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In this study, two virus concentration methods, namely Adsorption-Extraction (AE) and Nanotrap® Magnetic Virus Particles (NMVP) along with commercially available extraction kits were used to quantify endogenous pepper mild mottle virus (PMMoV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in nucleic acid extracted from 48 wastewater samples collected over six events from eight wastewater treatment plants (WWTPs). The main aim was to determine which workflow (i.e., concentration and extraction methods) produces greater concentrations of endogenous PMMoV and SARS-CoV-2 gene copies (GC) in comparison with each other. Turbidity and total suspended solids (TSS) of wastewater samples within and among the eight WWTPs were highly variable (41-385 NTU and 77-668 mg/L TSS). In 58 % of individual wastewater samples, the log 10 GC concentrations of PMMoV were greater by NMVP workflow compared to AE workflow. Paired measurements of PMMoV GC/10 mL from AE and NMVP across all 48 wastewater samples were weakly correlated (r = 0.455, p = 0.001) and demonstrated a poor linear relationship (r 2 = 0.207). The log 10 GC concentrations of SARS-CoV-2 in 69 % of individual samples were greater by AE workflow compared to NMVP workflow. In contrast to PMMoV, the AE and NMVP derived SARS-CoV-2 GC counts were strongly correlated (r = 0.859, p < 0.001) and demonstrated a strong linear relationship (r 2 = 0.738). In general, the PMMoV GC achieved by the NMVP workflow decreased with increasing turbidity, but the PMMoV GC by the AE workflow did not appear to be as sensitive to either turbidity or TSS levels. These findings suggest that wastewater sample turbidity or suspended solids concentration, and the intended target for analysis should be considered when validating an optimal workflow for wastewater surveillance of viruses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Breastfeeding has many health, economic and environmental benefits for both the infant and pregnant individual. Due to these benefits, the World Health Organization and Health Canada recommend exclusive breastfeeding for the first six months of life. The purpose of this study is to examine the prevalence of exclusive and any breastfeeding in Canada for at least six months, and factors associated with breastfeeding cessation prior to six months., Methods: We performed a secondary analysis of breastfeeding-related questions asked on the cross-sectional 2017-2018 Canadian Community Health Survey. Our sample comprised 5,392 females aged 15-55 who had given birth in the five years preceding the survey. Descriptive statistics were carried out to assess the proportion of females exclusively breastfeeding and doing any breastfeeding for at least six months by demographic and behavioural factors. We also assessed, by baby's age, trends in the introduction of solids and liquids, breastfeeding cessation and the reasons females stopped breastfeeding. Multivariate log binominal regression was used to examine the association between breastfeeding at six months and selected maternal characteristics hypothesized a priori to be associated with breastfeeding behaviour., Results: Overall, for at least six months, 35.6% (95% confidence interval (CI): 33.3%-37.8%) of females breastfed exclusively and 62.2% (95% CI: 60.0%-64.4%) did any breastfeeding. The largest decline in exclusive breastfeeding occurred in the first month. Factors most strongly associated with breastfeeding for at least six months were having a bachelor's or higher degree, having a normal body mass index, being married and daily co-sleeping. Insufficient milk supply was given as the most common reason for breastfeeding cessation irrespective of when females stopped breastfeeding., Conclusion: Six-month exclusive breastfeeding rates in Canada remain below targets set by the World Health Assembly. Continued efforts, including investment in monitoring of breastfeeding rates, are needed to promote and support exclusive breastfeeding, especially among females vulnerable to early cessation., (© 2023. Crown.)

We compared reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and RT digital PCR (RT-dPCR) platforms for the trace detection of SARS-CoV-2 RNA in low-prevalence COVID-19 locations in Queensland, Australia, using CDC N1 and CDC N2 assays. The assay limit of detection (ALOD), PCR inhibition rates, and performance characteristics of each assay, along with the positivity rates with the RT-qPCR and RT-dPCR platforms, were evaluated by seeding known concentrations of exogenous SARS-CoV-2 in wastewater. The ALODs using RT-dPCR were approximately 2-5 times lower than those using RT-qPCR. During sample processing, the endogenous ( n = 96) and exogenous ( n = 24) SARS-CoV-2 wastewater samples were separated, and RNA was extracted from both wastewater eluates and pellets (solids). The RT-dPCR platform demonstrated a detection rate significantly greater than that of RT-qPCR for the CDC N1 and CDC N2 assays in the eluate (N1, p = 0.0029; N2, p = 0.0003) and pellet (N1, p = 0.0015; N2, p = 0.0067) samples. The positivity results also indicated that for the analysis of SARS-CoV-2 RNA in wastewater, including the eluate and pellet samples may further increase the detection sensitivity using RT-dPCR., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

During the coronavirus disease 2019 (COVID-19) pandemic, wastewater surveillance has become an important tool for monitoring the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within communities. In particular, reverse transcription-quantitative PCR (RT-qPCR) has been used to detect and quantify SARS-CoV-2 RNA in wastewater, while monitoring viral genome mutations requires separate approaches such as deep sequencing. A high throughput sequencing platform (ATOPlex) that uses a multiplex tiled PCR-based enrichment technique has shown promise in detecting variants of concern (VOC) while also providing virus quantitation data. However, detection sensitivities of both RT-qPCR and sequencing can be impacted through losses occurring during sample handling, virus concentration, nucleic acid extraction, and RT-qPCR. Therefore, process limit of detection (PLOD) assessments are required to estimate the gene copies of target molecule to attain specific probability of detection. In this study, we compare the PLOD of four RT-qPCR assays (US CDC N1 and N2, China CDC N and ORF1ab) for detection of SARS-CoV-2 to that of ATOPlex sequencing by seeding known concentrations of gamma-irradiated SARS-CoV-2 into wastewater. Results suggest that among the RT-qPCR assays, US CDC N1 was the most sensitive, especially at lower SARS-CoV-2 seed levels. However, when results from all RT-qPCR assays were combined, it resulted in greater detection rates than individual assays, suggesting that application of multiple assays is better suited for the trace detection of SARS-CoV-2 from wastewater samples. Furthermore, while ATOPlex offers a promising approach to SARS-CoV-2 wastewater surveillance, this approach appears to be less sensitive compared to RT-qPCR under the experimental conditions of this study, and may require further refinements. Nonetheless, the combination of RT-qPCR and ATOPlex may be a powerful tool to simultaneously detect/quantify SARS-CoV-2 RNA and monitor emerging VOC in wastewater samples., (Copyright © 2022. Published by Elsevier Ltd.)

Monitoring SARS-CoV-2 RNA in sewer systems, upstream of a wastewater treatment plant, is an effective approach for understanding potential COVID-19 transmission in communities with higher spatial resolutions. Passive sampling devices provide a practical solution for frequent sampling within sewer networks where the use of autosamplers is not feasible. Currently, the design of upstream sampling is impeded by limited understanding of the fate of SARS-CoV-2 RNA in sewers and the sensitivity of passive samplers for the number of infected individuals in a catchment. In this study, passive samplers containing electronegative membranes were applied for at least 24-h continuous sampling in sewer systems. When monitoring SARS-CoV-2 along a trunk sewer pipe, we found RNA signals decreased proportionally to increasing dilutions, with non-detects occurring at the end of pipe. The passive sampling membranes were able to detect SARS-CoV-2 shed by >2 COVID-19 infection cases in 10,000 people. Moreover, upstream monitoring in multiple sewersheds using passive samplers identified the emergence of SARS-CoV-2 in wastewater one week ahead of clinical reporting and reflected the spatiotemporal spread of a COVID-19 cluster within a city. This study provides important information to guide the development of wastewater surveillance strategies at catchment and subcatchment levels using different sampling techniques., (Copyright © 2022. Published by Elsevier Ltd.)

