Influenza A virus reassortment is strain dependent.

RNA viruses can exchange genetic material during coinfection, an interaction that creates novel strains with implications for viral evolution and public health. Influenza A viral genetic exchange can occur when genome segments from distinct strains reassort in coinfected cells. Predicting potential genomic reassortment between influenza strains has been a long-standing goal. Experimental coinfection studies have shed light on factors that limit or promote reassortment. However, determining the reassortment potential between diverse Influenza A strains has remained elusive. To address this challenge, we developed a high throughput genotyping approach to quantify reassortment among a diverse panel of human influenza virus strains encompassing two pandemics (swine and avian origin), three specific epidemics, and both circulating human subtypes A/H1N1 and A/H3N2. We found that reassortment frequency (the proportion of reassortants generated) is an emergent property of specific pairs of strains where strain identity is a predictor of reassortment frequency. We detect little evidence that antigenic subtype drives reassortment as intersubtype (H1N1xH3N2) and intrasubtype reassortment frequencies were, on average, similar. Instead, our data suggest that certain strains bias the reassortment frequency up or down, independently of the coinfecting partner. We observe that viral productivity is also an emergent property of coinfections, but uncorrelated to reassortment frequency; thus viral productivity is a separate factor affecting the total number of reassortants produced. Assortment of individual segments among progeny and pairwise segment combinations within progeny generally favored homologous combinations. These outcomes were not related to strain similarity or shared subtype but reassortment frequency was closely correlated to the proportion of both unique genotypes and of progeny with heterologous pairwise segment combinations. We provide experimental evidence that viral genetic exchange is potentially an individual social trait subject to natural selection, which implies the propensity for reassortment is not evenly shared among strains. This study highlights the need for research incorporating diverse strains to discover the traits that shift the reassortment potential to realize the goal of predicting influenza virus evolution resulting from segment exchange.

The Speciation and Coordination of a Deep Earth Carbonate-Silicate-Metal Melt.

Ab initio molecular dynamics calculations on a carbonate-silicate-metal melt were performed to study speciation and coordination changes as a function of pressure and temperature. We examine in detail the bond abundances of specific element pairs and the distribution of coordination environments over conditions spanning Earth's present-day mantle. Average coordination numbers increase continuously from 4 to 8 for Fe and Mg, from 4 to 6 for Si, and from 2 to 4 for C from 1 to 148 GPa (4,000 K). Speciation across all pressure and temperature conditions is complex due to the unusual bonding of carbon. With the increasing pressure, C-C and C-Fe bonding increase significantly, resulting in the formation of carbon polymers, C-Fe clusters, and the loss of carbonate groups. The increased bonding of carbon with elements other than oxygen indicates that carbon begins to replace oxygen as an anion in the melt network. We evaluate our results in the context of diamond formation and of metal-silicate partitioning behavior of carbon. Our work has implications for properties of carbon and metal-bearing silicate melts, such as viscosity, electrical conductivity, and reactivity with surrounding phases.

A quality improvement study: Optimizing pneumococcal vaccination rates in children with cochlear implants.

Children with cochlear implants are at increased risk of invasive pneumococcal disease, with national and international guidelines recommending additional pneumococcal vaccines for these children. This study aimed to examine the pneumococcal immunization status and rate of invasive pneumococcal disease in children with cochlear implants at a tertiary paediatric hospital over a 12-year period. Additionally, the impacts of vaccination reminders and a dedicated immunization clinic on pneumococcal vaccination rates were assessed. This quality improvement study included 200 children who had received a cochlear implant through the Children's Hearing Implant Program at a tertiary paediatric hospital servicing the state of Western Australia. The majority of children (88%) were not up to date with additionally recommended pneumococcal vaccinations. Over the 12-year study period, 2% of children developed invasive pneumococcal disease associated with cochlear implant infections. Generic and personalized electronic immunization reminders improved pneumococcal vaccine up-take in this paediatric cochlear implant setting from 12% (19/153) at baseline to 49% (75/153, p < 0.0001) post implementation. The value of a nurse-led dedicated immunization clinic was also demonstrated with all children (42/42, 100%) up to date with Prevenar13 and the majority (34/42, 81%) up to date with Pneumovax23 post initiation of this referral pathway. These data support the expansion of this model to other medically-at-risk paediatric groups that have been highlighted consistently to be under-vaccinated.

