A hot-Jupiter progenitor on a super-eccentric retrograde orbit.

Giant exoplanets orbiting close to their host stars are unlikely to have formed in their present configurations1. These 'hot Jupiter' planets are instead thought to have migrated inward from beyond the ice line and several viable migration channels have been proposed, including eccentricity excitation through angular-momentum exchange with a third body followed by tidally driven orbital circularization2,3. The discovery of the extremely eccentric (e = 0.93) giant exoplanet HD 80606 b (ref. 4) provided observational evidence that hot Jupiters may have formed through this high-eccentricity tidal-migration pathway5. However, no similar hot-Jupiter progenitors have been found and simulations predict that one factor affecting the efficacy of this mechanism is exoplanet mass, as low-mass planets are more likely to be tidally disrupted during periastron passage6-8. Here we present spectroscopic and photometric observations of TIC 241249530 b, a high-mass, transiting warm Jupiter with an extreme orbital eccentricity of e = 0.94. The orbit of TIC 241249530 b is consistent with a history of eccentricity oscillations and a future tidal circularization trajectory. Our analysis of the mass and eccentricity distributions of the transiting-warm-Jupiter population further reveals a correlation between high mass and high eccentricity.

The making of child and adolescent psychiatrists in Australia and New Zealand.

Child and adolescent psychiatry has an opportunity to adapt alongside the advancements in medical knowledge, post-graduate training, epidemiological realities and clinical service models. Here, we are guided by the mental health needs of our community's young and their families in our review of child and adolescent psychiatry training in Australia and New Zealand. We recognise that training must respond to clinical demand and service reform while ensuring a range of clinical and educational experiences to deliver expectable competencies in order to produce child and adolescent psychiatrists that meet the communities' needs now and in the future. We argue that training programmes be subject to rigorous evaluation by embedding continuing cycles of improvement including regular review and international bench marking.

International perspective on integrated care models in child and adult mental health.

The dearth of child and adolescent mental health services (CAMHS) is a global problem. Integrating CAMHS in primary care has been offered as a solution. We sampled integrated care perspectives from colleagues around the world. Our findings include various models of integrated care namely: the stepped care model in Australia; shared care in the United Kingdom (UK) and Spain; school-based collaborative care in Qatar, Singapore and the state of Texas in the US; collaborative care in Canada, Brazil, US, and Uruguay; coordinated care in the US; and, developing collaborative care models in low-resource settings, like Kenya and Micronesia. These findings provide insights into training initiatives necessary to build CAMHS workforce capacity using integrated care models, each with the ultimate goal of improving access to care. Despite variations and progress in implementing integrated care models internationally, common challenges exist: funding within complex healthcare systems, limited training mechanisms, and geopolitical/policy issues. Supportive healthcare policy, robust training initiatives, ongoing quality improvement and measurement of outcomes across programs would provide data-driven support for the expansion of integrated care and ensure its sustainability.

Pilot study of a noninvasive real-time optical backscatter probe in liver transplantation.

Transplantation of severely steatotic donor livers is associated with early allograft dysfunction and poorer graft survival. Histology remains the gold standard diagnostic of donor steatosis despite the lack of consensus definition and its subjective nature. In this prospective observational study of liver transplant patients, we demonstrate the feasibility of using a handheld optical backscatter probe to assess the degree of hepatic steatosis and correlate the backscatter readings with clinical outcomes. The probe is placed on the surface of the liver and emits red and near infrared light from the tip of the device and measures the amount of backscatter of light from liver tissue via two photodiodes. Measurement of optical backscatter (Mantel-Cox P < 0.0001) and histopathological scoring of macrovesicular steatosis (Mantel-Cox P = 0.046) were predictive of 5-year graft survival. Recipients with early allograft dysfunction defined according to both Olthoff (P = 0.0067) and MEAF score (P = 0.0097) had significantly higher backscatter levels from the donor organ. Backscatter was predictive of graft loss (AUC 0.75, P = 0.0045). This study demonstrates the feasibility of real-time measurement of optical backscatter in donor livers. Early results indicate readings correlate with steatosis and may give insight to graft outcomes such as early allograft dysfunction and graft loss.

Relative survival and quality of life benefits of pancreas-kidney transplantation, deceased kidney transplantation and dialysis in type 1 diabetes mellitus-a probabilistic simulation model.

