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Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging cause of human infection with invasive disease incidence and clinical manifestations comparable to the closely related species, Streptococcus pyogenes. Through systematic genomic analyses of 501 disseminated SDSE strains, we demonstrate extensive overlap between the genomes of SDSE and S. pyogenes. More than 75% of core genes are shared between the two species with one third demonstrating evidence of cross-species recombination. Twenty-five percent of mobile genetic element (MGE) clusters and 16 of 55 SDSE MGE insertion regions were shared across species. Assessing potential cross-protection from leading S. pyogenes vaccine candidates on SDSE, 12/34 preclinical vaccine antigen genes were shown to be present in >99% of isolates of both species. Relevant to possible vaccine evasion, six vaccine candidate genes demonstrated evidence of inter-species recombination. These findings demonstrate previously unappreciated levels of genomic overlap between these closely related pathogens with implications for streptococcal pathobiology, disease surveillance and prevention.

BACKGROUND: Streptococcus pyogenes, or group A Streptococcus (GAS), infections contribute to a high burden of disease in Aboriginal Australians, causing skin infections and immune sequelae such as rheumatic heart disease. Controlling skin infections in these populations has proven difficult, with transmission dynamics being poorly understood. We aimed to identify the relative contributions of impetigo and asymptomatic throat carriage to GAS transmission. METHODS: In this genomic analysis, we retrospectively applied whole genome sequencing to GAS isolates that were collected as part of an impetigo surveillance longitudinal household survey conducted in three remote Aboriginal communities in the Northern Territory of Australia between Aug 6, 2003, and June 22, 2005. We included GAS isolates from all throats and impetigo lesions of people living in two of the previously studied communities. We classified isolates into genomic lineages based on pairwise shared core genomes of more than 99% with five or fewer single nucleotide polymorphisms. We used a household network analysis of epidemiologically and genomically linked lineages to quantify the transmission of GAS within and between households. FINDINGS: We included 320 GAS isolates in our analysis: 203 (63%) from asymptomatic throat swabs and 117 (37%) from impetigo lesions. Among 64 genomic lineages (encompassing 39 emm types) we identified 264 transmission links (involving 93% of isolates), for which the probable source was asymptomatic throat carriage in 166 (63%) and impetigo lesions in 98 (37%). Links originating from impetigo cases were more frequent between households than within households. Households were infected with GAS for a mean of 57 days (SD 39 days), and once cleared, reinfected 62 days (SD 40 days) later. Increased household size and community presence of GAS and scabies were associated with slower clearance of GAS. INTERPRETATION: In communities with high prevalence of endemic GAS-associated skin inf

BACKGROUND: Preterm birth is the greatest cause of death up to five years of age and an important contributor to lifelong disability. There is increasing evidence that a meaningful proportion of early births may be prevented, but widespread introduction of effective preventive strategies will require financial support. AIMS: This study estimated the economic cost to the Australian government of preterm birth, up to 18 years of age. MATERIALS AND METHODS: A decision-analytic model was developed to estimate the costs of preterm birth in Australia for a hypothetical cohort of 314 814 children, the number of live births in 2016. Costs to Australia's eight jurisdictions included medical expenditures and additional costs to educational services. RESULTS: The total cost of preterm birth to the Australian government associated with the annual cohort was estimated at $1.413 billion (95% CI 1047-1781). Two-thirds of the costs were borne by healthcare services during the newborn period and one-quarter of the costs by educational services providing special assistance. For each child, the costs were highest for those born at the earliest survivable gestational age, but the larger numbers of children born at later gestational ages contributed heavily to the overall economic burden. CONCLUSION: Preterm birth leaves many people with lifelong disabilities and generates a significant economic burden to society. The costs extend beyond those to the healthcare system and include additional educational needs. Assessments of economic costs should inform economic evaluations of interventions aimed at the prevention or treatment of preterm birth.

