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Unlike for many other respiratory infections, the seasonality of pertussis is not well understood. While evidence of seasonal fluctuations in pertussis incidence has been noted in some countries, there have been conflicting findings including in the context of Australia. We investigated this issue by analysing the seasonality of pertussis notifications in Australia using monthly data from January 1991 to December 2016. Data were made available for all states and territories in Australia except for the Australian Capital Territory and were stratified into age groups. Using a time-series decomposition approach, we formulated a generalised additive model where seasonality is expressed using cosinor terms to estimate the amplitude and peak timing of pertussis notifications in Australia. We also compared these characteristics across different jurisdictions and age groups. We found evidence that pertussis notifications exhibit seasonality, with peaks observed during the spring and summer months (November–January) in Australia and across different states and territories. During peak months, notifications are expected to increase by about 15% compared with the yearly average. Peak notifications for children <5 years occurred 1–2 months later than the general population, which provides support to the theory that older household members remain an important source of pertussis infection for younger children. In addition, our results provide a more comprehensive spatial picture of seasonality in Australia, a feature lacking in previous studies. Finally, our findings suggest that seasonal forcing may be useful to consider in future population transmission models of pertussis.
Over the past 25 years, numerous studies of polymers utilizing both X-ray diffraction (XRD) and differential scanning calorimetry (DSC) have been reported in the literature. These studies have suffered because the two techniques must be performed on separate samples and under conditions that are often dissimilar. By combining the two techniques into one instrument, typical problems encountered with variations in sample preparation and thermal and atmospheric environment are eliminated. This is quite important in the study of polymers since one must match not only temperatures between the two techniques, but also heating rates as well. Matched thermal conditions are necessary because polymer properties such as crystallinity and crystallite size depend on both the temperature and thermal history of the sample under study.
Community-acquired pneumonia (CAP) results in substantial numbers of hospitalisations and deaths in older adults. There are known lifestyle and medical risk factors for pneumococcal disease but the magnitude of the additional risk is not well quantified in Australia. We used a large population-based prospective cohort study of older adults in the state of New South Wales (45 and Up Study) linked to cause-specific hospitalisations, disease notifications and death registrations from 2006 to 2015. We estimated the age-specific incidence of CAP hospitalisation (ICD-10 J12-18), invasive pneumococcal disease (IPD) notification and presumptive non-invasive pneumococcal CAP hospitalisation (J13 + J18.1, excluding IPD), comparing those with at least one risk factor to those with no risk factors. The hospitalised case-fatality rate (CFR) included deaths in a 30-day window after hospitalisation. Among 266 951 participants followed for 1 850 000 person-years there were 8747 first hospitalisations for CAP, 157 IPD notifications and 305 non-invasive pneumococcal CAP hospitalisations. In persons 65–84 years, 54.7% had at least one identified risk factor, increasing to 57.0% in those ⩾85 years. The incidence of CAP hospitalisation in those ⩾65 years with at least one risk factor was twofold higher than in those without risk factors, 1091/100 000 (95% confidence interval (CI) 1060–1122) compared with 522/100 000 (95% CI 501–545) and IPD in equivalent groups was almost threefold higher (18.40/100 000 (95% CI 14.61–22.87) vs. 6.82/100 000 (95% CI 4.56–9.79)). The CFR increased with age but there were limited difference by risk status, except in those aged 45 to 64 years. Adults ⩾65 years with at least one risk factor have much higher rates of CAP and IPD suggesting that additional risk factor-based vaccination strategies may be cost-effective.
To evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2years.
In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine.
Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used to compare AE frequencies for long-term treatment with those for short-term treatment (ARM-TD and AIM-TD). This analysis reports results up to 2 years (Week106).
343 patients were enrolled (111 patients received placebo in the parent study and 232 received deutetrabenazine). There were 331.4 patient-years of exposure in this analysis. Through Week 106, EAIRs of AEs were comparable to or lower than those observed with short-term deutetrabenazine and placebo, including AEs of interest (akathisia/restlessness [long-term EAIR: 0.02; short-term EAIR range: 0–0.25], anxiety [0.09; 0.13–0.21], depression [0.09; 0.04–0.13], diarrhea [0.06; 0.06–0.34], parkinsonism [0.01; 0–0.08], somnolence/sedation [0.09; 0.06–0.81], and suicidality [0.02; 0–0.13]). The frequency of SAEs (EAIR 0.15) was similar to those observed with short-term placebo (0.33) and deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.08), dose reduction (0.17), and dose suspension (0.06) were uncommon.
