Attention exerts a strong influence over neuronal processing in cortical areas. It selectively increases firing rates and affects tuning properties, including changing receptive field locations and ...sizes. Although these effects are well studied, their cellular mechanisms are poorly understood. To study the cellular mechanisms, we combined iontophoretic pharmacological analysis of cholinergic receptors with single cell recordings in V1 while rhesus macaque monkeys (Macaca mulatta) performed a task that demanded top-down spatial attention. Attending to the receptive field of the V1 neuron under study caused an increase in firing rates. Here we show that this attentional modulation was enhanced by low doses of acetylcholine. Furthermore, applying the muscarinic antagonist scopolamine reduced attentional modulation, whereas the nicotinic antagonist mecamylamine had no systematic effect. These results demonstrate that muscarinic cholinergic mechanisms play a central part in mediating the effects of attention in V1.
Many problems arising in applications result in the need to probe a probability distribution for functions. Examples include Bayesian nonparametric statistics and conditioned diffusion processes. ...Standard MCMC algorithms typically become arbitrarily slow under the mesh refinement dictated by nonparametric description of the unknown function. We describe an approach to modifying a whole range of MCMC methods, applicable whenever the target measure has density with respect to a Gaussian process or Gaussian random field reference measure, which ensures that their speed of convergence is robust under mesh refinement. Gaussian processes or random fields are fields whose marginal distributions, when evaluated at any finite set of N points, are RN -valued Gaussians. The algorithmic approach that we describe is applicable not only when the desired probability measure has density with respect to a Gaussian process or Gaussian random field reference measure, but also to some useful non-Gaussian reference measures constructed through random truncation. In the applications of interest the data is often sparse and the prior specification is an essential part of the overall modelling strategy. These Gaussian-based reference measures are a very flexible modelling tool, finding wide-ranging application. Examples are shown in density estimation, data assimilation in fluid mechanics, subsurface geophysics and image registration. The key design principle is to formulate the MCMC method so that it is, in principle, applicable for functions; this may be achieved by use of proposals based on carefully chosen time-discretizations of stochastic dynamical systems which exactly preserve the Gaussian reference measure. Taking this approach leads to many new algorithms which can be implemented via minor modification of existing algorithms, yet which show enormous speed-up on a wide range of applied problems.
Chlorhexidine (CHX) is a commonly used antiseptic mouthwash, used by dental practitioners and the public, due to its antimicrobial effects. The aim of this article was to provide a narrative review ...of current antimicrobial uses of CHX relevant to dentistry in the context of oral diseases, highlighting need for further studies to support its safe and appropriate use.
Randomised controlled trials, systematic reviews and national (UK and US) guidelines were consulted where available, with search terms for each subject category entered into MEDLINE, PubMed, Google Scholar and the Cochrane database.
Some evidence existed to support adjunctive short-term use of CHX to manage dental plaque, and reduce clinical symptoms of gingivitis, dry socket, as well as reduce aerosolisation of bacteria. However, use must be weighed alongside the less desirable effects of CHX, including extrinsic staining of teeth, antimicrobial resistance to antiseptic agents and the rare, but fatal, allergic reactions to CHX. Conversely, evidence for the effectiveness of chlorhexidine to manage or prevent periodontitis, dental caries, necrotising periodontal diseases, peri-implantitis, and infections associated with extraction and aerosolised viruses remains less certain.
The use of CHX in dentistry and oral healthcare continues to be widespread and thus it is important that dental practitioners understand that, based on its differential mechanisms of action on different microbes, appropriate clinical and dental use of CHX should be oral disease specific. However, further scientific and clinical research is required before full recommendations can be made.
Recent studies clarify where the most vulnerable species live, where and how humanity changes the planet, and how this drives extinctions. We assess key statistics about species, their distribution, ...and their status. Most are undescribed. Those we know best have large geographical ranges and are often common within them. Most known species have small ranges. The numbers of small-ranged species are increasing quickly, even in well-known taxa. They are geographically concentrated and are disproportionately likely to be threatened or already extinct. Current rates of extinction are about 1000 times the likely background rate of extinction. Future rates depend on many factors and are poised to increase. Although there has been rapid progress in developing protected areas, such efforts are not ecologically representative, nor do they optimally protect biodiversity.
Spheroidal carbonaceous particles (SCPs) are a component of fly-ash, the particulate by-product of industrial high temperature combustion of fuel-oil and coal-series fuels. We provide the first ...evidence that these indelible markers of industrialisation have been deposited in Antarctic ice, thousands of kilometres from any potential source. The earliest observed particle was deposited in an ice layer from 1936 CE. While depositional fluxes are low, chemical analysis of individual SCPs indicates a coal combustion origin.
Transgender healthcare is a rapidly evolving interdisciplinary field. In the last decade, there has been an unprecedented increase in the number and visibility of transgender and gender diverse (TGD) ...people seeking support and gender-affirming medical treatment in parallel with a significant rise in the scientific literature in this area. The World Professional Association for Transgender Health (WPATH) is an international, multidisciplinary, professional association whose mission is to promote evidence-based care, education, research, public policy, and respect in transgender health. One of the main functions of WPATH is to promote the highest standards of health care for TGD people through the Standards of Care (SOC). The SOC was initially developed in 1979 and the last version (SOC-7) was published in 2012. In view of the increasing scientific evidence, WPATH commissioned a new version of the Standards of Care, the SOC-8.
