The properties of discs around planets and brown dwarfs as evidence for disc fragmentation

Direct imaging searches have revealed many very low mass objects, including a small number of planetary-mass objects, as wide-orbit companions to young stars. The formation mechanism of these objects remains uncertain. In this paper, we present the predictions of the disc fragmentation model regarding the properties of the discs around such low-mass objects. We find that the discs around objects that have formed by fragmentation in discs hosted by Sun-like stars (referred to as parent discs and parent stars) are more massive than expected from the M disc-M∗relation (which is derived for stars with masses M∗>0.2M). Accordingly, the accretion rates on to these objects are also higher than expected from thė M∗−M∗relation. Moreover, there is no significant correlation between the mass of the brown dwarf or planet with the mass of its disc nor with the accretion rate from the disc on to it. The discs around objects that form by disc fragmentation have larger than expected masses as they accrete gas from the disc of their parent star during the first few kyr after they form. The amount of gas that they accrete and therefore their mass depend on how they move in their parent disc and how they interact with it. Observations of disc masses and accretion rates on to very low mass objectsareconsistentwiththepredictionsofthediscfragmentationmodel.Futureobservations (e.g. by Atacama Large Millimeter/submillimeter Array) of disc masses and accretion rates on to substellar objects that have even lower masses (young planets and young, low-mass brown dwarfs), where the scaling relations predicted by the disc fragmentation model diverge significantly from the corresponding relations established for higher mass stars, will test the predictions of this model

Guidance on the Use of Complex Systems Models for Economic Evaluations of Public Health Interventions

To help health economic modelers respond to demands for greater use of complex systems models in public health. To propose identifiable features of such models and support researchers to plan public health modeling projects using these models. A working group of experts in complex systems modeling and economic evaluation was brought together to develop and jointly write guidance for the use of complex systems models for health economic analysis. The content of workshops was informed by a scoping review. A public health complex systems model for economic evaluation is defined as a quantitative, dynamic, non-linear model that incorporates feedback and interactions among model elements, in order to capture emergent outcomes and estimate health, economic and potentially other consequences to inform public policies. The guidance covers: when complex systems modeling is needed; principles for designing a complex systems model; and how to choose an appropriate modeling technique. This paper provides a definition to identify and characterize complex systems models for economic evaluations and proposes guidance on key aspects of the process for health economics analysis. This document will support the development of complex systems models, with impact on public health systems policy and decision making

Sequencing, Mapping, and Analysis of 27,455 Maize Full-Length cDNAs

Full-length cDNA (FLcDNA) sequencing establishes the precise primary structure of individual gene transcripts. From two libraries representing 27 B73 tissues and abiotic stress treatments, 27,455 high-quality FLcDNAs were sequenced. The average transcript length was 1.44 kb including 218 bases and 321 bases of 5′ and 3′ UTR, respectively, with 8.6% of the FLcDNAs encoding predicted proteins of fewer than 100 amino acids. Approximately 94% of the FLcDNAs were stringently mapped to the maize genome. Although nearly two-thirds of this genome is composed of transposable elements (TEs), only 5.6% of the FLcDNAs contained TE sequences in coding or UTR regions. Approximately 7.2% of the FLcDNAs are putative transcription factors, suggesting that rare transcripts are well-enriched in our FLcDNA set. Protein similarity searching identified 1,737 maize transcripts not present in rice, sorghum, Arabidopsis, or poplar annotated genes. A strict FLcDNA assembly generated 24,467 non-redundant sequences, of which 88% have non-maize protein matches. The FLcDNAs were also assembled with 41,759 FLcDNAs in GenBank from other projects, where semi-strict parameters were used to identify 13,368 potentially unique non-redundant sequences from this project. The libraries, ESTs, and FLcDNA sequences produced from this project are publicly available. The annotated EST and FLcDNA assemblies are available through the maize FLcDNA web resource (www.maizecdna.org)

Ethical, legal and social aspects of human cerebral organoids and their governance in Germany, the United Kingdom and the United States

Human cerebral organoids (HCOs) are model systems that enable researchers to investigate the human brain in ways that had previously been impossible. The emergence of HCOs was accompanied by both expert and layperson discussions concerning the possibility of these novel entities developing sentience or consciousness. Such concerns are reflected in deliberations about how to handle and regulate their use. This perspective article resulted from an international and interdisciplinary research retreat “Ethical, Legal and Social Aspects of Human Cerebral Organoids and their Governance in Germany, the United Kingdom and the United States”, which took place in Tübingen, Germany, in August 2022. The retreat focused on whether HCO research requires new ethical and regulatory approaches. It addressed epistemic issues around the detection and theorisation of consciousness, ethical concerns around moral status and research conduct, difficulties for legislation and guidelines managing these entities, and public engagement

