on the productivity of ewes in low body condition.

AIM: To determine if there was a benefit from treating ewes with a low body condition score (BCS) with long acting anthelmintic products pre-lambing and to compare the effects of two commonly used treatment options. METHODS: The study was conducted on a single commercial hill country sheep and beef property in the central North Island of New Zealand. Mixed age twin-bearing ewes were preselected by the farmer as being in poor condition 4 weeks before the planned start of lambing, and were sequentially drafted into three equal groups identified with coloured ear tags. The negative control group (n=199) received no anthelmintic treatment; the other two groups received either a controlled release capsule (CRC) containing abamectin, albendazole, Se and Co (n=200) or a long-acting injection of moxidectin (n=200). All ewes were body condition scored (1-5 scale) and weighed at pre-lambing, docking (65 days after treatment) and at weaning (127 days after treatment). Faecal nematode egg counts (FEC) were carried out on 10 ewes from each group at these three times. Most lambs were matched to the ewe treatment groups at weaning, and weighed. RESULTS: At weaning the mean body weight of ewes treated with moxidectin was 3.2 (95% CI=2.3-4.3) kg heavier than controls, and of ewes treated with CRC was 3.6 (95% CI=2.5-4.5) kg heavier than control ewes (p<0.001). At the start of the trial only 61/599 (10.2%) ewes had a BCS≥3. At weaning, more ewes treated with CRC (140/194; 72%) or moxidectin (122/187; 65%) had a BCS≥3 than control ewes (55/179 (31%); p<0.001). In lambs that were matched with ewes from the treatment groups, the mean weight at weaning of lambs from ewes treated with moxidectin was 2.6 (95% CI=1.9-3.3) kg heavier, and from ewes treated with CRC was 2.6 (95% CI=1.9-3.4) kg heavier than lambs from control ewes (p<0.001). CONCLUSIONS AND CLINICAL RELEVANCE: Treating twin-bearing ewes with low BCS pre-lambing with long acting anthelmintic treatments (moxidectin long acting injection or CRC) resulted in an increase in mean body weight of the ewes and lambs at weaning. There were no significant differences between the two pre-lambing treatments used. These results were based on a single property and thus cannot be generalised to all properties where management conditions and parasite populations may differ.

Prevention of fetal infection in heifers challenged with bovine viral diarrhoea virus type 1a by vaccination with a type 1c or type 1a vaccine.

AIMS: To evaluate a vaccine containing type 1c bovine viral diarrhoea (BVD) virus for prevention of fetal infection in pregnant heifers when challenged with New Zealand BVD virus type 1a 6 months after vaccination, compared to unvaccinated heifers and heifers vaccinated with a vaccine containing type 1a BVD virus. METHODS: Fifty five crossbred Friesian heifers, free from BVD virus and antibody, were randomly allocated to three groups. Twenty five heifers were vaccinated twice with a vaccine containing type 1c BVD virus (T1c group), and 10 heifers with a vaccine containing type 1a BVD virus (T1a group), and 20 heifers were unvaccinated (NC group). After oestrus synchronisation the heifers were bred by artificial insemination followed by natural bull mating. Six months after booster vaccination 15 heifers from the T1c group, eight from the T1a group, and 15 from the NC group, were exposed to four calves that were persistently infected with type 1a BVD virus, for 4 weeks. At the beginning of the challenge phase 36/38 heifers were 72-74 days pregnant and 2/38 heifers were approximately 53 days pregnant. Approximately 52 days after the start of the challenge the heifers were subjected to euthanasia and fetal tissues were collected for the detection of BVD virus by ELISA in fetal heart blood and PCR in fetal tissues. RESULTS: Based on PCR results, BVD virus was detected in 15/15 fetuses in the NC group, compared to 4/14 fetuses in the T1c group and 3/8 fetuses in the T1a group. The proportion of BVD virus-positive fetuses was lower in both vaccinated groups compared to the NC group (p<0.002), but there was no difference in proportions between the vaccinated groups (p=1.00). Fetal protection, expressed as the prevented fraction, was 71.4 (95% CI=41.9-91.6)% and 62.5 (95% CI=24.5-91.5)% for the T1c and T1a groups, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The vaccines containing killed type 1c and type 1a BVD viruses significantly reduced fetal infection following challenge with a New Zealand type 1a BVD virus. Prevention of fetal infection by vaccination may not be 100%, and the risk of persistently infected calves being born to some vaccinated cattle should be acknowledged and managed as part of a BVD control programme.