In photosynthesis, solar energy is absorbed and converted into chemical energy. Chlorophyll embedded in proteins absorb light and transfer excitation energy to reaction centers where charge separation occurs. However, the solar flux incident on photosynthetic organisms is highly variable, requiring complex feedback systems to regulate the excitation pressure on reaction centers and prevent excess absorbed energy from causing damage. During periods of transient high light, excess absorbed energy is dissipated as heat. This is routinely observed as the quenching of chlorophyll fluorescence, and often broadly referred to as non-photochemical quenching (NPQ). Understanding the mechanisms through which photosynthetic systems dissipate excess energy and regulate excitation pressure in response to variable light conditions requires extensive quantitative modeling of the photosynthetic system and energy dissipation to interpret experimental observations. This review discusses efforts to model energy dissipation, or quenching, in Arabidopsis thaliana and their connections to models of regulatory systems that control quenching. We begin with a review of theory used to describe energy transfer and experimental data obtained to construct energy transfer models of the photosynthetic antenna system that underlie the interpretation of chlorophyll fluorescence quenching. Second, experimental evidence leading to proposed molecular mechanisms of quenching and the implications for modeling are discussed. The initial incorporation of depictions of proposed mechanisms into quantitative energy transfer models is reviewed. Finally, the necessity of connecting energy transfer models that include molecular models of quenching mechanisms with regulatory models is discussed.

In photosynthesis, solar energy is absorbed and converted into chemical energy. Chlorophyll embedded in proteins absorb light and transfer excitation energy to reaction centers where charge separation occurs. However, the solar flux incident on photosynthetic organisms is highly variable, requiring complex feedback systems to regulate the excitation pressure on reaction centers and prevent excess absorbed energy from causing damage. During periods of transient high light, excess absorbed energy is dissipated as heat. This is routinely observed as the quenching of chlorophyll fluorescence, and often broadly referred to as non-photochemical quenching (NPQ). Understanding the mechanisms through which photosynthetic systems dissipate excess energy and regulate excitation pressure in response to variable light conditions requires extensive quantitative modeling of the photosynthetic system and energy dissipation to interpret experimental observations. This review discusses efforts to model energy dissipation, or quenching, in Arabidopsis thaliana and their connections to models of regulatory systems that control quenching. We begin with a review of theory used to describe energy transfer and experimental data obtained to construct energy transfer models of the photosynthetic antenna system that underlie the interpretation of chlorophyll fluorescence quenching. Second, experimental evidence leading to proposed molecular mechanisms of quenching and the implications for modeling are discussed. The initial incorporation of depictions of proposed mechanisms into quantitative energy transfer models is reviewed. Finally, the necessity of connecting energy transfer models that include molecular models of quenching mechanisms with regulatory models is discussed.

OBJECTIVES: To understand complaint risk among mental health practitioners compared with physical health practitioners. DESIGN: Retrospective cohort study, using incidence rate ratios (IRRs) to analyse complaint risk and a multivariate regression model to identify predictors of complaints. SETTING: National study using complaints data from health regulators in Australia. PARTICIPANTS: All psychiatrists and psychologists ('mental health practitioners') and all physicians, optometrists, physiotherapists, osteopaths and chiropractors ('physical health practitioners') registered to practice in Australia between 2011 and 2016. OUTCOME MEASURES: Incidence rates, source and nature of complaints to regulators. RESULTS: In total, 7903 complaints were lodged with regulators over the 6-year period. Most complaints were lodged by patients and their families. Mental health practitioners had a complaint rate that was more than twice that of physical health practitioners (complaints per 1000 practice years: psychiatrists 119.1 vs physicians 48.0, p<0.001; psychologists 21.9 vs other allied health 7.5, p<0.001). Their risk of complaints was especially high in relation to reports, records, confidentiality, interpersonal behaviour, sexual boundary breaches and the mental health of the practitioner. Among mental health practitioners, male practitioners (psychiatrists IRR: 1.61, 95% CI 1.39 to 1.85; psychologists IRR: 1.85, 95% CI 1.65 to 2.07) and older practitioners (≥65 years compared with 36-45 years: psychiatrists IRR 2.37, 95% CI 1.95 to 2.89; psychologists IRR 1.78, 95% CI 1.47 to 2.14) were at increased risk of complaints. CONCLUSIONS: Mental health practitioners were more likely to be the subject of complaints than physical health practitioners. Areas of increased risk are related to professional ethics, communication skills and the health of mental health practitioners themselves. Further research could usefully explore whether addressing these risk factors through training