Measurement of Lepton-Jet Correlation in Deep-Inelastic Scattering with the H1 Detector Using Machine Learning for Unfolding.

The first measurement of lepton-jet momentum imbalance and azimuthal correlation in lepton-proton scattering at high momentum transfer is presented. These data, taken with the H1 detector at HERA, are corrected for detector effects using an unbinned machine learning algorithm (multifold), which considers eight observables simultaneously in this first application. The unfolded cross sections are compared with calculations performed within the context of collinear or transverse-momentum-dependent factorization in quantum chromodynamics as well as Monte Carlo event generators.

Clindamycin adjunctive therapy for severe Staphylococcus aureus treatment evaluation (CASSETTE)-an open-labelled pilot randomized controlled trial.

BACKGROUND: Combination antibiotic therapy with an antitoxin agent, such as clindamycin, is included in some guidelines for severe, toxin-mediated Staphylococcus aureus infections. The evidence to support this practice is currently limited to in vitro, animal and observational human case-series data, with no previous randomized controlled trials (RCTs). OBJECTIVES: This pilot RCT aimed to determine the feasibility of conducting a clinical trial to examine if adjunctive clindamycin with standard therapy has greater efficacy than standard therapy alone for S. aureus infections. METHODS: We performed an investigator-initiated, open-label, multicentre, pilot RCT (ACTRN12617001416381p) in adults and children with severe S. aureus infections, randomized to standard antibiotic therapy with or without clindamycin for 7 days. RESULTS: Over 28 months, across nine sites, 127 individuals were screened and 34 randomized, including 11 children (32%). The primary outcome-number of days alive and free of systemic inflammatory response syndrome ≤14 days-was similar between groups: clindamycin (3 days [IQR 1-6]) versus standard therapy (4 days [IQR 0-8]). The 90 day mortality was 0% (0/17) in the clindamycin group versus 24% (4/17) in the standard therapy group. Secondary outcomes-microbiological relapse, treatment failure or diarrhoea-were similar between groups. CONCLUSIONS: As the first clinical trial assessing adjunctive clindamycin for S. aureus infections, this study indicates feasibility and that adults and children can be incorporated into one trial using harmonized endpoints, and there were no safety concerns. The CASSETTE trial will inform the definitive S. aureus Network Adaptive Platform (SNAP) trial, which includes an adjunctive clindamycin domain and participants with non-severe disease.

A plant-infecting subviral RNA associated with poleroviruses produces a subgenomic RNA which resists exonuclease XRN1 in vitro.

Subviral agents are nucleic acids which lack the features for classification as a virus. Tombusvirus-like associated RNAs (tlaRNAs) are subviral positive-sense, single-stranded RNAs that replicate autonomously, yet depend on a coinfecting virus for encapsidation and transmission. TlaRNAs produce abundant subgenomic RNA (sgRNA) upon infection. Here, we investigate how the well-studied tlaRNA, ST9, produces sgRNA and its function. We found ST9 is a noncoding RNA, due to its lack of protein coding capacity. We used resistance assays with eukaryotic Exoribonuclease-1 (XRN1) to investigate sgRNA production via incomplete degradation of genomic RNA. The ST9 3' untranslated region stalled XRN1 very near the 5' sgRNA end. Thus, the XRN family of enzymes drives sgRNA accumulation in ST9-infected tissue by incomplete degradation of ST9 RNA. This work suggests tlaRNAs are not just parasites of viruses with compatible capsids, but also mutually beneficial partners that influence host cell RNA biology.

The importance of animal welfare and Veterinary Services in a changing world.

