Comparison of the effects of high and low milk-replacer feeding regimens on health and growth of crossbred dairy heifers

Context: Pre-weaning growth in dairy heifers is highly dependent on the amount of milk fed. Both milk replacer (MR) and associated labour are costly, encouraging restricted milk rations and once-a-day feeding. Aims: This study compared performance relating to the growth and health of calves receiving one of two commercial feeding regimens: High or Low. Methods: All heifers born during the Spring (January–March) calving block on a commercial UK farm with mixed-breed genetics were recruited at birth, randomly assigned to the High (n = 104, receiving MR-A) or Low (n = 88, receiving MR-B) feed group and reared indoors on straw bedding, with free access to concentrate. Both groups initially received MR twice daily. The High group continued to receive MR twice daily throughout the experiment, whereas the Low group calves were reduced to a single MR feed daily during Weeks 4–8. Blood samples were taken in Weeks 1 and 6 to assess passive transfer and measure circulating insulin-like growth factor 1 (IGF1). The Wisconsin calf-scoring system was used to assess health of calves in Weeks 1, 2, 4, 6 and 8 and at 6 months and size was also measured at these times. Data were analysed by univariate and multivariate models. Key results: Passive transfer was good in both groups (serum total protein (mean ± s.d.) 60.9 ± 9.1 mg/mL) with no differences in pre-weaning disease incidence; diarrhoea occurred in 64.5% and bovine respiratory disease in 26.3% of calves. High group calves were significantly heavier, taller and longer at all pre-weaning examinations except recruitment owing to more growth in the first month, and remained significantly larger at 6 months: weight 157 ± 8 vs 149 ± 7 kg, height 103 ± 5 vs 100 ± 5 cm, length 90 ± 4 vs 88 ± 5 cm. Plasma IGF1 concentrations at around Week 6 were doubled in the High group (101 ± 38.6 vs 55 ± 34.1 ng/mL). Bovine respiratory disease was associated with reduced weight gain. Heifers with diarrhoea were leaner at weaning. High feed group, weight at recruitment and good passive transfer were positively associated with weight at 6 months. Conclusions: Higher feeding levels pre-weaning increased growth rates and IGF1, although the disease incidence was unaffected. Implications: Previous studies have shown that more growth and higher IGF1 pre-weaning are associated with a lower age at first calving and an increased chance of reaching the end of first lactation. These in turn improve long-term performance

Spatially Resolved Images of Dust Belt(s) Around the Planet-hosting Subgiant Kappa CrB

We present Herschel spatially resolved images of the debris disc orbiting the subgiant Kappa CrB. Not only are these the first resolved images of a debris disc orbiting a subgiant, but Kappa CrB is a rare example of an intermediate mass star where a detailed study of the structure of the planetary system can be made, including both planets and planetesimal belt(s). The only way to discover planets around such stars using the radial velocity technique is to observe 'retired' A stars, which are cooler and slower rotators compared to their main-sequence counterparts. A planetary companion has already been detected orbiting the subgiant Kappa CrB, with revised parameters of m sin i = 2.1MJ and apl = 2.8AU (Johnson et al. 2008a). We present additional Keck I HIRES radial velocity measurements that provide evidence for a second planetary companion, alongside Keck II AO imaging that places an upper limit on the mass of this companion. Modelling of our Herschel images shows that the dust is broadly distributed, but cannot distinguish between a single wide belt (from 20 to 220AU) or two narrow dust belts (at around 40 and 165AU). Given the existence of a second planetary companion beyond approximately 3AU it is possible that the absence of dust within approximately 20AU is caused by dynamical depletion, although the observations are not inconsistent with depletion of these regions by collisional erosion, which occurs at higher rates closer to the star.Comment: Updated abstrac

Forming new sex partnerships while overseas: findings from the third British national survey of sexual attitudes & lifestyles (Natsal-3)

Objectives: Travelling away from home presents opportunities for new sexual partnerships, which may be associated with sexually transmitted infection (STI) risk. We examined the prevalence of, and factors associated with, reporting new sexual partner(s) while overseas, and whether this differed by partners’ region of residence. Methods: We analysed data from 12 530 men and women aged 16–74 years reporting ≥1 sexual partner(s) in the past 5 years in Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), a probability survey undertaken 2010–2012. Results: 9.2% (95% CI 8.3% to 10.1%) of men and 5.3% (4.8% to 5.8%) of women reported new sexual partner(s) while overseas in the past 5 years. This was strongly associated with higher partner numbers and other sexual and health risk behaviours. Among those with new partners while overseas, 72% of men and 58% of women reported partner(s) who were not UK residents. Compared with those having only UK partners while abroad, these people were more likely to identify as ‘White Other’ or ‘Non-White’ (vs White British ethnicity), report higher partner numbers, new partners from outside the UK while in the UK and paying for sex (men only) all in the past 5 years. There was no difference in reporting STI diagnosis/es during this time period. Conclusions: Reporting new partners while overseas was associated with a range of sexual risk behaviours. Advice on sexual health should be included as part of holistic health advice for all travellers, regardless of age, destination or reason for travel