These results confirm the safety outcomes seen in the ARM-TD and AIM-TD parent studies, demonstrating that deutetrabenazine is well tolerated for long-term use in TD patients.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California,USA
Funding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel
To evaluate long-term efficacy of deutetrabenazine in patients with tardive dyskinesia (TD) by examining response rates from baseline in Abnormal Involuntary Movement Scale (AIMS) scores. Preliminary results of the responder analysis are reported in this analysis.
In the 12-week ARM-TD and AIM-TD studies, the odds of response to deutetrabenazine treatment were higher than the odds of response to placebo at all response levels, and there were low rates of overall adverse events and discontinuations associated with deutetrabenazine.
Patients with TD who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration and a long-term maintenance phase. The cumulative proportion of AIMS responders from baseline was assessed. Response was defined as a percent improvement from baseline for each patient from 10% to 90% in 10% increments. AlMS score was assessed by local site ratings for this analysis.
343 patients enrolled in the extension study (111 patients received placebo in the parent study and 232 patients received deutetrabenazine). At Week 54 (n=145; total daily dose [mean±standard error]: 38.1±0.9mg), 63% of patients receiving deutetrabenazine achieved ≥30% response, 48% of patients achieved ≥50% response, and 26% achieved ≥70% response. At Week 80 (n=66; total daily dose: 38.6±1.1mg), 76% of patients achieved ≥30% response, 59% of patients achieved ≥50% response, and 36% achieved ≥70% response. Treatment was generally well tolerated.
Patients who received long-term treatment with deutetrabenazine achieved response rates higher than those observed in positive short-term studies, indicating clinically meaningful long-term treatment benefit.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California, USA.
Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.
During the summer of 2016, the Hawaii Department of Health responded to the second-largest domestic foodborne hepatitis A virus (HAV) outbreak in the post-vaccine era. The epidemiological investigation included case finding and investigation, sequencing of RNA positive clinical specimens, product trace-back and virologic testing and sequencing of HAV RNA from the product. Additionally, an online survey open to all Hawaii residents was conducted to estimate baseline commercial food consumption. We identified 292 confirmed HAV cases, of whom 11 (4%) were possible secondary cases. Seventy-four (25%) were hospitalised and there were two deaths. Among all cases, 94% reported eating at Oahu or Kauai Island branches of Restaurant Chain A, with 86% of those cases reporting raw scallop consumption. In contrast, a food consumption survey conducted during the outbreak indicated 25% of Oahu residents patronised Restaurant Chain A in the 7 weeks before the survey. Product trace-back revealed a single distributor that supplied scallops imported from the Philippines to Restaurant Chain A. Recovery, amplification and sequence comparison of HAV recovered from scallops revealed viral sequences matching those from case-patients. Removal of product from implicated restaurants and vaccination of those potentially exposed led to the cessation of the outbreak. This outbreak further highlights the need for improved imported food safety.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
We investigated risk factors for severe acute lower respiratory infections (ALRI) among hospitalised children <2 years, with a focus on the interactions between virus and age. Statistical interactions between age and respiratory syncytial virus (RSV), influenza, adenovirus (ADV) and rhinovirus on the risk of ALRI outcomes were investigated. Of 1780 hospitalisations, 228 (12.8%) were admitted to the intensive care unit (ICU). The median (range) length of stay (LOS) in hospital was 3 (1–27) days. An increase of 1 month of age was associated with a decreased risk of ICU admission (rate ratio (RR) 0.94; 95% confidence intervals (CI) 0.91–0.98) and with a decrease in LOS (RR 0.96; 95% CI 0.95–0.97). Associations between RSV, influenza, ADV positivity and ICU admission and LOS were significantly modified by age. Children <5 months old were at the highest risk from RSV-associated severe outcomes, while children >8 months were at greater risk from influenza-associated ICU admissions and long hospital stay. Children with ADV had increased LOS across all ages. In the first 2 years of life, the effects of different viruses on ALRI severity varies with age. Our findings help to identify specific ages that would most benefit from virus-specific interventions such as vaccines and antivirals.
The use of monthly intranasal mupirocin was associated with a significant reduction in the rate of methicillin-resistant Staphylococcus aureus transmission and Staphylococcus aureus invasive infection in a large neonatal intensive care unit. Resistance to mupirocin emerged over time, but it was rare and was not associated with adverse clinical outcomes.
Current commercial poultry production in the UK faces many challenges which make it difficult to confidently predict the future. Changing legislation, responding largely to welfare pressures, is one such challenge. Additionally, consumer demands are widening. Eggs and meat from stock which is organically produced, or fed on rations containing no genetically modified ingredients, or free range produced, or corn fed are some of the assurances sought by the purchaser and consumer. Although the market place already offers such produce it is difficult to predict the extent to which they will penetrate a market which developed largely through the use of intensive production systems. The alternatives to intensively produced eggs and meat are more expensive to produce and therefore purchase and consequently are susceptible to changes in standards of living and the affluence of the consumer.
