Hendra virus (HeV) continues to cause fatal infection in horses and threaten infection in close-contact humans in eastern Australia. Species of Pteropus bats (flying-foxes) are the natural reservoir of the virus. We caught and sampled flying-foxes from a multispecies roost in southeast Queensland, Australia on eight occasions between June 2013 and June 2014. The effects of sample date, species, sex, age class, body condition score (BCS), pregnancy and lactation on HeV antibody prevalence, log-transformed median fluorescent intensity (lnMFI) values and HeV RNA status were assessed using unbalanced generalised linear models. A total of 1968 flying-foxes were sampled, comprising 1012 Pteropus alecto, 742 P. poliocephalus and 214 P. scapulatus. Sample date, species and age class were each statistically associated with HeV RNA status, antibody status and lnMFI values; BCS was statistically associated with HeV RNA status and antibody status. The findings support immunologically naïve sub-adult P. alecto playing an important role in maintaining HeV infection at a population level. The biological significance of the association between BCS and HeV RNA status, and BCS and HeV antibody status, is less clear and warrants further investigation. Contrary to previous studies, we found no direct association between HeV infection and pregnancy or lactation. The findings in P. poliocephalus suggest that HeV exposure in this species may not result in systemic infection and virus excretion, or alternatively, may reflect assay cross-reactivity with another (unidentified) henipavirus.

Overweight and obesity may increase risk of disease progression in men with prostate cancer, but there have been few studies of weight loss interventions in this patient group. In this study overweight or obese men treated for prostate cancer were randomised to a self-help diet and activity intervention with telephone-based dietitian support or a wait-list mini-intervention group. The intervention group had an initial group meeting, a supporting letter from their urological consultant, three telephone dietitian consultations at 4-week intervals, a pedometer and access to web-based diet and physical activity resources. At 12 weeks, men in both groups were given digital scales for providing follow-up weight measurements, and the wait-list group received a mini-intervention of the supporting letter, a pedometer and access to the web-based resources. Sixty-two men were randomised; fifty-four completed baseline and 12-week measurements, and fifty-one and twenty-seven provided measurements at 6 and 12 months, respectively. In a repeated-measures model, mean difference in weight change between groups (wait-list mini-intervention minus intervention) at 12 weeks was −2·13 (95 % CI −3·44, −0·82) kg (P = 0·002). At 12 months the corresponding value was −2·43 (95 % CI −4·50, −0·37) kg (P = 0·022). Mean difference in global quality of life score change between groups at 12 weeks was 12·3 (95 % CI 4·93, 19·7) (P = 0·002); at 12 months there were no significant differences between groups. Results suggest the potential of self-help diet and physical activity intervention with trained support for modest but sustained weight loss in this patient group.

Background: Buprenorphine/naloxone (bup/nal) is a partial opioid agonist/antagonist and recommended first line treatment for opioid use disorder (OUD). Emergency departments (EDs) are a key point of contact with the healthcare system for patients living with OUD. Aim Statement: We implemented a multi-disciplinary quality improvement project to screen patients for OUD, initiate bup/nal for eligible individuals, and provide rapid next business day walk-in referrals to addiction clinics in the community. Measures & Design: From May to September 2018, our team worked with three ED sites and three addiction clinics to pilot the program. Implementation involved alignment with regulatory requirements, physician education, coordination with pharmacy to ensure in-ED medication access, and nurse education. The project is supported by a full-time project manager, data analyst, operations leaders, physician champions, provincial pharmacy, and the Emergency Strategic Clinical Network leadership team. For our pilot, our evaluation objective was to determine the degree to which our initiation and referral pathway was being utilized. We used administrative data to track the number of patients given bup/nal in ED, their demographics and whether they continued to fill bup/nal prescriptions 30 days after their ED visit. Addiction clinics reported both the number of patients referred to them and the number of patients attending their referral. Evaluation/Results: Administrative data shows 568 opioid-related visits to ED pilot sites during the pilot phase. Bup/nal was given to 60 unique patients in the ED during 66 unique visits. There were 32 (53%) male patients and 28 (47%) female patients. Median patient age was 34 (range: 21 to 79). ED visits where bup/nal was given had a median length of stay of 6 hours 57 minutes (IQR: 6 hours 20 minutes) and Canadian Triage Acuity Scores as follows: Level 1 – 1 (2%), Level 2 – 21 (32%), Level 3 – 32 (48%), Level 4 – 11 (17%), Level 5 – 1 (2%). 51 (77%) of these visits led to discharge. 24 (47%) discharged patients given bup/nal in ED continued to fill bup/nal prescriptions 30 days after their index ED visit. EDs also referred 37 patients with OUD to the 3 community clinics, and 16 of those individuals (43%) attended their first follow-up appointment. Discussion/Impact: Our pilot project demonstrates that with dedicated resources and broad institutional support, ED patients with OUD can be appropriately initiated on bup/nal and referred to community care.