BACKGROUND: Compared with other doctors, surgeons are at an increased risk of medicolegal events, including patient complaints and negligence claims. This retrospective study aimed to describe the frequency and nature of complaints involving surgeons compared with physicians. METHODS: We assembled a national data set of complaints about surgeons and physicians lodged with medical regulators in Australia from 2011 to 2016. We classified the complaints into 19 issues across four domains: treatment and procedures, other performance, professional conduct and health. We assessed differences in complaint risk using incidence rate ratios (IRRs). Finally, we used a multivariate model to identify predictors of complaints among surgeons. RESULTS: The rate of complaints was 2.3 times higher for surgeons than physicians (112 compared with 48 complaints per 1000 practice years, P < 0.001). Two-fifths (41%) of the higher rate of complaints among surgeons was attributable to issues other than treatments and procedures, including fees (IRR = 2.68), substance use (IRR = 2.10), communication (IRR = 1.98) and interpersonal behaviour (IRR = 1.92). Male surgeons were at a higher risk of complaints, as were specialists in orthopaedics, plastic surgery and neurosurgery. DISCUSSION: Surgeons are more than twice as likely to attract complaints as their physician peers. This elevated risk arises partly from involvement in surgical procedures and treatments, but also reflects wider concerns about interpersonal skills, professional ethics and substance use. Improved understanding of these patterns may assist efforts to reduce harm and support safe practise.

OBJECTIVE: To describe the frequency, nature and outcomes of reports about health practitioners made by their treating practitioners under Australia's new mandatory reporting system. DESIGN AND SETTING: Retrospective case file review and analysis of treating practitioner reports received by the Australian Health Practitioner Regulation Agency between 1 November 2011 and 31 January 2013, and of the outcomes of the completed investigations of these reports to November 2014. MAIN OUTCOME MEASURES: Characteristics of treating practitioners and reported practitioners; nature of the care relationship; grounds for report; regulatory action taken in response to report. RESULTS: Of 846 mandatory reports about medical practitioners, 64 (8%) were by treating practitioners. A minority of reports (14 of 64) were made by a practitioner-patient's regular care provider; most (50 of 64) arose from an encounter during an acute admission, first assessment or informal corridor consultation. The reported practitioner-patients were typically being treated for mental illness (28 of 64) or substance misuse (25 of 64). In 80% of reports (50 of 64), reporters described practitioner-patients who exhibited diminished insight, dishonesty, disregard for patient safety, or an intention to self-harm. CONCLUSIONS: The nature and circumstances of the typical treating practitioner report challenge assumptions expressed in policy debates about the merits of the new mandatory reporting law. Mandatory reports by treating practitioners are rare. The typical report is about substance misuse or mental illness, is made by a doctor who is not the patient's regular care provider, and identifies an impediment to safely managing the risk posed by the practitioner-patient within the confines of the treating relationship.