Animal welfare is an essential component of the future of sustainable agriculture and the United Nations Sustainable Development Goals. There is growing global recognition of the importance of animal welfare, which must always be considered as part of the decision-making around food and nutrition security. Veterinary Services, encompassing public and private veterinarians and para-veterinarians, are custodians of animal welfare and key players in future actions to improve it. The welfare of animals is everyone's responsibility, from the individual farmer and practitioner to policymakers at the national and intergovernmental level. In this paper, after providing background information about current animal welfare issues and identifying animal welfare risks, the authors make a number of recommendations for action at the institutional and individual level. They do so because while the former is essential to generate change at scale and effective resourcing, the latter can create immediate action at a local level and drive change from the ground up. Without coordinated action from Veterinary Services, opportunities to improve animal welfare, alongside human and environmental health and well-being, may very well be lost, and animal welfare may fail to improve or even be at risk of decline.

L'accélération de la perturbation numérique depuis quelques années est spectaculaire, transformant tous les secteurs de l'économie, y compris la production animale, la santé animale et le bien-être des animaux. Les auteurs s'intéressent à certaines technologies numériques de pointe qui pourraient influencer le devenir des Services vétérinaires. Toutes ces technologies sont orientées données et trouvent leur illustration dans trois exemples qui se répartissent dans les catégories suivantes : a) les technologies sans fil et mobiles appliquées au suivi de la santé animale, à la surveillance des maladies, aux notifications des foyers et à l'échange d'informations ; b) les technologies avancées de traitement des données, dont les mégadonnées et l'analytique de données qui servent à mettre en évidence des structures sous-jacentes, à extraire des schémas prédictifs, à relever des corrélations et à générer d'autres informations ; c) des technologies prometteuses comme les applications « blockchain ¼ (chaînes de blocs) utilisées pour une gestion efficace et efficiente de diverses chaînes d'approvisionnement en intrants. Les auteurs résument brièvement les défis actuels associés au recours accru à ces technologies dans le secteur de la santé animale et en font ressortir certaines répercussions sur les Services vétérinaires. Les technologies numériques vont profondément affecter les modalités de la prestation des services de santé animale ainsi que la gestion des systèmes de santé animale. Par conséquent, il est crucial que les Services vétérinaires anticipent cette évolution et s'adaptent à la transformation numérique en cours. L'investissement dans les nouvelles technologies et les efforts visant à doter les professionnels vétérinaires actuels et futurs des compétences et des connaissances numériques nécessaires pour rester informés et au centre de l'innovation numérique dans le domaine de la santé animale doivent être les priorités des prochaines années.

El bienestar animal es un componente esencial de la agricultura sostenible del futuro y de los Objetivos de Desarrollo Sostenible fijados por las Naciones Unidas. Su importancia está cada vez más clara en todo el mundo. El bienestar de los animales debe ser siempre tenido en cuenta en los procesos decisorios que tocan a la seguridad alimentaria y nutricional. Los Servicios Veterinarios, que comprenden tanto a los veterinarios públicos y privados como al personal paraveterinario, son custodios del bienestar animal y agentes clave de toda acción futura encaminada a mejorarlo. Para lograr que el bienestar animal mejore desde ahora mismo, allí donde haga falta, y asegurar que siga un rumbo de constante progreso en el futuro, es preciso que todos los interlocutores, desde los productores y cuidadores hasta los planificadores de políticas de ámbito nacional e intergubernamental, hagan suya esta responsabilidad. Tras presentar información básica sobre los actuales problemas de bienestar animal y señalar los riesgos existentes en la materia, los autores formulan una serie de recomendaciones para actuar tanto desde las instituciones como a título individual, sabedores de que el primer nivel es fundamental para inducir cambios a gran escala y movilizar recursos eficazmente, mientras que el segundo puede generar inmediatamente acciones a escala local e impulsar desde ahí cambios en sentido ascendente. A falta de una labor coordinada de los Servicios Veterinarios, es muy posible que se pierdan oportunidades para mejorar el bienestar animal, junto con la salud y el bienestar de personas y ecosistemas, y que los niveles de bienestar animal no mejoren o, incluso, corran peligro de deterioro.

SARS-CoV-2 detection and genomic sequencing from hospital surface samples collected at UC Davis.