For patients with type 1 diabetes mellitus who progress to the point of requiring renal replacement therapy, the relative benefits of simultaneous pancreas and kidney transplantation (SPK) and deceased donor kidney transplantation across different age categories compared to dialysis are uncertain. Using Australian and New Zealand registry data from 2006 to 2016, a probabilistic Markov model (n = 10 000) was built comparing patient survival between SPK and deceased donor kidney transplantation with dialysis. Compared to dialysis, the average life years saved (LYS) and quality-adjusted life years (QALY) for SPK and deceased donor kidney transplantation were 5.48 [95% CI 5.47, 5.49] LYS and 6.48 [6.47, 6.49] QALY, and 3.38 [3.36, 3.40] LYS and 2.46 [2.45, 2.47] QALY, respectively. For recipients aged 50 years or younger, receiving a deceased donor kidney, the average incremental gains compared to dialysis were 4.13 [4.10, 4.16] LYS and 2.99 [2.97, 3.01] QALY, and for recipients older than 50 years, 3.05 [3.02, 3.08] LYS and 2.25 [2.23, 2.27] QALY. Compared to dialysis, SPK transplantation incurs the greatest benefits in LYS and QALY for patients with type 1 diabetes requiring renal replacement therapy. Patients older than 50 years still experience survival benefits from deceased donor kidney transplantation compared to dialysis.

CAMH in Primary Care Fiji: developing child and adolescent mental health in primary care.

OBJECTIVE: To describe the CAMH in Primary Care Fiji Project. METHODS: The context; process of development and planning; aims and goals; delivery and outcome are described. RESULTS: Two CAMH in Primary Care Fiji training workshops were delivered in 2017 and 2018 with positive structured and unstructured feedback. CONCLUSION: A successful, collaboratively developed, culturally appropriate and replicable training for primary care in CAMH is possible.

Child and Adolescent Psychiatry International Relations (CAPIR): building bridges for psychiatry workforce capacity with Pacific Island nations.

OBJECTIVE: To describe the span of work of child and adolescent psychiatrists in Australia and New Zealand in recent years aimed at collaborative efforts to build mental health capacity in the Pacific Island nations of Fiji, Samoa, Cook Islands, Tonga, Kiribati, Vanuatu, Solomon Islands and Papua New Guinea. METHOD: Steps taken to coordinate resourcing, networking, delivery of appropriate initiatives, establishing and maintaining key relationships with partners are described. RESULTS: Engagement with Pacific nations mental health professionals, ministries of health, NGOs, universities, multilateral agencies and professional and international organisations has expanded and strengthened since 2013. CONCLUSIONS: Planned and staged implementation of initiatives can harness RANZCP (and its faculties and interest groups) goodwill to effectively contribute to psychiatry and mental health capacity building in partnerships with Pacific Island nations to address mental health needs over the life-span.

Pasifika Study Group: a child and adolescent mental health capacity building and leadership workshop with Pacific nations doctors and psychiatrists.

OBJECTIVE: To describe the Pasifika Study Group (PSG), a biennial workshop for Pacific nations psychiatrists and doctors working in psychiatry under the auspices of the Royal Australian and New Zealand College of Psychiatry Faculty of Child and Adolescent Psychiatry. METHOD: Since 2013 the PSG has brought together doctors and other health professionals from eight Pacific nations for a two-day study group. RESULTS: On evaluation the PSG is considered informative and relevant and participants were generally confident of adapting the material to their own context. CONCLUSION: The PSG demonstrates a successful approach to regional engagement in mental health in the Pacific region.

Transcriptomic profiling of purified patient-derived dopamine neurons identifies convergent perturbations and therapeutics for Parkinson's disease.

While induced pluripotent stem cell (iPSC) technologies enable the study of inaccessible patient cell types, cellular heterogeneity can confound the comparison of gene expression profiles between iPSC-derived cell lines. Here, we purified iPSC-derived human dopaminergic neurons (DaNs) using the intracellular marker, tyrosine hydroxylase. Once purified, the transcriptomic profiles of iPSC-derived DaNs appear remarkably similar to profiles obtained from mature post-mortem DaNs. Comparison of the profiles of purified iPSC-derived DaNs derived from Parkinson's disease (PD) patients carrying LRRK2 G2019S variants to controls identified significant functional convergence amongst differentially-expressed (DE) genes. The PD LRRK2-G2019S associated profile was positively matched with expression changes induced by the Parkinsonian neurotoxin rotenone and opposed by those induced by clioquinol, a compound with demonstrated therapeutic efficacy in multiple PD models. No functional convergence amongst DE genes was observed following a similar comparison using non-purified iPSC-derived DaN-containing populations, with cellular heterogeneity appearing a greater confound than genotypic background.

An abundance of small exoplanets around stars with a wide range of metallicities.