OBJECTIVE: To explore the views and experiences of health sector professionals in Australia regarding a new national law requiring treating practitioners to report impaired health practitioners whose impairments came to their attention in the course of providing treatment. METHOD: We conducted a thematic analysis of in-depth, semistructured interviews with 18 health practitioners and 4 medicolegal advisors from Australia's 6 states, each of whom had experience with applying the new mandatory reporting law in practice. RESULTS: Interviewees perceived the introduction of a mandatory reporting law as a response to failures of the profession to adequately protect the public from impaired practitioners. Mandatory reporting of impaired practitioners was reported to have several benefits: it provides treating practitioners with a 'lever' to influence behaviour, offers protections to those who make reports and underscores the duty to protect the public from harm. However, many viewed it as a blunt instrument that did not sufficiently take account of the realities of clinical practice. In deciding whether or not to make a report, interviewees reported exercising clinical discretion, and being influenced by three competing considerations: protection of the public, confidentiality of patient information and loyalty to their profession. CONCLUSIONS: Competing ethical considerations limit the willingness of Australian health practitioners to report impaired practitioner-patients under a mandatory reporting law. Improved understanding and implementation of the law may bolster the public protection offered by mandatory reports, reduce the need to breach practitioner-patient confidentiality and help align the law with the loyalty that practitioners feel to support, rather than punish, their impaired colleagues.

Inbred strains of mice are powerful models for understanding human pregnancy complications. For example, the exclusive mating of CBA/J females to DBA/2J males increases fetal resorption to 20-35% with an associated decline in placentation and maintenance of maternal Th1 immunity. More recently other complications of pregnancy, IUGR and preeclampsia, have been reported in this model. The aim of this study was to qualify whether the CBA/CaH substrain female can substitute for CBA/J to evoke a phenotype of embryonic/fetal mortality and IUGR. (CBA/CaH × DBA/2J) F1 had significantly higher embryonic/fetal mortality mortality (p = 0.0063), smaller fetuses (p < 0.0001), and greater prevalence of IUGR (<10th percentile; 47% vs 10%) than (CBA/CaH × Balb/c) F1. Placentae from IUGR fetuses from all mating groups were significantly smaller (p < 0.0001) with evidence of thrombosis and fibrosis when compared to normal-weight fetuses ( > 10th percentile). In addition, placentae of "normal-weight" (CBA/CaH × DBA/2J) F1 were significantly smaller (p < 0.0006) with a greater proportion of labyrinth (p = 0.0128) and an 11-fold increase in F4/80 + macrophage infiltration (p < 0.0001) when compared to placentae of (CBA/CaH × Balb/c) F1. In conclusion, the embryonic/fetal mortality and IUGR phenotype is not exclusive to CBA/J female mouse, and CBA/CaH females can be substituted to provide a model for the assessment of novel therapeutics.

OBJECTIVES: To examine interhospital variation in rates of induction of labour (IOL) to identify potential targets to reduce high rates of practice variation. DESIGN: Population-based record linkage cohort study. SETTING: New South Wales, Australia, 2010-2011. PARTICIPANTS: All women with live births of ≥24 weeks gestation in 72 hospitals. PRIMARY OUTCOME MEASURE: Variation in hospital IOL rates adjusted for differences in case-mix, according to 10 mutually exclusive groups derived from the Robson caesarean section classification; groups were categorised by parity, plurality, fetal presentation, prior caesarean section and gestational age. RESULTS: The overall IOL rate was 26.7% (46,922 of 175,444 maternities were induced), ranging from 9.7% to 41.2% (IQR 21.8-29.8%) between hospitals. Nulliparous and multiparous women at 39-40 weeks gestation with a singleton cephalic birth were the greatest contributors to the overall IOL rate (23.5% and 20.2% of all IOL respectively), and had persisting high unexplained variation after adjustment for case-mix (adjusted hospital IOL rates ranging from 11.8% to 44.9% and 7.1% to 40.5%, respectively). In contrast, there was little variation in interhospital IOL rates among multiparous women with a singleton cephalic birth at ≥41 weeks gestation, women with singleton non-cephalic pregnancies and women with multifetal pregnancies. CONCLUSIONS: 7 of the 10 groups showed high or moderate unexplained variation in interhospital IOL rates, most pronounced for women at 39-40 weeks gestation with a singleton cephalic birth. Outcomes associated with divergent practice require determination, which may guide strategies to reduce practice variation.