RATIONALE: There is little doubt that aerosols play a major role in the transmission of SARS-CoV-2. The significance of the presence and infectivity of this virus on environmental surfaces, especially in a hospital setting, remains less clear. OBJECTIVES: We aimed to analyze surface swabs for SARS-CoV-2 RNA and infectivity, and to determine their suitability for sequence analysis. METHODS: Samples were collected during two waves of COVID-19 at the University of California, Davis Medical Center, in COVID-19 patient serving and staff congregation areas. qRT-PCR positive samples were investigated in Vero cell cultures for cytopathic effects and phylogenetically assessed by whole genome sequencing. MEASUREMENTS AND MAIN RESULTS: Improved cleaning and patient management practices between April and August 2020 were associated with a substantial reduction of SARS-CoV-2 qRT-PCR positivity (from 11% to 2%) in hospital surface samples. Even though we recovered near-complete genome sequences in some, none of the positive samples (11 of 224 total) caused cytopathic effects in cultured cells suggesting this nucleic acid was either not associated with intact virions, or they were present in insufficient numbers for infectivity. Phylogenetic analysis suggested that the SARS-CoV-2 genomes of the positive samples were derived from hospitalized patients. Genomic sequences isolated from qRT-PCR negative samples indicate a superior sensitivity of viral detection by sequencing. CONCLUSIONS: This study confirms the low likelihood that SARS-CoV-2 contamination on hospital surfaces contains infectious virus, disputing the importance of fomites in COVID-19 transmission. Ours is the first report on recovering near-complete SARS-CoV-2 genome sequences directly from environmental surface swabs.

Pollen Loads of Flower Visitors to Açaí Palm (Euterpe oleracea) and Implications for Management of Pollination Services.

Understanding the functional roles of different pollinator species is crucial to the development of sustainable farming practices in pollinator-dependent crops. However, this can be challenging for crop plants in tropical regions with hyper-diverse pollinator communities. Here, we assess pollen loads of different insect visitors to inflorescences of açaí palm (Euterpe oleracea), the most important native crop in the Amazon estuary region. Flower-visiting insects were collected from pistillate (female) inflorescences at eight sites, including four managed floodplain forests and four plantations. Pollinator Importance Value Index (PIVI) and Relative Importance (RI) scores were calculated for common visitor taxa (≥ 10 individuals) using sum visit frequencies and median pollen loads. Pollen load analyses revealed that over seventy insect taxa, including bees, flies, beetles, wasps and ants, were effective vectors of E. oleracea pollen. Native bees, including both solitary and eusocial taxa, were the most efficient pollen vectors, with median pollen loads at least eight times higher than those of the next best insect group (flies). Insect pollen loads were at their highest between 0800 and 1300 hours, and four insect taxa had RI scores > 0.05, including two meliponine bees belonging to the Trigona genus (Trigona branneri Cockerell and Trigona pallens Fabricius) and two halictid bee genera (Augochloropsis and Dialictus). Our results suggest that native bees play an important role in açaí pollination and should be the primary focus of pollinator management in açaí production systems.

Phylogenetic classification of a group of self-replicating RNAs that are common in co-infections with poleroviruses.

Tombusvirus-like associated RNAs (tlaRNAs) are positive-sense single-stranded RNAs found in plants co-infected with viruses of the genus Polerovirus. TlaRNAs depend upon capsid proteins supplied in trans by the co-infecting polerovirus vector for transmission and intra-host systemic movement. Here, the full-length genomes of five tlaRNAs were determined using a combination of RT-PCR and next-generation sequencing, and evidence is provided for an additional tlaRNA associated with potato leafroll virus. Phylogenetic analyses based on conserved domains of the RdRp placed tlaRNAs as a monophyletic clade clustering with members of the family Tombusviridae and comprising three different subclades. Full-length clones of tlaRNAs from two of three subclades were confirmed to replicate autonomously, and each produces a subgenomic RNA during infection.

Adjunctive protein synthesis inhibitor antibiotics for toxin suppression in Staphylococcus aureus infections: a systematic appraisal.

Protein synthesis inhibitor antibiotics inhibit synthesis of new proteins, including exotoxins and other important virulence determinants in Staphylococcus aureus. A summary of the literature regarding the use of adjunctive protein synthesis inhibitors for toxin suppression in the setting of S. aureus infections is presented.

Determination of the strong coupling constant α s ( m Z ) in next-to-next-to-leading order QCD using H1 jet cross section measurements: H1 Collaboration.