The abundance of heavy elements (metallicity) in the photospheres of stars similar to the Sun provides a 'fossil' record of the chemical composition of the initial protoplanetary disk. Metal-rich stars are much more likely to harbour gas giant planets, supporting the model that planets form by accumulation of dust and ice particles. Recent ground-based surveys suggest that this correlation is weakened for Neptunian-sized planets. However, how the relationship between size and metallicity extends into the regime of terrestrial-sized exoplanets is unknown. Here we report spectroscopic metallicities of the host stars of 226 small exoplanet candidates discovered by NASA's Kepler mission, including objects that are comparable in size to the terrestrial planets in the Solar System. We find that planets with radii less than four Earth radii form around host stars with a wide range of metallicities (but on average a metallicity close to that of the Sun), whereas large planets preferentially form around stars with higher metallicities. This observation suggests that terrestrial planets may be widespread in the disk of the Galaxy, with no special requirement of enhanced metallicity for their formation.

Transiting circumbinary planets Kepler-34 b and Kepler-35 b.

Most Sun-like stars in the Galaxy reside in gravitationally bound pairs of stars (binaries). Although long anticipated, the existence of a 'circumbinary planet' orbiting such a pair of normal stars was not definitively established until the discovery of the planet transiting (that is, passing in front of) Kepler-16. Questions remained, however, about the prevalence of circumbinary planets and their range of orbital and physical properties. Here we report two additional transiting circumbinary planets: Kepler-34 (AB)b and Kepler-35 (AB)b, referred to here as Kepler-34 b and Kepler-35 b, respectively. Each is a low-density gas-giant planet on an orbit closely aligned with that of its parent stars. Kepler-34 b orbits two Sun-like stars every 289 days, whereas Kepler-35 b orbits a pair of smaller stars (89% and 81% of the Sun's mass) every 131 days. The planets experience large multi-periodic variations in incident stellar radiation arising from the orbital motion of the stars. The observed rate of circumbinary planets in our sample implies that more than ∼1% of close binary stars have giant planets in nearly coplanar orbits, yielding a Galactic population of at least several million.

Decoding the hallmarks of allograft dysfunction with a comprehensive pan-organ transcriptomic atlas.

The pathogenesis of allograft (dys)function has been increasingly studied using 'omics'-based technologies, but the focus on individual organs has created knowledge gaps that neither unify nor distinguish pathological mechanisms across allografts. Here we present a comprehensive study of human pan-organ allograft dysfunction, analyzing 150 datasets with more than 12,000 samples across four commonly transplanted solid organs (heart, lung, liver and kidney, n = 1,160, 1,241, 1,216 and 8,853 samples, respectively) that we leveraged to explore transcriptomic differences among allograft dysfunction (delayed graft function, acute rejection and fibrosis), tolerance and stable graft function. We identified genes that correlated robustly with allograft dysfunction across heart, lung, liver and kidney transplantation. Furthermore, we developed a transfer learning omics prediction framework that, by borrowing information across organs, demonstrated superior classifications compared to models trained on single organs. These findings were validated using a single-center prospective kidney transplant cohort study (a collective 329 samples across two timepoints), providing insights supporting the potential clinical utility of our approach. Our study establishes the capacity for machine learning models to learn across organs and presents a transcriptomic transplant resource that can be employed to develop pan-organ biomarkers of allograft dysfunction.

A Neptune-mass exoplanet in close orbit around a very low-mass star challenges formation models.

Theories of planet formation predict that low-mass stars should rarely host exoplanets with masses exceeding that of Neptune. We used radial velocity observations to detect a Neptune-mass exoplanet orbiting LHS 3154, a star that is nine times less massive than the Sun. The exoplanet's orbital period is 3.7 days, and its minimum mass is 13.2 Earth masses. We used simulations to show that the high planet-to-star mass ratio (>3.5 × 10-4) is not an expected outcome of either the core accretion or gravitational instability theories of planet formation. In the core-accretion simulations, we show that close-in Neptune-mass planets are only formed if the dust mass of the protoplanetary disk is an order of magnitude greater than typically observed around very low-mass stars.

Lysine 624 of the amyloid precursor protein (APP) is a critical determinant of amyloid ß peptide length: support for a sequential model of γ-secretase intramembrane proteolysis and regulation by the amyloid ß precursor protein (APP) juxtamembrane region.