Building on the recent advances in next-generation sequencing, the integration of genomics, proteomics, metabolomics, and other approaches hold tremendous promise for precision medicine. The approval and adoption of these rapidly advancing technologies and methods presents several regulatory science considerations that need to be addressed. To better understand and address these regulatory science issues, a Clinical and Translational Science Award Working Group convened the Regulatory Science to Advance Precision Medicine Forum. The Forum identified an initial set of regulatory science gaps. The final set of key findings and recommendations provided here address issues related to the lack of standardization of complex tests, preclinical issues, establishing clinical validity and utility, pharmacogenomics considerations, and knowledge gaps.

Unusual speleothems, associated with hyperalkaline (pH > 12) groundwaters have formed within a shallow, abandoned railway tunnel at Peak Dale, Derbyshire, UK. The hyperalkaline groundwaters are produced by the leaching of a thin layer (<2 m) of old lime-kiln waste on the soil-bedrock surface above the tunnel by rainwater. This results in a different reaction and chemical process to that more commonly associated with the formation of calcium carbonate speleothems from Ca-HCO3-type groundwaters and degassing of CO2. Stalagmites within the Peak Daletunnel have grown rapidly (averaging 33 mm y–1), following the closure of the tunnel 70 years ago. They have an unusual morphology comprising a central sub-horizontally-laminated column of micro- to nano-crystalline calcium carbonate encompassed by an outer sub-vertical assymetricripple-laminated layer. The stalagmites are composed largely of secondary calcite forming pseudomorphs (<1 mm) that we believe to be predominantly after the 'cold climate' calcium carbonate polymorph, ikaite (calcium carbonate hexahydrate: CaCO3·6H2O), withminor volumes of small (<5 μm) pseudomorphs after vaterite. The tunnel has a near constant temperature of 8–9°C, which is slightly above the previously published crystallization temperatures for ikaite (<6°C). Analysis of a stalagmite actively growing at the time ofsampling, and preserved immediately within a dry nitrogen cryogenic vessel, indicates that following crystallization of ikaite, decomposition to calcite occurs rapidly, if not instantaneously. We believe this is the first occurrence of this calcium carbonate polymorph observed within speleothems.

The nutrient choline is necessary for membrane synthesis and methyl donation, with increased requirements during lactation. The majority of immune development occurs postnatally, but the importance of choline supply for immune development during this critical period is unknown. The objective of this study was to determine the importance of maternal supply of choline during suckling on immune function in their offspring among rodents. At parturition, Sprague–Dawley dams were randomised to either a choline-devoid (ChD; n 7) or choline-sufficient (ChS, 1 g/kg choline; n 10) diet with their offspring euthanised at 3 weeks of age. In a second experiment, offspring were weaned to a ChS diet until 10 weeks of age (ChD-ChS, n 5 and ChS-ChS, n 9). Splenocytes were isolated, and parameters of immune function were measured. The ChD offspring received less choline in breast milk and had lower final body and organ weight compared with ChS offspring (P<0·05), but this effect disappeared by week 10 with choline supplementation from weaning. ChD offspring had a higher proportion of T cells expressing activation markers (CD71 or CD28) and a lower proportion of total B cells (CD45RA+) and responded less to T cell stimulation (lower stimulation index and less IFN-γ production) ex vivo (P<0·05). ChD-ChS offspring had a lower proportion of total and activated CD4+ T cells, and produced less IL-6 after mitogen stimulation compared with cells from ChS-ChS (P<0·05). Our study suggests that choline is required in the suckling diet to facilitate immune development, and choline deprivation during this critical period has lasting effects on T cell function later in life.