The overall goal of SOC-8 is to provide health care professionals (HCPs) with clinical guidance to assist TGD people in accessing safe and effective pathways to achieving lasting personal comfort with their gendered selves with the aim of optimizing their overall physical health, psychological well-being, and self-fulfillment.
The SOC-8 is based on the best available science and expert professional consensus in transgender health. International professionals and stakeholders were selected to serve on the SOC-8 committee. Recommendation statements were developed based on data derived from independent systematic literature reviews, where available, background reviews and expert opinions. Grading of recommendations was based on the available evidence supporting interventions, a discussion of risks and harms, as well as the feasibility and acceptability within different contexts and country settings.
A total of 18 chapters were developed as part of the SOC-8. They contain recommendations for health care professionals who provide care and treatment for TGD people. Each of the recommendations is followed by explanatory text with relevant references. General areas related to transgender health are covered in the chapters Terminology, Global Applicability, Population Estimates, and Education. The chapters developed for the diverse population of TGD people include Assessment of Adults, Adolescents, Children, Nonbinary, Eunuchs, and Intersex Individuals, and people living in Institutional Environments. Finally, the chapters related to gender-affirming treatment are Hormone Therapy, Surgery and Postoperative Care, Voice and Communication, Primary Care, Reproductive Health, Sexual Health, and Mental Health.
The SOC-8 guidelines are intended to be flexible to meet the diverse health care needs of TGD people globally. While adaptable, they offer standards for promoting optimal health care and guidance for the treatment of people experiencing gender incongruence. As in all previous versions of the SOC, the criteria set forth in this document for gender-affirming medical interventions are clinical guidelines; individual health care professionals and programs may modify these in consultation with the TGD person.
The Red River shear zone (RRSZ) is a major left‐lateral strike‐slip shear zone, containing a ductilely deformed metamorphic core bounded by brittle strike‐slip and normal faults, which stretches for ...>1000 km from Tibet through Yunnan and North Vietnam to the South China Sea. The RRSZ exposes four high‐grade metamorphic core complexes along its length. Various lithologies from the southernmost core complex, the Day Nui Con Voi (DNCV), North Vietnam, provide new constraints on the tectonic and metamorphic evolution of this region prior to and following the initial India–Asia collision. Analysis of a weakly deformed anatectic paragneiss using P–T pseudosections constructed in the MnO–Na2O–CaO–K2O–FeO–MgO–Al2O3–SiO2–H2O–TiO2–O (MnNCKFMASHTO) system provides prograde, peak and retrograde metamorphic conditions, and in situ U–Th–Pb geochronology of metamorphic monazite yields texturally controlled age constraints. Tertiary metamorphism and deformation, overprinting earlier Triassic metamorphism associated with the Indosinian orogeny and possible Cretaceous metamorphism, are characterized by peak metamorphic conditions of ~805 °C and ~8.5 kbar between c. 38 and 34 Ma. Exhumation occurred along a steep retrograde P–T path with final melt crystallizing at the solidus at ≥~5.5 kbar at ~790 °C. Further exhumation at ~640–700 °C and ~4–5 kbar at c. 31 Ma occurred at subsolidus conditions. U–Pb geochronological analysis of monazite from a strongly deformed pre‐kinematic granite dyke from the flank of the DNCV provides further evidence for exhumation at this time. Magmatic grains suggest initial emplacement at 66.0 ± 1.0 Ma prior to the India–Asia collision, whereas grains with metamorphic characteristics indicate later growth at 30.6 ± 0.4 Ma. Monazite grains from a cross‐cutting post‐kinematic dyke within the core of the DNCV antiform provide a minimum age constraint of 25.2 ± 1.4 Ma for the termination of fabric development. A separate and significant episode of monazite growth at c. 83–69 Ma is suggested to be the result of fluid‐assisted recrystallization following the emplacement of magmatic units.
The most common form of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting adult motor neurons, is caused by dominant mutations in the ubiquitously expressed Cu-Zn Superoxide ...dismutase (SOD1). In chimeric mice that are mixtures of normal and SOD1 mutant-expressing cells, toxicity to motor neurons is shown to require damage from mutant SOD1 acting within nonneuronal cells. Normal motor neurons in SOD1 mutant chimeras develop aspects of ALS pathology. Most important, nonneuronal cells that do not express mutant SOD1 delay degeneration and significantly extend survival of mutant-expressing motor neurons.
Pleuropulmonary blastoma is a rare childhood malignancy of lung mesenchymal cells that can remain dormant as epithelial cysts or progress to high-grade sarcoma. Predisposing germline loss-of-function ...DICER1 variants have been described. We sought to uncover additional contributors through whole exome sequencing of 15 tumor/normal pairs, followed by targeted resequencing, miRNA analysis and immunohistochemical analysis of additional tumors. In addition to frequent biallelic loss of TP53 and mutations of NRAS or BRAF in some cases, each case had compound disruption of DICER1: a germline (12 cases) or somatic (3 cases) loss-of-function variant plus a somatic missense mutation in the RNase IIIb domain. 5p-Derived microRNA (miRNA) transcripts retained abnormal precursor miRNA loop sequences normally removed by DICER1. This work both defines a genetic interaction landscape with DICER1 mutation and provides evidence for alteration in miRNA transcripts as a consequence of DICER1 disruption in cancer.
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