Extending the new era of genomic testing into pregnancy management: A proposed model for Australian prenatal services.

BACKGROUND: Trio exome sequencing can be used to investigate congenital abnormalities identified on pregnancy ultrasound, but its use in an Australian context has not been assessed. AIMS: Assess clinical outcomes and changes in management after expedited genomic testing in the prenatal period to guide the development of a model for widespread implementation. MATERIALS AND METHODS: Forty-three prospective referrals for whole exome sequencing, including 40 trios (parents and pregnancy), two singletons and one duo were assessed in a tertiary hospital setting with access to a state-wide pathology laboratory. Diagnostic yield, turn-around time (TAT), gestational age at reporting, pregnancy outcome, change in management and future pregnancy status were assessed for each family. RESULTS: A clinically significant genomic diagnosis was made in 15/43 pregnancies (35%), with an average TAT of 12 days. Gestational age at time of report ranged from 16 + 5 to 31 + 6 weeks (median 21 + 3 weeks). Molecular diagnoses included neuromuscular and skeletal disorders, RASopathies and a range of other rare Mendelian disorders. The majority of families actively used the results in pregnancy decision making as well as in management of future pregnancies. CONCLUSIONS: Rapid second trimester prenatal genomic testing can be successfully delivered to investigate structural abnormalities in pregnancy, providing crucial guidance for current and future pregnancy management. The time-sensitive nature of this testing requires close laboratory and clinical collaboration to ensure appropriate referral and result communication. We found the establishment of a prenatal coordinator role and dedicated reporting team to be important facilitators. We propose this as a model for genomic testing in other prenatal services.

Multicenter Randomized Trial of Intermittently Scanned Continuous Glucose Monitoring Versus Self-Monitoring of Blood Glucose in Individuals With Type 2 Diabetes and Recent-Onset Acute Myocardial Infarction: Results of the LIBERATES Trial.

OBJECTIVE: To analyze the impact of modern glucose-monitoring strategies on glycemic and patient-related outcomes in individuals with type 2 diabetes (T2D) and recent myocardial infarction (MI) and assess cost effectiveness. RESEARCH DESIGN AND METHODS: LIBERATES was a multicenter two-arm randomized trial comparing self-monitoring of blood glucose (SMBG) with intermittently scanned continuous glucose monitoring (isCGM), also known as flash CGM, in individuals with T2D and recent MI, treated with insulin and/or a sulphonylurea before hospital admission. The primary outcome measure was time in range (TIR) (glucose 3.9-10 mmol/L/day) on days 76-90 post-randomization. Secondary and exploratory outcomes included time in hypoglycemia, hemoglobin A1c (HbA1c), clinical outcome, quality of life (QOL), and cost effectiveness. RESULTS: Of 141 participants randomly assigned (median age 63 years; interquartile range 53, 70), 73% of whom were men, isCGM was associated with increased TIR by 17 min/day (95% credible interval -105 to +153 min/day), with 59% probability of benefit. Users of isCGM showed lower hypoglycemic exposure (<3.9 mmol/L) at days 76-90 (-80 min/day; 95% CI -118, -43), also evident at days 16-30 (-28 min/day; 95% CI -92, 2). Compared with baseline, HbA1c showed similar reductions of 7 mmol/mol at 3 months in both study arms. Combined glycemic emergencies and mortality occurred in four isCGM and seven SMBG study participants. QOL measures marginally favored isCGM, and the intervention proved to be cost effective. CONCLUSIONS: Compared with SMBG, isCGM in T2D individuals with MI marginally increases TIR and significantly reduces hypoglycemic exposure while equally improving HbA1c, explaining its cost effectiveness. Studies are required to understand whether these glycemic differences translate into longer-term clinical benefit.

Parkinson's disease and palliative care: a quality of care Delphi study.

OBJECTIVES: Extending palliative care services to those with long-term neurological conditions is a current aim of UK health policy. Lack of holistic guidelines for palliative and end-of-life care, and differing models of service provision, has resulted in heterogeneity in care access and quality. There is a need for evidence-based standards of care to audit Parkinson's services and drive improvements. METHODS: A two-stage Delphi process was used to achieve consensus on statements that define quality standards in palliative care for patients with Parkinson's disease (PD). An expert panel was selected to comprise healthcare professionals, patients and carers based in the UK; this panel evaluated the statements via a Delphi survey. Quantitative and qualitative analysis of the results informed modifications between the Delphi rounds. RESULTS: A final set of 16 statements was produced, reflecting aspirational standards of palliative care in PD. These statements, split into four domains ('Structures and processes of care', 'Preparing for the end of life', ' Care in the last weeks of life' and 'Care in the last days of life') underline the importance of joint working between generalist and specialist services, individualised care and early and regular advance care planning. CONCLUSIONS: The Delphi process has established a set of standards which can be integrated within and guide services, helping to improve the quality and equality of care. Further work remains to establish the effectiveness of different models of service provision, including the implementation of keyworkers and telemedicine.