Interleukin-34 (IL-34) is a cytokine that supports the viability and differentiation of macrophages. An important cytokine for the development of epidermal immunity, IL-34, is present and plays a role in the immunity of the oral environment. IL-34 has been linked to inflammatory periodontal diseases, which involve innate phagocytes, including macrophages. Whether IL-34 can alter the ability of macrophages to effectively interact with oral microbes is currently unclear. Using macrophages derived from human blood monocytes with either the canonical cytokine colony-stimulating factor (CSF)1 or IL-34, we compared the ability of the macrophages to phagocytose, kill, and respond through the production of cytokines to the periodontal keystone pathogen Porphyromonas gingivalis. While macrophages derived from both cytokines were able to engulf the bacterium equally, IL-34-derived macrophages were much less capable of killing internalized P. gingivalis. Of the macrophage cell surface receptors known to interact with P. gingivalis, dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin was found to have the largest variation between IL-34- and CSF1-derived macrophages. We also found that upon interaction with P. gingivalis, IL-34-derived macrophages produced significantly less of the neutrophil chemotactic factor IL-8 than macrophages derived in the presence of CSF1. Mechanistically, we identified that the levels of IL-8 corresponded with P. gingivalis survival and dephosphorylation of the major transcription factor NF-κB p65. Overall, we found that macrophages differentiated in the presence of IL-34, a dominant cytokine in the oral gingiva, have a reduced ability to kill the keystone pathogen P. gingivalis and may be susceptible to specific bacteria-mediated cytokine modification., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

On the 26th of November 2021, the World Health Organization (WHO) designated the newly detected B.1.1.529 lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the Omicron Variant of Concern (VOC). The genome of the Omicron VOC contains more than 50 mutations, many of which have been associated with increased transmissibility, differing disease severity, and potential to evade immune responses developed for previous VOCs such as Alpha and Delta. In the days since the designation of B.1.1.529 as a VOC, infections with the lineage have been reported in countries around the globe and many countries have implemented travel restrictions and increased border controls in response. We putatively detected the Omicron variant in an aircraft wastewater sample from a flight arriving to Darwin, Australia from Johannesburg, South Africa on the 25th of November 2021 via positive results on the CDC N1, CDC N2, and del(69-70) RT-qPCR assays per guidance from the WHO. The Australian Northern Territory Health Department detected one passenger onboard the flight who was infected with SARS-CoV-2, which was determined to be the Omicron VOC by sequencing of a nasopharyngeal swab sample. Subsequent sequencing of the aircraft wastewater sample using the ARTIC V3 protocol with Nanopore and ATOPlex confirmed the presence of the Omicron variant with a consensus genome that clustered with the B.1.1.529 BA.1 sub-lineage. Our detection and confirmation of a single onboard Omicron infection via aircraft wastewater further bolsters the important role that aircraft wastewater can play as an independent and unintrusive surveillance point for infectious diseases, particularly coronavirus disease 2019., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Effective wastewater surveillance of SARS-CoV-2 RNA requires the rigorous characterization of the limit of detection resulting from the entire sampling process - the process limit of detection (PLOD). Yet to date, no studies have gone beyond quantifying the assay limit of detection (ALOD) for RT-qPCR or RT-dPCR assays. While the ALOD is the lowest number of gene copies (GC) associated with a 95% probability of detection in a single PCR reaction, the PLOD represents the sensitivity of the method after considering the efficiency of all processing steps (e.g., sample handling, concentration, nucleic acid extraction, and PCR assays) to determine the number of GC in the wastewater sample matrix with a specific probability of detection. The primary objective of this study was to estimate the PLOD resulting from the combination of primary concentration and extraction with six SARS-CoV-2 assays: five RT-qPCR assays (US CDC N1 and N2, China CDC N and ORF1ab (CCDC N and CCDC ORF1ab), and E&#95;Sarbeco RT-qPCR, and one RT-dPCR assay (US CDC N1 RT-dPCR) using two models (exponential survival and cumulative Gaussian). An adsorption extraction (AE) concentration method (i.e., virus adsorption on membrane and the RNA extraction from the membrane) was used to concentrate gamma-irradiated SARS-CoV-2 seeded into 36 wastewater samples. Overall, the US CDC N1 RT-dPCR and RT-qPCR assays had the lowest ALODs (< 10 GC/reaction) and PLODs (<3,954 GC/50 mL; 95% probability of detection) regardless of the seeding level and model used. Nevertheless, consistent amplification and detection rates decreased when seeding levels were < 2.32 × 10 3 GC/50 mL even for US CDC N1 RT-qPCR and RT-dPCR assays. Consequently, when SARS-CoV-2 RNA concentrations are expected to be low, it may be necessary to improve the positive detection rates of wastewater surveillance by analyzing additional field and RT-PCR replicates. To the best of our knowledge, this is the first study to assess the SARS-CoV-2 PLOD for wastewater and provides important insights on the analytical limitations for trace detection of SARS-CoV-2 RNA in wastewater., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

The European rabbit (Oryctolagus cuniculus) is one of the most devastating invasive species in Australia. Since the 1950s, myxoma virus (MYXV) and rabbit haemorrhagic disease virus (RHDV) have been used to manage overabundant rabbit populations. Resistance to MYXV was observed within a few years of the release. More recently, resistance to lethal RHDV infection has also been reported, undermining the efficiency of landscape-scale rabbit control. Previous studies suggest that genetic resistance to lethal RHDV infection may differ locally between populations, yet the mechanisms of genetic resistance remain poorly understood. Here, we used genotyping by sequencing (GBS) data representing a reduced representation of the genome, to investigate Australian rabbit populations. Our aims were to understand the relationship between populations and identify possible genomic signatures of selection for RHDV resistance. One population we investigated had previously been reported to show levels of resistance to lethal RHDV infection. This population was compared to three other populations with lower or no previously reported RHDV resistance. We identified a set of novel candidate genes that could be involved in host-pathogen interactions such as virus binding and infection processes. These genes did not overlap with previous studies on RHDV resistance carried out in different rabbit populations, suggesting that multiple mechanisms are feasible. These findings provide useful insights into the different potential mechanisms of genetic resistance to RHDV virus which will inform future functional studies in this area., (© 2021 Wiley-VCH GmbH.)