This paper briefly describes current commercial practices and some of the specific challenges arising from new legislation.
A description of some specific requirements of birds highlights areas where improvements, in terms of performance, production efficiency, and welfare might be gained. Since the overwhelming majority of eggs and meat is produced in intensive, highly automated systems, there is an obvious need for an integrated approach featuring engineers and the poultry industry to refine and further develop technology which better serves the birds, and ultimately, the consumer.
It is concluded that the UK cannot compete in production costs with some other areas of the world and as retailers increasingly source their goods worldwide, the UK poultry producer may have to resort to the production of products which satisfy niche demands.
Scientists have long known that certain pesticides, industrial chemicals and heavy metals have a detrimental impact on the reproductive health of a wide range of species (including humans) by disrupting the endocrine system. As exposure to, and the effects of, ‘endocrine disrupters’ are likely to be more pronounced in wild species with a short gestation period and life-cycle we have chosen to develop non-invasive tools based upon faecal steroid analysis to monitor the reproductive status of the short-tailed field vole (Microtus agrestis). This approach is hoped to eventually provide a sensitive means of detecting environmental disturbances that could adversely affect humans, livestock and wildlife by establishing the the field vole as a terrestrial biomarker. Faecal steroid hormone analysis has already been demonstrated as being a convenient and reliable means of diagnosing reproductive state in a large range of mammalian species (including gazelle, rhino, macaque and mice), however, as of yet little is known regarding the hormonal changes that occur during pregnancy in M. agrestis.
Reliable and affordable technology for collecting and managing livestock production process information is being developed. The advances in data measurement, collection and transfer technology enable us to retrieve information from one or more remote sites to be processed and managed centrally. This opens up the opportunity to advance from open loop, prescriptive production to closed loop systems where factors influencing the actual performance of animals are used to modify and improve their production parameters (feed, environment, medication). We strive from producing animals by predicting what is needed using outdated data, to measuring what is actually happening as they grow, processing this information and acting to optimise animal performance by modifying production parameters in real time.
This paper describes commercially available systems that make possible the retrieval, collection, processing and distribution of near real time production information. Various aspects of production management using this technology are discussed, and examples of how it can be applied to monitor water usage, how it relates to pig performance and how energy usage can be influenced, are considered.
In ewe lambs, acceleration of growth and accumulation of both muscle and fat leads to earlier sexual maturity and better reproductive performance. The next stage in the development of this theme is to test whether these aspects of growth in young ewes affect milk production in their first lactation and the growth of their first progeny. We studied 75 young Merino ewes that had known phenotypic values for depth of eye muscle (EMD) and fat (FAT), and known Australian Sheep Breeding Values for post-weaning weight (PWT) and depths of eye muscle (PEMD) and fat (PFAT). They lambed for the first time at 1 year of age. Their lambs were weighed weekly from birth to weaning at 10 weeks to determine live weight gain and weaning weight. Progeny birth weight was positively associated with live weight gain and weaning weight (P<0.001). The PWT of the mothers was positively associated with birth weight (P<0.01), live weight gain and weaning weight of the progeny (P<0.05); however, these progeny traits were not influenced by EMD, FAT, PEMD, PFAT of the mothers (P>0.05). The PWT of the sire was positively associated with live weight gain (P<0.05) and weaning weight of the progeny (P<0.01). At around day 20 postpartum, we measured milk production and milk composition (fat, protein, lactose, total solids). Milk production was influenced positively by birth type (single or twin; P<0.05) and negatively by birth weight (P<0.05), but not by mother phenotype or genotype, sire genotype of the mother or the sex of the progeny (P>0.05). The concentrations of fat, protein, lactose and total solids in the milk were not affected by the phenotype or genotype of the mothers or of the sires of the mothers, or by the sex of the progeny (P>0.05). We conclude that selection of young Merino ewes for better growth, and more rapid accumulation of muscle and fat, will lead to progeny that are heavier at birth, grow faster and are heavier at weaning. Moreover, milk production and composition do not seem to be affected by the genetic merit of the mother for post-weaning live weight or PEMD or PFAT. Therefore, Merino ewes can lamb at 1 year of age without affecting the production objectives of the Merino sheep industry.
The solar magnesium II core-to-wing ratio has been a well-studied proxy for chromospheric activity since 1978. Daily measurements at high spectral (0.1 nm) resolution began with the launch of the Solar Radiation and Climate Experiment (SORCE) in 2003. The next generation of measurements from the Extreme Ultraviolet Sensor (EUVS) on the Geostationary Operational Environmental Satellite 16 (GOES-16) will add high time cadence (every 30 seconds) to the observational Mg II irradiance record. We present a comparison of the two measurements during the period of overlap.