Functional and phylogenetic responses of motile cryptofauna to habitat degradation.

Biodiversity of terrestrial and marine ecosystems, including coral reefs, is dominated by small, often cryptic, invertebrate taxa that play important roles in ecosystem structure and functioning. While cryptofauna community structure is determined by strong small-scale microhabitat associations, the extent to which ecological and environmental factors shape these communities are largely unknown, as is the relative importance of particular microhabitats in supporting reef trophodynamics from the bottom up. The goal of this study was to address these knowledge gaps, provided coral reefs are increasingly exposed to multiple disturbances and environmental gradients that influence habitat complexity, condition and ecosystem functioning. We compared the density, biomass, size range, phylogenetic diversity and functional roles of motile cryptofauna in Palau, Western Micronesia, among four coral-derived microhabitats representing various states of degradation (live coral [Acropora and Pocillopora], dead coral and coral rubble) from reefs along a gradient of effluent exposure. In total, 122 families across ten phyla were identified, dominated by the Arthropoda (Crustacea) and Mollusca. Cryptofauna biomass was greatest in live Pocillopora, while coral rubble contained the greatest density and diversity. Size ranges were broader in live corals than both dead coral and rubble. From a bottom-up perspective, effluent exposure had mixed effects on cryptic communities including a decline in total biomass in rubble. From a top-down perspective, cryptofauna were generally unaffected by predator biomass. Our data show that, as coral reef ecosystems continue to decline in response to more frequent and severe disturbances, habitats other than live coral may become increasingly important in supporting coral reef biodiversity and food webs.

Global status, impacts, and management of rocky temperate mesophotic ecosystems.

The ecology and function of rocky temperate mesophotic ecosystems (TMEs) remain poorly understood globally despite their widespread distribution. They typically occur at 20-150 m (the limit of photosynthesis), and on rocky substratum they support rich benthic communities and mobile fauna. We determined the distribution of rocky TMEs, their conservation status, and their most characteristic biological groups. Rocky TMEs were dominated by algae, turf-invertebrate matrices (<50 m only), sponges, bryozoans, and cnidarians. The community composition of TMEs differed significantly from shallow (0-15 m) subtidal reefs. Data were geographically biased and variable, available only from the North and South Atlantic, Mediterranean, and Temperate Australasia. Degree of protection of rocky TMEs varied considerably across the world. The biggest threats to rocky TMEs were identified changes in temperature, sedimentation rates, nutrient concentrations, and certain fishing types. We propose a conservation framework to inform future rocky TME management and conservation, highlighting the need to recognize the importance of these biologically diverse and functionally important ecosystems.

Resumen La ecología y la función de los ecosistemas mesofóticos templados (TME) rocosos todavía no están muy comprendidas a nivel mundial a pesar de su amplia distribución. Comúnmente se encuentran entre los 20 y los 150 metros (el límite de la fotosíntesis) sobre sustratos rocosos que mantienen comunidades bénticas diversas y fauna móvil. Determinamos la distribución, estado de conservación y grupos biológicos más característicos de los TME rocosos. Estos ecosistemas estuvieron dominados por algas, matrices de invertebrados de pastos marinos (solamente a <50 m), esponjas marinas, briozoos y cnidarios. La composición comunitaria de los TME difirió significativamente de los arrecifes submareales someros (0-15 m). Los datos estuvieron sesgados geográficamente y fueron variables, pues sólo estaban disponibles para el Atlántico norte y sur, el Mediterráneo y la Australasia templada. El nivel de protección de los TME rocosos varió considerablemente en todo el mundo. Las principales amenazas que enfrenta este ecosistema son los cambios en la temperatura, las tasas de sedimentación, la concentración de nutrientes y ciertos tipos de pesca. Proponemos un encuadre de conservación para orientar a futuro la gestión y conservación de los TME, el cual destaque la necesidad de reconocer la importancia de estos ecosistemas biológicamente diversos y funcionalmente importantes.