Wastewater surveillance for pathogens using reverse transcription-polymerase chain reaction (RT-PCR) is an effective and resource-efficient tool for gathering community-level public health information, including the incidence of coronavirus disease-19 (COVID-19). Surveillance of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) in wastewater can potentially provide an early warning signal of COVID-19 infections in a community. The capacity of the world's environmental microbiology and virology laboratories for SARS-CoV-2 RNA characterization in wastewater is increasing rapidly. However, there are no standardized protocols or harmonized quality assurance and quality control (QA/QC) procedures for SARS-CoV-2 wastewater surveillance. This paper is a technical review of factors that can cause false-positive and false-negative errors in the surveillance of SARS-CoV-2 RNA in wastewater, culminating in recommended strategies that can be implemented to identify and mitigate some of these errors. Recommendations include stringent QA/QC measures, representative sampling approaches, effective virus concentration and efficient RNA extraction, PCR inhibition assessment, inclusion of sample processing controls, and considerations for RT-PCR assay selection and data interpretation. Clear data interpretation guidelines (e.g., determination of positive and negative samples) are critical, particularly when the incidence of SARS-CoV-2 in wastewater is low. Corrective and confirmatory actions must be in place for inconclusive results or results diverging from current trends (e.g., initial onset or reemergence of COVID-19 in a community). It is also prudent to perform interlaboratory comparisons to ensure results' reliability and interpretability for prospective and retrospective analyses. The strategies that are recommended in this review aim to improve SARS-CoV-2 characterization and detection for wastewater surveillance applications. A silver lining of the COVID-19 pandemic is that the efficacy of wastewater surveillance continues to be demonstrated during this global crisis. In the future, wastewater should also play an important role in the surveillance of a range of other communicable diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

The oral cavity is a complex environment constantly exposed to antigens from food and the oral microbiota. Innate immune cells play an essential role in maintaining health and homeostasis in the oral environment. However, these cells also play a significant role in disease progression. This review will focus on two innate phagocytes in the oral cavity: macrophages and neutrophils, and examine their roles during homeostasis and disease development, with a focus on periodontal disease and cancer. Macrophages have a well-known ability to polarize and be activated towards a variety of phenotypes. Several studies have found that macrophages' polarization changes can play an essential role in maintaining health in the oral cavity and contribute to disease. Recent data also finds that neutrophils display phenotypic heterogeneity in the oral cavity. In both cases, we focus on what is known about how these cellular changes alter these immune cells' interactions with the oral microbiota, including how such changes can lead to worsening, rather than improving, disease states., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Metcalfe, Anselmi, Escobar, Visser and Kay.)

To support public-health-related disease surveillance and monitoring, it is crucial to concentrate both enveloped and non-enveloped viruses from domestic wastewater. To date, most concentration methods were developed for non-enveloped viruses, and limited studies have directly compared the recovery efficiency of both types of viruses. In this study, the effectiveness of two different concentration methods (Concentrating pipette (CP) method and an adsorption-extraction (AE) method amended with MgCl 2 ) were evaluated for untreated wastewater matrices using three different viruses (SARS-CoV-2 (seeded), human adenovirus 40/41 (HAdV 40/41), and enterovirus (EV)) and a wastewater-associated bacterial marker gene targeting Lachnospiraceae (Lachno3). For SARS-CoV-2, the estimated mean recovery efficiencies were significantly greater by as much as 5.46 times, using the CP method than the AE method amended with MgCl 2 . SARS-CoV-2 RNA recovery was greater for samples with higher titer seeds regardless of the method, and the estimated mean recovery efficiencies using the CP method were 25.1 ± 11% across ten WWTPs when wastewater samples were seeded with 5 × 10 4 gene copies (GC) of SARS-CoV-2. Meanwhile, the AE method yielded significantly greater concentrations of indigenous HAdV 40/41 and Lachno3 from wastewater compared to the CP method. Finally, no significant differences in indigenous EV concentrations were identified in comparing the AE and CP methods. These data indicate that the most effective concentration method varies by microbial analyte and that the priorities of the surveillance or monitoring program should be considered when choosing the concentration method., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Objectives: Genomics is moving rapidly into mainstream medicine through clinical genomic testing and consumer-initiated online DNA testing. The aim of this study was to identify Australian general practitioners' (GPs') views on genomics, impact on practice and educational needs to inform continuing education., Method: Semi-structured interviews were conducted, with constant comparative inductive analysis and governance from a national taskforce., Results: Twenty-eight GPs (43% female) were interviewed; 71% worked in a metropolitan workplace. Most initially reported little experience with genetic/genomic tests but, when prompted, recognised encountering genomics, mainly non-invasive prenatal and single-gene tests. Many GPs referred patients for cancer screening to genetic services or specialists. GPs reported needing continuing education and resources, with preferences underpinned by relevance to practice., Discussion: GPs are integrating genomic testing into care, mainly through prenatal screening, and anticipate further impact. They want diverse and context-dependent education but are unaware of some available resources, such as The Royal Australian College of General Practitioners' Genomics in general practice guideline.

Piglet castration results in acute pain and stress to the animal. There is a critical need for effective on-farm methods of pain mitigation. Local anaesthesia using Tri-Solfen ® (Animal Ethics Pty Ltd., Melbourne, Australia), a topical local anaesthetic and antiseptic formulation instilled to the wound during surgery, is a newly evolving on-farm method to mitigate castration pain. To investigate the efficacy of Tri-Solfen ® , instilled to the wound during the procedure, to alleviate subsequent castration-related pain in neonatal piglets, we performed a large, negatively controlled, randomised field trial in two commercial pig farms in Europe. Piglets (173) were enrolled and randomised to undergo castration with or without Tri-Solfen ® , instilled to the wound immediately following skin incision. A 30 s wait period was then observed prior to completing castration. Efficacy was investigated by measuring pain-induced motor and vocal responses during the subsequent procedure and post-operative pain-related behaviour in treated versus untreated piglets. There was a significant reduction in nociceptive motor and vocal response during castration and in the post-operative pain-related behaviour response in Tri-Solfen ® -treated compared to untreated piglets, in the first 30 min following castration. Although not addressing pain of skin incision, Tri-Solfen ® is effective to mitigate subsequent acute castration-related pain in piglets under commercial production conditions.

Statement of Problem: Direct-metal laser-sintering (DMLS) technologies are being used to manufacture removable partial denture frameworks; however, the build parameters are not well documented., Purpose: The purpose of this in vitro study was to investigate the impact of 3 different build angulations on a dental cobalt-chromium (Sint-Tech ST2724G) alloy by comparing the tensile properties and nanoindentation hardness. The null hypothesis was that no change would be found in the tensile properties of the different build angulation groups., Material and Methods: Dumbbell-shaped tensile specimens were produced by using stereolithographic models in accordance with American Society for Testing and Materials testing standard E8/E8M-16ae1. Specimens (n=10) were fabricated by using DMLS additive manufacturing with 3 different angulations (0, 45, and 90 degrees). Tensile testing was carried out to assess yield strength (0.2% permanent offset), elongation (%) at failure, and ultimate tensile strength (GPa). Scanning electron microscope (SEM) images were used to analyze the fracture surfaces. One 10×10×10 mm cube specimen at each orientation was prepared, and nanoindentation was used to determine hardness and elastic modulus. One-way ANOVA was used to evaluate the overall effects with interaction between groups and post hoc testing applied where the interaction was statistically significant (α=.05)., Results: The 45-degree build angulation resulted in the lowest mean elastic modulus of 213.3 GPa and the highest tensile strength of 1180.9 MPa. The 90-degree build angulation resulted in the highest mean elongation of 10.6% and the highest elastic modulus of 234.0 MPa. Within comparison of the different angulations indicated that various groups had statistically significant differences (P<.05). The SEM analysis indicated different fracture topography among the different build angles., Conclusions: The cobalt-chromium dental alloy manufactured by DMLS produced favorable mechanical properties. The SEM analysis combined with the tensile test results suggest that the direction of the build angle in relation to the laser melt pattern does impact the mechanical properties of the alloy., (Copyright © 2020 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: A new instrument was designed specifically to evaluate nurses' knowledge, attitude, and practice toward patients who use opioids. This study team developed and tested the psychometric properties of the Perception of Opioid Use Survey (POUS) instrument., Methods: The instrument was tested among 306 nurses at a 183 bed acute care community hospital, with psychometric evaluation for validity, reliability, and exploratory factor analysis., Results: Internal consistency results were Cronbach's alpha = .550 for the overall scale and each subscale: Self-Efficacy = .796, Attitudes = .744, Community Impact = .806, and Causative Factors = .763., Conclusions: Psychometric testing results support that the POUS is valid, reliable, and significantly correlated with theoretically selected variables., (© Copyright 2021 Springer Publishing Company, LLC.)