The strong coupling constant α s is determined from inclusive jet and dijet cross sections in neutral-current deep-inelastic ep scattering (DIS) measured at HERA by the H1 collaboration using next-to-next-to-leading order (NNLO) QCD predictions. The dependence of the NNLO predictions and of the resulting value of α s ( m Z ) at the Z-boson mass m Z are studied as a function of the choice of the renormalisation and factorisation scales. Using inclusive jet and dijet data together, the strong coupling constant is determined to be α s ( m Z ) = 0.1157 ( 20 ) exp ( 29 ) th . Complementary, α s ( m Z ) is determined together with parton distribution functions of the proton (PDFs) from jet and inclusive DIS data measured by the H1 experiment. The value α s ( m Z ) = 0.1142 ( 28 ) tot obtained is consistent with the determination from jet data alone. The impact of the jet data on the PDFs is studied. The running of the strong coupling is tested at different values of the renormalisation scale and the results are found to be in agreement with expectations.

Double ovulation and occurrence of twinning in alpacas (Vicugna pacos).

Twin births are rare in alpacas despite the high incidence of double ovulation and are undesirable because they contribute to early and late pregnancy loss, abortion, and birth of nonviable neonates. The objective of the present study was to determine the incidence and outcome of twin pregnancy in double-ovulating alpacas by retrospective and prospective analysis. Data from double-ovulating females (N = 41) presented for pregnancy diagnosis were analyzed to determine pregnancy status at three stages after mating (14-16, 25-30, and 45-53 days). In a prospective study, adult reproductively sound alpacas (n = 21) were examined by ultrasonography to determine the incidence of multiple ovulations. A subset of those alpacas (n = 10) were euthanized either at 9 days (n = 5) or 14 days (n = 5) after a single mating and administration of GnRH to determine presence and number of embryos. A total of 31 cycles were included in the study to determine the incidence of multiple ovulations. In the retrospective study, twin pregnancies were identified between 25 and 30 days in 47.1% of double-ovulating females. There were more twins from bilateral ovulations (62.5%) than from unilateral ovulations (37.5%). Twin pregnancies were either reduced to a singleton (62.5%) or lost completely (37.5%). One set of twins remained viable until Day 52. In the prospective study, double ovulation occurred in 18.8% of the cycles. Two embryos were collected from two of the four double-ovulating females. In conclusion, twin conception is not rare in alpacas. A high rate of spontaneous reduction of twin pregnancies occurs before Day 45. However, a significant proportion of twin pregnancy may result in loss of both embryos. Determination of the number of ovulations (CL) at the time of early pregnancy diagnosis (14-16 days) should be an integral part of any pregnancy evaluation.

Musculoskeletal injury rates in Thoroughbred racehorses following local corticosteroid injection.

A retrospective cohort study was performed to compare the rates of musculoskeletal injury (MSI) in horses receiving local corticosteroid injection (LCI) with those that were untreated and those prior to treatment. Of the 1911 study horses, 392 had been treated. A LCI was defined as any injection of corticosteroid into or adjacent to a synovial structure, muscle, or tendon/ligament. A MSI was defined as any limb injury identified by a veterinarian, following which the horse did not race for at least 6 months, or was retired. Hazard ratios (HR) comparing hazard of injury following injection to that in non-injected horses and prior to injection were calculated using Cox proportional hazards models. At least one LCI was administered to 392 horses (20.5%; median 2, range 1-16). Most LCIs were performed bilaterally (70.9%) and intra-articularly into the carpal (49.7%) or fore fetlock (29.3%) joints. There were 219 MSIs of which carpal injuries (47%), fore fetlock (22%) and forelimb tendon injuries (16%) were the most common. The incidence rate of MSI in untreated horses and those prior to injection was 1.22 (95% CI 1.04-1.44) injuries/100 horse-months, and following LCI the hazard of MSI was greater (HR 4.83, 3.54-6.61, P<0.001). The hazard ratio returned to levels indistinguishable from before treatment after 49 days. The hazard of MSI in horses following second and subsequent LCIs in the data collection period was greater than in horses following their first LCI (HR 2.10, 1.31-3.36, P=0.002). There was a positive association between LCI and subsequent musculoskeletal injury rates which was most likely due to progression of the musculoskeletal condition which prompted treatment. Assuming horses that received LCI were at increased risk of MSI subsequently, any beneficial effects of the LCI were insufficient to counter this increased risk for at least 49 days after the injection.