Communication of nutrition information by influencers on social media: A scoping review.

ISSUE ADDRESSED: Although government promoted public health, social media and media campaigns have communicated nutrition information, the Australian population remains chronic under-consumers of fruit and vegetables and overconsumers of ultra-processed foods. This scoping review aimed to determine how social media influencers (SMI) communicate nutrition information and the factors that influence the popularity of messages. Identified factors could inform how governments may utilise social media to impact positively on food choices. METHODS: Nine databases were searched in the past 5 years (2016-2021). After relevant sources were identified, entire texts of the grey literature and the "Results" sections of the academic literature were coded. Using Microsoft Word, each key feature of the relevant text was highlighted, and the relevant code was recorded. Inductive coding was utilised where codes were created based on the text itself. These codes were then sorted iteratively into relevant themes and subthemes. RESULTS: Eleven studies were included. From these sources, five themes were identified. These were, (i) promoting dietary change, (ii) certain modes/styles of content delivery, (iii) an attractive individual, (iv) language features and (v) appearing connected to the audience. CONCLUSION: SMI are selective in their content and communication techniques to ensure their nutrition messages are popular with social media users. These methods exhibited by SMI could inform strategies to build trust in government messages about food and nutrition.

Hospice care access inequalities: a systematic review and narrative synthesis.

BACKGROUND: Inequalities in access to hospice care is a source of considerable concern; white, middle-class, middle-aged patients with cancer have traditionally been over-represented in hospice populations. OBJECTIVE: To identify from the literature the demographic characteristics of those who access hospice care more often, focusing on: diagnosis, age, gender, marital status, ethnicity, geography and socioeconomic status. DESIGN: Systematic literature review and narrative synthesis. METHOD: Searches of Medline, PsycINFO, CINAHL, Web of Science, Assia and Embase databases from January 1987 to end September 2019 were conducted. Inclusion criteria were peer-reviewed studies of adult patients in the UK, Australia, New Zealand and Canada, receiving inpatient, day, outpatient and community hospice care. Of the 45 937 titles retrieved, 130 met the inclusion criteria. Narrative synthesis of extracted data was conducted. RESULTS: An extensive literature search demonstrates persistent inequalities in hospice care provision: patients without cancer, the oldest old, ethnic minorities and those living in rural or deprived areas are under-represented in hospice populations. The effect of gender and marital status is inconsistent. There is a limited literature concerning hospice service access for the LGBTQ+ community, homeless people and those living with HIV/AIDS, diabetes and cystic fibrosis. CONCLUSION: Barriers of prognostic uncertainty, institutional cultures, particular needs of certain groups and lack of public awareness of hospice services remain substantial challenges to the hospice movement in ensuring equitable access for all.

Preimplantation Genetic Testing for Monogenic Conditions: Is Cell-Free DNA Testing the Next Step?

Genetic assessment of an embryo via preimplantation genetic testing (PGT) represents an important reproductive option for couples wanting to try and improve success rates from in vitro fertilisation (IVF) cycles, as well as reduce their risk of having a child born with a genetic condition. Currently, biopsy of the developing embryo prior to transfer allows genetic assessment of an embryo for either chromosome copy number (aneuploidy [PGT-A] or segmental rearrangement [PGT-SR]) or to avoid the transmission of a single gene condition (monogenic conditions [PGT-M]). However, this technology is invasive and commands considerable resources. Non-invasive PGT (niPGT) offers a potential alternate mode of embryonic analysis. Whilst the utility of niPGT-A has been recently explored, there has been limited consideration of niPGT-M as an option for couples at risk of passing on a single gene or chromosomal condition. This review examines the historical and current clinical context of preimplantation embryonic analysis for monogenic conditions, in addition to important considerations surrounding the origin and analysis of cell-free deoxyribose nucleic acid (cfDNA), whether it is sourced via blastocentesis or spent embryonic culture medium (SCM). Future capabilities of this testing modality will almost certainly be enhanced by integration of whole genome sequencing into everyday practice. In addition, the increased utilisation of reproductive carrier screening as part of standard reproductive healthcare will likely result in the identification of a larger high-risk population. As a result, stratification of limited and highly specialised reproductive genetic resources will be required. Prospective parents should continue to be made aware of the limitations of this technology, with prenatal confirmatory testing remaining an essential part of antenatal care in these patients. However, niPGT-M poses an important alternate testing modality for high-risk couples, particularly in the setting of embryos that cannot be biopsied for traditional PGT-M and as demand for this treatment continues to grow.