Objective: Even as genomic medicine is implemented globally, there remains a lack of rigorous, national assessments of physicians' current genomic practice and continuing genomics education needs. The aim of this study was to address this gap., Design: A cross-sectional survey, informed by qualitative data and behaviour change theory, to assess the current landscape of Australian physicians' genomic medicine practice, perceptions of proximity and individual preparedness, and preferred models of practice and continuing education. The survey was advertised nationally through 10 medical colleges, 24 societies, 62 hospitals, social media, professional networks and snowballing., Results: 409 medical specialists across Australia responded, representing 30 specialties (majority paediatricians, 20%), from mainly public hospitals (70%) in metropolitan areas (75%). Half (53%) had contacted their local genetics services and half (54%) had ordered or referred for a gene panel or exome/genome sequencing test in the last year. Two-thirds (67%) think genomics will soon impact their practice, with a significant preference for models that involved genetics services (p<0.0001). Currently, respondents mainly perform tasks associated with pretest family history taking and counselling, but more respondents expect to perform tasks at all stages of testing in the future, including tasks related to the test itself, and reporting results. While one-third (34%) recently completed education in genomics, only a quarter (25%) felt prepared to practise. Specialists would like (more) education, particularly on genomic technologies and clinical utility, and prefer this to be through varied educational strategies., Conclusions: This survey provides data from a breadth of physician specialties that can inform models of genetic service delivery and genomics education. The findings support education providers designing and delivering education that best meet learner needs to build a competent, genomic-literate workforce. Further analyses are underway to characterise early adopters of genomic medicine to inform strategies to increase engagement., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Widespread, quality genomics education for health professionals is required to create a competent genomic workforce. A lack of standards for reporting genomics education and evaluation limits the evidence base for replication and comparison. We therefore undertook a consensus process to develop a recommended minimum set of information to support consistent reporting of design, development, delivery, and evaluation of genomics education interventions., Methods: Draft standards were derived from literature (25 items from 21 publications). Thirty-six international experts were purposively recruited for three rounds of a modified Delphi process to reach consensus on relevance, clarity, comprehensiveness, utility, and design., Results: The final standards include 18 items relating to development and delivery of genomics education interventions, 12 relating to evaluation, and 1 on stakeholder engagement., Conclusion: These Reporting Item Standards for Education and its Evaluation in Genomics (RISE2 Genomics) are intended to be widely applicable across settings and health professions. Their use by those involved in reporting genomics education interventions and evaluation, as well as adoption by journals and policy makers as the expected standard, will support greater transparency, consistency, and comprehensiveness of reporting. Consequently, the genomics education evidence base will be more robust, enabling high-quality education and evaluation across diverse settings.

Background: The extent of intracerebral hemorrhage (ICH) removal conferred survival and functional benefits in the minimally invasive surgery with thrombolysis in intracerebral hemorrhage evacuation (MISTIE) III trial. It is unclear whether this similarly impacts outcome with craniotomy (open surgery) or whether timing from ictus to intervention influences outcome with either procedure., Objective: To compare volume evacuation and timing of surgery in relation to outcomes in the MISTIE III and STICH (Surgical Trial in Intracerebral Hemorrhage) trials., Methods: Postoperative scans were performed in STICH II, but not in STICH I; therefore, surgical MISTIE III cases with lobar hemorrhages (n = 84) were compared to STICH II all lobar cases (n = 259) for volumetric analyses. All MISTIE III surgical patients (n = 240) were compared to both STICH I and II (n = 722) surgical patients for timing analyses. These were investigated using cubic spline modeling and multivariate risk adjustment., Results: End-of-treatment ICH volume ≤28.8 mL in MISTIE III and ≤30.0 mL in STICH II had increased probability of modified Rankin Scale (mRS) 0 to 3 at 180 d (P = .01 and P = .003, respectively). The effect in the MISTIE cohort remained significant after multivariate risk adjustments. Earlier surgery within 62 h of ictus had a lower probability of achieving an mRS 0 to 3 at 180 d with STICH I and II (P = .0004), but not with MISTIE III. This remained significant with multivariate risk adjustments. There was no impact of timing until intervention on mortality up to 47 h with either procedure., Conclusion: Thresholds of ICH removal influenced outcome with both procedures to a similar extent. There was a similar likelihood of achieving a good outcome with both procedures within a broad therapeutic time window., (© Congress of Neurological Surgeons 2021.)

Background: Consumer genomic testing for nutrition and wellness, (nutritional genomics), is becoming increasingly popular. Concurrently, health-care practitioners (HPs) working in private practice (including doctors interested in integrative medicine, private genetic counsellors, pharmacists, dieticians, naturopaths and nutritionists) are involved as test facilitators or interpreters., Objective: To explore Australian consumers' and HPs' experiences with nutrigenomic testing., Method: Semi-structured in-depth interviews were conducted using predominantly purposive sampling. The two data sets were analysed individually, then combined, using a constant comparative, thematic approach., Results: Overall, 45 interviews were conducted with consumers (n = 18) and HPs (n = 27). Many of the consumer interviewees experienced chronic ill-health. Nutrigenomic testing was perceived as empowering and a source of hope for answers. While most made changes to their diet/supplements post-test, self-reported health improvements were small. A positive relationship with their HP appeared to minimize disappointment. HPs' adoption and views of nutrigenomic testing varied. Those enthusiastic about testing saw the possibilities it could offer. However, many felt nutrigenomic testing was not the only 'tool' to utilize when offering health care., Discussion: This research highlights the important role HPs play in consumers' experiences of nutrigenomics. The varied practice suggests relevant HPs require upskilling in this area to at least support their patients/clients, even if nutrigenomic testing is not part of their practice., Patient or Public Contribution: Advisory group included patient/public group representatives who informed study design; focus group participants gave feedback on the survey from which consumer interviewees were sourced. This informed the HP data set design. Interviewees from HP data set assisted with snowball sampling., (© 2021 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Background: Toxicity management is a challenge with cancer treatment, including oral anticancer drugs. A review of claims data showed that a majority of publically funded oral anticancer drugs were filled in the community where pharmacists may not necessarily possess the specialized knowledge, skills, and experience required to provide effective patient care. A survey of community pharmacists in Ontario was conducted to identify the behaviours and preferences of community pharmacists specific to the management of treatment-related toxicities in order to standardize cancer care in this area., Methods: An electronic questionnaire was distributed to approximately 5000 community pharmacists. The 21-question survey gathered information on the demographic profile of the pharmacists, basic geographic and socioeconomic variables associated with their practice setting, current toxicity management practices, education and training needs, and preferences for communicating with other providers., Results: Of 349 pharmacists, almost all (94.9%) were interested in managing chemotherapy-related toxicities as part of their work, but the majority (77.1%) did not feel that their current level of pharmacy training has provided them with an oncology education sufficient for the demands of their practice. Approximately 52% of respondents indicated that they have reached out to the health care provider at a cancer centre, and of those, 72.7% reported that their questions were resolved within 48 h. More than half of all survey respondents (53.9%) indicated that they would prefer to receive a response within 12 h from cancer centres., Conclusions: The results of this study support the need to provide community pharmacists with oncology-specific training and timely correspondences from providers at prescribing institutions in order to manage toxicities.