Data were pooled from three Australian sentinel general practice influenza surveillance networks to estimate Australia-wide influenza vaccine coverage and effectiveness against community presentations for laboratory-confirmed influenza for the 2012, 2013 and 2014 seasons. Patients presenting with influenza-like illness at participating GP practices were swabbed and tested for influenza. The vaccination odds of patients testing positive were compared with patients testing negative to estimate influenza vaccine effectiveness (VE) by logistic regression, adjusting for age group, week of presentation and network. Pooling of data across Australia increased the sample size for estimation from a minimum of 684 to 3,683 in 2012, from 314 to 2,042 in 2013 and from 497 to 3,074 in 2014. Overall VE was 38% [95% confidence interval (CI) 24–49] in 2012, 60% (95% CI 45–70) in 2013 and 44% (95% CI 31–55) in 2014. For A(H1N1)pdm09 VE was 54% (95% CI–28 to 83) in 2012, 59% (95% CI 33–74) in 2013 and 55% (95% CI 39–67) in 2014. For A(H3N2), VE was 30% (95% CI 14–44) in 2012, 67% (95% CI 39–82) in 2013 and 26% (95% CI 1–45) in 2014. For influenza B, VE was stable across years at 56% (95% CI 37–70) in 2012, 57% (95% CI 30–73) in 2013 and 54% (95% CI 21–73) in 2014. Overall VE against influenza was low in 2012 and 2014 when A(H3N2) was the dominant strain and the vaccine was poorly matched. In contrast, overall VE was higher in 2013 when A(H1N1)pdm09 dominated and the vaccine was a better match. Pooling data can increase the sample available and enable more precise subtype- and age group-specific estimates, but limitations remain.

It is now recognized that diffuse matter in space plays a decisive role in the evolution of our Galaxy and of similar galaxies. Primordial gas—together with gas ejected in planetary nebulae, stellar winds, novae, supernovae, and other types of stars—has accumulated to form a complex medium containing regions with densities ranging from 10–3 to 106 particles cm-3 and with temperatures ranging from 10 K to 106 K. From time to time, part of the interstellar medium collapses to form stars. In order to understand the evolution of the Galaxy, it is essential to understand how energy, mass, trace elements, and dust grains are deposited into the interstellar medium by stars. It is also essential to understand the mechanisms that initiate star formation in certain regions, and how the ensuing collapse develops in space and time.

We reconcile two scaling laws that have been proposed in the literature for the slip length associated with a moving contact line in diffuse interface models, by demonstrating each to apply in a different regime of the ratio of the microscopic interfacial width $l$ and the macroscopic diffusive length $l_{D}=(M{\it\eta})^{1/2}$ , where ${\it\eta}$ is the fluid viscosity and $M$ the mobility governing intermolecular diffusion. For small $l_{D}/l$ we find a diffuse interface regime in which the slip length scales as ${\it\xi}\sim (l_{D}l)^{1/2}$ . For larger $l_{D}/l>1$ we find a sharp interface regime in which the slip length depends only on the diffusive length, ${\it\xi}\sim l_{D}\sim (M{\it\eta})^{1/2}$ , and therefore only on the macroscopic variables ${\it\eta}$ and $M$ , independent of the microscopic interfacial width $l$ . We also give evidence that modifying the microscopic interfacial terms in the model’s free energy functional appears to affect the value of the slip length only in the diffuse interface regime, consistent with the slip length depending only on macroscopic variables in the sharp interface regime. Finally, we demonstrate the dependence of the dynamic contact angle on the capillary number to be in excellent agreement with the theoretical prediction of Cox (J. Fluid Mech., vol. 168, 1986, p. 169), provided we allow the slip length to be rescaled by a dimensionless prefactor. This prefactor appears to converge to unity in the sharp interface limit, but is smaller in the diffuse interface limit. The excellent agreement of results obtained using three independent numerical methods, across several decades of the relevant dimensionless variables, demonstrates our findings to be free of numerical artefacts.

Secretory immunoglobulin A (IgA) plays a critical role in gut mucosal immune defense. Initially provided by breastmilk, IgA production by the infant gut is gradually stimulated by developing gut microbiota. This study reports associations between infant fecal IgA concentrations 4 months after birth, breastfeeding status and other pre/postnatal exposures in 47 infants in the Canadian Healthy Infant Longitudinal Development cohort. Breastfed infants and first-born infants had higher median fecal IgA concentrations (23.11 v. 9.34 µg/g protein, P<0.01 and 22.19 v. 8.23 µg/g protein, P=0.04). IgA levels increased successively with exclusivity of breastfeeding (β-coefficient, 0.37, P<0.05). This statistical association was independent of maternal parity and household pets. In the absence of breastfeeding, female sex and pet exposure elevated fecal IgA to levels found in breastfed infants. In addition to breastfeeding, infant fecal IgA associations with pre/postnatal exposures may affect gut immunity and risk of allergic disease.

