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Comets: looking ahead.

ABSTRACT: We outline the key questions about comets that must be answered in order to understand cometary formation in the context of the protoplanetary disc and the role of comets in the formation and evolution of the solar system. We then discuss the new understanding of comets from Rosetta and from other recent advances, including work presented by others at the discussion meeting. Finally, we suggest some key directions for future projects to better address the above questions.This article is part of the themed issue 'Cometary science after Rosetta'.

SUBMITTER: A'Hearn MF

PROVIDER: S-EPMC5454229 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Comets: looking ahead.

A'Hearn Michael F MF

Philosophical transactions. Series A, Mathematical, physical, and engineering sciences 20170701 2097

We outline the key questions about comets that must be answered in order to understand cometary formation in the context of the protoplanetary disc and the role of comets in the formation and evolution of the solar system. We then discuss the new understanding of comets from Rosetta and from other recent advances, including work presented by others at the discussion meeting. Finally, we suggest some key directions for future projects to better address the above questions.This article is part of ...[more]

PMID: 28554980

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Newborn screening for galactosemia in the United States: looking back, looking around, and looking ahead.

Project description:It has been 50 years since the first newborn screening (NBS) test for galactosemia was conducted in Oregon, and almost 10 years since the last US state added galactosemia to their NBS panel. During that time an estimated >2,500 babies with classic galactosemia have been identified by NBS. Most of these infants were spared the trauma of acute disease by early diagnosis and intervention, and many are alive today because of NBS. Newborn screening for galactosemia is a success story, but not yet a story with a completely happy ending. NBS, follow-up testing, and intervention for galactosemia continue to present challenges that highlight gaps in our knowledge. Here we compare galactosemia screening and follow-up data from 39 NBS programs gathered from the states directly or from public sources. On some matters the programs agreed: for example, those providing relevant data all identify classic galactosemia in close to 1/50,000 newborns and recommend immediate and lifelong dietary restriction of galactose for those infants. On other matters the programs disagree. For example, Duarte galactosemia (DG) detection rates vary dramatically among states, largely reflecting differences in screening approach. For infants diagnosed with DG, >80% of the programs surveyed recommend complete or partial dietary galactose restriction for the first year of life, or give mixed recommendations; <20% recommend no intervention. This disparity presents an ongoing dilemma for families and healthcare providers that could and should be resolved.

| S-EPMC4413015 | biostudies-literature

Looking ahead in working memory to guide sequential behaviour.

Project description:Working memory can maintain multiple sensory representations to serve unfolding sequential behaviour, such as while making tea or planning a route. How the human mind juggles internal representations as they become relevant to guide sequential behaviour remains poorly understood. Specifically, while there is good evidence that we can flexibly switch priorities among representations in working memory1-4, it is unclear how and when dormant memory representations are brought into focus during sequential behaviour. Capitalising on a recently established and temporally precise gaze marker of internal selection5,6, we reveal that the focus in the mind moves to the next-relevant memory representation while behaviour associated with the presently relevant memory representation is still ongoing. Thus, like visual sampling of external objects in the world7-9, internal visual sampling also 'looks ahead' to the next object in memory during sequential behaviour.

| S-EPMC8231093 | biostudies-literature

Gene therapy for primary immunodeficiencies: looking ahead, toward gene correction.

Project description:Allogeneic hematopoietic stem cell transplantation is the treatment of choice for severe primary immunodeficiencies (PIDs). For patients lacking an HLA-identical donor, gene therapy is an attractive therapeutic option. Approaches based on insertion of a functional gene by using viral vectors have provided proof of concept for the ability of gene therapy to cure PIDs. However, leukemic transformation as a result of insertional mutagenesis has been observed, prompting development of novel approaches based on introduction of DNA double-strand breaks into the endogenous locus to achieve gene correction, or into a safe genomic location ("safe harbor"). Homing endonucleases and zinc finger nucleases are target-specific endonucleases that induce site-specific DNA double-strand breaks, facilitating homologous recombination around their target sites to achieve gene correction or gene insertion into safe harbors. An alternative approach to achieve site-specific insertion of functional genes is based on transposons, DNA elements that spontaneously translocate from a specific chromosomal location to another. These novel tools may lead to efficient and safer strategies to achieve gene therapy for PIDs and other disorders.

| S-EPMC3105180 | biostudies-literature

Syntactic Versus Memory Accounts of the Sentence Comprehension Deficits of Specific Language Impairment: Looking Back, Looking Ahead.