The aim of crystallographic structure solution is typically to determine an atomic model which accurately accounts for an observed diffraction pattern. A key step in this process is the refinement of the parameters of an initial model, which is most often determined by molecular replacement using another structure which is broadly similar to the structure of interest. In macromolecular crystallography, the resolution of the data is typically insufficient to determine the positional and uncertainty parameters for each individual atom, and so stereochemical information is used to supplement the observational data. Here, a new approach to refinement is evaluated in which a `shift field' is determined which describes changes to model parameters affecting whole regions of the model rather than individual atoms only, with the size of the affected region being a key parameter of the calculation which can be changed in accordance with the resolution of the data. It is demonstrated that this approach can improve the radius of convergence of the refinement calculation while also dramatically reducing the calculation time., (open access.)

The situation of the COVID-19 pandemic reminds us that we permanently need high-value flexible solutions to urgent clinical needs including simplified diagnostic technologies suitable for use in the field and for delivering targeted therapeutics. From our perspective nanotechnology is revealed as a vital resource for this, as a generic platform of technical solutions to tackle complex medical challenges. It is towards this perspective and focusing on nanomedicine that we take issue with Prof Park's recent editorial published in the Journal of Controlled Release. Prof. Park argued that in the last 15 years nanomedicine failed to deliver the promised innovative clinical solutions to the patients (Park, K. The beginning of the end of the nanomedicine hype. Journal of Controlled Release, 2019; 305, 221-222 [1]. We, the ETPN (European Technology Platform on Nanomedicine) [2], respectfully disagree. In fact, the more than 50 formulations currently in the market, and the recent approval of 3 key nanomedicine products (e. g. Onpattro, Hensify and Vyxeos), have demonstrated that the nanomedicine field is concretely able to design products that overcome critical barriers in conventional medicine in a unique manner, but also to deliver within the cells new drug-free therapeutic effects by using pure physical modes of action, and therefore make a difference in patients lives. Furthermore, the >400 nanomedicine formulations currently in clinical trials are expecting to bring novel clinical solutions (e.g. platforms for nucleic acid delivery), alone or in combination with other key enabling technologies to the market, including biotechnologies, microfluidics, advanced materials, biomaterials, smart systems, photonics, robotics, textiles, Big Data and ICT (information & communication technologies) more generally. However, we agree with Prof. Park that " it is time to examine the sources of difficulty in clinical translation of nanomedicine and move forward ". But for reaching this goal, the investments to support clinical translation of promising nanomedicine formulations should increase, not decrease. As recently encouraged by EMA in its roadmap to 2025, we should create more unity through a common knowledge hub linking academia, industry, healthcare providers and hopefully policy makers to reduce the current fragmentation of the standardization and regulatory body landscape. We should also promote a strategy of cross-technology innovation, support nanomedicine development as a high value and low-cost solution to answer unmet medical needs and help the most promising innovative projects of the field to get better and faster to the clinic. This global vision is the one that the ETPN chose to encourage for the last fifteen years. All actions should be taken with a clear clinical view in mind, " without any fanfare", to focus "on what matters in real life", which is the patient and his/her quality of life. This ETPN overview of achievements in nanomedicine serves to reinforce our drive towards further expanding and growing the maturity of nanomedicine for global healthcare, accelerating the pace of transformation of its great potential into tangible medical breakthroughs., Competing Interests: Declaration of Competing Interest Matthieu GERMAIN and Agnes POTTIER are co-inventors of patent applications related to Hensify product (Nanobiotix) described in this article. Alexandre CECCALDI is employee of ETPN. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. Credit authors statement, (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Phagocytic cells are crucial components of the innate immune system preventing Candida albicans mucosal infections. Streptococcus gordonii and Pseudomonas aeruginosa often colonize mucosal sites, along with C. albicans , and yet interkingdom interactions that might alter the survival and escape of fungi from macrophages are not understood. Murine macrophages were coinfected with S. gordonii or P. aeruginosa , along with C. albicans to evaluate changes in fungal survival. S. gordonii increased C. albicans survival and filamentation within macrophage phagosomes, while P. aeruginosa reduced fungal survival and filamentation. Coinfection with S. gordonii resulted in greater escape of C. albicans from macrophages and increased size of fungal microcolonies formed on macrophage monolayers, while coinfection with P. aeruginosa reduced macrophage escape and produced smaller microcolonies. Microcolonies formed in the presence of P. aeruginosa cells outside macrophages also had significantly reduced size that was not found with P. aeruginosa phenazine deletion mutants. S. gordonii cells, as well as S. gordonii heat-fixed culture supernatants, increased C. albicans microcolony biomass but also resulted in microcolony detachment. A heat-resistant, trypsin-sensitive pheromone processed by S. gordonii Eep was needed for these effects. The majority of fungal microcolonies formed on human epithelial monolayers with S. gordonii supernatants developed as large floating structures with no detectable invasion of epithelium, along with reduced gene expression of C. albicans HYR1 , EAP1 , and HWP2 adhesins. However, a subset of C. albicans microcolonies was smaller and had greater epithelial invasiveness compared to microcolonies grown without S. gordonii Thus, bacteria can alter the killing and escape of C. albicans from macrophages and contribute to changes in C. albicans pathogenicity. IMPORTANCE Candida albicans is the predominant fungus colonizing the oral cavity that can have both synergistic and antagonistic interactions with other bacteria. Interkingdom polymicrobial associations modify fungal pathogenicity and are believed to increase microbial resistance to innate immunity. However, it is not known how these interactions alter fungal survival during phagocytic killing. We demonstrated that secreted molecules of S. gordonii and P. aeruginosa alter C. albicans survival within the phagosome of macrophages and alter fungal pathogenic phenotypes, including filamentation and microcolony formation. Moreover, we provide evidence for a dual interaction between S. gordonii and C. albicans such that S. gordonii signaling peptides can promote C. albicans commensalism by decreasing microcolony attachment while increasing invasion in epithelial cells. Our results identify bacterial diffusible factors as an attractive target to modify virulence of C. albicans in polymicrobial infections., (Copyright © 2020 Salvatori et al.)