Manual therapy, exercise therapy, or both, in addition to usual care, for osteoarthritis of the hip or knee. 2: economic evaluation alongside a randomized controlled trial.

OBJECTIVE: To evaluate the cost effectiveness of manual physiotherapy, exercise physiotherapy, and a combination of these therapies for patients with osteoarthritis of the hip or knee. METHODS: 206 Adults who met the American College of Rheumatology criteria for hip or knee osteoarthritis were included in an economic evaluation from the perspectives of the New Zealand health system and society alongside a randomized controlled trial. Resource use was collected using the Osteoarthritis Costs and Consequences Questionnaire. Quality-adjusted life years (QALYs) were calculated using the Short Form 6D. Willingness-to-pay threshold values were based on one to three times New Zealand's gross domestic product (GDP) per capita of NZ$ 29,149 (in 2009). RESULTS: All three treatment programmes resulted in incremental QALY gains relative to usual care. From the perspective of the New Zealand health system, exercise therapy was the only treatment to result in an incremental cost utility ratio under one time GDP per capita at NZ$ 26,400 (-$34,081 to $103,899). From the societal perspective manual therapy was cost saving relative to usual care for most scenarios studied. Exercise therapy resulted in incremental cost utility ratios regarded as cost effective but was not cost saving. For most scenarios combined therapy was not as cost effective as the two therapies alone. CONCLUSIONS: In this study, exercise therapy and manual therapy were more cost effective than usual care at policy relevant values of willingness-to-pay from both the perspective of the health system and society. Trial registration number Australian New Zealand Clinical Trials Registry ACTRN12608000130369.

Effects of vasectomy on seminal plasma alkaline phosphatase in male alpacas (Vicugña pacos).

Azoospermia is a common finding in male alpacas which present for infertility. The challenge is to differentiate azoospermia of testicular origin from non-testicular origin. In several species, alkaline phosphatase (AP) concentrations in seminal plasma have been used as a diagnostic marker of contributions of the testis and epididymis to the ejaculate. The purpose of this study was to determine whether AP assay could differentiate testicular from non-testicular azoospermia in male alpacas. An experimental model of bilateral outflow obstruction (pre-scrotal vasectomy) was used in 22 male alpacas, aged 2-9 years. No reproductive history was available. Animals were submitted for electroejaculation (EE) under general anaesthesia and vasectomy performed. Five weeks later, animals were submitted for EE. Vasectomy was not successful in one animal, which was removed from analysis. AP levels were compared in seminal plasma in the pre- and post-vasectomy samples. The mean ± SEM concentration of AP in pre-vasectomy seminal plasma was 504.29 ± 166.45 U/l (range 10-2910); the post-vasectomy levels were 252.48 ± 81.77 U/l (range 0-1640; p = 0.06). In 71.4% of animals, AP levels decreased, varying from 18% to 100% reduction. Results of this study suggest that AP is not produced exclusively by the testis and epididymis in alpacas and that AP assay is not a valid diagnostic test for determination of origin of azoospermia; the gold standard for diagnosis of origin of azoospermia remains testicular biopsy.

Manual therapy, exercise therapy, or both, in addition to usual care, for osteoarthritis of the hip or knee: a randomized controlled trial. 1: clinical effectiveness.