Radial diffusion experiments have been carried out to assess the migration of 36Cl, as chloride, through a cementitious backfill material. Further experiments in the presence of cellulose degradation products were performed to assess the effect of organic ligands on the extent and rate of chloride diffusion. Results show that breakthrough of 36Cl is dependent on chloride concentration: as the carrier concentration increases, both breakthrough time and the quantity retained by the cement matrix decreases. Experiments in the presence of cellulose degradation products also show a decrease in time to initial breakthrough. However, uptake at various carrier concentrations in the presence of organic ligands converges at 45% of the initial concentration as equilibrium is reached. The results are consistent with organic ligands blocking sites on the cement that would otherwise be available for chloride binding, though further work is required to confirm that this is the case. Post-experimental digital autoradiographs of the cement cylinders, and elemental mapping showed evidence of increased 36Cl activity associated with black ash-like particles in the matrix, believed to correspond to partially hydrated glassy calcium-silicate-sulfate-rich clinker.

Listeria monocytogenes is a foodborne pathogen that can cause bacteraemia, meningitis, and complications during pregnancy. In July 2012, molecular subtyping identified indistinguishable L. monocytogenes isolates from six patients and two samples of different cut and repackaged cheeses. A multistate outbreak investigation was initiated. Initial analyses identified an association between eating soft cheese and outbreak-related illness (odds ratio 17·3, 95% confidence interval 2·0–825·7) but no common brand. Cheese inventory data from locations where patients bought cheese and an additional location where repackaged cheese yielded the outbreak strain were compared to identify cheeses for microbiological sampling. Intact packages of imported ricotta salata yielded the outbreak strain. Fourteen jurisdictions reported 22 cases from March–October 2012, including four deaths and a fetal loss. Six patients ultimately reported eating ricotta salata; another reported eating cheese likely cut with equipment also used for contaminated ricotta salata, and nine more reported eating other cheeses that might also have been cross-contaminated. An FDA import alert and US and international recalls followed. Epidemiology-directed microbiological testing of suspect cheeses helped identify the outbreak source. Cross-contamination of cheese highlights the importance of using validated disinfectant protocols and routine cleaning and sanitizing after cutting each block or wheel.

Choline demands during lactation are high; however, detailed knowledge is lacking regarding the optimal dietary intake during this critical period. The present study was designed to determine the effects of varying intakes of choline on maternal immune function during lactation. Primiparous Sprague–Dawley rats (n 42) were randomised 24-48 h before birth and fed the following diets for 21 d: choline-devoid (0 g choline/kg diet; D, n 10); 1·0 g choline/kg diet (C1, n 11); 2·5 g choline/kg diet (C2·5, n 10); 6·2 g choline/kg diet (C6, n 11). Splenocytes were isolated and stimulated ex vivo with concanavalin A, lipopolysaccharide (LPS) or CD3/CD28. D and C6 dams had lower final body weight, spleen weight and average pup weight than C1 dams (P< 0·05). There was a linear relationship between free choline concentration in pup stomach contents with maternal dietary choline content (P< 0·001, r 2 0·415). Compared with C1 and C2·5, D spleens had a lower proportion of mature T cells and activated suppressor cells, and this resulted in reduced cytokine production after stimulation (P< 0·05). Feeding 6·2 g choline/kg diet resulted in a higher cytokine production after stimulation with CD3/CD28 (P< 0·05). Except for a higher IL-6 production after LPS stimulation with cells from the C2·5 dams (P< 0·05), there were no differences between the C1 and C2·5 dams. For the first time, we show that feeding lactating mothers a diet free of choline has substantial effects on their immune function and on offspring growth. Additionally, excess dietary choline had adverse effects on maternal and offspring body weight but only minimal effects on maternal immune function.

The 2013 multistate outbreaks contributed to the largest annual number of reported US cases of cyclosporiasis since 1997. In this paper we focus on investigations in Texas. We defined an outbreak-associated case as laboratory-confirmed cyclosporiasis in a person with illness onset between 1 June and 31 August 2013, with no history of international travel in the previous 14 days. Epidemiological, environmental, and traceback investigations were conducted. Of the 631 cases reported in the multistate outbreaks, Texas reported the greatest number of cases, 270 (43%). More than 70 clusters were identified in Texas, four of which were further investigated. One restaurant-associated cluster of 25 case-patients was selected for a case-control study. Consumption of cilantro was most strongly associated with illness on meal date-matched analysis (matched odds ratio 19·8, 95% confidence interval 4·0–∞). All case-patients in the other three clusters investigated also ate cilantro. Traceback investigations converged on three suppliers in Puebla, Mexico. Cilantro was the vehicle of infection in the four clusters investigated; the temporal association of these clusters with the large overall increase in cyclosporiasis cases in Texas suggests cilantro was the vehicle of infection for many other cases. However, the paucity of epidemiological and traceback information does not allow for a conclusive determination; moreover, molecular epidemiological tools for cyclosporiasis that could provide more definitive linkage between case clusters are needed.