Objective: To explore midwives' roles and education requirements in newborn bloodspot screening (NBS) for genetic conditions, as programs and supporting education evolve over time., Background: NBS processes are evolving and will continue to evolve with new genetic and genomic technologies. Midwives have a critical role in facilitating NBS, as they are the primary healthcare professional to interact with parents at the time of collecting the bloodspot. As new consent processes and genomic technologies are incorporated into NBS, midwives need to stay up-to-date with these changes, so that parents can make an informed decision about having the test and future use of the DNA sample., Research Design/setting: We used a cross-sectional approach to analyse midwives' knowledge and behaviour in 2005/6 and 2016, with changes in NBS processes and education introduced in 2011., Findings: We found midwives' NBS knowledge improved in 8/18 areas after a 10-year period, mostly related to process changes, but there was also an increase in misconceptions regarding which conditions are screened. Areas of significant improvement were not consistently explained by participation in continuing professional development (CPD). We found midwives used official brochures and NBS collection cards to guide discussions with families. Changes to the NBS collection cards, together with the content of CPD materials, aligned with the significant improvements and deficits we observed. When considering potential changes to future maternity care that incorporates emerging genomic technologies, midwives indicated the main barrier was their lack of knowledge; the majority (60.3%) reported supervision support to attend genomics CPD., Key Conclusions: Changes in NBS practice should be implemented through multifaceted programs that include education sessions and procedural prompts. The NBS collection card should be seen not just as a legal consent document but also as an educational tool., Implications for Practice: As NBS programs evolve through the addition of conditions screened for or changes to technology or consent processes, multiple strategies should be applied to upskill midwives to ensure they can best support parents to make informed choices., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

As the Canadian population ages, healthcare systems have become increasingly interested in exploring new ways to deliver services to frail older adults, and in particular older adults with dementia. The Specialized Seniors Clinics (SSCs) are an innovative integrated network of six outpatient clinics in BC's Fraser Health Authority that utilize interprofessional teams to provide comprehensive geriatric assessments and care planning for frail older adults. The SSCs provided approximately 19,000 appointments in the past fiscal year, and clients and primary care physicians are highly satisfied with the model. This article describes the SSC model and provides reflection on the model development, implementation and standardization processes., (Copyright © 2019 Longwoods Publishing.)

Targeted genomic education and training of professionals have been identified as core components of strategies and implementation plans for the use of genomics in health care systems. Education needs to be effective and support the sustained and appropriate use of genomics in health care. Evaluation of education programs to identify effectiveness is challenging. Furthermore, those responsible for development and delivery are not necessarily trained in education and/or evaluation. Program logic models have been used to support the development and evaluation of education programs by articulating a logical explanation as to how a program intends to produce the desired outcomes. These are highly relevant to genomic education programs, but do not appear to have been widely used to date. To assist those developing and evaluating genomic education programs, and as a first step towards enabling identification of effective genomic education approaches, we developed a consensus program logic model for genomic education. We drew on existing literature and a co-design process with 24 international genomic education and evaluation experts to develop the model. The general applicability of the model to the development of programs was tested by program convenors across four diverse settings. Conveners reported on the utility and relevance of the logic model across development, delivery and evaluation. As a whole, their feedback suggests that the model is flexible and adaptive across university award programs, competency development and continuing professional development activities. We discuss this program logic model as a potential best practice mechanism for developing genomic education, and to support development of an evaluation framework and consistent standards to evaluate and report genomic education program outcomes and impacts., (Copyright © 2019 Nisselle, Martyn, Jordan, Kaunein, McEwen, Patel, Terrill, Bishop, Metcalfe and Gaff.)

Developing a competent workforce will be crucial to realizing the promise of genomic medicine. The preparedness of medical specialists without specific genetic qualifications to play a role in this workforce has long been questioned, prompting widespread calls for education across the spectrum of medical training. Adult learning theory indicates that for education to be effective, a perceived need to learn must first be established. Medical specialists have to perceive genomic medicine as relevant to their clinical practice. Here, we review what is currently known about medical specialists' perceptions of genomics, compare these findings to those from the genetics era, and identify areas for future research. Previous studies reveal that medical specialists' views on the clinical utility of genomic medicine are mixed and are often tempered by several concerns. Specialists generally perceive their confidence and understanding to be lacking; subsequently, they welcome additional educational support, although specific needs are rarely detailed. Similar findings from the genetics era suggest that these challenges are not necessarily new but on a different scale and relevant to more specialties as genomic applications expand. While existing strategies developed for genetic education and training may be suitable for genomic education and training, investigating the educational needs of a wider range of specialties is critically necessary to determine if tailored approaches are needed and, if so, to facilitate these. Other interventions are also required to address some of the additional challenges identified in this review, and we encourage readers to see education as part of a broader implementation strategy., (Copyright © 2019 Crellin, McClaren, Nisselle, Best, Gaff and Metcalfe.)

Purpose: To evaluate the effectiveness of implementing yoga into the treatment of patients with chronic low back pain. Design: Quantitative analysis with opportunity for qualitative feedback. Method: Effectiveness of this complementary treatment was assessed using a pretest/posttest design of patients who volunteered to participate in yoga classes as part of their back pain management. Measurements included low back pain rating, perception of back pain interference with daily activities, and self-efficacy in dealing with chronic low back pain. Findings: Although no statistically significant findings were found due to the small sample size, most participants demonstrated improved individual scores on all measurement surveys including qualitative comments. Conclusion: Based on the findings of this pilot study, further studies on implementing yoga into the treatment of chronic low back pain are encouraged.

Ets1 is emerging as a key transcription factor that is required to prevent autoimmunity in mice and humans. Ets1 is expressed in both B and T cells, and mice lacking Ets1 are characterized by excess B and T cell activation, leading to enhanced formation of Ab-secreting cells and high titers of autoantibodies. In humans, genome-wide association studies have detected associations of single nucleotide polymorphisms in the human ETS1 gene with autoimmune diseases, including lupus. An increased fraction of CD4 + T cells from Ets1 -/- mice have an activated effector-memory phenotype, and there are aberrations in differentiation that contribute to the autoimmune phenotype. In vitro studies of B cells suggest that Ets1 may have B cell-intrinsic effects as well. To confirm B cell-intrinsic roles for Ets1, we crossed CD19-Cre mice to mice with a floxed allele of Ets1. Mice with a B cell-specific deletion of Ets1 show increases in B cell activation, numbers of Ab-secreting cells, and levels of autoantibodies, despite the fact that T cells are normal. However, when compared with conventional Ets1 knockout mice, mice with B cell-specific loss of Ets1 have a significantly milder phenotype. These results demonstrate that Ets1 is required in B cells to prevent autoimmune responses but that loss of Ets1 activity in other cell types is required for maximal autoimmune phenotypes., (Copyright © 2019 The Authors.)

We aimed to determine capacity and readiness of Australian clinical genetic healthcare professionals to provide genomic medicine. An online survey was administered to individuals with genetic counseling or clinical genetics qualifications in Australia. Data collected included: education, certification, continuing professional development (CPD), employment, and genetic versus genomic clinical practice. Of the estimated 630 clinical genetic healthcare professionals in Australia, 354 completed the survey (56.2% response rate). Explanatory interviews were conducted with 5.5% of the genetic counselor respondents. Those working clinically reported being involved in aspects of whole exome or genome sequencing (48.6% genetic counselors, 88.6% clinical geneticists). Most genetic counselors (74.2%) and clinical geneticists (87.0%) had attended genomics CPD in the last two years, with 61.0% and 39.1% self-funding, respectively. Genetic counselors desire broad involvement in genomics, including understanding classifying and interpreting results to better counsel patients. The majority of respondents (89.9%) were satisfied with their job and 91.6% planned to work in genetics until retirement. However, 14.1% of the genetic counselors in clinical roles and 24.6% of the clinical geneticists planned to retire within 10 years. This is the first national audit of clinical genetic healthcare professionals, revealing the Australian workforce is motivated and prepared to embrace new models to deliver genomic medicine but consideration of education and training is required to meet demand., (© 2019 National Society of Genetic Counselors.)