The Baltimore declaration toward the exploration of organoid intelligence

We, the participants of the First Organoid Intelligence Workshop - "Forming an OI Community" (22-24 February 2022), call on the international scientific community to explore the potential of human brain-based organoid cell cultures to advance our understanding of the brain and unleash new forms of biocomputing while recognizing and addressing the associated ethical implications. The term "organoid intelligence" (OI) has been coined to describe this research and development approach (1) in a manner consistent with the term "artificial intelligence" (AI) - used to describe the enablement of computers to perform tasks normally requiring human intelligence. OI has the potential for diverse and far-reaching applications that could benefit humankind and our planet, and which urge the strategic development of OI as a collaborative scientific discipline. OI holds promise to elucidate the physiology of human cognitive functions such as memory and learning. It presents game-changing opportunities in biological and hybrid computing that could overcome significant limitations in silicon-based computing. It offers the prospect of unparalleled advances in interfaces between brains and machines. Finally, OI could allow breakthroughs in modeling and treating dementias and other neurogenerative disorders that cause an immense and growing disease burden globally. Realizing the world-changing potential of OI will require scientific breakthroughs. We need advances in human stem cell technology and bioengineering to recreate brain architectures and to model their potential for pseudo-cognitive capabilities. We need interface breakthroughs to allow us to deliver input signals to organoids, measure output signals, and employ feedback mechanisms to model learning processes. We also need novel machine learning, big data, and AI technologies to allow us to understand brain organoids

Fracture in the Elderly Multidisciplinary Rehabilitation (FEMuR): study protocol for a phase II randomised feasibility study of a multidisciplinary rehabilitation package following hip fracture

Objective: To conduct a rigorous feasibility study for a future definitive parallel-group randomised controlled trial (RCT) and economic evaluation of an enhanced rehabilitation package for hip fracture.Setting: Recruitment from 3 acute hospitals in North Wales. Intervention delivery in the community.Participants: Older adults (aged ≥65) who received surgical treatment for hip fracture, lived independently prior to fracture, had mental capacity (assessed by clinical team) and received rehabilitation in the North Wales area.Intervention: Remote randomisation to usual care (control) or usual care+enhanced rehabilitation package (intervention), including six additional home-based physiotherapy sessions delivered by a physiotherapist or technical instructor, novel information workbook and goal-setting diary.Primary and secondary outcome measures: Primary: Barthel Activities of Daily Living (BADL). Secondary measures included Nottingham Extended Activities of Daily Living scale (NEADL), EQ-5D, ICECAP capability, a suite of self-efficacy, psychosocial and service-use measures and costs. Outcome measures were assessed at baseline and 3-month follow-up by blinded researchers.Results: 62 participants were recruited, 61 randomised (control 32; intervention 29) and 49 (79%) completed 3-month follow-up. Minimal differences occurred between the 2 groups for most outcomes, including BADL (adjusted mean difference 0.5). The intervention group showed a medium-sized improvement in the NEADL relative to the control group, with an adjusted mean difference between groups of 3.0 (Cohen's d 0.63), and a trend for greater improvement in self-efficacy and mental health, but with small effect sizes. The mean cost of delivering the intervention was £231 per patient. There was a small relative improvement in quality-adjusted life year in the intervention group. No serious adverse events relating to the intervention were reported.Conclusions: The trial methods were feasible in terms of eligibility, recruitment and retention. The effectiveness and cost-effectiveness of the rehabilitation package should be tested in a phase III RCT

Genetic Regulation of Human Brain Size Evolution

<p>The neocortex expanded spectacularly during human origins. That expansion is thought to form the foundation for our cognitive faculties underlying abstract reasoning and socialization. The human neocortex differs from that of other great apes in several notable regards including altered cell cycle, prolonged corticogenesis, and massively increased size. However, despite decades of effort, little progress has been made in uncovering the genetic contributions that underlie these differences that distinguish our species from closely related primate, such as chimpanzees. A subset of highly conserved non-coding regions that show rapid sequence changes along the human lineage are candidate loci for the development and evolution of uniquely human traits. Several studies have identified human-accelerated enhancers, but none have linked an expression difference to a organismal traits, such as brain sizes. Here we report the discovery of a human-accelerated regulatory enhancer (HARE5) near the Wnt receptor FRIZZLED-8 (FZD8). Using a variety of approaches, we demonstrate dramatic differences in human and chimpanzee HARE5 activity, with human HARE5 driving significantly strong expression. We show that HARE5 likely regulates FZD8 and that expression differences influence cell cycle kinetics, cortical layers, and brain size. At present, this would provide the first evidence of a human-chimpanzee genetic difference influencing the evolution of brain size.</p>Dissertatio