Project description:PurposeCompared with same-age typically developing peers, school-age children with specific language impairment (SLI) exhibit significant deficits in spoken sentence comprehension. They also demonstrate a range of memory limitations. Whether these 2 deficit areas are related is unclear. The present review article aims to (a) review 2 main theoretical accounts of SLI sentence comprehension and various studies supporting each and (b) offer a new, broader, more integrated memory-based framework to guide future SLI research, as we believe the available evidence favors a memory-based perspective of SLI comprehension limitations.MethodWe reviewed the literature on the sentence comprehension abilities of English-speaking children with SLI from 2 theoretical perspectives.ResultsThe sentence comprehension limitations of children with SLI appear to be more fully captured by a memory-based perspective than by a syntax-specific deficit perspective.ConclusionsAlthough a memory-based view appears to be the better account of SLI sentence comprehension deficits, this view requires refinement and expansion. Current memory-based perspectives of adult sentence comprehension, with proper modification, offer SLI investigators new, more integrated memory frameworks within which to study and better understand the sentence comprehension abilities of children with SLI.

| S-EPMC5399765 | biostudies-literature

Looking back to look ahead: a vision for soil denitrification research.

Project description:Denitrification plays a critical role in regulating ecosystem nutrient availability and anthropogenic reactive nitrogen (N) production. Its importance has inspired an increasing number of studies, yet it remains the most poorly constrained term in terrestrial ecosystem N budgets. We censused the peer-reviewed soil denitrification literature (1975-2015) to identify opportunities for future studies to advance our understanding despite the inherent challenges in studying the process. We found that only one-third of studies reported estimates of both nitrous oxide (N2 O) and dinitrogen (N2 ) production fluxes, often the dominant end products of denitrification, while the majority of studies reported only net N2 O fluxes or denitrification potential. Of the 236 studies that measured complete denitrification to N2 , 49% used the acetylene inhibition method, 84% were conducted in the laboratory, 81% were performed on surface soils (0-20 cm depth), 75% were located in North America and Europe, and 78% performed treatment manipulations, mostly of N, carbon, or water. To improve understanding of soil denitrification, we recommend broadening access to technologies for new methodologies to measure soil N2 production rates, conducting more studies in the tropics and on subsoils, performing standardized experiments on unmanipulated soils, and using more precise terminology to refer to measured process rates (e.g., net N2 O flux or denitrification potential). To overcome the greater challenges in studying soil denitrification, we envision coordinated research efforts based on standard reporting of metadata for all soil denitrification studies, standard protocols for studies contributing to a Global Denitrification Research Network, and a global consortium of denitrification researchers to facilitate sharing ideas, resources, and to provide mentorship for researchers new to the field.

| S-EPMC6940507 | biostudies-literature

Looking ahead: When do you find the next item in foraging visual search?

Project description:Many real-world visual tasks involve searching for multiple instances of a target (e.g., picking ripe berries). What strategies do observers use when collecting items in this type of search? Do they wait to finish collecting the current item before starting to look for the next target, or do they search ahead for future targets? We utilized behavioral and eye-tracking measures to distinguish between these two possibilities in foraging search. Experiment 1 used a color wheel technique in which observers searched for T shapes among L shapes while all items independently cycled through a set of colors. Trials were abruptly terminated, and observers reported both the color and location of the next target that they intended to click. Using observers' color reports to infer target-finding times, we demonstrate that observers found the next item before the time of the click on the current target. We validated these results in Experiment 2 by recording fixation locations around the time of each click. Experiment 3 utilized a different procedure, in which all items were intermittently occluded during the trial. We then calculated a distribution of when targets were visible around the time of each click, allowing us to infer when they were most likely found. In a fourth and final experiment, observers indicated the locations of multiple future targets after the search was abruptly terminated. Together, our results provide converging evidence to demonstrate that observers can find the next target before collecting the current target and can typically forage one to two items ahead.

| S-EPMC7343403 | biostudies-literature

Clusterin: Review of research progress and looking ahead to direction in hepatocellular carcinoma.