Determination of an Interaction Network between an Extracellular Bacterial Pathogen and the Human Host

A major gap in understanding infectious diseases is the lack of information about molecular interaction networks between pathogens and the human host. Haemophilus ducreyi causes the genital ulcer disease chancroid in adults and is a leading cause of cutaneous ulcers in children in the tropics. We developed a model in which human volunteers are infected on the upper arm with H. ducreyi until they develop pustules. To define the H. ducreyi and human interactome, we determined bacterial and host transcriptomic and host metabolomic changes in pustules. We found that in vivo H. ducreyi transcripts were distinct from those in the inocula, as were host transcripts in pustule and wounded control sites. Many of the upregulated H. ducreyi genes were found to be involved in ascorbic acid and anaerobic metabolism and inorganic ion/nutrient transport. The top 20 significantly expressed human pathways showed that all were involved in immune responses. We generated a bipartite network for interactions between host and bacterial gene transcription; multiple positively correlated networks contained H. ducreyi genes involved in anaerobic metabolism and host genes involved with the immune response. Metabolomic studies showed that pustule and wounded samples had different metabolite compositions; the top ion pathway involved ascorbate and aldarate metabolism, which correlated with the H. ducreyi transcriptional response and upregulation of host genes involved in ascorbic acid recycling. These data show that an interactome exists between H. ducreyi and the human host and suggest that H. ducreyi exploits the metabolic niche created by the host immune response.IMPORTANCE Dual RNA sequencing (RNA-seq) offers the promise of determining an interactome at a transcriptional level between a bacterium and the host but has yet to be done on any bacterial infection in human tissue. We performed dual RNA-seq and metabolomics analyses on wounded and infected sites following experimental infection of the arm with H. ducreyi Our results suggest that H. ducreyi survives in an abscess by utilizing l-ascorbate as an alternative carbon source, possibly taking advantage of host ascorbic acid recycling, and that H. ducreyi also adapts by upregulating genes involved in anaerobic metabolism and inorganic ion and nutrient transport. To our knowledge, this is the first description of an interaction network between a bacterium and the human host at a site of infection

Preclinical Analysis of JAA-F11, a Specific Anti-Thomsen-Friedenreich Antibody via Immunohistochemistry and In Vivo Imaging.

The tumor specificity of JAA-F11, a novel monoclonal antibody specific for the Thomsen-Friedenreich cancer antigen (TF-Ag-alpha linked), has been comprehensively studied by in vitro immunohistochemical (IHC) staining of human tumor and normal tissue microarrays and in vivo biodistribution and imaging by micro-positron emission tomography imaging in breast and lung tumor models in mice. The IHC analysis detailed herein is the comprehensive biological analysis of the tumor specificity of JAA-F11 antibody performed as JAA-F11 is progressing towards preclinical safety testing and clinical trials. Wide tumor reactivity of JAA-F11, relative to the matched mouse IgG3 (control), was observed in 85% of 1269 cases of breast, lung, prostate, colon, bladder, and ovarian cancer. Staining on tissues from breast cancer cases was similar regardless of hormonal or Her2 status, and this is particularly important in finding a target on the currently untargetable triple-negative breast cancer subtype. Humanization of JAA-F11 was recently carried out as explained in a companion paper "Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and In Vitro Efficacy Analysis" (Neoplasia 19: 716-733, 2017), and it was confirmed that humanization did not affect chemical specificity. IHC studies with humanized JAA-F11 showed similar binding to human breast tumor tissues. In vivo imaging and biodistribution studies in a mouse syngeneic breast cancer model and in a mouse-human xenograft lung cancer model with humanized 124I- JAA-F11 construct confirmed in vitro tumor reactivity and specificity. In conclusion, the tumor reactivity of JAA-F11 supports the continued development of JAA-F11 as a targeted cancer therapeutic for multiple cancers, including those with unmet need

A discussion of statistical methods to characterise early growth and its impact on bone mineral content later in childhood