From data compilation to model validation: comparing three ecosystem models of the Tasman and Golden Bays, New Zealand.

The Tasman and Golden Bays (TBGB) are a semi-enclosed embayment system in New Zealand that supports numerous commercial and recreational activities. We present three ecosystem models of the TBGB ecosystem with varying levels of complexity, aimed at contributing as tools to aid in understanding this ecosystem and its responses to anthropogenic and natural pressures. We describe the process of data compilation through to model validation and analyse the importance of knowledge gaps with respect to model dynamics and results. We compare responses in all three models to historical fishing, and analyse similarities and differences in the dynamics of the three models. We assessed the most complex of the models against initialisation uncertainty and sensitivity to oceanographic variability and found it most sensitive to the latter. We recommend that scenarios relating to ecosystem dynamics of the TBGB ecosystem include sensitivities, especially oceanographic uncertainty, and compare responses across all three models where it is possible to do so.

Calorie provision from citrate anticoagulation in continuous renal replacement therapy in critical care.

BACKGROUND: Citrate is used as a regional anticoagulant for continuous veno-venous haemofiltration and provides 0.59 kcal/mmol. Previous studies hypothesised continuous veno-venous haemofiltration can provide 200-1300 kcal/day dependent on the anticoagulant and replacement solutions used. The aim of this study was to calculate the calorie load from citrate in our patient group. METHODS: An equation derived from a paper by Oudemans-van Straaten was used to estimate calorie provision from citrate. Citrate calorie load was defined as the difference between the citrate in the filter circuit and the removal by continuous veno-venous haemofiltration. Clinical data were recorded on 20 consecutive patients admitted to intensive care unit and commenced on citrate continuous veno-venous haemofiltration using prismacitrate 18/0 by Gambro, a tri-sodium citrate solution. Clinical data recorded included patient demographics, filter settings including blood flow, filtration factor, citrate dose and time on filtration daily. RESULTS: A total of 20 critically ill patients received continuous veno-venous haemofiltration for treatment of a new acute kidney injury, mean age 66 years, 65% male. Mean duration of continuous veno-venous haemofiltration was 3.7 days. Mean daily time on filtration was 20 h/day. Mean filtration fraction, citrate dose and blood flow were 30%, 3 mmol/L and 123 ml/min, respectively. Our calculation showed that a mean of 9.5 ± 1.7 cal/h were provided from citrate with a mean daily calorie load of 196 ± 69 kcal. CONCLUSIONS: Continuous veno-venous haemofiltration with tri-sodium citrate provided an additional 196 ± 69 kcal/day. The calorie load from citrate continuous veno-venous haemofiltration should be calculated regularly as changes in filter settings, in particular citrate dose and blood flow can have a significant impact on calorie provision.

E2F/Dp inactivation in fat body cells triggers systemic metabolic changes.

The E2F transcription factors play a critical role in controlling cell fate. In Drosophila, the inactivation of E2F in either muscle or fat body results in lethality, suggesting an essential function for E2F in these tissues. However, the cellular and organismal consequences of inactivating E2F in these tissues are not fully understood. Here, we show that the E2F loss exerts both tissue-intrinsic and systemic effects. The proteomic profiling of E2F-deficient muscle and fat body revealed that E2F regulates carbohydrate metabolism, a conclusion further supported by metabolomic profiling. Intriguingly, animals with E2F-deficient fat body had a lower level of circulating trehalose and reduced storage of fat. Strikingly, a sugar supplement was sufficient to restore both trehalose and fat levels, and subsequently rescued animal lethality. Collectively, our data highlight the unexpected complexity of E2F mutant phenotype, which is a result of combining both tissue-specific and systemic changes that contribute to animal development.

Mangroves reduce the vulnerability of coral reef fisheries to habitat degradation.

Despite general and wide-ranging negative effects of coral reef degradation on reef communities, hope might exist for reef-associated predators that use nursery habitats. When reef structural complexity is lost, refuge density declines and prey vulnerability increases. Here, we explore whether the presence of nursery habitats can promote high predator productivity on degraded reefs by mitigating the costs of increased vulnerability in early life, whilst allowing for the benefits of increased food availability in adulthood. We apply size-based ecosystem models of coral reefs with high and low structural complexity to predict fish biomass and productivity in the presence and absence of mangrove nurseries. Our scenarios allow us to elucidate the interacting effects of refuge availability and ontogenetic habitat shifts for fisheries productivity. We find that low complexity, degraded reefs with nurseries can support fisheries productivity that is equal to or greater than that in complex reefs that lack nurseries. We compare and validate model predictions with field data from Belize. Our results should inform reef fisheries management strategies and protected areas now and into the future.