Project description:Liver cancer, a large proportion of which is hepatocellular carcinoma (HCC), is diagnosed in more than 700000 people each year worldwide. Liver cancer is particularly prevalent in Asia, Sub-Saharan Africa and the South Pacific, where hepatitis B and hepatitis C infection rates are very high. However, due to resistance to chemotherapy, patients with intermediate and advanced-stage disease cannot benefit from this treatment. Clusterin, which is overexpressed in many different cancers, is a stress-induced cytoprotective protein that confers treatment resistance. Custirsen (OGX-011) is a novel 2'-methoxyethyl modified phosphorothioate antisense oligonucleotide that targets secretory clusterin protein expression and is currently in clinical trials for patients with different cancers. In recent years, a number of different clinical trials have been performed, and two phase III clinical trials of custirsen evaluating combinations with chemotherapy in patients with metastatic castration-resistant prostate cancer and metastatic non-small cell lung cancer are currently in progress. The aims of this review are to summarize the current state of research on clusterin, predict future research directions and analyze the potential of the clinical application of custirsen in HCC.

| S-EPMC4507096 | biostudies-literature

Looking Ahead: Visual and Anatomical Endpoints in Future Trials of Diabetic Macular Ischemia.

Project description:Diabetic macular ischemia (DMI) is a common complication of diabetic retinopathy that can lead to progressive and irreversible visual loss. Despite substantial clinical burden, there are no treatments for DMI, no validated clinical trial endpoints, and few clinical trials focusing on DMI. Therefore, generating consensus on validated endpoints that can be used in DMI for the development of effective interventions is vital. In this review, we discuss potential endpoints appropriate for use in clinical trials of DMI, and consider the data required to establish acceptable and meaningful endpoints. A combination of anatomical, functional, and patient-reported outcome measures will provide the most complete picture of changes that occur during the progression of DMI. Potential endpoint measures include change in size of the foveal avascular zone measured by optical coherence tomography angiography and change over time in best-corrected visual acuity. However, these endpoints must be supported by further research. We also recommend studies to investigate the natural history and progression of DMI. In addition to improving understanding of how patient demographics and comorbidities such as diabetic macular edema affect clinical trial endpoints, these studies would help to build the consensus definition of DMI that is currently missing from clinical practice and research.

| S-EPMC8619758 | biostudies-literature

Celebrating 1 Year of <i>ATS Scholar</i>. Looking Back and Envisioning the Road Ahead.

Project description: Not available

| S-EPMC8043282 | biostudies-literature

Looking Ahead: Health Impact Assessment of Front-Of-Pack Nutrition Labelling Schema as a Public Health Measure.

Project description:This study aimed to describe the underlying process, used methods and major recommendations emerging from a comprehensive and prospective health impact assessment of the endorsement of a front-of-pack nutrition labelling (FOP-NL) system by the Portuguese health authorities. A mixed-methods approach was used to gather information on the impact of four FOP-NL schemes on consumers' selection of food products according to the perception of their nutritional quality, combining a systematic literature review, focus groups (FG), in-depth individual interviews, and an open-label crossover randomized controlled study. The relevance of FOP-NL as a public health promotion policy has emerged as a consensual idea among either FGs' participants (i.e., consumers and experts), or interviewed stakeholders. Although all of the evaluated FOP-NLs result better than no system on promoting the choice of the healthiest product, the effectiveness of easy-to-interpret FOP-NL among vulnerable groups raised concerns related to the need of integrating specific nutritional information to promote a better self-management of chronic diseases, and related to the level of literacy of consumers, which could impair the usage of FOP-NL. Educational campaigns addressing skills to use FOP-NL is recommended. Furthermore, a monitoring strategy should be considered to evaluate the long-term effectiveness of this policy in promoting healthier food choices, and in reducing diet-related non-communicable diseases burden.

| S-EPMC7913662 | biostudies-literature

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