γ-Secretase is a multiprotein intramembrane cleaving aspartyl protease (I-CLiP) that catalyzes the final cleavage of the amyloid ß precursor protein (APP) to release the amyloid ß peptide (Aß). Aß is the primary component of senile plaques in Alzheimer's disease (AD), and its mechanism of production has been studied intensely. γ-Secretase executes multiple cleavages within the transmembrane domain of APP, with cleavages producing Aß and the APP intracellular domain (AICD), referred to as γ and ε, respectively. The heterogeneous nature of the γ cleavage that produces various Aß peptides is highly relevant to AD, as increased production of Aß 1-42 is genetically and biochemically linked to the development of AD. We have identified an amino acid in the juxtamembrane region of APP, lysine 624, on the basis of APP695 numbering (position 28 relative to Aß) that plays a critical role in determining the final length of Aß peptides released by γ-secretase. Mutation of this lysine to alanine (K28A) shifts the primary site of γ-secretase cleavage from 1-40 to 1-33 without significant changes to ε cleavage. These results further support a model where ε cleavage occurs first, followed by sequential proteolysis of the remaining transmembrane fragment, but extend these observations by demonstrating that charged residues at the luminal boundary of the APP transmembrane domain limit processivity of γ-secretase.

Piloting online training in the Pacific-Ophelia project for child and adolescent mental health.

INTRODUCTION: In June 2020, St Vincent's Mental Health, Fiji National University, and the Royal Australian and New Zealand College of Psychiatrists, Faculty of Child and Adolescent Psychiatry collaborated to deliver online, specialized child and adolescent mental health (CAMH) training to Pacific-based healthcare workers. This accompanying research aimed to understand the telehealth model and structures that would sustain an engaged community of practice and support the development of professional networks across the Pacific. METHOD: Quantitative and qualitative feedback was analyzed to understand participation and self-rated measures of skills, knowledge, and confidence in providing health care for children and young people, as well as experiences of training, including access, engagement, and applicability of the initiative to the Pacific Islands health care organizations. RESULTS: Ophelia Training was able to meet the stated learning objectives. The data from all stakeholders identifies the value of a telehealth initiative incorporating training, technical assistance, knowledge networks, and professional coaching as a capacity building approach. CONCLUSION: This program offers an integration of research and practice. This regional approach to understanding telehealth capacity for Pacific Island mental health services is valuable for informing decision-making with respect to clinical care, management, workforce training and policy. It also provided an opportunity to improve health inequalities, by improving access to CAMH training via telehealth.

Pancreas transplantation outside the USA: an update.

PURPOSE OF REVIEW: Due to the extreme lack of an international registry of pancreas transplantation, the purpose of this review was to conduct an extensive collection of data on the activity of pancreas transplantation in non-United States areas. RECENT FINDINGS: Over 10 000 pancreas transplants were collected in non-US areas. These countries together account for annual activity of about 1100 pancreas transplants out of which 85% are simultaneous pancreas-kidney transplants. Europe stands with 6766 pancreas transplantation, followed by Latin America with 1945, Canada with 671, Oceania with 499, Asia with 222 and Africa with five. Adding this activity of pancreas transplantation to the US data, we reach the mark of about 32 000 pancreas transplants performed worldwide and the overall activity roughly 'jumps' to approximately 2300 procedures annually. SUMMARY: From the data collected in this article, it is possible to have a current dimension of the pancreas transplantation activity worldwide. This study should serve as a stimulus for the creation of a single international registry and guide future analysis and protocols in the pancreas transplantation field in different continents.

The relationship between tendency to attend to detail, sensory sensitivity, and affective response to food cues - A registered report.

Understanding the underlying drivers of food choice remains a challenge and has highlighted the need for measures that capture data over and above that offered by self-reporting tools. Consequently, a growing body of research has set out to interpret facial responses to food cues to offer a greater insight into the emotional responses that may drive food acceptance. However, interpreting facial responses is challenging, as there are numerous factors that may influence affective response to foods, including expectation, context, and individual differences. Existing findings suggest there is a link between autistic traits and sensory sensitivities; research highlights further links between sensory sensitivities and eating behaviour, and autistic traits and eating behaviour, with a body of research focusing on the autistic trait attention to detail (ATD). As such, the current study aimed to examine rapid facial activity in response to foods cues while capturing these individual differences present in the general population. This study found no evidence to suggest facial responses to food pictures were linked with attention to detail or hyper-sensitivity. The findings did support a general link between self-reported pleasantness ratings of viewed foods and activity of facial muscles. Post-hoc analyses suggested scoring on the social skills sub-scale of the Autism Quotient (AQ) was associated with levator activity while viewing pictures low in pleasantness. This study offers a greater understanding of variations, at the individual level, which are associated with affective response to foods, and may help to inform the development of tools that set out to predict food acceptance.