OBJECTIVE: To evaluate the clinical effectiveness of manual physiotherapy and/or exercise physiotherapy in addition to usual care for patients with osteoarthritis (OA) of the hip or knee. DESIGN: In this 2 × 2 factorial randomized controlled trial, 206 adults (mean age 66 years) who met the American College of Rheumatology criteria for hip or knee OA were randomly allocated to receive manual physiotherapy (n = 54), multi-modal exercise physiotherapy (n = 51), combined exercise and manual physiotherapy (n = 50), or no trial physiotherapy (n = 51). The primary outcome was change in the Western Ontario and McMaster osteoarthritis index (WOMAC) after 1 year. Secondary outcomes included physical performance tests. Outcome assessors were blinded to group allocation. RESULTS: Of 206 participants recruited, 193 (93.2%) were retained at follow-up. Mean (SD) baseline WOMAC score was 100.8 (53.8) on a scale of 0-240. Intention to treat analysis showed adjusted reductions in WOMAC scores at 1 year compared with the usual care group of 28.5 (95% confidence interval (CI) 9.2-47.8) for usual care plus manual therapy, 16.4 (-3.2 to 35.9) for usual care plus exercise therapy, and 14.5 (-5.2 to 34.1) for usual care plus combined exercise therapy and manual therapy. There was an antagonistic interaction between exercise therapy and manual therapy (P = 0.027). Physical performance test outcomes favoured the exercise therapy group. CONCLUSIONS: Manual physiotherapy provided benefits over usual care, that were sustained to 1 year. Exercise physiotherapy also provided physical performance benefits over usual care. There was no added benefit from a combination of the two therapies. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry ACTRN12608000130369.

Increased mortality risk in congestive heart failure patients with comorbid sleep apnoea: 10-year follow up.

We aimed to determine the mortality rates of a congestive heart failure (CHF) research cohort during a 10-year follow up and compare survival between those with CHF only (controls), CHF and central sleep apnoea, and CHF and obstructive sleep apnoea. There was a significant detriment of survival in patients with CHF/central sleep apnoea compared with both CHF/obstructive sleep apnoea patients (mean survival time difference 3.8 years, P = 0.005) and controls (mean survival time difference 4.0 years, P = 0.01).

An outbreak of severe iodine-deficiency goitre in a sheep flock in north-east Victoria.

BACKGROUND: Several outbreaks of goitre, considered to be related to iodine deficiency, occurred in sheep flocks throughout Victoria in 2010. OBJECTIVE: We describe one outbreak in Merino-Border Leicester-cross ewes and their lambs in north-east Victoria that appeared to be associated with increased rainfall and pasture growth, particularly during the preceding summer and autumn. RESULTS: The outbreak was characterised by a four-fold increase in neonatal lamb deaths and goitre, alopecia and poor skeletal development in the lambs. Most cases occurred in lambs born to 2-year-old crossbred ewes that had grazed long, lush perennial pastures throughout their entire pregnancy, whereas few cases occurred in mature crossbred or Merino ewes that had grazed shorter, annual pastures on hill country for 3 weeks in late pregnancy but were otherwise managed similarly. CONCLUSION: Existing recommendations for south-eastern Australia are that only spring-lambing ewes in iodine-deficient areas require iodine supplementation to prevent goitre in years with high autumn-winter rainfall. Aspects of this outbreak suggest that ewes lambing at other times of the year and grazing abundant pasture for prolonged periods may also require supplementation to prevent goitre, even if autumn-winter rainfall does not exceed previously established thresholds.

Cardioventilatory coupling and inter-breath variability in children referred for polysomnography.

Measures of respiratory variability including cardioventilatory coupling (CVC), were examined in 8 Down syndrome (DS), 4 Prader Willi syndrome (PWS) and 42 non-syndromic children (median age 7 years) referred for diagnostic polysomnography. Inspiratory onsets (I) and corresponding ECG R waves were determined, I-I, R-R and R-I intervals derived, and ventilatory frequency (f), standard deviation of f (SDf), coefficient of variation of f (CVf), median I-I and kurtosis and skewness I-I calculated. Proportional Shannon Entropy of the RI(-1) interval (SHα) was measured to quantitate CVC. SHα varied with age (p=0.02), oxygen saturation (p<0.05) and PWS diagnosis (p=0.001) in Stage 4 but not REM sleep. SDf and CVf varied with sleep state (p<0.00001) as did kurtosis I-I (p<0.0001) and skewness I-I (p=0.004). Ventilatory frequency decreased with age in REM sleep (p=0.03) and increased in obese children in REM (p=0.02) and Stage 4 sleep (p=0.004). Sleep state influences respiratory variability in children and CVC may confer a physiological advantage in children with PWS.