Taking action to protect patients from impaired colleagues is a long-standing ethical and professional obligation. In 2010, this responsibility was codified in law with the introduction, across Australia, of a new mandatory reporting regimen. While several concerns remain to be addressed, mandatory reporting has the potential not only to reinforce the primacy of patient safety, but also to open internal dialogue about the profession's response to concerns about practitioner health and well-being. Four years after the introduction of the scheme, key challenges include ensuring the reporting threshold is appropriately defined and clearly understood, improving access to evidence-based health programmes for practitioners, and strengthening upstream protections to prevent and minimise impairment at its roots.

Placental development requires coordinated angiogenesis regulated by multiple factors including angiopoietins. Previously we demonstrated that the concentration of angiopoietin-2 (Ang-2) in the sera of women rises markedly in pregnancy in early gestation. This increase is reduced in pregnancies subsequently complicated by intrauterine growth restriction (IUGR). We now show that the concentration of Ang-2, but not Ang-1, in maternal serum is increased during normal pregnancy, peaking at the end of the first trimester. We also demonstrate that a key source of the elevated Ang-2 levels during pregnancy is decidual endothelial cells (DECs) but not cytotrophoblasts. Secretion of Ang-2 by DECs relies on the release from intracellular stores and the synthesis of new Ang-2 protein and is regulated by serum factors at a translational level. Further studies on the role of Ang-2 during pregnancy are warranted as well as the evaluation of Ang-2 as a marker to predict adverse pregnancy outcomes. © 2012.

Placental development requires coordinated angiogenesis regulated by multiple factors including angiopoietins. Previously we demonstrated that the concentration of angiopoietin-2 (Ang-2) in the sera of women rises markedly in pregnancy in early gestation. This increase is reduced in pregnancies subsequently complicated by intrauterine growth restriction (IUGR). We now show that the concentration of Ang-2, but not Ang-1, in maternal serum is increased during normal pregnancy, peaking at the end of the first trimester. We also demonstrate that a key source of the elevated Ang-2 levels during pregnancy is decidual endothelial cells (DECs) but not cytotrophoblasts. Secretion of Ang-2 by DECs relies on the release from intracellular stores and the synthesis of new Ang-2 protein and is regulated by serum factors at a translational level. Further studies on the role of Ang-2 during pregnancy are warranted as well as the evaluation of Ang-2 as a marker to predict adverse pregnancy outcomes. © 2012.

The aim of this study was to investigate whether maternal serum levels of angiopoietin-2 (Ang-2) and pregnancy-associated plasma protein A (PAPP-A) are associated with subsequent intrauterine growth restriction (IUGR). Ang-2 was measured in 29 nonpregnant and 44 pregnant women at 10-13 weeks of gestation. The median concentration of Ang-2 was 26.61 ng/ml in normal pregnant women compared with 1.71 ng/ml in nonpregnant controls (P < 0.01). Women who subsequently developed severe IUGR had lower levels of Ang-2 compared with normal pregnant controls (P < 0.01). PAPP-A levels were similar in all pregnant groups. These findings suggest that Ang-2 should be evaluated for its ability to predict pregnancies that later are affected by IUGR. © RCOG 2007 BJOG An International Journal of Obstetrics and Gynaecology.

The aim of this study was to investigate whether maternal serum levels of angiopoietin-2 (Ang-2) and pregnancy-associated plasma protein A (PAPP-A) are associated with subsequent intrauterine growth restriction (IUGR). Ang-2 was measured in 29 nonpregnant and 44 pregnant women at 10-13 weeks of gestation. The median concentration of Ang-2 was 26.61 ng/ml in normal pregnant women compared with 1.71 ng/ml in nonpregnant controls (P < 0.01). Women who subsequently developed severe IUGR had lower levels of Ang-2 compared with normal pregnant controls (P < 0.01). PAPP-A levels were similar in all pregnant groups. These findings suggest that Ang-2 should be evaluated for its ability to predict pregnancies that later are affected by IUGR. © RCOG 2007 BJOG An International Journal of Obstetrics and Gynaecology.