Ultraviolet (UV) Solar spectral Irradiance (SSI) has been measured from orbit on a regular basis since the beginning of the space age. These observations span four Solar Cycles, and they are crucial for our understanding of the Sun-Earth connection and space weather. SSI at these wavelengths are the main drivers for the upper atmosphere including the production and destruction of ozone in the stratosphere. The instruments that measure UV SSI not only require good preflight calibration, but also need a robust method to maintain that calibration on orbit. We will give an overview of the catalog of current and former UV SSI measurements along with the calibration philosophy of each instrument and an estimation of the uncertainties in the published irradiances.
A key to long-term sustainable enhancement of viable livestock production is the introduction of genetic traits that ensure that fertility and meat quality characteristics are compatible with farming environments and market needs. For example, the sheep industry could benefit if daughters of hill-breed ewes were of a crossbred genotype that enhances both carcass characteristics and fertility traits. Use of sires that confer better conformation is an option but does not significantly boost prolificacy. Introduction of the ‘Inverdale’ fecundity gene could change this. On a flock basis in the Romney breed, mean ovulation is increased by 1.0 and litter size by 0.6 in adult ewes carrying a single copy of this gene (designated as FecXI because it is on the X chromosome; Davis et al. 1992). Carrier males transmit it to all of their female offspring, these being heterozygous carriers of the gene unless it also is maternally inherited. In the latter instance, young would be infertile the homozygous genotype confers an undesirable ‘streak ovary’ phenotype. Although a number of sheep breeds world-wide exhibit significant ‘single gene’ effects on ovulation and litter size (Montgomery et al. 2001), Scottish hill sheep breeds show no evidence of this. Consequently, all ewe lambs generated by crossing these hill ewes with a ram carrying the Inverdale gene should be heterozygous. To ascertain whether such animals exhibit enhanced fecundity, an on-farm study investigated ovulation incidence in cyclic ewe lambs born to Cheviot or Scottish Blackface ewes that had been bred to Texel rams carrying a single copy of the ‘Inverdale’ gene.
There is anecdotal evidence that certain sheep breeds, reared in a particular way, produce unusual or characteristic tastes in cooked meat. Such effects could be linked to differences in meat fatty acid composition associated with the consumption of different diets. This study investigated eating quality and fat composition in 4 distinctively different breed x feeding system groups.
Four groups of 20 ram lambs were obtained as follows: Pure Soays (SO) finished off grass in April from commercial breeders; Pure Welsh Mountain (WM) finished off upland grass in October from ADAS Pwllpeiran; Suffolk x Mules from Harper Adams College finished off concentrates (grains) (SC) in April; and Suffolk x mules from the same source finished off grass (SG) in May. The animals were transported to Langford where they were slaughtered in Bristol University's abattoir.
There is increasing interest in the use of red clover (Trifolium pratense) as a high protein forage crop to finish growing lambs. Red clover contains the isoflavanoid compound formononetin which is converted to the non-steroidal oestrogen analogue equol by rumen micro-organisms. Equol is absorbed by the animal, and can have significant effects, such as suppressing reproductive cycling in ewes. Very few commercial red clover varieties have been bred with a low formononetin content to prevent this problem. Although human health benefits have been linked to the consumption of oestrogenically active compounds in foods such as soya (Kurzer and Xu, 1997), there is a need to investigate the presence of oestrogenically active compounds in animal products. The objective of this study was to investigate plasma metabolite and hormone concentrations, and the residual levels of equol in meat, of lambs grazing two varieties of red clover differing in their formononetin contents, compared to control animals grazing grass.
The observational material for this study consists of a series of 19 I plates (IVN+RG715) of the southern half of the LMC taken by the UK Schmidt Telescope over a six year period from 1977–1983. A small region of size 28′x56′ centred on α(1950) = 5 28 50.7, δ(1950) = −69 31 56 was scanned on all plates with a PDS microdensitometer and magnitudes were derived for typically 14000 stars per scan area. All magnitudes were converted to a common system by comparison of magnitudes to a standard plate; this comparison showed the individual rms measurement error to be 0.13 mag. No photoelectric standard sequence exists in the region studied but the instrumental magnitudes have been converted to preliminary IK magnitudes by using the IK magnitudes given by Blanco, McCarthy and Blanco (1980) for some of the red stars in the field.
More than 3000 radial velocity observations across the face of the Crab Nebula are used to investigate its 3-dimensional properties. In the standard model it consists of a thick hollow shell with synchrotron emission from within. We show that the thick shell is composed of bright inner and faint outer components