Aim: Analysis of dispensings of prescription medicines in New Zealand in 2006/07 reported large inequities between Māori and non-Māori. This present study has now updated the earlier work by describing variations in disease burden-adjusted medicines access by ethnicity in 2012/13, and changes over time., Method: The update has linked prescription medicine data with burden of disease estimates by ethnicity for 2012/13 and comparing with 2006/07. This has re-examined the shortfall in prescriptions for Māori vs non-Māori adjusting for age, population and burden of disease (ie, health loss, in disability-adjusted life years (DALYs))., Results: After adjusting for age, population and burden of disease, large inequalities still existed for Māori compared with non-Māori, with generally no improvement over the six years. In 2012/13, Māori had 41% lower dispensings overall than non-Māori; this was nominally worse compared with the 37% relative gap in 2006/07, but the trend was not statistically significant. Many complexities and limitations hamper valid interpretation, but large inequities in access and persistence, across many therapeutic groups, remain. The full University of Auckland report details these inequities., Conclusion: Large inequities in medicines access for Māori continue. Inequities in access are unacceptable, their causes likely complex and entrenched; we believe they need deeper understanding of systems and barriers, pragmatic ways to monitor outcomes, and an all-of-sector approach and beyond. PHARMAC has committed to strategic action to eliminate inequities in access to medicines by 2025, recognising it needs partners to drive the necessary change. Kei a tātou tonu katoa te wero kia mahikaha, kia mahi tino mōhio, me te mahitahi (The challenge continues for us to work harder, work smarter, and work together); everyone in the health sector has a role., Competing Interests: KB, JH, RJ were the members of the Auckland UniServices team contracted by PHARMAC to update the original PHARMAC analysis. SM, JU, CP, ĀA are or were PHARMAC staff. JU was PHARMAC’s Director Engagement and Implementation; SM, JU, ĀA commissioned the Auckland UniServices update and reviewed its earlier drafts.

Oral streptococci are generally considered commensal organisms; however, they are becoming recognized as important associate pathogens during the development of periodontal disease as well as being associated with several systemic diseases, including as a causative agent of infective endocarditis. An important virulence determinant of these bacteria is an ability to evade destruction by phagocytic cells, yet how this subversion occurs is mostly unknown. Using Streptococcus gordonii as a model commensal oral streptococcus that is also associated with disease, we find that resistance to reactive oxygen species (ROS) with an active ability to damage phagosomes allows the bacterium to avoid destruction within macrophages. This ability to survive relies not only on the ROS resistance capabilities of the bacterium but also on ROS production by macrophages, with both being required for maximal survival of internalized bacteria. Importantly, we also show that this dependence on ROS production by macrophages for resistance has functional significance: S. gordonii intracellular survival increases when macrophages are polarized toward an activated (M1) profile, which is known to result in prolonged phagosomal ROS production compared to that of alternatively (M2) polarized macrophages. We additionally find evidence of the bacterium being capable of both delaying the maturation of and damaging phagosomes. Taken together, these results provide essential insights regarding the mechanisms through which normally commensal oral bacteria can contribute to both local and systemic inflammatory disease., (Copyright © 2018 American Society for Microbiology.)

What Is Known and Objective: Interventions intended to slow the emergence and spread of antibacterial resistance through enhanced antimicrobial stewardship will be more effective if informed by an accurate knowledge of current patterns of antibacterial consumption. For example, knowledge of the relative magnitude of community antibacterial consumption in relation to hospital antibacterial consumption within each nation or region should help guide decisions about the relative importance of community and hospital antimicrobial stewardship programmes. It is commonly stated that community antibacterial consumption comprises approximately 80% of total national antibacterial consumption. We aimed to determine this proportion across a large range of nations., Methods: We measured community and hospital antibacterial consumption in New Zealand during 2015, from both reimbursement and purchase data, and compared the New Zealand data with those reported from a large range of other nations during similar time periods., Results and Discussion: Community antibacterial consumption comprised approximately 85%-95% of total antibacterial consumption in all nations for which data were available, and in New Zealand comprised a higher proportion than in any other nation. The proportion of total antibacterial consumption comprised by community consumption was significantly higher in countries with relatively high levels of total antibacterial consumption than in countries with relatively low levels of total antibacterial consumption., What Is New and Conclusion: The high proportion of total antibacterial consumption comprised by community antibacterial consumption suggests devoting particular attention to improved community antimicrobial stewardship. These results suggest that improving antimicrobial stewardship in the community may provide greater overall benefits in combating antibacterial resistance than improving antimicrobial stewardship in hospitals., (© 2017 John Wiley & Sons Ltd.)

Resistance mechanisms are typically uncovered by identifying sequence variation in known candidate genes, however this strategy can be problematic for species with no reference data in known relatives. Here we take a genomic approach to identify resistance to pyrethroids in the redlegged earth mite, Halotydeus destructor, a member of the Penthalidae family of mites that are virtually uncharacterized genetically. Based on shallow genome sequencing followed by a genome assembly, we first identified contigs of the H. destructor parasodium channel gene. By linking variation in this gene to known resistant phenotypes, we located a single nucleotide polymorphism in resistant mites. This polymorphism results in a leucine (L) to phenylalanine (F) amino acid substitution in the II6 region (predicted) of the gene (L1024F). This novel mutation has not previously been linked to pyrethroid resistance, although other polymorphisms have been identified in the two-spotted spider mite, Tetranychus urticae at the same locus (L1024V). The sequencing approach was successful in generating a candidate polymorphism that was then validated using laboratory bioassays and field surveys. A high throughput Illumina-based sequencing diagnostic was developed to rapidly assess resistance allele frequencies in pools of mites sourced from hundreds of populations across Australia. Resistance was confirmed to be widespread in the southern wheatbelt region of Western Australia. Two different resistance mutations were identified in field populations, both resulting in the same amino acid substitution. The frequency and distribution of resistance amplicon haplotypes suggests at least two, and probably more independent origins of resistance., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: To evaluate disease control and survival after stereotactic body radiotherapy (SBRT) for lung metastases from colorectal cancer and to identify prognostic factors after treatment., Methods: Patients with metastatic colorectal cancer to the lungs treated with SBRT from 2002 to 2013 were identified from a prospectively maintained database. Patients may have received prior systemic therapy, radiotherapy to nonthoracic sites and/or resection of thoracic and/or nonthoracic metastases. Endpoints were timed from end of SBRT and included overall survival (OS), progression-free survival, distant metastases-free survival, and local failure-free survival. Univariate and multivariate analysis using Cox proportional hazard modeling was used to identify prognostic factors., Results: Sixty-five patients were identified. Before SBRT, 69.2% and 33.8% of patients received systemic therapy and lung-directed local therapy, respectively, for metastatic disease. At the time of SBRT, 64.6% had lung-only involvement. Median survivals were: OS of 20.3 months (95% confidence intervals [CI], 15.9-27.0 mo), progression-free survival of 5.7 months (95% CI, 3.2-7.0 mo), distant metastases-free survival of 5.8 months (95% CI, 3.2-7.6 mo), and local failure-free survival of 15.4 months (95% CI, 8.5-21.1 mo). Nearly all (98%) patients developed distant progression. Extra lung and liver involvement at the time of initial metastases (hazard ratios [HR] 2.10) and extra lung involvement at SBRT (HR 2.67) were the only independent predictors of OS. Net gross target volume of >14.1 mL (HR 2.49) was the only independent predictor of local failure-free survival., Conclusions: Reasonable survival and local control can be achieved with SBRT. We identified several prognostic factors testable in future prospective trials that may help improve patient selection.