Rbf Activates the Myogenic Transcriptional Program to Promote Skeletal Muscle Differentiation.

The importance of the retinoblastoma tumor suppressor protein pRB in cell cycle control is well established. However, less is known about its role in differentiation during animal development. Here, we investigated the role of Rbf, the Drosophila pRB homolog, in adult skeletal muscles. We found that the depletion of Rbf severely reduced muscle growth and altered myofibrillogenesis but only minimally affected myoblast proliferation. We identified an Rbf-dependent transcriptional program in late muscle development that is distinct from the canonical role of Rbf in cell cycle control. Unexpectedly, Rbf acts as a transcriptional activator of the myogenic and metabolic genes in the growing muscles. The genomic regions bound by Rbf contained the binding sites of several factors that genetically interacted with Rbf by modulating Rbf-dependent phenotype. Thus, our results reveal a distinctive role for Rbf as a direct activator of the myogenic transcriptional program that drives late muscle differentiation.

Deep reefs of the Great Barrier Reef offer limited thermal refuge during mass coral bleaching.

Our rapidly warming climate is threatening coral reefs as thermal anomalies trigger mass coral bleaching events. Deep (or "mesophotic") coral reefs are hypothesised to act as major ecological refuges from mass bleaching, but empirical assessments are limited. We evaluated the potential of mesophotic reefs within the Great Barrier Reef (GBR) and adjacent Coral Sea to act as thermal refuges by characterising long-term temperature conditions and assessing impacts during the 2016 mass bleaching event. We found that summer upwelling initially provided thermal relief at upper mesophotic depths (40 m), but then subsided resulting in anomalously warm temperatures even at depth. Bleaching impacts on the deep reefs were severe (40% bleached and 6% dead colonies at 40 m) but significantly lower than at shallower depths (60-69% bleached and 8-12% dead at 5-25 m). While we confirm that deep reefs can offer refuge from thermal stress, we highlight important caveats in terms of the transient nature of the protection and their limited ability to provide broad ecological refuge.

High refuge availability on coral reefs increases the vulnerability of reef-associated predators to overexploitation.

Refuge availability and fishing alter predator-prey interactions on coral reefs, but our understanding of how they interact to drive food web dynamics, community structure and vulnerability of different trophic groups is unclear. Here, we apply a size-based ecosystem model of coral reefs, parameterized with empirical measures of structural complexity, to predict fish biomass, productivity and community structure in reef ecosystems under a broad range of refuge availability and fishing regimes. In unfished ecosystems, the expected positive correlation between reef structural complexity and biomass emerges, but a non-linear effect of predation refuges is observed for the productivity of predatory fish. Reefs with intermediate complexity have the highest predator productivity, but when refuge availability is high and prey are less available, predator growth rates decrease, with significant implications for fisheries. Specifically, as fishing intensity increases, predators in habitats with high refuge availability exhibit vulnerability to over-exploitation, resulting in communities dominated by herbivores. Our study reveals mechanisms for threshold dynamics in predators living in complex habitats and elucidates how predators can be food-limited when most of their prey are able to hide. We also highlight the importance of nutrient recycling via the detrital pathway, to support high predator biomasses on coral reefs.

Multiple Stressors and the Functioning of Coral Reefs.

Coral reefs provide critical services to coastal communities, and these services rely on ecosystem functions threatened by stressors. By summarizing the threats to the functioning of reefs from fishing, climate change, and decreasing water quality, we highlight that these stressors have multiple, conflicting effects on functionally similar groups of species and their interactions, and that the overall effects are often uncertain because of a lack of data or variability among taxa. The direct effects of stressors on links among functional groups, such as predator-prey interactions, are particularly uncertain. Using qualitative modeling, we demonstrate that this uncertainty of stressor impacts on functional groups (whether they are positive, negative, or neutral) can have significant effects on models of ecosystem stability, and reducing uncertainty is vital for understanding changes to reef functioning. This review also provides guidance for future models of reef functioning, which should include interactions among functional groups and the cumulative effect of stressors.