Background Many statistical methods are available to model longitudinal growth data and relate derived summary measures to later outcomes. Aim To apply and compare commonly used methods to a realistic scenario including pre- and postnatal data, missing data and confounders. Subjects and methods Data were collected from 753 offspring in the Southampton Women’s Survey with measurements of bone mineral content (BMC) at age 6 years. Ultrasound measures included crown-rump length (11 weeks’ gestation) and femur length (19 and 34 weeks’ gestation); postnatally, infant length (birth, 6 and 12 months) and height (2 and 3 years) were measured. A residual growth model, two-stage multilevel linear spline model, joint multilevel linear spline model, SITAR and a growth mixture model were used to relate growth to 6-year BMC. Results Results from the residual growth, two-stage and joint multilevel linear spline models were most comparable: an increase in length at all ages was positively associated with BMC, the strongest association being with later growth. Both SITAR and the growth mixture model demonstrated that length was positively associated with BMC. Conclusions Similarities and differences in results from a variety of analytic strategies need to be understood in the context of each statistical methodology

Spatially resolved images of dust belt(s) around the planet-hosting subgiant κ CrB

We present Herschel spatially resolved images of the debris disc orbiting the subgiant κ Coronae Borealis (κ CrB). Not only are these the first resolved images of a debris disc orbiting a subgiant, but κ CrB is a rare example of an intermediate mass star where a detailed study of the structure of the planetary system can be made, including both planets and planetesimal belt(s). The only way to discover planets using the radial velocity technique around such stars is to observe ‘retired’ A stars, which are cooler and slower rotators compared to their main-sequence counterparts. A planetary companion has already been detected orbiting the subgiant κ CrB, with revised parameters of msin i = 2.1 M_J and a_(pl) = 2.8 au (Johnson et al. 2008). We present additional Keck I HIRES (High Resolution Echelle Spectrometer) radial velocity measurements that provide evidence for a second planetary companion, alongside Keck II adaptive optics imaging that places an upper limit on the mass of this companion. Modelling of our Herschel images shows that the dust is broadly distributed, but cannot distinguish between a single wide belt (from 20 to 220 au) or two narrow dust belts (at around 40 and 165 au). Given the existence of a second planetary companion beyond ∼3 au it is possible that the absence of dust within ∼20 au is caused by dynamical depletion, although the observations are not inconsistent with depletion of these regions by collisional erosion, which occurs at higher rates closer to the star

Presence of a prothrombotic state in people with idiopathic pulmonary fibrosis: a population-based case-control study

BACKGROUND: Laboratory studies suggest that the clotting cascade is activated in fibrotic lungs. Since humans vary in their tendency to clot due to a variety of inherited or acquired defects, we investigated whether a prothrombotic state increases the chance of developing idiopathic pulmonary fibrosis (IPF) and/or worsens the prognosis of IPF. METHODS: We recruited 211 incident cases of IPF and 256 age-and sex-matched general population controls and collected data on medical history, medication, smoking habit, blood samples as well as lung function and high-resolution CT scans done as part of routine clinical care. A prothrombotic state was defined as the presence of at least one inherited or acquired clotting defect or marker of fibrinolytic dysfunction. We used logistic regression to quantify the association between a prothrombotic state and IPF adjusted for age, sex, smoking habit and highly sensitive C reactive protein. Cox regression was used to determine the influence of a prothrombotic state on survival. RESULTS: Cases were more than four times more likely than controls to have a prothrombotic state (OR 4.78, 95% CI 2.93 to 7.80; p<0.0001). Cases with a prothrombotic state were also likely to have more severe disease (forced vital capacity <70% predicted) at presentation (OR 10.79, 95% CI 2.43 to 47.91) and had a threefold increased risk of death (HR 3.26, 95% CI 1.09 to 9.75). CONCLUSIONS: People with IPF are more likely to have a prothrombotic state than general population controls and the presence of a prothrombotic state has an adverse impact on survival

Absorption spectrum in the wings of the potassium second resonance doublet broadened by helium

We have measured the reduced absorption coefficients occurring in the wings of the potassium 4S-5P doublet lines at 404.414 nm and at 404.720 nm broadened by helium gas at pressures of several hundred Torr. At the experimental temperature of 900 K, we have detected a shoulder-like broadening feature on the blue wing of the doublet which is relatively flat between 401.8 nm and 402.8 nm and which drops off rapidly for shorter wavelengths, corresponding to absorption from the X doublet Sigma+ state to the C doublet Sigma+ state of the K-He quasimolecule. The accurate measurements of the line profiles in the present work will sharply constrain future calculations of potential energy surfaces and transition dipole moments correlating to the asymptotes He-K(5p), He-K(5s), and He-K(3d).Comment: 2 figure