The impact of anthropogenic factors arising from point and non-point pollution sources at a multi commodity marine port and its surrounding ecosystems were studied using sediment samples collected from a number of onshore (Gladstone Harbour and Facing Island) and offshore (Heron Island and Fitzroy Reefs) sites in Australia's Central Queensland. Sediment samples were analyzed for trace metals, organic carbon, polycyclic aromatic hydrocarbons (PAH), emerging chemicals of concern (ECC) and sterols. Similarly, the biological and biochemical interaction between the reef and its environment was analyzed by the multi-omic tools of next-generation sequencing characterization of the bacterial community and microbial community metabolic profiling. Overall, the trace elements were observed at the lower end of the Australian environmental guideline values at the offshore sites, while higher values were observed for the onshore locations Nickel and copper were observed above the high trigger value threshold at the onshore sites. The levels of PAH were below limits of detection across all sites. However, some of the ECC and sterols were observed at higher concentrations at both onshore and offshore locations, notably, the cholesterol family sterols and 17α-ethynylestradiol. Multi-omic analyses also indicated possible thermal and photo irradiation stressors on the bacterial communities at all the tested sites. The observed populations of γ-proteobacteria were found in combination with an increased pool of fatty acids that indicate fatty acid synthesis and utilisation of the intermediates of the shikimate pathways. This study demonstrates the value of applying a multi-omics approach for ecological assessments, in which a more detailed assessment of physical and chemical contaminants and their impact on the community bacterial biome is obtained., (Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.)

Aims: Type 2 diabetes mellitus (T2DM) is a significant public health issue in New Zealand. Effective management and glycaemic control is critical for reducing diabetes-related complications. Treatment guidelines are well established in New Zealand. Using dispensing data as a proxy for prescribing data, this paper aims to describe the pattern of first- and second-line antidiabetic agent (AA) dispensing for T2DM in New Zealand and assess adherence with treatment guidelines., Methods: Analysis of national dispensing data for AA medications using the Pharmaceutical Collection database from 2007/08 to 2015/16., Results: Metformin monotherapy remains the most commonly prescribed first-line T2DM medication prescribed, accounting for 85% of initial agents prescribed. Sulfonylureas are the most common second-line agents used, accounting for 70% of all second-line agents., Conclusion: There is a high degree of adherence with the T2DM treatment guidelines in New Zealand., Competing Interests: The authors are (or were at the time of writing) employees of PHARMAC; the views expressed do not necessarily represent those of PHARMAC.

Tobacco consumption is a significant national public health issue. The waste it generates-tobacco product waste (TPW)-is also an environmental hazard. Targeting TPW through novel policies/regulations-such as a cigarette butt deposit scheme-may serve the dual purposes of reducing an environment nuisance and progressing Aotearoa New Zealand to its goal of being smokefree by 2025., Competing Interests: Nil.

Most catchments discharging into the Great Barrier Reef lagoon have elevated loads of suspended sediment, nutrients, and pesticides, including photosystem II inhibiting herbicides, associated with upstream agricultural land use. To investigate potential impacts of declining water quality on fish physiology, RNA sequencing (RNASeq) was used to characterize and compare the hepatic transcriptomes of barramundi (Lates calcarifer) captured from 2 of these tropical river catchments in Queensland, Australia. The Daintree and Tully Rivers differ in upstream land uses, as well as sediment, nutrient, and pesticide loads, with the area of agricultural land use and contaminant loads lower in the Daintree. In fish collected from the Tully River, transcripts involved in fatty acid metabolism, amino acid metabolism, and citrate cycling were also more abundant, suggesting elevated circulating cortisol concentrations, whereas transcripts involved in immune responses were less abundant. Fish from the Tully also had an increased abundance of transcripts associated with xenobiotic metabolism. Previous laboratory-based studies observed similar patterns in fish and amphibians exposed to the agricultural herbicide atrazine. If these transcriptomic patterns are manifested at the whole organism level, the differences in water quality between the 2 rivers may alter fish growth and fitness. Environ Toxicol Chem 2017;36:103-112. © 2016 SETAC., (© 2016 SETAC.)

This paper uses consumer health informatics as a framework to explore whether and how direct-to-consumer personal genomic testing can be regarded as a form of information which assists consumers to manage their health. It presents findings from qualitative content analysis of web sites that offer testing services, and of transcripts from focus groups conducted as part a study of the Australian public's expectations of personal genomics. Content analysis showed that service offerings have some features of consumer health information but lack consistency. Focus group participants were mostly unfamiliar with the specifics of test reports and related information services. Some of their ideas about aids to knowledge were in line with the benefits described on provider web sites, but some expectations were inflated. People were ambivalent about whether these services would address consumers' health needs, interests and contexts and whether they would support consumers' health self-management decisions and outcomes. There is scope for consumer health informatics approaches to refine the usage and the utility of direct-to-consumer personal genomic testing. Further research may focus on how uptake is affected by consumers' health literacy or by services' engagement with consumers about what they really want.

Background: Advances in genetic technologies and ultrasound screening techniques have increased the ability to predict and diagnose congenital anomalies during pregnancy. As a result more prospective parents than ever before will receive a prenatal diagnosis of a fetal abnormality. Little is known about how Australian women and men experience receiving a prenatal diagnosis and how they make their decision about whether or not to continue the pregnancy., Aims: This qualitative study aims to describe parental experiences and examine how best to provide support after a prenatal diagnosis., Results: Individual in-depth interviews were conducted with 102 women and men approximately six weeks post-diagnosis of fetal abnormality. Data were elicited using a narrative, chronological approach and women (n = 75) and a sample of male partners (n = 27) were separately interviewed. Thematic analysis, involving a rigorous process of qualitative coding, enabled iterative development and validation of emergent themes. Participants identified that the shock of the diagnosis can be lessened when good care is delivered, by provision of: clear, accurate and respectful communication; empathic, non-judgemental, professional support; timely access to further testing and appointments; seamless interactions with services and administration; appropriate choices about invasive testing; acknowledgment of the enormity and unexpected nature of the diagnosis, and of the subsequent decision-making challenges; and discussion of the myriad feelings likely to emerge throughout the process., Conclusions: This study has demonstrated the importance of providing timely access to accurate information and supportive, non-judgemental care for women and their partners following prenatal diagnosis of a fetal abnormality., (© 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Publicly funded cancer medicines listed on the New Zealand Pharmaceutical Schedule were compared with those listed on the Australian Pharmaceutical Benefits Scheme. To quantify the health gains offered by the cancer medicines funded in Australia but not in New Zealand, clinical trial data reporting median progression-free survival (PFS) and overall survival (OS) were sought. The differences in the median PFS and OS for the unfunded medicines, relative to the comparator medicine funded in NZ, were then assessed against the American Society of Clinical Oncology Cancer Research Committee (ASCO-CRC) recommended targets for clinically meaningful health gains. Our analysis confirms that, whilst New Zealand funds fewer cancer medicines than Australia, most of the additional medicines funded in Australia do not deliver clinically meaningful health gains as defined by the ASCO-CRC guidance. This suggests that New Zealand is not missing substantive opportunities for improvements to New Zealand's cancer survival rates through additional medicines funding. A policy of funding more new cancer medicines in order to achieve numerical parity with Australia or other countries would not result in substantive health improvement and would cost significantly more, and investing the millions of dollars needed to achieve funding parity with other countries would not represent good value for money in terms of delivering the best health outcomes for all New Zealanders, rather selective funding of new medicines that demonstrate clear clinical benefit and that are cost-effective and affordable is the sensible approach., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)