Dietary inflammatory index, Mediterranean diet score, and lung cancer: a prospective study.

PURPOSE: To investigate prospectively the associations of Dietary Inflammatory Index (DII) and Mediterranean Diet Score (MDS) with lung cancer. METHODS: We used data from men and women aged 40-69 years at recruitment in 1990-1994, who were participants in the Melbourne Collaborative Cohort Study (n = 35,303). A total of 403 incident lung cancer cases were identified over an average 18-year follow-up. Hazard ratios (HR) were estimated using Cox regression, adjusting for smoking status and other risk factors, with age as the time metric. RESULTS: An inverse correlation was observed between the DII and MDS (ρ = -0.45), consistent with a higher DII being pro-inflammatory and less 'healthy,' while a high MDS reflects a 'healthier' diet. The DII was positively associated with risk of lung cancer in current smokers [HRQ4 vs Q1 = 1.70 (1.02, 2.82); Ptrend = 0.008] (p interaction between DII quartiles and smoking status = 0.03). The MDS was inversely associated with lung cancer risk overall [HR7-9 vs 0-3 = 0.64 (0.45, 0.90); Ptrend = 0.005] and for current smokers (HR7-9 vs 0-3 = 0.38 (0.19, 0.75); Ptrend = 0.005) (p interaction between MDS categories and smoking status = 0.31). CONCLUSIONS: The MDS showed an inverse association with lung cancer risk, especially for current smokers. A high DII, indicating a more pro-inflammatory diet, was associated with risk of lung cancer only for current smokers. A healthy diet may reduce the risk of lung cancer, especially in smokers.

Effects of antibiotic dry-cow therapy and internal teat sealant on milk somatic cell counts and clinical and subclinical mastitis in early lactation.

The objective of this study was to determine the efficacy of an internal teat sealant (TS; Teatseal; Zoetis Australia, Silverwater, NSW, Australia), when used in combination with antibiotic dry-cow therapy (ADCT) administered at dry-off, on milk individual somatic cell count (ISCC), milk production and components, and the incidence of clinical and subclinical mastitis in dairy cows up to 60 d after calving, when compared with ADCT only. Multiparous Holstein, Jersey, or Holstein cross cows (n=2,200) from 8 farms in southern and eastern Australia were randomly assigned to treatment of all 4 quarters with ADCT alone or with ADCT plus TS (ADCT + TS) at dry-off in this randomized, multisite clinical trial. Individual milk yield, fat and protein percentages, and ISCC were measured at intervals of 14±3 d after calving for the first 60 d of lactation. The first measurement occurred between 10 and 24 d after calving. Clinical mastitis and health events were recorded from dry-off to 60 d of lactation. Milk samples were collected from first cases of clinical mastitis and subjected to bacteriology. Treatment and the interaction of treatment by time did not affect milk yield, ISCC weighted by milk yield, or fat and protein percentages. Treatment with ADCT + TS decreased geometric mean ISCC compared with treatment with ADCT alone over the first 60 d of lactation. Geometric mean ISCC (×10(3) cells/mL) was 32.0 [95% confidence interval (CI): 26.8 to 38.3] and 43.5 (95% CI: 36.2 to 52.1) for ADCT + TS and ADCT alone, respectively. The odds of at least 1 case of subclinical mastitis (ISCC ≥250,000 cells/mL) were 1.9 times higher (95% CI: 1.4 to 2.6) with ADCT alone in the first 60 d of lactation compared with ADCT + TS. Use of ADCT + TS reduced the estimated incidence of at least 1 case of subclinical mastitis on all 8 farms, compared with use of ADCT alone. Only 4 cows that calved 40 to 100 d after dry-off had a first case of clinical mastitis in the dry period. Five percent of cows (76 cases from 1,528 cows included in this analysis) that calved 40 to 100 d after dry-off had a first case of clinical mastitis between 0 and 60 d in milk. Of these first cases of clinical mastitis, 43 cases (5.7% of 761 cows) occurred in the ADCT group and 33 (4.3% of 767 cows) in the ADCT + TS group, but this was not significantly different. Proportional hazards estimates of survival showed no difference in the number of days postcalving to detection of first cases of clinical mastitis between the ADCT and ADCT + TS groups over the first 60 d postpartum. The estimated hazard ratio for clinical mastitis over this period in the ADCT + TS cows (relative to ADCT alone) was 0.70 (95% CI: 0.43 to 1.14). The combination of ADCT and TS provides benefits over ADCT use alone through improved prevention of subclinical mastitis and reduced ISCC in the first 60 d of lactation.

A psychometric investigation of health-related quality of life measures for paediatric neurodevelopment assessment: Reliability and concurrent validity of the PEDS-QL, CHU-9D, and the EQ-5D-Y.

There is a need for tools that can provide a brief assessment of functioning for children with neurodevelopmental conditions, including health-related quality of life (HR-QoL). This study evaluated the psychometric properties of three commonly used and well known HR-QoL measures in a cohort of children presenting to clinical developmental assessment services. The most common diagnoses received in these assessment services were autism spectrum disorders. Findings showed good internal consistency for the PedsQL and the CHU-9D, but not the EQ-5D-Y. This research also found that the CHU-9D, EQ-5D-Y, and PedsQL correlated with relevant functioning domains assessed by the VABS-III. Overall, the measures showed that children with neurodevelopmental conditions experienced poor HR-QoL. The majority of children (>86%) met cut-off criteria for significant health concerns on the PedsQL. On the EQ-5D-Y and CHU-9D, they showed reduced HR-QoL particularly on domains relating to school and homework, being able to join in activities, looking after self, and doing usual activities. This study supports the use of the CHU-9D and PedsQL in this population to assess and potentially track HR-QoL in a broad neurodevelopment paediatric population.

The relationship between body mass index prior to old age and disability in old age.

OBJECTIVES: To analyse the relationship between body mass index (BMI) in middle-age and disability status in old-age using data from the Melbourne Collaborative Cohort Study (MCCS). METHODS: A total of 41 514 participants enroled in the MCCS between 1990-1994. Height and weight were measured at baseline and disability, defined as limitations to self-care activities of daily living (ADLs) and self-care plus mobility activities, was identified at follow-up (2003-2007). In all, 6300 participants were <65 years at baseline, 70 years at follow-up and not missing BMI at baseline or ADLs at follow-up. The association between BMI in six categories (BMI 18.5-22.5; 22.5-25; 25-27.5; 27.5-30; 30-35; 35+) and disability status was analysed using logistic regression. Models were stratified by sex, and sequentially adjusted for age, education, country of birth, then smoking, alcohol, fruit and vegetable intake, and physical activity. RESULTS: Adjusted odds ratios for composite self-care ADL and mobility limitations compared with BMI 18.5-22.5 kg m(-2) were 1.73 (95%CI 1.14-2.64) for BMI 30-35 kg m(-2) and 3.46 (1.78-6.73) for BMI 35+ kg m(-2) in males. In females, adjusted odds ratios were 1.29 (1.00-1.68) for BMI 22.5-25 kg m(-2), 1.74 (1.35-2.24) for BMI 25-27.5 kg m(-2), 2.58 (1.98-3.36) for BMI 27.5-30 kg m(-2), 2.74 (2.10-3.58) for BMI 30-35 kg m(-2) and 4.21 (3.12-5.88) for BMI 35+ kg m(-2). CONCLUSION: A graded relationship was observed between BMI and disability in males and females, across the continuum of BMI. These results highlight the importance of a healthy body weight at middle age in order to reduce the risk of disability in old age.

Growth, respiration and nutrient acquisition by the arbuscular mycorrhizal fungus Glomus mosseae and its host plant Plantago lanceolata in cooled soil.

Although plant phosphate uptake is reduced by low soil temperature, arbuscular mycorrhizal (AM) fungi are responsible for P uptake in many plants. We investigated growth and carbon allocation of the AM fungus Glomus mosseae and a host plant (Plantago lanceolata) under reduced soil temperature. Plants were grown in compartmented microcosm units to determine the impact on both fungus and roots of a constant 2.7 °C reduction in soil temperature for 16 d. C allocation was measured using two (13)CO(2) pulse labels. Although root growth was reduced by cooling, AM colonization, growth and respiration of the extraradical mycelium (ERM) and allocation of assimilated (13)C to the ERM were all unaffected; the frequency of arbuscules increased. In contrast, root respiration and (13)C content and plant P and Zn content were all reduced by cooling. Cooling had less effect on N and K, and none on Ca and Mg content. The AM fungus G. mosseae was more able to sustain activity in cooled soil than were the roots of P. lanceolata, and so enhanced plant P content under a realistic degree of soil cooling that reduced plant growth. AM fungi may therefore be an effective means to promote plant nutrition under low soil temperatures.